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1
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Chung Y, Lee HW, Park JH, Yoo CH, Son BH, Kim K. Mutant pattern of p53 predicts local recurrence and poor survival rate in gastric cancer. Histol Histopathol 2023; 38:999-1007. [PMID: 36847420 DOI: 10.14670/hh-18-596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2023]
Abstract
BACKGROUND TP53 mutation is a poor prognostic factor for various organ malignancies such as colorectal cancer, breast cancer, ovarian cancer, hepatocellular carcinoma, lung adenocarcinoma and clinical pathologists previously evaluated it using immunohistochemistry for p53. The clinicopathologic significance of p53 expression in gastric cancer remains unclear due to inconsistent classification methods. METHODS Immunohistochemistry for p53 protein was performed using tissue microarray blocks generated from 725 cases of gastric cancer, and p53 expression was divided into three staining patterns using a semi-quantitative ternary classifier: heterogeneous (wild type), overexpression, and absence (mutant pattern). RESULTS Mutant pattern of p53 expression had a male predominance, greater frequency in cardia/fundus, higher pT stage, frequent lymph node metastasis, local recurrence clinically, and more differentiated histology microscopically compared with wild type. In survival analysis, p53 mutant pattern was associated with worse recurrent-free survival and overall survival rates, and significance was maintained in subgroup analysis of early versus advanced gastric cancers. In Cox regression analysis, p53 mutant pattern was a significant predicting factor for local recurrence (relative risk (RR=4.882, p<0.001)) and overall survival (RR=2.040, p=0.007). The p53 mutant pattern remained significant for local recurrence (RR=2.934, p=0.018) in multivariate analyses. CONCLUSIONS Mutant p53 pattern on immunohistochemistry was a significant prognostic factor for local recurrence and poor overall survival in gastric cancer.
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Affiliation(s)
- Yumin Chung
- Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Hyoun Wook Lee
- Department of Pathology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea
| | - Jung Ho Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Chang Hak Yoo
- Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Byung Ho Son
- Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyungeun Kim
- Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
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2
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Halim F, Azhar Y, Suwarman S, Hernowo B. p53 Mutation as Plausible Predictor for Endocrine Resistance Therapy in Luminal Breast Cancer. F1000Res 2022; 11:330. [PMID: 36519010 PMCID: PMC9718986 DOI: 10.12688/f1000research.108628.2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/11/2022] [Indexed: 12/05/2022] Open
Abstract
Endocrine therapy resistance in Luminal Breast Cancer is a significant issue to be tackled, but currently, no specific biomarker could be used to anticipate this event. p53 mutation is widely known as one of Breast Cancer's most prominent genetic alterations. Its mutation could generate various effects in Estrogen Receptor and Progesterone Receptor molecular works, tangled in events leading to the aggravation of endocrine therapy resistance. Hence the possibility of p53 mutation utilization as an endocrine therapy resistance predictive biomarker is plausible. The purpose of this review is to explore the latest knowledge of p53 role in Estrogen Receptor and Progesterone Receptor molecular actions, thus aggravating the Endocrine Therapy resistance in Luminal Breast Cancer, from which we could define possibilities and limitations to utilize p53 as the predictive biomarker of endocrine therapy resistance in Luminal Breast Cancer.
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Affiliation(s)
- Freda Halim
- Department of Surgery, Pelita Harapan University, Tangerang, Indonesia,
| | - Yohana Azhar
- Department of Surgery - Oncology, Head and Neck Division, Hasan Sadikin General Hospital, Universitas Padjajaran, Bandung, Indonesia
| | - Suwarman Suwarman
- Department of Anesthesiology and Intensive Care, Hasan Sadikin General Hospital, Universitas Padjajaran, Bandung, Indonesia
| | - Bethy Hernowo
- Department of Anatomical Pathology, Universitas Padjajaran, Bandung, West Java, Indonesia
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D'Alessandro R, Refolo MG, Schirizzi A, De Leonardis G, Donghia R, Guerra V, Giannelli G, Lolli IR, Laterza MM, De Vita F, Messa C, Lotesoriere C. Variations in Circulating Levels of Angiopoietin-2 Over Time Are Predictive of Ramucirumab-Paclitaxel Therapy Outcome in Advanced Gastric Cancer: Results of Prospective Study. Front Oncol 2022; 12:862116. [PMID: 35463372 PMCID: PMC9019360 DOI: 10.3389/fonc.2022.862116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 02/25/2022] [Indexed: 11/13/2022] Open
Abstract
The combination of paclitaxel and ramucirumab is the second-line therapy of choice in the treatment of advanced gastric cancer. To date, no biomarkers are available in gastric cancer to predict the outcome of antiangiogenic therapy. The present prospective study included 35 patients undergoing second-line therapy with ramucirumab and paclitaxel. Serum samples were systematically collected from the beginning of therapy and at each cycle until disease progression. Multiplex analysis of a panel of angiogenic factors identified markers for which the changes at defined time intervals were significantly different in patients with progression-free survival ≤3 (Rapid Progression Group) compared to those with progression-free survival >3 (Control Disease Group). Comparative analysis revealed significantly different results in the two groups of patients for VEGFC and Angiopoietin-2, both involved in angiogenesis and lymphangiogenesis. VEGFC increased in the progressive-disease group, while it decreased in the control-disease group. This decrease persisted beyond the third cycle, and it was statistically significant compared to the basal level in patients with longer progression-free survival. Angiopoietin-2 decreased significantly after 2 months of therapy. At progression time, there was a significant increase in VEGFC and Angiopoietin-2, suggesting the activation pathways counteracting the blockade of VEGFR2 by ramucirumab. Overall results showed that a greater change in VEGFC and Angiopoietin-2 levels measured at the beginning of the third cycle of therapy corresponded to a lower risk of progression and thus to longer progression-free survival.
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Affiliation(s)
- Rosalba D'Alessandro
- Laboratory of Experimental Oncology, National Institute of Gastroenterology, "Saverio de Bellis" Research Hospital, Castellana Grotte, Italy
| | - Maria Grazia Refolo
- Laboratory of Experimental Oncology, National Institute of Gastroenterology, "Saverio de Bellis" Research Hospital, Castellana Grotte, Italy
| | - Annalisa Schirizzi
- Laboratory of Experimental Oncology, National Institute of Gastroenterology, "Saverio de Bellis" Research Hospital, Castellana Grotte, Italy
| | - Giampiero De Leonardis
- Laboratory of Experimental Oncology, National Institute of Gastroenterology, "Saverio de Bellis" Research Hospital, Castellana Grotte, Italy
| | - Rossella Donghia
- National Institute of Gastroenterology, "Saverio de Bellis" Research Hospital, Castellana Grotte, Italy
| | - Vito Guerra
- National Institute of Gastroenterology, "Saverio de Bellis" Research Hospital, Castellana Grotte, Italy
| | - Gianluigi Giannelli
- Scientific Direction, National Institute of Gastroenterology "Saverio de Bellis", Research Hospital, Castellana Grotte, Italy
| | - Ivan Roberto Lolli
- Medical Oncology Unit, National Institute of Gastroenterology, "Saverio de Bellis" Research Hospital, Castellana Grotte, Italy
| | - Maria Maddalena Laterza
- Complex Operating Unit Oncologia, Local Health Authority Napoli 2 Nord, P.O. "S.M. delle Grazie", Naples, Italy
| | - Ferdinando De Vita
- Division of Medical Oncology, Department of Precision Medicine, School of Medicine, University of Study of Campania "Luigi Vanvitelli", Naples, Italy
| | - Caterina Messa
- Laboratory of Experimental Oncology, National Institute of Gastroenterology, "Saverio de Bellis" Research Hospital, Castellana Grotte, Italy
| | - Claudio Lotesoriere
- Medical Oncology Unit, National Institute of Gastroenterology, "Saverio de Bellis" Research Hospital, Castellana Grotte, Italy
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4
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Lee HS, Lee IH, Kang K, Park SI, Jung M, Yang SG, Kwon TW, Lee DY. A Network Pharmacology Perspective Investigation of the Pharmacological Mechanisms of the Herbal Drug FDY003 in Gastric Cancer. Nat Prod Commun 2022; 17. [DOI: 10.1177/1934578x211073030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2025] Open
Abstract
Gastric cancer (GC) is one of the most common and deadly malignant tumors worldwide. While the application of herbal drugs for GC treatment is increasing, the multicompound–multitarget pharmacological mechanisms involved are yet to be elucidated. By adopting a network pharmacology strategy, we investigated the properties of the anticancer herbal drug FDY003 against GC. We found that FDY003 reduced the viability of human GC cells and enhanced their chemosensitivity. We also identified 8 active phytochemical compounds in FDY003 that target 70 GC-associated genes and proteins. Gene ontology (GO) enrichment analysis suggested that the targets of FDY003 are involved in various cellular processes, such as cellular proliferation, survival, and death. We further identified various major FDY003 target GC-associated pathways, including PIK3-Akt, MAPK, Ras, HIF-1, ErbB, and p53 pathways. Taken together, the overall analysis presents insight at the systems level into the pharmacological activity of FDY003 against GC.
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Affiliation(s)
- Ho-Sung Lee
- The Fore, Songpa-gu, Seoul, Republic of Korea
- Forest Hospital, Jongno-gu, Seoul, Republic of Korea
| | - In-Hee Lee
- The Fore, Songpa-gu, Seoul, Republic of Korea
| | - Kyungrae Kang
- Forest Hospital, Jongno-gu, Seoul, Republic of Korea
| | - Sang-In Park
- Forestheal Hospital, Songpa-gu, Seoul, Republic of Korea
| | - Minho Jung
- Forest Hospital, Songpa-gu, Seoul, Republic of Korea
| | - Seung Gu Yang
- Kyunghee Naro Hospital, Bundang-gu, Seongnam, Republic of Korea
| | - Tae-Wook Kwon
- Forest Hospital, Jongno-gu, Seoul, Republic of Korea
| | - Dae-Yeon Lee
- The Fore, Songpa-gu, Seoul, Republic of Korea
- Forest Hospital, Jongno-gu, Seoul, Republic of Korea
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Tamagawa H, Aoyama T, Numata M, Maezawa Y, Kazama K, Astumi Y, Hara K, Kano K, Yukawa N, Saeki H, Godai T, Oshima T, Goda M, Rino Y, Masuda M. Prognostic significance of the preoperative C-reactive protein-to-albumin ratio in patients with colorectal cancer. J Cancer Res Ther 2021; 17:1075-1080. [PMID: 34528567 DOI: 10.4103/jcrt.jcrt_355_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Background The aim of the present study was to determine the utility of the C-reactive protein-to-albumin ratio (CAR) for predicting the overall survival (OS) in locally advanced colorectal cancer (CRC) patients. Patients and Methods This retrospective multicenter study was performed using data from a prospectively maintained database of pathological Stage II or III patients undergoing CRC surgery at the Yokohama City University, Department of Surgery, and its affiliated institutions between April 2000 and March 2016. The risk factors for the OS were identified. Results A CAR of 0.03 was considered to be the optimal cutoff point for classification based on the 1-, 3-, and 5-year survival rates and receiver operating characteristic curve. The OS rates at 3 and 5 years after surgery were 92.4% and 85.7% in the CAR-low group, respectively, and 86.7% and 81.1% in the CAR-high group. A multivariate analysis showed that the CAR was a significant independent risk factor for the OS. When comparing the patients' demographic and clinical characteristics between the CAR ≤0.03 and >0.03 groups, the incidence of patients who received adjuvant chemotherapy and the incidence of postoperative complications were significantly different between the two groups. Conclusion The present study showed that the preoperative CAR was a risk factor for the OS in patients who underwent surgery for CRC. To improve the patients' survival, CAR might be a useful tool for devising treatment strategies.
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Affiliation(s)
- Hiroshi Tamagawa
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Toru Aoyama
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Masakatsu Numata
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Yukio Maezawa
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Keisuke Kazama
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Yosuke Astumi
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Kentaro Hara
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Kazuki Kano
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Norio Yukawa
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Hiroyuki Saeki
- Department of Surgery, Yokohama Minamikyousai Hospital, Yokohama, Japan
| | - Tenii Godai
- Department of Surgery, Fujisawa Shonandai Hospital, Fujisawa, Japan
| | - Takashi Oshima
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Motohiko Goda
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Yasushi Rino
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Munetaka Masuda
- Department of Surgery, Yokohama City University, Yokohama, Japan
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Murad LD, Silva TDQ, Schilithz AOC, Monteiro MC, Murad LB, Fialho E. Body Mass Index Alters the Predictive Value of the Neutrophil-to-Lymphocyte Ratio and Systemic Inflammation Response Index in Laryngeal Squamous Cell Carcinoma Patients. Nutr Cancer 2021; 74:1261-1269. [PMID: 34278900 DOI: 10.1080/01635581.2021.1952447] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Laryngeal squamous cell carcinoma (LSCC) is a frequent cancer subtype among head and neck cancers. Exacerbated inflammation and nutritional deficit are common features in this type of cancer and can be used as a prognostic marker. This study aimed to investigate the relationship between body mass index (BMI), neutrophil-to-lymphocyte ratio (NLR), and systemic inflammation response index (SIRI) on overall survival (OS) of LSCC patients. In this retrospective cohort study, 168 patients were followed for 5 years. Data on clinical factors, patients' life habits, height, weight, and hematological parameters were collected. BMI, NLR, and SIRI were calculated. Pretreatment NLR≥ 2.02 and SIRI≥ 1160.85 were independent prognostic factors for poor OS. Low BMI did not significantly affect the OS. However, the inflammatory parameters had their predictive capacity altered when stratified by the BMI classification. NLR≥ 2.02 + Low BMI or SIRI≥ 1160.85 + Low BMI increased in 8.6 and 3.8 times the risk of death, respectively. In contrast, stratification by normal/high BMI classification eliminated the predictive capacity of NLR and SIRI. Here, we demonstrated the possible ability of BMI to change the prognostic capacity of inflammatory markers NLR and SIRI in patients with LSCC.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1952447.
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Affiliation(s)
- Luana Dalbem Murad
- Nutrition and Dietetics Section, Brazilian National Cancer Institute José Alencar Gomes da Silva (INCA), Rio de Janeiro, RJ, Brazil.,Basic and Experimental Nutrition Department, Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Thays de Queiroz Silva
- Basic and Experimental Nutrition Department, Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Arthur Orlando Corrêa Schilithz
- Nutrition and Dietetics Section, Brazilian National Cancer Institute José Alencar Gomes da Silva (INCA), Rio de Janeiro, RJ, Brazil
| | - Mariana Costa Monteiro
- Basic and Experimental Nutrition Department, Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Leonardo Borges Murad
- Nutrition and Dietetics Section, Brazilian National Cancer Institute José Alencar Gomes da Silva (INCA), Rio de Janeiro, RJ, Brazil
| | - Eliane Fialho
- Basic and Experimental Nutrition Department, Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
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Different effects of p53 protein overexpression on the survival of gastric cancer patients according to Lauren histologic classification: a retrospective study. Gastric Cancer 2021; 24:844-857. [PMID: 33598811 DOI: 10.1007/s10120-021-01163-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 01/21/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Inactivation of TP53, a tumor suppressor gene, is associated with the development of several malignancies, including gastric cancer (GC). The present study aimed to evaluate the correlation between the overexpression of p53 and survival in different Lauren-type GCs. METHODS From May 2003 to December 2019, 3608 GC patients treated endoscopically or surgically at the Seoul National University Bundang Hospital were enrolled for the study. Immunohistochemical staining for p53 was performed on all endoscopic and surgical gastric specimens. Clinicopathologic characteristics with Lauren classification, survival rate, and cancer recurrence were analyzed according to p53 overexpression. RESULTS Among 3608 GC patients, p53 overexpression was seen in 1334 patients (37%). p53 overexpression was associated with lower depth of invasion (P = 0.026) and Early gastric cancer (P = 0.044) in intestinal-type GC, and with advanced TNM stage (P < 0.001) and Advanced gastric cancer (P < 0.001) in diffuse-type GC. The overall survival (OS) and GC-specific survival (GCSS) were significantly lower in p53 overexpression positive patients. This significance was more pronounced and enhanced in the diffuse-type GC and was absent in the intestinal-type GC. In multivariate analyses, p53 overexpression was associated with poor OS in both subtypes of GC and cancer recurrence in diffuse-type GC. (OS in intestinal-type: adjusted hazard ratio [aHR] = 1.423, P = 0.022; OS in diffuse-type: aHR = 1.401 P = 0.035; cancer recurrence in diffuse-type: aHR = 1.502, P = 0.039). CONCLUSION p53 overexpression was associated with poor prognosis in GC, especially in diffuse-type. In addition, p53 overexpression was associated with early stage disease in intestinal-type GC and with advanced stage disease in diffuse-type GC.
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8
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Isoforms of the p53 Family and Gastric Cancer: A Ménage à Trois for an Unfinished Affair. Cancers (Basel) 2021; 13:cancers13040916. [PMID: 33671606 PMCID: PMC7926742 DOI: 10.3390/cancers13040916] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 02/06/2021] [Accepted: 02/17/2021] [Indexed: 12/17/2022] Open
Abstract
Simple Summary The p53 family is a complex family of transcription factors with different cellular functions that are involved in several physiological processes. A massive amount of data has been accumulated on their critical role in the tumorigenesis and the aggressiveness of cancers of different origins. If common features are observed, there are numerous specificities that may reflect particularities of the tissues from which the cancers originated. In this regard, gastric cancer tumorigenesis is rather remarkable, as it is induced by bacterial and viral infections, various chemical carcinogens, and familial genetic alterations, which provide an example of the variety of molecular mechanisms responsible for cell transformation and how they impact the p53 family. This review summarizes the knowledge gathered from over 40 years of research on the role of the p53 family in gastric cancer, which still displays one of the most elevated mortality rates amongst all types of cancers. Abstract Gastric cancer is one of the most aggressive cancers, with a median survival of 12 months. This illustrates its complexity and the lack of therapeutic options, such as personalized therapy, because predictive markers do not exist. Thus, gastric cancer remains mostly treated with cytotoxic chemotherapies. In addition, less than 20% of patients respond to immunotherapy. TP53 mutations are particularly frequent in gastric cancer (±50% and up to 70% in metastatic) and are considered an early event in the tumorigenic process. Alterations in the expression of other members of the p53 family, i.e., p63 and p73, have also been described. In this context, the role of the members of the p53 family and their isoforms have been investigated over the years, resulting in conflicting data. For instance, whether mutations of TP53 or the dysregulation of its homologs may represent biomarkers for aggressivity or response to therapy still remains a matter of debate. This uncertainty illustrates the lack of information on the molecular pathways involving the p53 family in gastric cancer. In this review, we summarize and discuss the most relevant molecular and clinical data on the role of the p53 family in gastric cancer and enumerate potential therapeutic innovative strategies.
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Giuppi M, La Salvia A, Evangelista J, Ghidini M. The Role and Expression of Angiogenesis-Related miRNAs in Gastric Cancer. BIOLOGY 2021; 10:biology10020146. [PMID: 33673057 PMCID: PMC7918665 DOI: 10.3390/biology10020146] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 02/08/2021] [Accepted: 02/08/2021] [Indexed: 02/07/2023]
Abstract
Gastric cancer (GC) is the fifth most frequently diagnosed malignant tumor and the third highest cause of cancer mortality worldwide. For advanced GC, many novel drugs and combinations have been tested, but results are still disappointing, and the disease is incurable in the majority of cases. In this regard, it is critical to investigate the molecular mechanisms underlying GC development. Angiogenesis is one of the hallmarks of cancer with a fundamental role in GC growth and progression. Ramucirumab, a monoclonal antibody that binds to vascular endothelial growth factor-2 (VEGFR-2), is approved in the treatment of advanced and pretreated GC. However, no predictive biomarkers for ramucirumab have been identified so far. Micro RNAs (miRNAs) are a class of evolutionarily-conserved single-stranded non-coding RNAs that play an important role (via post-transcriptional regulation) in essentially all biologic processes, such as cell proliferation, differentiation, apoptosis, survival, invasion, and migration. In our review, we aimed to analyze the available data on the role of angiogenesis-related miRNAs in GC.
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Affiliation(s)
- Martina Giuppi
- Faculty of Medicine, CEU San Pablo University, 28003 Madrid, Spain;
| | - Anna La Salvia
- Department of Oncology, University Hospital 12 de Octubre, 28041 Madrid, Spain;
| | - Jessica Evangelista
- Thoracic Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy;
| | - Michele Ghidini
- Oncology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
- Correspondence: ; Tel.: +39-02-5503-2660; Fax: +39-02-5503-2659
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10
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Pectasides E, Chatzidakis I, Kotoula V, Koliou GA, Papadopoulou K, Giannoulatou E, Giannouzakos VG, Bobos M, Papavasileiou C, Chrisafi S, Florou A, Pectasides D, Fountzilas G. Prognostic Biomarkers in Early-stage Gastric Adenocarcinoma Treated With Adjuvant Chemoradiotherapy. Cancer Genomics Proteomics 2020; 17:277-290. [PMID: 32345669 DOI: 10.21873/cgp.20188] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 02/21/2020] [Accepted: 02/29/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND/AIM Early-stage gastric cancer has a high risk of recurrence, despite trimodality therapy with surgery, chemotherapy and radiation. To improve patient selection for adjuvant chemoradiotherapy, we evaluated the prognostic significance of immunohistochemical and genetic biomarkers in patients with resected gastric adenocarcinoma. PATIENTS AND METHODS Tumors from 119 patients were subjected to immunohistochemistry for 12 protein biomarkers, as well as next-generation sequencing. Clinical and biomarker data were available for 91 patients. RESULTS EBV-positive tumors and tumors with mutations had higher intratumoral CD8 tumor-infiltrating lymphocyte density (p=0.009 and p=0.017, respectively). PIK3CA mutations were correlated with VEGFA overexpression (p=0.042), while KRAS mutations and HER2 expression were mutually exclusive (p=0.036). PTEN expression univariately confirmed longer overall survival (HR=0.27; p=0.046), while there was a trend between the presence of KRAS mutations and inferior disease-free and overall survival. CONCLUSION PTEN protein expression and KRAS mutations may predict disease outcome in early-stage gastric cancer. These results need to be further validated in larger cohorts.
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Affiliation(s)
- Eirini Pectasides
- Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, U.S.A.
| | - Ioannis Chatzidakis
- Second Department of Internal Medicine, Propaedeutic, Oncology Section, National and Kapodistrian University of Athens, University General Hospital Attikon, Athens, Greece
| | - Vassiliki Kotoula
- Department of Pathology, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece.,Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece
| | | | - Kyriaki Papadopoulou
- Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Eleni Giannoulatou
- Bioinformatics and Systems Medicine Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.,The University of New South Wales, Kensington, NSW, Australia
| | - Vasilios G Giannouzakos
- Department of Radiation Therapy, Papageorgiou Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece
| | - Mattheos Bobos
- Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Christos Papavasileiou
- Surgical Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece
| | - Sofia Chrisafi
- Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Aikaterini Florou
- Second Department of Internal Medicine, Propaedeutic, Oncology Section, National and Kapodistrian University of Athens, University General Hospital Attikon, Athens, Greece
| | - Dimitrios Pectasides
- Second Department of Internal Medicine, Propaedeutic, Oncology Section, National and Kapodistrian University of Athens, University General Hospital Attikon, Athens, Greece
| | - George Fountzilas
- Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece.,Aristotle University of Thessaloniki, Thessaloniki, Greece.,German Oncology Center, Limassol, Cyprus
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11
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Sakamoto Y, Mima K, Imai K, Miyamoto Y, Tokunaga R, Akiyama T, Daitoku N, Hiyoshi Y, Iwatsuki M, Nagai Y, Baba Y, Iwagami S, Yamashita YI, Yoshida N, Baba H. Preoperative C-reactive protein-to-albumin ratio and clinical outcomes after resection of colorectal liver metastases. Surg Oncol 2020; 35:243-248. [PMID: 32932221 DOI: 10.1016/j.suronc.2020.09.014] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 08/13/2020] [Accepted: 09/08/2020] [Indexed: 12/16/2022]
Abstract
PURPOSE Accumulating evidence suggests that the inflammatory tumor microenvironment can potentiate tumor progression and metastasis. The C-reactive protein-to-albumin ratio (CAR) is a novel inflammation-based prognostic score. This study was performed to examine the associations of the preoperative CAR with clinical outcomes in patients with colorectal liver metastases (CRLM) after curative resection. METHODS We retrospectively assessed the preoperative CAR in 184 patients who underwent curative resection for CRLM from November 2001 to January 2018 at Kumamoto University (Kumamoto, Japan). The optimal cutoff level of the preoperative CAR was determined by survival classification and regression tree (CART) analysis. We compared clinicopathological factors and prognoses between the high-CAR and low-CAR groups. A Cox proportional hazards model was used to calculate hazard ratios (HRs), controlling for potential confounders. RESULTS A higher preoperative CAR was associated with worse overall survival (OS) (p < 0.0001) and recurrence-free survival (RFS) (p = 0.003). Applying survival CART analysis, the high-CAR group comprised 33 patients (17.9%). In the multivariate analyses, a high CAR was independently associated with shorter OS (HR, 2.82; 95% confidence interval, 1.63-4.72; p = 0.0004) and RFS (HR, 1.62; 95% confidence interval, 1.02-2.49; p = 0.040). A high CAR was associated with a large tumor size, high serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels, high intraoperative blood loss, and more postoperative complications. CONCLUSION A high preoperative CAR is associated with shorter OS and RFS and might serve as a prognostic marker for patients with CRLM after curative resection.
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Affiliation(s)
- Yuki Sakamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Kosuke Mima
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; Department of Surgery, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yuji Miyamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Ryuma Tokunaga
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Takahiko Akiyama
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Nobuya Daitoku
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yukiharu Hiyoshi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Masaaki Iwatsuki
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yohei Nagai
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yoshifumi Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Shiro Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yo-Ichi Yamashita
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Naoya Yoshida
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
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12
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Utsumi M, Aoki H, Nagahisa S, Nishimura S, Une Y, Kimura Y, Watanabe M, Taniguchi F, Arata T, Katsuda K, Tanakaya K. Preoperative C-Reactive Protein/Albumin Ratio as a Predictive Factor for Gallbladder Carcinoma. In Vivo 2020; 34:1901-1908. [PMID: 32606161 PMCID: PMC7439860 DOI: 10.21873/invivo.11986] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 04/06/2020] [Accepted: 04/08/2020] [Indexed: 12/26/2022]
Abstract
BACKGROUND/AIM The C-reactive protein (CRP) to albumin ratio (CAR) is associated with outcomes in patients with sepsis. We aimed to evaluate the significance of preoperative CAR in therapeutic outcomes after gallbladder carcinoma (GBC) resection. PATIENTS AND METHODS Fifty-three patients who underwent surgical resection for GBC between January 2008 and September 2019 were enrolled. We retrospectively investigated the relation between preoperative CAR and overall and disease-free survival. RESULTS The optimal cut-off CAR was 0.07. Multivariate analysis showed that i) R1 or R2 resection (p=0.033), ii) advanced tumor stage (p=0.047), iii) CAR≥0.07 (p=0.011), and iv) postoperative complications (p=0.028) were significant independent predictors of overall survival; moreover, higher carbohydrate antigen levels (p=0.036) and R1 or R2 resection (p<0.001) were significant independent predictors of disease-free survival. CONCLUSION Preoperative CAR may be a significant independent predictor of long-term outcomes after GBC resection.
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Affiliation(s)
- Masashi Utsumi
- Department of Surgery, National Hospital Organization, Iwakuni Clinical Center, Yamaguchi, Japan
| | - Hideki Aoki
- Department of Surgery, National Hospital Organization, Iwakuni Clinical Center, Yamaguchi, Japan
| | - Seichi Nagahisa
- Department of Surgery, National Hospital Organization, Iwakuni Clinical Center, Yamaguchi, Japan
| | - Seitaro Nishimura
- Department of Surgery, National Hospital Organization, Iwakuni Clinical Center, Yamaguchi, Japan
| | - Yuta Une
- Department of Surgery, National Hospital Organization, Iwakuni Clinical Center, Yamaguchi, Japan
| | - Yuji Kimura
- Department of Surgery, National Hospital Organization, Iwakuni Clinical Center, Yamaguchi, Japan
| | - Megumi Watanabe
- Department of Surgery, National Hospital Organization, Iwakuni Clinical Center, Yamaguchi, Japan
| | - Fumitaka Taniguchi
- Department of Surgery, National Hospital Organization, Iwakuni Clinical Center, Yamaguchi, Japan
| | - Takashi Arata
- Department of Surgery, National Hospital Organization, Iwakuni Clinical Center, Yamaguchi, Japan
| | - Koh Katsuda
- Department of Surgery, National Hospital Organization, Iwakuni Clinical Center, Yamaguchi, Japan
| | - Kohji Tanakaya
- Department of Surgery, National Hospital Organization, Iwakuni Clinical Center, Yamaguchi, Japan
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13
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Dan J, Tan J, Huang J, Zhang X, Guo Y, Huang Y, Yang J. The dynamic change of neutrophil to lymphocyte ratio is predictive of pathological complete response after neoadjuvant chemotherapy in breast cancer patients. Breast Cancer 2020; 27:982-988. [PMID: 32306184 DOI: 10.1007/s12282-020-01096-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 04/12/2020] [Indexed: 01/10/2023]
Abstract
BACKGROUND The pre-treatment neutrophil-lymphocyte ratio (NLR) has been reported to be a predictive factor for pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) in breast cancer patients. However, whether the dynamic change of post-treatment neutrophil to lymphocyte ratio (delta-NLR) can better predict the same outcome remains unclear. MATERIALS AND METHODS We retrospectively analyzed 242 consecutive patients affected by breast cancer and candidates of NACT. The complete blood cell counts before and after NACT were evaluated to calculate NLR. The relationships between delta-NLR and pCR, along with other clinical-pathological characteristics were analyzed. Univariate and multivariate analyses were performed using a logistic regression model. RESULTS Of the 242 patients, 65 (26.9%) achieved a pCR. Pre-treatment NLR and post-treatment NLR were not significantly associated with pCR if analyzed separately in multivariate analyses. However, when combining together, patients with delta-NLR < 0 profile achieved a significantly higher rate of pCR compared to those with delta-NLR ≥ 0 (OR 2.84, 95% CI 1.35-5.96, p = 0.006). Additionally, the predictive value of delta-NLR was independent from common prognostic factors such as Ki-67, and molecular subtypes. CONCLUSIONS Delta-NLR, rather than pre-treatment or post-treatment NLR is associated with pCR rate, suggesting that the dynamic change of NLR may be an important factor predicting the response to NACT in breast cancer patients.
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Affiliation(s)
- Jiaqiang Dan
- Department of Breast Surgery, Chengdu Fifth People's Hospital, Chengdu, 611130, Sichuan, People's Republic of China.
| | - Jinya Tan
- Department of Rheumatology and Immunology, Wenjiang District People's Hospital of Chengdu City, Chengdu, 611130, Sichuan, People's Republic of China
| | - Junhua Huang
- Department of Breast Surgery, Chengdu Fifth People's Hospital, Chengdu, 611130, Sichuan, People's Republic of China
| | - Xiaoli Zhang
- Department of Breast Surgery, Chengdu Fifth People's Hospital, Chengdu, 611130, Sichuan, People's Republic of China
| | - Yao Guo
- Department of Breast Surgery, Chengdu Fifth People's Hospital, Chengdu, 611130, Sichuan, People's Republic of China
| | - Yunkun Huang
- Department of Breast Surgery, Chengdu Fifth People's Hospital, Chengdu, 611130, Sichuan, People's Republic of China
| | - Jin Yang
- Department of Breast Surgery, Chengdu Fifth People's Hospital, Chengdu, 611130, Sichuan, People's Republic of China
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14
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Van Cutsem E, Muro K, Cunningham D, Bodoky G, Sobrero A, Cascinu S, Ajani J, Oh SC, Al-Batran SE, Wainberg ZA, Wijayawardana SR, Melemed S, Ferry D, Hozak RR, Ohtsu A. Biomarker analyses of second-line ramucirumab in patients with advanced gastric cancer from RAINBOW, a global, randomized, double-blind, phase 3 study. Eur J Cancer 2020; 127:150-157. [PMID: 32014812 DOI: 10.1016/j.ejca.2019.10.026] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Revised: 10/21/2019] [Accepted: 10/27/2019] [Indexed: 01/11/2023]
Abstract
BACKGROUND The RAINBOW trial showed that second-line ramucirumab with paclitaxel prolongs overall survival (OS) and progression-free survival (PFS) compared with placebo plus paclitaxel for treatment of advanced gastric/gastroesophageal junction cancer. Plasma samples were collected from patients during the trial and tested to identify predictive and prognostic biomarkers. PATIENTS AND METHODS Circulating factors in plasma samples from mutually exclusive subsets of RAINBOW patients were assayed using: Intertek assays (24 markers, 380 samples, 57% of patients) and Lilly-developed assay (LDA) platform (5 markers, 257 samples, 39% of patients). Time-trend plots were generated for each marker from the Intertek assays. Baseline patient data were dichotomized into low- and high-marker subgroups. Markers were analyzed for predictive effects using interaction models and for prognostic effects using main-effects models. RESULTS The Intertek and LDA populations were representative of the full trial population. Plasma levels of VEGF-D and PlGF increased from baseline levels during treatment, then declined after treatment discontinued. Angiopoietin-2 exhibited a decrease during treatment, then increased after treatment discontinuation. No clear time trend was evident with the other markers. Analyses of baseline biomarker expression and its relationship with efficacy variables found no biomarker was predictive for efficacy outcomes, including VEGF-D. However, CRP, HGF, ICAM-3, IL-8, SAA, and VCAM-1 were identified as potential prognostic markers with low baseline levels corresponding to longer OS and PFS. CONCLUSIONS Pharmacodynamic and prognostic relationships were found from the exploratory biomarker analyses in RAINBOW; however, no predictive markers for ramucirumab in gastric cancer were identified in this trial.
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Affiliation(s)
- E Van Cutsem
- Digestive Oncology, University Hospitals Gasthuisberg, Leuven and KULeuven, Leuven, Belgium.
| | - K Muro
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
| | | | - G Bodoky
- Department of Oncology, St. László Hospital, Budapest, Hungary
| | - A Sobrero
- Medical Oncology, IRCCS Ospedale San Martino IST, Genova, Italy
| | - S Cascinu
- Department of Medical Oncology, Università Politecnica Delle Marche, Ancona, Italy
| | - J Ajani
- Department of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - S C Oh
- Korea University Guro Hospital, Seoul, South Korea
| | - S E Al-Batran
- Institute of Clinical Cancer Research (IKF), UCT- University Cancer Center, Frankfurt, Germany
| | - Z A Wainberg
- Medical Hematology and Oncology, University of California Los Angeles, Los Angeles, CA, USA
| | | | - S Melemed
- Eli Lilly and Company, Indianapolis, IN, USA
| | - D Ferry
- Eli Lilly and Company, Bridgewater, NJ, USA
| | - R R Hozak
- Eli Lilly and Company, Indianapolis, IN, USA
| | - A Ohtsu
- Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
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15
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Yahagi N, Fujimoto A, Horii J, Uraoka T, Shimoda M, Takabayashi K, Nisizawa T, Goto O, Ochiai Y, Maehata T, Nakayama A, Kato M, Hosoe N, Naganuma M. Dual red imaging: a novel endoscopic imaging technology visualizing thick blood vessels in the gastrointestinal wall. Endosc Int Open 2019; 7:E1632-E1635. [PMID: 31788544 PMCID: PMC6877423 DOI: 10.1055/a-0749-0075] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2018] [Accepted: 09/24/2018] [Indexed: 12/12/2022] Open
Abstract
Background Dual red imaging (DRI), a novel image-enhanced endoscopy (IEE) technology, has the potential to improve the visibility of blood vessels in deeper tissue using 600 nm and 630 nm wavelength lights in the red band. Aim To confirm the feasibility of DRI in visualization of vessels in deeper tissue and identify pathologically the features of blood vessels visualized by DRI. Methods Study 1: visibility of blood vessels was assessed by five observers in 137 pairs of DRI and white light imaging (WLI) images. The scores for the visibility of thick blood vessels were measured for randomized images and compared with the scoring template as a reference. The difference in visibility score between DRI and WLI was compared in each pair of images. Study 2: blood vessels detected only by DRI were examined pathologically using two pig stomachs. Results Study 1: The mean visibility scores of DRI and WLI for each observer were 1.69 - 2.26 and 1.31 - 1.67, respectively. The mean difference in visibility score and 95 % confidence interval for the five observers was 0.59 [0.46 - 0.72], 0.54 [0.40 - 0.68], 0.34 [0.18 - 0.49], 0.51 [0.36 - 0.66], and 0.71 [0.54 - 0.88]. The visibility was statistically significantly better in DRI than in WLI for all observers ( P < 0.0001). Study 2: three blood vessels were observed only by DRI. All of these blood vessels were located at a depth of 1000 - 1500 µm from the mucosal surface. The diameter of these blood vessels exceeded 80 - 200 µm. Conclusions DRI can feasibly detect thick blood vessels in the deep mucosa or submucosa of the gastrointestinal tract.
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Affiliation(s)
- Naohisa Yahagi
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo, Japan
| | - Ai Fujimoto
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo, Japan
- Department of Gastroenterology, National Hospital Organization, Tokyo Medical Center, Tokyo, Japan
| | - Joichiro Horii
- Department of Gastroenterology, National Hospital Organization, Fukuyama Medical Center, Fukuyama, Hiroshima, Japan
| | - Toshio Uraoka
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Masayuki Shimoda
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Kaoru Takabayashi
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan
| | - Toshihiro Nisizawa
- Department of Gastroenterology, National Hospital Organization, Tokyo Medical Center, Tokyo, Japan
| | - Osamu Goto
- Department of Gastroenterology, Nippon Meidal School, Graduate School of Medicine Tokyo, Japan
| | - Yasutoshi Ochiai
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo, Japan
| | - Tadateru Maehata
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo, Japan
| | - Atushi Nakayama
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo, Japan
| | - Motohiko Kato
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo, Japan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Naoki Hosoe
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan
| | - Makoto Naganuma
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
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16
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Wang Y, Xiao H, Wang C, Wu H, He H, Yao C, Cui J, Li W. M-phase phosphoprotein 8 promotes gastric cancer growth and metastasis via p53/Bcl-2 and EMT-related signaling pathways. J Cell Biochem 2019; 121:2330-2342. [PMID: 31692032 DOI: 10.1002/jcb.29456] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 10/10/2019] [Indexed: 12/29/2022]
Abstract
BACKGROUND The main issue of this study is to demonstrate whether M-phase phosphoprotein 8 (MPP8) affect gastric tumor growth and metastasis. METHODS Retrospective study was proceeded in 280 patients' surgical specimens with different disease stages. Loss-of-function assays, including 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide, flow cytometry, and transwell assays were performed to evaluate the biological function of MPP8 in gastric cancer cells. Apoptosis and metastasis relative biomarkers were measured by quantitative real-time polymerase chain reaction and Western blot analysis. RESULTS Compared with normal adjacent tissues, obviously elevated MPP8 expression was found in gastric cancer tissues. Elevated MPP8 expression was associated with male sex (vs female sex), intermediate differentiation (vs poorly differentiated cancer), and later stage (vs earlier stage). Furthermore, MPP8 overexpression in tumor tissues was marginally associated with a poor prognosis, with a significant relationship between MPP8 overexpression and prognosis among patients with poorly differentiated gastric cancer. Inhibition of MPP8 in these cells significantly suppressed proliferation and colony formation, promoted apoptosis, and repressed invasion. Furthermore, silencing of MPP8 remarkably increased apoptosis-related proteins (p53, Bax, and PARP) expression, but downregulated Bcl-2 expression. Silencing of MPP8 also decreased the expression of metastasis pathway-related proteins (N-cadherin and vimentin), and as well as the levels of anti-oncogene ZEB1, MET, and KRAS mRNA. CONCLUSION Our findings demonstrated that MPP8 might be an oncogene by positively regulating gastric cancer cell function through the p53/Bcl-2 and epithelial to mesenchymal transition-related signaling pathways.
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Affiliation(s)
- Yizhuo Wang
- Department of Cancer Center, First Hospital of Jilin University, Changchun, China
| | - Huijie Xiao
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Chang Wang
- Department of Cancer Center, First Hospital of Jilin University, Changchun, China
| | - Haitao Wu
- Department of Cancer Center, First Hospital of Jilin University, Changchun, China
| | - Hua He
- Department of Cancer Center, First Hospital of Jilin University, Changchun, China
| | - Cheng Yao
- Department of Cancer Center, First Hospital of Jilin University, Changchun, China
| | - Jiuwei Cui
- Department of Cancer Center, First Hospital of Jilin University, Changchun, China
| | - Wei Li
- Department of Cancer Center, First Hospital of Jilin University, Changchun, China
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17
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Abstract
OBJECTIVE This meta-analysis evaluates the prognosis value of C-reactive protein to albumin ratio (CAR) in colorectal cancer. METHODS Embase, PubMed, and Web of Science were searched. Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were used as effective values. RESULTS A total of 6 studies with 1942 patients were included in this study. Pooled results revealed that elevated pretreatment CAR was related with poorer overall survival (OS) (HR: 2.09, 95%CI: 1.78-2.45, P < .001) in colorectal cancer. CONCLUSION Elevated CAR was associated with poor prognosis in colorectal cancer. Thus CAR might be used as a prognostic system and classification of colorectal patients in clinical potential.
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Affiliation(s)
- Fan Wang
- Xinjiang Medical University, Urumqi
| | - Pei Li
- Dushanzi People's Hospital, Kelamayi
| | - Feng-sen Li
- National Clinical Research Base of Traditional Chinese Medicine, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, Xinjiang, China
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18
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Zulfiqar M, Bluth MH, Bhalla A. Molecular Diagnostics in Esophageal and Gastric Neoplasms: 2018 Update. Clin Lab Med 2019; 38:357-365. [PMID: 29776635 DOI: 10.1016/j.cll.2018.02.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Esophageal cancer (EC) is rapidly increasing in incidence in the United States. Genetic changes associated with the development of EC involve the p16, p53, and APC genes. Human epidermal growth factor 2 (HER-2) overexpression is seen in gastroesophageal junction carcinoma and a subset gastric carcinoma (GC). Interestingly, up to 50% cases of GC are related to Helicobacter pylori infection and up to 16% are related to EBV infection. Microsatellite instability is observed in up to 39% of GC and cell free nucleic acid analysis provides additional opportunities for diagnosis and prognosis of disease.
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Affiliation(s)
- Muhammad Zulfiqar
- Southeastern Pathology Associates (SEPA Labs), 203 Indigo Drive, Brunswick, GA 31525, USA.
| | - Martin H Bluth
- Southeastern Pathology Associates (SEPA Labs), 203 Indigo Drive, Brunswick, GA 31525, USA; Department of Pathology, Wayne State University School of Medicine, 540 East Canfield Street, Detroit, MI 48201, USA; Pathology Laboratories, Michigan Surgical Hospital, 21230 Dequindre Road, Warren, MI 48091, USA
| | - Amarpreet Bhalla
- Department of Pathology and Anatomical Sciences, Jacobs School of Buffalo, 955 Main Street, Buffalo, NY 14203, USA
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19
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Zhou T, Yu ST, Chen WZ, Xie R, Yu JC. Pretreatment albumin globulin ratio has a superior prognostic value in laryngeal squamous cell carcinoma patients: a comparison study. J Cancer 2019; 10:594-601. [PMID: 30719156 PMCID: PMC6360422 DOI: 10.7150/jca.28817] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Accepted: 12/14/2018] [Indexed: 12/12/2022] Open
Abstract
Background: Many inflammation-based markers have been reported their prognostic significance. Current study was designed to explore the prognostic value of albumin/globulin ratio (AGR), along with other inflammation-based markers, including neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and lymphocyte/monocyte ratio (LMR) in laryngeal squamous cell carcinoma (LSCC) patients. Method: This study was a retrospective analysis of the data related to 232 newly diagnosed LSCC patients. The potential prognostic factors were evaluated by univariate and multivariate survival analysis. The correlation between AGR and other prognostic factors were analyzed, and the area under the curve (AUC) were compared. Results: AGR, NLR, PLR and LMR were found to be associated with several aggressive clinicopathological features and poor prognosis. In multivariate analysis, AGR, NLR, PLR, LMR were independent prognostic markers of the shorter OS. However, NLR, PLR, and LMR showed no significance with the shorter DFS. AGR remained an independent prognostic marker for the shorter DFS. Furthermore, AGR was a superior prognosis factor than NLR, PLR, LMR in LSCC patients. Conclusion: AGR might be a promising marker to better predicting prognosis of LSCC patients. Future studies are warranted to validate our finding.
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Affiliation(s)
- Tao Zhou
- Department of Thyroid and Neck Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Shi-Tong Yu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Wan-Zhi Chen
- Department of Thyroid and Neck Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Rong Xie
- Department of Thyroid and Neck Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Ji-Chun Yu
- Department of Thyroid and Neck Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
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20
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Oh SE, Choi MG, Seo SW. ASO Author Reflections: Use of the Survival Recurrent Network for Prediction of Overall Survival in Patients with Gastric Cancer. Ann Surg Oncol 2018; 26:539-540. [PMID: 30539490 DOI: 10.1245/s10434-018-7044-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Indexed: 11/18/2022]
Affiliation(s)
- Sung Eun Oh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Min-Gew Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
| | - Sung Wook Seo
- Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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21
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Memeo R, de Blasi V, Adam R, Goéré D, Laurent A, de'Angelis N, Piardi T, Lermite E, Herrero A, Navarro F, Sa Cunha A, Pessaux P. Postoperative Infectious Complications Impact Long-Term Survival in Patients Who Underwent Hepatectomies for Colorectal Liver Metastases: a Propensity Score Matching Analysis. J Gastrointest Surg 2018; 22:2045-2054. [PMID: 29992519 DOI: 10.1007/s11605-018-3854-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Accepted: 06/18/2018] [Indexed: 01/31/2023]
Abstract
OBJECTIVE Postoperative complications strongly impact the postoperative course and long-term outcome of patients who underwent liver resection for colorectal liver metastases (CRLM). Among them, infectious complications play a relevant role. The aim of this study was to evaluate if infectious complications still impact overall and disease-free survival after liver resection for CRLM once patients were matched with a propensity score matching analysis based on Fong's criteria. METHODS A total of 2281 hepatectomies were analyzed from a multicentric retrospective cohort of hepatectomies. Patients were matched with a 1:3 propensity score analysis in order to compare patients with (INF+) and without (INF-) postoperative infectious complications. RESULTS Major resection (OR = 1.69 (1.01-2.89), p = 0.05) and operative time (OR = 1.1 (1.1-1.3), p = 0.05) were identified as risk factors of infectious complications. After propensity score matching, infectious complications are associated with overall survival (OS), with 1-, 3-, 5-year OS at 94, 81, and 66% in INF- and 92, 66, and 57% in INF+ respectively (p = 0.01). Disease-free survival (DFS) was also different with regard to 1-, 3-, 5-year survival at 65, 41, and 22% in R0 vs. 50, 28, and 17% in INF+ (p = 0.007). CONCLUSION Infectious complications are associated with decreased overall and disease-free survival rates.
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Affiliation(s)
- Riccardo Memeo
- Institut Hospitalo-Universitaire (IHU), Institute for Minimally Invasive Hybrid Image-Guided Surgery, Université de Strasbourg, Strasbourg, France
- Institut de Recherche Contre les Cancers de l'Appareil Digestif (IRCAD), Strasbourg, France
- General, Digestive, and Endocrine Surgery, Nouvel Hôpital Civil, Strasbourg, France
| | - Vito de Blasi
- Institut Hospitalo-Universitaire (IHU), Institute for Minimally Invasive Hybrid Image-Guided Surgery, Université de Strasbourg, Strasbourg, France
- Institut de Recherche Contre les Cancers de l'Appareil Digestif (IRCAD), Strasbourg, France
- General, Digestive, and Endocrine Surgery, Nouvel Hôpital Civil, Strasbourg, France
| | - Rene Adam
- Department of Surgery, Hôpital Paul Brousse, Villejuif, France
| | - Diane Goéré
- Department of Surgery, Institut Gustave Roussy, Villejuif, France
| | - Alexis Laurent
- Department of Surgery, Hôpital Henri Mondor, Créteil, France
| | | | - Tullio Piardi
- Department of Surgery, Hôpital de Robert Debré, Reims, France
| | - Emilie Lermite
- Department of Surgery, Centre Hospitalo-Universitaire, Angers, France
| | - Astrid Herrero
- Department of Digestive Surgery, Hôpital Saint-Eloi, Montpellier, France
| | - Francis Navarro
- Department of Digestive Surgery, Hôpital Saint-Eloi, Montpellier, France
| | | | - Patrick Pessaux
- Institut Hospitalo-Universitaire (IHU), Institute for Minimally Invasive Hybrid Image-Guided Surgery, Université de Strasbourg, Strasbourg, France.
- Institut de Recherche Contre les Cancers de l'Appareil Digestif (IRCAD), Strasbourg, France.
- General, Digestive, and Endocrine Surgery, Nouvel Hôpital Civil, Strasbourg, France.
- , Strasbourg, France.
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22
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Li C, Tian W, Zhao F, Li M, Ye Q, Wei Y, Li T, Xie K. Systemic immune-inflammation index, SII, for prognosis of elderly patients with newly diagnosed tumors. Oncotarget 2018; 9:35293-35299. [PMID: 30450158 PMCID: PMC6219675 DOI: 10.18632/oncotarget.24293] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2017] [Accepted: 01/02/2018] [Indexed: 02/05/2023] Open
Abstract
Background Cancer in the elderly has become a common problem due in part to the increase in life expectancy. Compared to younger counterparts, the biological characteristics of tumors and their responsiveness to therapy may differ in elderly patients, and the elderly also can have a decreased tolerance to anticancer therapy. In addition, there is less evidence from clinical trials to guide physicians in treating aged patients with solid tumors. Thus, we often face a dilemma as to how actively to treat these patients and it would be highly useful to have a simple and powerful indicator of their prognosis. In this paper we evaluated the predictive value of the Systemic Immune-inflammation Index, SII, in determining the one-year survival and tumor differentiation status in elderly patients with newly diagnosed solid tumors. Results A high SII > 390×109 cells/L was correlated with poor tumor differentiation (χ2 = 9.791, P = 0.002) and poor one-year survival (χ2 = 7.658, P = 0.006). Patients with low SII had improved survival and better tumor differentiation (Stage I-II). The SII was not associated with Ki-67 expression. Materials and Methods Data from 119 patients, 70 to 89 years of age with newly diagnosed solid tumors in 2014 were retrospectively analyzed. The patients were divided into two groups according to age: (1) 70-75 years of age and (2) over 75 years of age. We calculated SII from the equation, SII = P x N/L, where P, N and L are the preoperative peripheral blood platelet, neutrophil and lymphocyte counts per liter respectively. The optimum cutoff point for SII for a favorable prognosis was determined to be 390×109 cells/L. For evaluation of SII as a prognostic indicator, the patients were divided into high SII (> 390×109 cells/L) and low SII (≤ 390×109 cells/L) groups. Individual values were used to determine the relationship between SII and one-year survival, tumor differentiation and Ki-67 expression in the two age groups. Conclusions SII was a robust indicator of tumor differentiation and one-year survival in elderly patients with newly diagnosed solid tumors. Patients in the high SII group showed poor tumor differentiation and poor prognosis compared to patients with a low SII score.
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Affiliation(s)
- Chan Li
- Department of Oncology, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.,Department of Oncology, People's Hospital of Xinjin, Chengdu, Sichuan 611430, P.R. China.,Department of Oncology, Xinjin Precision Tumor Hospital, Chengdu, Sichuan 611430, P.R. China
| | - Wei Tian
- Department of Operation Management, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 610072, P.R. China.,School of Medicine, University of Electronic Science and Technology of China, Chengdu 611731, P.R. China
| | - Feng Zhao
- Department of Operation Management, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 610072, P.R. China.,State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Meng Li
- Department of Oncology, People's Hospital of Xinjin, Chengdu, Sichuan 611430, P.R. China.,Department of Oncology, Xinjin Precision Tumor Hospital, Chengdu, Sichuan 611430, P.R. China
| | - Qin Ye
- Department of Biomedical Engineering, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, P.R. China
| | - Yuquan Wei
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Tao Li
- Department of Oncology, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.,Department of Radiation Oncology, Sichuan Cancer Hospital and Institute, Chengdu, Sichuan 610041, P.R. China
| | - Ke Xie
- Department of Operation Management, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 610072, P.R. China.,Department of Biomedical Engineering, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, P.R. China.,Department of Oncology, People's Hospital of Xinjin, Chengdu, Sichuan 611430, P.R. China.,Department of Oncology, Xinjin Precision Tumor Hospital, Chengdu, Sichuan 611430, P.R. China
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23
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Curea FG, Hebbar M, Ilie SM, Bacinschi XE, Trifanescu OG, Botnariuc I, Anghel RM. Current Targeted Therapies in HER2-Positive Gastric Adenocarcinoma. Cancer Biother Radiopharm 2018; 32:351-363. [PMID: 29265917 DOI: 10.1089/cbr.2017.2249] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Gastric cancer is one of the most common types of cancer in the world, usually diagnosed at an advanced stage. Despite the advances in specific anticancer agents' development, the survival rates remain modest, even in early stages. In 15%-20% of cases, the human epidermal growth factor receptor 2 (HER2) overexpression was identified. We conducted a general review to summarize the progress that has been made in the targeted treatment of HER2-positive esogastric junction or gastric adenocarcinoma. According to our findings, trastuzumab is the only validated anti-HER2 agent in locally advanced or metastatic disease and its adjuvant effectiveness is assessed in a RTOG phase III study. In a previously treated advanced disease, the maytansine derivate TDM 1 failed to be approved as a second-line regimen, and the tyrosine kinase inhibitor, lapatinib, shows modest results. The antiangiogenics have not been analyzed in specific populations and targeting the mesenchymal-epithelial transition factor (MET) receptor, overexpressed in up to 46% of the advanced disease, seems encouraging. Regarding the checkpoint inhibitors, based on KEYNOTE 059 multilevel ongoing trial, stratified according to the HER2 and programmed death-ligand (PD-L) 1 status, pembrolizumab was approved for third-line treatment of gastric or gastroesophageal junction adenocarcinoma.
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Affiliation(s)
- Fabiana G Curea
- 1 Department of Oncology-Radiotherapy, Institute of Oncology "Prof. Dr. Alexandru Trestioreanu," Bucharest, Romania
| | - Mohamed Hebbar
- 2 Department of Medical Oncology, University Hospital , Lille, France
| | - Silvia M Ilie
- 1 Department of Oncology-Radiotherapy, Institute of Oncology "Prof. Dr. Alexandru Trestioreanu," Bucharest, Romania .,3 University of Medicine and Pharmacy "Carol Davila," Bucharest, Romania
| | - Xenia E Bacinschi
- 1 Department of Oncology-Radiotherapy, Institute of Oncology "Prof. Dr. Alexandru Trestioreanu," Bucharest, Romania .,3 University of Medicine and Pharmacy "Carol Davila," Bucharest, Romania
| | - Oana G Trifanescu
- 1 Department of Oncology-Radiotherapy, Institute of Oncology "Prof. Dr. Alexandru Trestioreanu," Bucharest, Romania .,3 University of Medicine and Pharmacy "Carol Davila," Bucharest, Romania
| | - Inga Botnariuc
- 1 Department of Oncology-Radiotherapy, Institute of Oncology "Prof. Dr. Alexandru Trestioreanu," Bucharest, Romania
| | - Rodica M Anghel
- 1 Department of Oncology-Radiotherapy, Institute of Oncology "Prof. Dr. Alexandru Trestioreanu," Bucharest, Romania .,3 University of Medicine and Pharmacy "Carol Davila," Bucharest, Romania
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24
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Wang Y, Chen Y, Yin H, Gu X, Shi Y, Dai G. Timing of chemotherapy-induced neutropenia is a prognostic factor in patients with advanced gastric cancer undergoing first-line chemotherapy with oxaliplatin and capecitabine: a retrospective study. Cancer Med 2018. [PMID: 29532995 PMCID: PMC5911608 DOI: 10.1002/cam4.1308] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Chemotherapy‐induced neutropenia (CIN) has been shown to be associated with improved clinical outcomes in patients with various solid tumors. This study retrospectively assessed the association between timing of CIN and prognosis in 321 patients with advanced gastric cancer (AGC) who finished at least one cycle of chemotherapy with oxaliplatin and capecitabine (XELOX). Primary landmark analyses were restricted to 274 patients who received four cycles of chemotherapy and lived for more than 4 months. CIN was categorized as early‐onset and non‐early‐onset. The correlation between timing of CIN with survival was analyzed by the Kaplan‐Meier method and a Cox proportional hazards model. Relative to patients with non‐early‐onset CIN, those with early‐onset CIN had significantly longer times to disease progression (hazard ratio [HR] 0.574; 95% confidence interval [CI] 0.453–0.729, P < 0.001) and death (HR: 0.607; 95% CI: 0.478–0.770, P < 0.001), consistent with results from the landmark group. In conclusion, timing of CIN may be a potential prognostic biomarker in patients with AGC receiving first‐line chemotherapy with XELOX. Early‐onset CIN predicts better survival.
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Affiliation(s)
- Yanrong Wang
- Medical Oncology Department 2, Chinese People's Liberation Army General Hospital, Beijing, 100853, China
| | - Yang Chen
- Medical Oncology Department 2, Chinese People's Liberation Army General Hospital, Beijing, 100853, China
| | - Hongyan Yin
- Medical Oncology Department 2, Chinese People's Liberation Army General Hospital, Beijing, 100853, China
| | - Xiaobin Gu
- Department of Radiation Oncology, First Hospital of Peking University, Beijing, 100034, China
| | - Yan Shi
- Medical Oncology Department 2, Chinese People's Liberation Army General Hospital, Beijing, 100853, China
| | - Guanghai Dai
- Medical Oncology Department 2, Chinese People's Liberation Army General Hospital, Beijing, 100853, China
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25
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Oh SE, Seo SW, Choi MG, Sohn TS, Bae JM, Kim S. Prediction of Overall Survival and Novel Classification of Patients with Gastric Cancer Using the Survival Recurrent Network. Ann Surg Oncol 2018; 25:1153-1159. [PMID: 29497908 DOI: 10.1245/s10434-018-6343-7] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND Artificial neural networks (ANNs) have been applied to many prediction and classification problems, and could also be used to develop a prediction model of survival outcomes for cancer patients. OBJECTIVE The aim of this study is to develop a prediction model of survival outcomes for patients with gastric cancer using an ANN. METHODS This study enrolled 1243 patients with stage IIA-IV gastric cancer who underwent D2 gastrectomy from January 2007 to June 2010. We used a recurrent neural network (RNN) to make the survival recurrent network (SRN), and patients were randomly sorted into a training set (80%) and a test set (20%). Fivefold cross-validation was performed with the training set, and the optimized model was evaluated with the test set. Receiver operating characteristic (ROC) curves and area under the curves (AUCs) were evaluated, and we compared the survival curves of the American Joint Committee on Cancer (AJCC) 8th stage groups with those of the groups classified by the SRN-predicted survival probability. RESULTS The test data showed that the ROC AUC of the SRN was 0.81 at the fifth year. The SRN-predicted survival corresponded closely with the actual survival in the calibration curve, and the survival outcome could be more discriminately classified by using the SRN than by using the AJCC staging system. CONCLUSION SRN was a more powerful tool for predicting the survival rates of gastric cancer patients than conventional TNM staging, and may also provide a more flexible and expandable method when compared with fixed prediction models such as nomograms.
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Affiliation(s)
- Sung Eun Oh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sung Wook Seo
- Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
| | - Min-Gew Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
| | - Tae Sung Sohn
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae Moon Bae
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sung Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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26
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Huang X, Shen W, Xi H, Zhang K, Cui J, Wei B, Chen L. Prognostic role of extracellular matrix metalloproteinase inducer/CD147 in gastrointestinal cancer: a meta-analysis of related studies. Oncotarget 2018; 7:81003-81011. [PMID: 27768590 PMCID: PMC5348372 DOI: 10.18632/oncotarget.12745] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Accepted: 10/03/2016] [Indexed: 11/29/2022] Open
Abstract
The prognostic role of Extracellular matrix metalloproteinase inducer (EMMPRIN/ CD147) in gastrointestinal cancer remains controversial. We systematically reviewed the evidence of assessment of CD147 expression in gastrointestinal cancer to help clarify this issue. Pubmed, Embase, Cochrane Library and Web of Science databases were searched to identify eligible studies to evaluate the association of CD147 expression and disease-free and overall survival of gastrointestinal cancer. Hazard ratios (HRs) were pooled to estimate the effect. CD147 overexpression was significantly correlated with poor disease-free survival (HR 2.38, 95% CI 1.43–3.97) and overall survival (HR 1.64, 95% CI 1.25–2.14) of cancer patients. Furthermore, CD147 overexpression was significantly association with TNM stage (TIII/TIV vs TI/TII: OR 3.60, 95% CI 1.85–7.01), the depth of invasion (T3/T4 vs T1/T2: OR 2.04, 95% CI 1.25–3.33), lymph node metastasis (positive vs negative: 2.35, 95% CI 1.14–4.86), distant metastasis (positive vs negative: OR 4.78, 95% CI 1.43–16.00). Our analyses demonstrate that CD147 was effectively predictive of worse prognosis in gastrointestinal cancer. Moreover, Identifying CD147 may help identify new drug targets for cancer therapy.
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Affiliation(s)
- Xiaohui Huang
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Weisong Shen
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
| | - Hongqing Xi
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Kecheng Zhang
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Jianxin Cui
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Bo Wei
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Lin Chen
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China
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27
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Chen L, Yan Y, Zhu L, Cong X, Li S, Song S, Song H, Xue Y. Systemic immune-inflammation index as a useful prognostic indicator predicts survival in patients with advanced gastric cancer treated with neoadjuvant chemotherapy. Cancer Manag Res 2017; 9:849-867. [PMID: 29276407 PMCID: PMC5733921 DOI: 10.2147/cmar.s151026] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND AND OBJECTIVE A novel systemic immune-inflammation index named SII (SII=N×P/L), which is based on neutrophil (N), platelet (P) and lymphocyte (L) counts, has emerged and reflects comprehensively the balance of host inflammatory and immune status. We aimed to evaluate the potential prognostic significance of SII in patients with advanced gastric cancer who received neoadjuvant chemotherapy. SUBJECTS AND METHODS The retrospective analysis included data from 107 patients with advanced gastric cancer undergoing neoadjuvant chemotherapy and 185 patients with pathology-proven gastric cancer. The optimal cutoff value of SII by receiver operating characteristic curve stratified patients into low SII (<600×109/L) and high SII (SII ≥600×109/L) groups. The clinical outcomes of disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier survival curves and compared using log-rank test. Univariate and multivariate Cox proportional hazards regression models were used to analyze the prognostic value of SII. RESULTS The results indicated that SII had prognostic significance using the cutoff value of 600×109/L on DFS and OS in univariate and multivariate Cox regression survival analyses. Low SII was associated with prolonged DFS and OS, and the mean DFS and OS for patients with low SII were longer than for those with high SII (57.22 vs 41.56 months and 62.25 vs 45.60 months, respectively). Furthermore, we found that patients with low SII had better 1-, 3- and 5-year rates of DFS and OS than those with high SII. In addition, patients with low SII were likely to receive DFS and OS benefits from neoadjuvant chemotherapy and postoperative chemotherapy. CONCLUSION SII may qualify as a noninvasive, cost-effective, convenient and reproducible prognostic indicator for patients with advanced gastric cancer undergoing neoadjuvant chemotherapy. It may help clinicians to identify those patients who will benefit from treatment strategy decisions.
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Affiliation(s)
- Li Chen
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang
| | - Ying Yan
- Department of Internal Oncology, Harbin The First Hospital, Harbin, Heilongjiang
| | - Lihua Zhu
- Department of Pathogen Biology, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei, China
| | - Xiliang Cong
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang
| | - Sen Li
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang
| | - Shubin Song
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang
| | - Hongjiang Song
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang
| | - Yingwei Xue
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang
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28
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Zhong L, Li C, Ren Y, Wu D. Prognostic value of 18F-fluorodeoxyglucose PET parameters and inflammation in patients with nasopharyngeal carcinoma. Oncol Lett 2017; 14:5004-5012. [PMID: 29085513 DOI: 10.3892/ol.2017.6816] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2015] [Accepted: 01/31/2017] [Indexed: 12/30/2022] Open
Abstract
The aim of the present study was to investigate the association between positron emission tomography (PET) parameters and peripheral inflammatory markers, and assess their prognostic value in nasopharyngeal carcinoma (NPC). A total of 121 patients with non-disseminated NPC were recruited. Pretreatment maximum standardized uptake values (SUVmax) of PET and peripheral inflammatory factors (leukocyte, neutrophil and monocyte counts) were recorded. Kaplan-Meier and multivariate analyses were used to identify predictors for progression-free survival (PFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LRFS). The results of the present study revealed that SUVmax at the primary tumor was positively correlated with leukocytes (P=0.025), neutrophils (P=0.009) and monocytes (P=0.043). SUVmax at regional lymph nodes (SUVmax-N) was significantly associated with monocytes (P=0.024). Kaplan-Meier analysis demonstrated that SUVmax-N (>10.15) significantly predicted PFS (P=0.004) and DMFS (P=0.003). In addition, neutrophils (>5.18) were significantly associated with PFS (P=0.001), DMFS (P=0.013) and LRFS (P<0.001). Multivariate analysis revealed that SUVmax-N and neutrophils retained independent prognostic significance for PFS (SUVmax-N, P=0.026; and neutrophils, P=0.033) and DMFS (SUVmax-N, P=0.026; and neutrophils, P=0.032). Furthermore, patients with SUVmax-N ≤10.15 and neutrophils ≤5.18 had significantly improved prognosis in PFS (96.4 vs. 58.5%, P<0.001), OS (95.7 vs. 81.1%, P=0.044), DMFS (96.4 vs. 67.0%, P<0.001) and LRFS (100 vs. 90.2%, P=0.036) compared with those with SUVmax-N >10.15 or neutrophils >5.18. In conclusion, SUVmax may be significantly associated with cancer-associated inflammation. SUVmax-N and neutrophils were independent prognostic indicators for PFS and DMFS. Combined assessment of SUVmax-N and neutrophils may lead to refinement of risk stratification in NPC.
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Affiliation(s)
- Liting Zhong
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Chunming Li
- Department of Oncology, Jiangmen Central Hospital, Jiangmen, Guangdong 529000, P.R. China
| | - Yunyan Ren
- Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
| | - Dehua Wu
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
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29
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Haruki K, Shiba H, Horiuchi T, Sakamoto T, Gocho T, Fujiwara Y, Furukawa K, Misawa T, Yanaga K. Impact of the C-reactive protein to albumin ratio on long-term outcomes after hepatic resection for colorectal liver metastases. Am J Surg 2017; 214:752-756. [PMID: 28187858 DOI: 10.1016/j.amjsurg.2017.02.001] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Revised: 01/06/2017] [Accepted: 02/03/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND The aim of this study is to investigate the association C-reactive protein to albumin (CRP/Alb) ratio, a novel inflammation based prognostic score, and long-term outcomes among patients with colorectal liver metastases (CRLM) after hepatic resection. METHODS We retrospectively investigated 106 patients who underwent hepatic resection for CRLM and explored the relationship between CRP/Alb ratio and long-term outcomes. RESULTS In multivariate analysis, more than 4 lymph node metastases (p = 0.003), presence of neo-adjuvant chemotherapy (p = 0.008) and CRP/Alb ratio ≥ 0.04 (p = 0.021) were independent and significant predictors of cancer recurrence, while more than 4 lymph node metastases (p = 0.001), presence of neo-adjuvant chemotherapy (p < 0.001), and CRP/Alb ratio ≥ 0.04 (p = 0.002) were independent and significant predictors of poor overall survival. CONCLUSIONS The CRP/Alb ratio seems to be a predictor of poor long-term outcomes in patients with CRLM after hepatic resection.
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Affiliation(s)
- Koichiro Haruki
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
| | - Hiroaki Shiba
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Takashi Horiuchi
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Taro Sakamoto
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Takeshi Gocho
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Yuki Fujiwara
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Kenei Furukawa
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Takeyuki Misawa
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Katsuhiko Yanaga
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
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30
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Akbari S, Hosseini M, Rezaei-Tavirani M, Rezaei-Tavirani M, Salehi SH, Alemrajabi M, Vaseghi-Maghvan P, Jahani-Sherafat S. Common and differential genetically pathways between ulcerative colitis and colon adenocarcinoma. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2017; 10:S93-S101. [PMID: 29511478 PMCID: PMC5838187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
AIM In the present study, genes of Ulcerative Colitis and Colon Adenocarcinoma (COAC) were extracted by string App in Cytoscape software version 3.5.1. Then protein- protein interaction (PPI) networks analyzed. BACKGROUND One of the most common chronic digestive problems is ulcerative colitis (UC) especially in developing countries. Prevalence of the disease is reported about 7.6 to 245 cases per 100,000 per year. UC can lead to colon cancer that is the third malignancy related death in the world. So awareness of the future of the patient with UC and the possibility of colon cancer is a very helpful approach. METHODS The analysis was based on centralities values. The goal is determining common gene pathways and differential gene pathways of the two diseases. RESULTS Results showed there are 11 and 29 central genes related to COAC and UC respectively. At least five common key genes between the two diseases were introduced. The number of 26 terms related to the common key genes were determined and clustered in seven clusters. CONCLUSION ALB, AKT1, TP53, SRC and MYC are the common genes that play crucial roles in the related biological processes of UC and COAC. Besides introducing the common genes the differentiate genes related to the two diseases were proposed.
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Affiliation(s)
- Somayeh Akbari
- Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mostafa Hosseini
- Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | | | | | | | - Mahdi Alemrajabi
- Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Padina Vaseghi-Maghvan
- Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Somayeh Jahani-Sherafat
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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31
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Lapeyre-Prost A, Terme M, Pernot S, Pointet AL, Voron T, Tartour E, Taieb J. Immunomodulatory Activity of VEGF in Cancer. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2016; 330:295-342. [PMID: 28215534 DOI: 10.1016/bs.ircmb.2016.09.007] [Citation(s) in RCA: 149] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The ability of tumor cells to escape tumor immunosurveillance contributes to cancer development. Factors produced in the tumor microenvironment create "tolerizing" conditions and thereby help the tumor to evade antitumoral immune responses. VEGF-A, already known for its major role in tumor vessel growth (neoangiogenesis), was recently identified as a key factor in tumor-induced immunosuppression. In particular, VEGF-A fosters the proliferation of immunosuppressive cells, limits T-cell recruitment into tumors, and promotes T-cell exhaustion. Antiangiogenic therapies have shown significant efficacy in patients with a variety of solid tumors, preventing tumor progression by limiting tumor-induced angiogenesis. VEGF-targeting therapies have also been shown to modulate the tumor-induced immunosuppressive microenvironment, enhancing Th1-type T-cell responses and increasing tumor infiltration by T cells. The immunomodulatory properties of VEGF-targeting therapies open up new perspectives for cancer treatment, especially through strategies combining antiangiogenic drugs with immunotherapy. Preclinical models and early clinical studies of these combined approaches have given promising results.
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Affiliation(s)
- A Lapeyre-Prost
- INSERM U970, PARCC (Paris Cardiovascular Research Center), Université Paris-Descartes, Paris, France
| | - M Terme
- INSERM U970, PARCC (Paris Cardiovascular Research Center), Université Paris-Descartes, Paris, France.
| | - S Pernot
- INSERM U970, PARCC (Paris Cardiovascular Research Center), Université Paris-Descartes, Paris, France; Service d'hépatogastroentérologie et d'oncologie digestive, Hôpital Européen Georges Pompidou, Paris, France
| | - A-L Pointet
- INSERM U970, PARCC (Paris Cardiovascular Research Center), Université Paris-Descartes, Paris, France; Service d'hépatogastroentérologie et d'oncologie digestive, Hôpital Européen Georges Pompidou, Paris, France
| | - T Voron
- INSERM U970, PARCC (Paris Cardiovascular Research Center), Université Paris-Descartes, Paris, France; Service de chirurgie digestive, Hôpital Européen Georges Pompidou, Paris, France
| | - E Tartour
- INSERM U970, PARCC (Paris Cardiovascular Research Center), Université Paris-Descartes, Paris, France; Service d'immunologie biologique. Hôpital Européen Georges Pompidou, Paris, France
| | - J Taieb
- INSERM U970, PARCC (Paris Cardiovascular Research Center), Université Paris-Descartes, Paris, France; Service d'hépatogastroentérologie et d'oncologie digestive, Hôpital Européen Georges Pompidou, Paris, France.
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Mulder KE, Ahmed S, Davies JD, Doll CM, Dowden S, Gill S, Gordon V, Hebbard P, Lim H, McFadden A, McGhie JP, Park J, Wong R. Report from the 17th Annual Western Canadian Gastrointestinal Cancer Consensus Conference; Edmonton, Alberta; 11-12 September 2015. ACTA ACUST UNITED AC 2016; 23:425-434. [PMID: 28050139 DOI: 10.3747/co.23.3384] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The 17th annual Western Canadian Gastrointestinal Cancer Consensus Conference (wcgccc) was held in Edmonton, Alberta, 11-12 September 2015. The wcgccc is an interactive multidisciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management of gastric cancer.
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Affiliation(s)
- K E Mulder
- Alberta: Medical Oncology (Mulder), Cross Cancer Institute, University of Alberta, Edmonton; Radiation Oncology (Doll) and Medical Oncology (Dowden), Tom Baker Cancer Centre, University of Calgary, Calgary
| | - S Ahmed
- Saskatchewan: Medical Oncology (Ahmed), Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon
| | - J D Davies
- British Columbia: Medical Oncology (Davies, Gill, Lim, McGhie) and Surgical Oncology (McFadden), BC Cancer Agency, University of British Columbia, Vancouver
| | - C M Doll
- Alberta: Medical Oncology (Mulder), Cross Cancer Institute, University of Alberta, Edmonton; Radiation Oncology (Doll) and Medical Oncology (Dowden), Tom Baker Cancer Centre, University of Calgary, Calgary
| | - S Dowden
- Alberta: Medical Oncology (Mulder), Cross Cancer Institute, University of Alberta, Edmonton; Radiation Oncology (Doll) and Medical Oncology (Dowden), Tom Baker Cancer Centre, University of Calgary, Calgary
| | - S Gill
- British Columbia: Medical Oncology (Davies, Gill, Lim, McGhie) and Surgical Oncology (McFadden), BC Cancer Agency, University of British Columbia, Vancouver
| | - V Gordon
- Manitoba: Medical Oncology (Gordon, Wong), Cancer Care Manitoba, and Surgery (Hebbard, Park), University of Manitoba, Winnipeg
| | - P Hebbard
- Manitoba: Medical Oncology (Gordon, Wong), Cancer Care Manitoba, and Surgery (Hebbard, Park), University of Manitoba, Winnipeg
| | - H Lim
- British Columbia: Medical Oncology (Davies, Gill, Lim, McGhie) and Surgical Oncology (McFadden), BC Cancer Agency, University of British Columbia, Vancouver
| | - A McFadden
- British Columbia: Medical Oncology (Davies, Gill, Lim, McGhie) and Surgical Oncology (McFadden), BC Cancer Agency, University of British Columbia, Vancouver
| | - J P McGhie
- British Columbia: Medical Oncology (Davies, Gill, Lim, McGhie) and Surgical Oncology (McFadden), BC Cancer Agency, University of British Columbia, Vancouver
| | - J Park
- Manitoba: Medical Oncology (Gordon, Wong), Cancer Care Manitoba, and Surgery (Hebbard, Park), University of Manitoba, Winnipeg
| | - R Wong
- Manitoba: Medical Oncology (Gordon, Wong), Cancer Care Manitoba, and Surgery (Hebbard, Park), University of Manitoba, Winnipeg
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Wang J, Wang S, Song X, Zeng W, Wang S, Chen F, Ding H. The prognostic value of systemic and local inflammation in patients with laryngeal squamous cell carcinoma. Onco Targets Ther 2016; 9:7177-7185. [PMID: 27920556 PMCID: PMC5123657 DOI: 10.2147/ott.s113307] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Background Cancer-related systemic inflammation has been demonstrated to be associated with poor outcome in multiple types of cancers. Meanwhile, the local inflammation, which is characterized by dense intratumoral immune infiltrate, is a favorable predictor of survival outcome. Purpose To evaluate the role of systemic and local inflammation in predicting outcome in patients with laryngeal squamous cell carcinoma. Patients and methods In this retrospective study, 120 patients who had undergone postoperative radiotherapy were enrolled. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as calculated from pretreatment whole blood counts, were used to indicate systemic inflammation. The optimal cutoff values of NLR and PLR were determined using receiver operating characteristic curve analysis. Tumor infiltrating lymphocytes (TILs) density, as assessed by pathologist review of hematoxylin and eosin-stained slides, was used to represent local inflammation. Overall survival (OS) and recurrence-free survival (RFS) were assessed using the Kaplan–Meier method and multivariate Cox regression analysis. Results The best cutoff was 2.79 for NLR and 112 for PLR. Kaplan–Meier analysis revealed that high NLR, high PLR, and low TILs density were significantly correlated with inferior OS and RFS, respectively (all P<0.05). The Cox proportional multivariate hazard model showed that a high pretreatment PLR and a low TILs density were both independently correlated with poor OS and RFS, respectively (all P<0.05). Conclusion Markers of systemic and local inflammation, especially PLR and TILs density, are reliable prognostic factors in patients with laryngeal squamous cell carcinoma.
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Affiliation(s)
- Jie Wang
- Department of Radiation Oncology, Eye, Ear, Nose, and Throat Hospital, Fudan University
| | - Shengzi Wang
- Department of Radiation Oncology, Eye, Ear, Nose, and Throat Hospital, Fudan University
| | - Xinmao Song
- Department of Radiation Oncology, Eye, Ear, Nose, and Throat Hospital, Fudan University
| | - Wenjiao Zeng
- Department of Pathology, Shanghai Medical School, Fudan University
| | - Shuyi Wang
- Department of Pathology, Eye, Ear, Nose, and Throat Hospital, Fudan University, Shanghai, People's Republic of China
| | - Fu Chen
- Department of Radiation Oncology, Eye, Ear, Nose, and Throat Hospital, Fudan University
| | - Hao Ding
- Department of Radiation Oncology, Eye, Ear, Nose, and Throat Hospital, Fudan University
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Ma L, Xu X, Zhang M, Zheng S, Zhang B, Zhang W, Wang P. Dynamic contrast-enhanced MRI of gastric cancer: Correlations of the pharmacokinetic parameters with histological type, Lauren classification, and angiogenesis. Magn Reson Imaging 2016; 37:27-32. [PMID: 27840273 DOI: 10.1016/j.mri.2016.11.004] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2016] [Accepted: 11/06/2016] [Indexed: 12/18/2022]
Abstract
PURPOSE To compare the pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in gastric cancers of different histological type and Lauren classification, and to investigate whether DCE-MRI parameters correlate with vascular endothelial growth factor (VEGF) expression levels in gastric cancer. METHODS Included were 32 patients with gastric cancer who underwent DCE-MRI of the upper abdomen before tumor resection. DCE-MRI parameters including the volume transfer coefficient (Ktrans), reverse reflux rate constant (Kep), and extracellular extravascular volume fraction (Ve) were calculated from the tumor region. Post-operative specimens were used for determination of histological differentiation (i.e., non-mucinous, mucinous, or signet-ring-cell adenocarcinoma) as well as Lauren classification (intestinal type or diffuse type). VEGF expression was examined for assessing angiogenesis. DCE-MRI parameters with different histological type and Lauren classification were compared using independent samples t-test and analysis of variance, respectively. Correlations between DCE-MRI parameters and VEGF expression grades were tested using Spearman correlation analysis. RESULTS Among gastric adenocarcinomas of three different histological types, mucinous adenocarcinomas showed a higher Ve and lower Ktrans than the others (P<0.01). Between the two Lauren classifications, the diffuse type showed a higher Ve than the intestinal type (P<0.001). The mean Ktrans showed a significantly positive correlation with VEGF (r=0.762, P<0.001). CONCLUSION DCE-MRI permits noninvasive prediction of tumor histological type and Lauren classification and estimation of tumor angiogenesis in gastric cancer. DCE-MRI parameters can be used as imaging biomarkers to predict the biologic aggressiveness of a tumor as well as patient prognosis.
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Affiliation(s)
- Liang Ma
- Department of Medical Imaging, Tongji Hospital, Tongji University, No. 389, Xincun Road, Putuo District, Shanghai 200065, China
| | - Xiaowen Xu
- Department of Medical Imaging, Tongji Hospital, Tongji University, No. 389, Xincun Road, Putuo District, Shanghai 200065, China
| | - Min Zhang
- Department of Medical Imaging, Tongji Hospital, Tongji University, No. 389, Xincun Road, Putuo District, Shanghai 200065, China
| | - Shaoqiang Zheng
- Department of Medical Imaging, Tongji Hospital, Tongji University, No. 389, Xincun Road, Putuo District, Shanghai 200065, China
| | - Bo Zhang
- Department of Medical Imaging, Tongji Hospital, Tongji University, No. 389, Xincun Road, Putuo District, Shanghai 200065, China
| | - Wei Zhang
- Department of Medical Imaging, Renji Hospital, Medical School of Jiaotong University, No. 160, Pujian Road, Pudong District, Shanghai 200127, China.
| | - Peijun Wang
- Department of Medical Imaging, Tongji Hospital, Tongji University, No. 389, Xincun Road, Putuo District, Shanghai 200065, China.
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Kimura J, Kunisaki C, Makino H, Oshima T, Ota M, Oba M, Takagawa R, Kosaka T, Ono HA, Akiyama H, Endo I. Evaluation of the Glasgow Prognostic Score in patients receiving chemoradiotherapy for stage III and IV esophageal cancer. Dis Esophagus 2016; 29:1071-1080. [PMID: 26471766 DOI: 10.1111/dote.12420] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
High Glasgow Prognostic scores (GPSs) have been associated with poor outcomes in various tumors, but the values of GPS and modified GPS (mGPS) in patients with advanced esophageal cancer receiving chemoradiotherapy (CRT) has not yet been reported. We have evaluated these with respect to predicting responsiveness to CRT and long-term survival. Between January 2002 and December 2011, tumor responses in 142 esophageal cancer patients (131 men and 11 women) with stage III (A, B and C) and IV receiving CRT were assessed. We assessed the value of the GPS as a predictor of a response to definitive CRT and also as a prognostic indicator in patients with esophageal cancer receiving CRT. We found that independent predictors of CRT responsiveness were Eastern Cooperative Oncology Group (ECOG) performance status, GPS and cTNM stage. Independent prognostic factors were ECOG performance status and GPS for progression-free survival and ECOG performance status, GPS and cTNM stage IV for disease-specific survival. GPS may be a novel predictor of CRT responsiveness and a prognostic indicator for progression-free and disease-specific survival in patients with advanced esophageal cancer. However, a multicenter study as same regime with large number of patients will be needed to confirm these outcomes.
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Affiliation(s)
- J Kimura
- Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - C Kunisaki
- Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - H Makino
- Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - T Oshima
- Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - M Ota
- Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - M Oba
- Department of Biostatistics and Epidemiology, Graduate School of Medicine, Yokohama-city University, Yokohama, Japan
| | - R Takagawa
- Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama-city University, Yokohama, Japan
| | - T Kosaka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama-city University, Yokohama, Japan
| | - H A Ono
- Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama-city University, Yokohama, Japan
| | - H Akiyama
- Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama-city University, Yokohama, Japan
| | - I Endo
- Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama-city University, Yokohama, Japan
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Fuchs CS, Tabernero J, Tomášek J, Chau I, Melichar B, Safran H, Tehfe MA, Filip D, Topuzov E, Schlittler L, Udrea AA, Campbell W, Brincat S, Emig M, Melemed SA, Hozak RR, Ferry D, Caldwell CW, Ajani JA. Biomarker analyses in REGARD gastric/GEJ carcinoma patients treated with VEGFR2-targeted antibody ramucirumab. Br J Cancer 2016; 115:974-982. [PMID: 27623234 PMCID: PMC5061911 DOI: 10.1038/bjc.2016.293] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Revised: 08/12/2016] [Accepted: 08/16/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Angiogenesis inhibition is an important strategy for cancer treatment. Ramucirumab, a human IgG1 monoclonal antibody that targets VEGF receptor 2 (VEGFR2), inhibits VEGF-A, -C, -D binding and endothelial cell proliferation. To attempt to identify prognostic and predictive biomarkers, retrospective analyses were used to assess tumour (HER2, VEGFR2) and serum (VEGF-C and -D, and soluble (s) VEGFR1 and 3) biomarkers in phase 3 REGARD patients with metastatic gastric/gastroesophageal junction carcinoma. METHODS A total of 152 out of 355 (43%) patients randomised to ramucirumab or placebo had ⩾1 evaluable biomarker result using VEGFR2 immunohistochemistry or HER2, immunohistochemistry or FISH, of blinded baseline tumour tissue samples. Serum samples (32 patients, 9%) were assayed for VEGF-C and -D, and sVEGFR1 and 3. RESULTS None of the biomarkers tested were associated with ramucirumab efficacy at a level of statistical significance. High VEGFR2 endothelial expression was associated with a non-significant prognostic trend toward shorter progression-free survival (high vs low HR=1.65, 95% CI=0.84,3.23). Treatment with ramucirumab was associated with a trend toward improved survival in both high (HR=0.69, 95% CI=0.38, 1.22) and low (HR=0.73, 95% CI=0.42, 1.26) VEGFR2 subgroups. The benefit associated with ramucirumab did not appear to differ by tumoural HER2 expression. CONCLUSIONS REGARD exploratory analyses did not identify a strong potentially predictive biomarker of ramucirumab efficacy; however, statistical power was limited.
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Affiliation(s)
- Charles S Fuchs
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA
| | - Josep Tabernero
- Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona 08035, Spain
| | - Jiří Tomášek
- Masaryk Memorial Cancer Institute, Faculty of Medicine, Masaryk University, Brno 656 53, Czech Republic
| | - Ian Chau
- Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK
| | - Bohuslav Melichar
- Onkologicka klinika, Lekarska fakulta Univerzity Palackeho a Fakultni nemocnice, I.P. Pavlova, 6, Olomouc 779 00, Czech Republic
| | - Howard Safran
- Brown University Oncology Research Group, 164 Summit Avenue, Fain 3, Providence, Rhode Island 02906, USA
| | - Mustapha A Tehfe
- Centre Hospitalier de Montréal, 1560 Sherbrooke East St, Montreal, Quebec H2L4M1, Canada
| | - Dumitru Filip
- Spitalul Judetean de Urgenta, Strada George Coşbuc 31, Baia Mare 430031, Romania
| | - Eldar Topuzov
- State Budgetary Educational Institution of Higher Professional Education (SBEIHPE), Northwest State Medical University na II Mechnikov, Ministry of Healthcare of the Russian Federation, Russia
| | - Luis Schlittler
- Hospital da Cida de Passo Fundo, Rua Tiradentes, 295 Centro, Passo Fundo, 99010-260, Brazil
| | | | | | | | - Michael Emig
- Lilly Deutschland GmbH, Werner-Reimers-Straße 2, Bad Homburg vor der Höhe 61352, Germany
| | - Symantha A Melemed
- Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA
| | - Rebecca R Hozak
- Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA
| | - David Ferry
- Eli Lilly and Company, 440 Route 22 East, Bridgewater, New Jersey 08807, USA
| | - C William Caldwell
- Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA
| | - Jaffer A Ajani
- The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 426, Houston, Texas 77030, USA
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Pavlakis N, Sjoquist KM, Martin AJ, Tsobanis E, Yip S, Kang YK, Bang YJ, Alcindor T, O'Callaghan CJ, Burnell MJ, Tebbutt NC, Rha SY, Lee J, Cho JY, Lipton LR, Wong M, Strickland A, Kim JW, Zalcberg JR, Simes J, Goldstein D. Regorafenib for the Treatment of Advanced Gastric Cancer (INTEGRATE): A Multinational Placebo-Controlled Phase II Trial. J Clin Oncol 2016; 34:2728-2735. [PMID: 27325864 PMCID: PMC5019744 DOI: 10.1200/jco.2015.65.1901] [Citation(s) in RCA: 172] [Impact Index Per Article: 19.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
PURPOSE We evaluated the activity of regorafenib, an oral multikinase inhibitor, in advanced gastric adenocarcinoma. PATIENTS AND METHODS We conducted an international (Australia and New Zealand, South Korea, and Canada) randomized phase II trial in which patients were randomly assigned at a two-to-one ratio and stratified by lines of prior chemotherapy for advanced disease (one v two) and region. Eligible patients received best supportive care plus regorafenib 160 mg or matching placebo orally on days 1 to 21 of each 28-day cycle until disease progression or prohibitive adverse events occurred. The primary end point was progression-free survival (PFS). Final analysis included data to December 31, 2014. RESULTS A total of 152 patients were randomly assigned from November 7, 2012, to February 25, 2014, yielding 147 evaluable patients (regorafenib, n = 97; placebo, n = 50). Baseline characteristics were balanced. Median PFS significantly differed between groups (regorafenib, 2.6 months; 95% CI, 1.8 to 3.1 and placebo, 0.9 months; 95% CI, 0.9 to 0.9; hazard ratio [HR], 0.40; 95% CI, 0.28 to 0.59; P < .001). The effect was greater in South Korea than in Australia, New Zealand, and Canada combined (HR, 0.12 v 0.61; interaction P < .001) but consistent across age, neutrophil-to-lymphocyte ratio, primary site, lines of chemotherapy, peritoneal metastasis presence, number of metastatic sites, and plasma vascular endothelial growth factor A. A survival trend in favor of regorafenib was seen (median, 5.8 months; 95% CI, 4.4 to 6.8 v 4.5 months; 95% CI, 3.4 to 5.2; HR, 0.74; P = .147). Twenty-nine patients assigned to placebo received open-label regorafenib after disease progression. Regorafenib toxicity was similar to that previously reported. CONCLUSION In this phase II trial, regorafenib was effective in prolonging PFS in refractory advanced gastric adenocarcinoma. Regional differences were found, but regorafenib was effective in both regional groups. A phase III trial is planned.
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Affiliation(s)
- Nick Pavlakis
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada.
| | - Katrin M Sjoquist
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada
| | - Andrew J Martin
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada
| | - Eric Tsobanis
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada
| | - Sonia Yip
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada
| | - Yoon-Koo Kang
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada
| | - Yung-Jue Bang
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada
| | - Thierry Alcindor
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada
| | - Christopher J O'Callaghan
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada
| | - Margot J Burnell
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada
| | - Niall C Tebbutt
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada
| | - Sun Young Rha
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada
| | - Jeeyun Lee
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada
| | - Jae-Yong Cho
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada
| | - Lara R Lipton
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada
| | - Mark Wong
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada
| | - Andrew Strickland
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada
| | - Jin Won Kim
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada
| | - John R Zalcberg
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada
| | - John Simes
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada
| | - David Goldstein
- Nick Pavlakis, Niall C. Tebbutt, Lara R. Lipton, John R. Zalcberg, John Simes, and David Goldstein, Australasian Gastro-Intestinal Trials Group; Nick Pavlakis, Royal North Shore Hospital, University of Sydney; Katrin M. Sjoquist, Andrew J. Martin, Eric Tsobanis, Sonia Yip, and John Simes, National Health and Medical Research Council Clinical Trials Centre, University of Sydney; Katrin M. Sjoquist, Cancer Care Centre, St George Hospital; Sonia Yip, Sydney Catalyst Translational Cancer Research Centre; Mark Wong, Westmead Hospital; David Goldstein, Prince of Wales Hospital, Sydney, New South Wales; Niall C. Tebbutt, Austin Health; Lara R. Lipton, Western Health; Andrew Strickland, Monash Medical Centre; John R. Zalcberg, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Yung-Jue Bang, Seoul National University Hospital; Sun Young Rha, Yonsei University College of Medicine; Jeeyun Lee, Samsung Medical Center, Sungkyunkwan University School of Medicine; Jae-Yong Cho, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul; Jin Won Kim, Seoul National University Bundang Hospital, Seongnam, South Korea; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec; Christopher J. O'Callaghan, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario; and Margot J. Burnell, Saint John Regional Hospital, Saint John, New Brunswick, Canada
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Ma Q, Liu W, Jia R, Jiang F, Duan H, Lin P, Zhang L, Long H, Zhao H, Ma G. Inflammation-based prognostic system predicts postoperative survival of esophageal carcinoma patients with normal preoperative serum carcinoembryonic antigen and squamous cell carcinoma antigen levels. World J Surg Oncol 2016; 14:141. [PMID: 27151090 PMCID: PMC4858859 DOI: 10.1186/s12957-016-0878-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Accepted: 04/19/2016] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The Glasgow Prognostic Score (GPS) is an established inflammation-based system that is used to predict the prognosis for several types of malignancies. In this retrospective study, we assessed the postoperative survival of 725 patients with non-metastatic esophageal squamous cell carcinoma who had normal preoperative serum tumor marker levels according to the GPS. METHODS Among 1394 patients who underwent esophagectomy between August 2006 and December 2010, 725 with normal preoperative serum levels of carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag) were enrolled. All demographic, pathologic, and survival data were analyzed retrospectively. Uni- and multivariate analyses were performed to evaluate the relationship with overall survival. The Kaplan-Meier analysis and log-rank tests were used to compare the survival curves between patients with GPS 0 (group A) and 1 or 2 (group B). RESULTS Patients in group A exhibited significantly better 3- and 5-year cancer-specific survival (CSS) rates (0.780 and 0.759, respectively) than those in group B (0.624 and 0.605, respectively). Multivariate Cox regression analysis revealed that age, tumor length, pathological tumor-node-metastasis (pTNM) stage, venous invasion, lymph node metastasis, serum albumin and C-reactive protein levels, and GPS were associated with postoperative survival of these patients. Further multivariate analysis confirmed that GPS was an independent prognostic factor. The Kaplan-Meier analysis and log-rank tests demonstrated a significant difference in CSS between groups A and B (P = 0.001). CONCLUSIONS GPS may be a valuable prognostic indicator for esophageal cancer patients with normal preoperative CEA and SCC-Ag serum levels.
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Affiliation(s)
- Qilong Ma
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Wengao Liu
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ran Jia
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Feng Jiang
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Hao Duan
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Peng Lin
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Guangdong Esophageal Cancer Institute, Guangzhou, China
| | - Lanjun Zhang
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.,Guangdong Esophageal Cancer Institute, Guangzhou, China
| | - Hao Long
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Hongyun Zhao
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. .,Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfengdong Road, Guangzhou, China.
| | - Guowei Ma
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. .,Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangdong Esophageal Cancer Institute, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfengdong Road, Guangzhou, China.
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Huang T, Qiu X, Xiao J, Wang Q, Wang Y, Zhang Y, Bai D. The prognostic role of Leucine-rich repeat-containing G-protein-coupled receptor 5 in gastric cancer: A systematic review with meta-analysis. Clin Res Hepatol Gastroenterol 2016; 40:246-53. [PMID: 26387842 DOI: 10.1016/j.clinre.2015.07.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2014] [Revised: 06/17/2015] [Accepted: 07/29/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND OBJECTIVE The prognostic value of Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) in gastric cancer remains controversial. To further investigate this relationship, we performed meta-analyses to systematically review the association between LGR5 expression and various clinical parameters in gastric cancer patients. METHOD Eligible studies from PubMed, Embase, Web of Science, CNKI (Chinese National Knowledge Infrastructure), Wangfang (Database of Chinese Ministry of Science & Technology) and CBM (China Biological Medicine) databases were evaluated to investigate the association of LGR5 expression with overall survival (OS) and clinicopathological features of gastric cancer. RESULTS LGR5 overexpression was significantly associated with poor OS in patients with gastric cancer (HR 1.66, 95% CI 1.02-2.69). LGR5 overexpression was also significantly associated with TNM stage (TIII/TIV vs TI/TII: OR 5.42, 95% CI 1.02-28.72) and lymph node metastasis (positive vs negative: OR 2.30, 95% CI 1.06-5.0). CONCLUSIONS Our meta-analysis indicates that LGR5 may be a predictive factor for invasion and metastasis, and poor prognosis in patients with gastric cancer.
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Affiliation(s)
- Tianchen Huang
- Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, 28, Jianshe Road, 450052 Zhengzhou, China; Anyang cancer hospital, 455000 Anyang, China
| | - Xinguang Qiu
- Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, 28, Jianshe Road, 450052 Zhengzhou, China.
| | - Jianan Xiao
- Anyang cancer hospital, 455000 Anyang, China
| | | | - Yanjun Wang
- Anyang cancer hospital, 455000 Anyang, China
| | - Yong Zhang
- Anyang cancer hospital, 455000 Anyang, China
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40
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Sanches JDS, de Aguiar RB, Parise CB, Suzuki JM, Chammas R, de Moraes JZ. Anti-bevacizumab idiotype antibody vaccination is effective in inducing vascular endothelial growth factor-binding response, impairing tumor outgrowth. Cancer Sci 2016; 107:551-5. [PMID: 27079440 PMCID: PMC4832859 DOI: 10.1111/cas.12903] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2015] [Revised: 01/29/2016] [Accepted: 01/31/2016] [Indexed: 11/30/2022] Open
Abstract
Tumors require blood supply and, to overcome this restriction, induce angiogenesis. Vascular endothelial growth factor (VEGF) plays an important role in this process, which explains the great number of antiangiogenic therapies targeting VEGF. The research and development of targeted therapy has led to the approval of bevacizumab, a humanized anti-VEGF monoclonal antibody (mAb), in clinical settings. However, side effects have been reported, usually as a consequence of bolus-dose administration of the antibody. This limitation could be circumvented through the use of anti-idiotype (Id) antibodies. In the present study, we evaluated the efficacy of an active VEGF-binding immune response generated by an anti-bevacizumab idiotype mAb, 10.D7. The 10.D7 anti-Id mAb vaccination led to detectable levels of VEGF-binding anti-anti-Id antibodies. In order to examine whether this humoral immune response could have implications for tumor development, 10.D7-immunized mice were challenged with B16-F10 tumor cells. Mice immunized with 10.D7 anti-Id mAb revealed reduced tumor growth when compared to control groups. Histological analyses of tumor sections from 10.D7-immunized mice showed increased necrotic areas, decreased CD31-positive vascular density and reduced CD68-positive cell infiltration. Our results encourage further therapeutic studies, particularly if one considers that the anti-Id therapeutic vaccination maintains stable levels of VEGF-binding antibodies, which might be useful in the control of tumor relapse.
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MESH Headings
- Angiogenesis Inhibitors/administration & dosage
- Angiogenesis Inhibitors/immunology
- Animals
- Antibodies, Anti-Idiotypic/administration & dosage
- Antibodies, Anti-Idiotypic/immunology
- Antibodies, Monoclonal/administration & dosage
- Antibodies, Monoclonal/immunology
- Bevacizumab/administration & dosage
- Bevacizumab/adverse effects
- Cell Line, Tumor
- Humans
- Melanoma, Experimental/drug therapy
- Melanoma, Experimental/immunology
- Melanoma, Experimental/pathology
- Mice
- Neovascularization, Pathologic/drug therapy
- Neovascularization, Pathologic/immunology
- Neovascularization, Pathologic/pathology
- Vascular Endothelial Growth Factor A/immunology
- Vascular Endothelial Growth Factor A/metabolism
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Affiliation(s)
- Jéssica de Souza Sanches
- Department of BiophysicsEscola Paulista de MedicinaUniversidade Federal de São PauloSão PauloBrazil
| | | | - Carolina Bellini Parise
- Department of BiophysicsEscola Paulista de MedicinaUniversidade Federal de São PauloSão PauloBrazil
| | - Juliana Mayumi Suzuki
- Department of BiophysicsEscola Paulista de MedicinaUniversidade Federal de São PauloSão PauloBrazil
| | - Roger Chammas
- Department of RadiologyFaculdade de MedicinaUniversidade de São PauloSão PauloBrazil
| | - Jane Zveiter de Moraes
- Department of BiophysicsEscola Paulista de MedicinaUniversidade Federal de São PauloSão PauloBrazil
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The C-reactive Protein to Albumin Ratio Predicts Long-Term Outcomes in Patients with Pancreatic Cancer After Pancreatic Resection. World J Surg 2016; 40:2254-60. [DOI: 10.1007/s00268-016-3491-4] [Citation(s) in RCA: 96] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Gazel E, Tastemur S, Acikgoz O, Yigman M, Olcucuoglu E, Camtosun A, Ceylan C, Ates C. Importance of neutrophil/lymphocyte ratio in prediction of PSA recurrence after radical prostatectomy. Asian Pac J Cancer Prev 2016; 16:1813-6. [PMID: 25773829 DOI: 10.7314/apjcp.2015.16.5.1813] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The aim of this study was to research the importance of the neutrophil to lymphocyte ratio (NLR) in prediction of PSA recurrence after radical prostatectomy, which has not been reported so far. MATERIALS AND METHODS The data of 175 patients who were diagnosed with localised prostate cancer and underwent retropubic radical prostatectomy was retrospectively examined. Patient pre-operative hemogram parameters of neutrophil count, lymphocyte count and NLR were assessed. The patients whose PSAs were too low to measure after radical prostatectomy in their follow-ups, and then had PSAs of 0,2 ng/mL were considered as patients with PSA recurrence. Patients with recurrence made up Group A and patients without recurrence made up Group B. RESULTS In terms of the power of NLR value in distinguishing recurrence, the area under OCC was statistically significant (p<0.001) .The value of 2.494 for NLR was found to be a cut-off value which can be used in order to distinguish recurrence according to Youden index. According to this, patients with a higher NLR value than 2.494 had higher rates of PSA recurrence with 89.7% sensitivity and 92.6% specificity. CONCLUSIONS There are certain parameters used in order to predict recurrence with today's literature data.We think that because NLR is easy to use in clinics and inexpensive, and also has high sensitivity and specificity values, it has the potential to be one of the parameters used in order to predict biochemical recurrence in future.
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Affiliation(s)
- Eymen Gazel
- Department of Urology, Turkey Yuksek Ihtisas Training and Research Hospital, Ankara, Turkey E-mail :
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Fu YP, Ni XC, Yi Y, Cai XY, He HW, Wang JX, Lu ZF, Han X, Cao Y, Zhou J, Fan J, Qiu SJ. A Novel and Validated Inflammation-Based Score (IBS) Predicts Survival in Patients With Hepatocellular Carcinoma Following Curative Surgical Resection: A STROBE-Compliant Article. Medicine (Baltimore) 2016; 95:e2784. [PMID: 26886627 PMCID: PMC4998627 DOI: 10.1097/md.0000000000002784] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
As chronic inflammation is involved in the pathogenesis and progression of hepatocellular carcinoma (HCC), we investigated the prognostic accuracy of a cluster of inflammatory scores, including the Glasgow Prognostic Score, modified Glasgow Prognostic Score, platelet to lymphocyte ratio, Prognostic Nutritional Index, Prognostic Index, and a novel Inflammation-Based Score (IBS) integrated preoperative and postoperative neutrophil to lymphocyte ratio in 2 independent cohorts. Further, we aimed to formulate an effective prognostic nomogram for HCC after hepatectomy.Prognostic value of inflammatory scores and Barcelona Clinic Liver Cancer (BCLC) stage were studied in a training cohort of 772 patients with HCC underwent hepatectomy. Independent predictors of survival identified in multivariate analysis were validated in an independent set of 349 patients with an overall similar clinical feature.In both training and validation cohorts, IBS, microscopic vascular invasion, and BCLC stage emerged as independent factors of overall survival (OS) and recurrence-free survival (RFS). The predictive capacity of the IBS in both OS and RFS appeared superior to that of the other inflammatory scores in terms of C-index. Additionally, the formulated nomogram comprised IBS resulted in more accurate prognostic prediction compared with BCLC stage alone.IBS is a novel and validated prognostic indicator of HCC after curative resection, and a robust HCC nomogram including IBS was developed to predict survival for patients after hepatectomy.
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Affiliation(s)
- Yi-Peng Fu
- From the Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School (Y-PF, X-CN, YY, X-YC, H-WH, J-XW, Z-FL, JZ, JF, S-JQ) and Biomedical Research Center, Zhongshan Hospital (XH, S-JQ), Fudan University; Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education (Y-PF, X-CN, YY, X-YC, H-WH, J-XW, Z-FL, JZ, JF, S-JQ), Shanghai, P.R. China; and Cancer Research Institute, Xiangya School of Medicine, Central South University (YC), Hunan, China
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Babacan NA, Eğilmez HR, Yücel B, Parlak I, Şeker MM, Kaçan T, Bahçeci A, Cihan S, Akinci B, Eriten B, Kılıçkap S. The prognostic value of UHRF-1 and p53 in gastric cancer. Saudi J Gastroenterol 2016; 22:25-9. [PMID: 26831603 PMCID: PMC4763524 DOI: 10.4103/1319-3767.173755] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND/AIMS This study aimed to examine whether UHRF-1 and p53 overexpression is a prognostic marker for gastric cancer. PATIENTS AND METHODS Sixty-four patients with gastric cancer (study group) and 23 patients with gastritis (control group) were evaluated. Immunohistochemistry was used to examine expression of UHRF-1 and p53 in gastric cancers and a control group diagnosed with gastritis. RESULTS The median age was 63 years (18-83 years) in the study group. UHRF-1 was positive in 15 (23%) patients with gastric cancer and fi ve (21.7%) patients with gastritis (P = 0.559). UHRF1 expression level in gastric cancer is more powerful than in gastritis (P = 0.046). Thirty-seven (61%) patients with gastric cancer and only one patient with gastritis were p53 positive (P < 0.001). After a median follow-up of 12 months (1-110), the 2-year overall survival rates were 55% and 30% in negative and positive p53, respectively (P = 0.084). Also, the 2-year overall survival rates were 45% and 53% in negative and positive UHRF-1, respectively (P = 0.132). CONCLUSION According to this study, UHRF-1 and p53 were not prognostic factors for gastric cancer, whereas they may have a diagnostic value for differentiating between gastric cancer and gastritis.
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Affiliation(s)
- Nalan A. Babacan
- Department of Medical Oncology, Cumhuriyet University School of Medicine, Sivas, Turkey,Address for correspondence: Dr. Nalan A. Babacan, University of Marmara - Istanbul, PO Box TR-58140, Istanbul, Turkey. E-mail:
| | | | - Birsen Yücel
- Department of Radiation Oncology, Cumhuriyet University School of Medicine, Sivas, Turkey
| | - Ilknur Parlak
- Department of Internal Medicine, Cumhuriyet University School of Medicine, Sivas, Turkey
| | - Mehmet Metin Şeker
- Department of Medical Oncology, Cumhuriyet University School of Medicine, Sivas, Turkey
| | - Turgut Kaçan
- Department of Medical Oncology, Cumhuriyet University School of Medicine, Sivas, Turkey
| | - Aykut Bahçeci
- Department of Medical Oncology, Cumhuriyet University School of Medicine, Sivas, Turkey
| | - Sener Cihan
- Department of Medical Oncology, Okmeydanı Education and Research Hospital, İstanbul, Turkey
| | - Bülent Akinci
- Department of Medical Oncology, Yıldırım Beyazıt University School of Medicine, Ankara, Turkey
| | - Berna Eriten
- Department of Pathology, Cumhuriyet University School of Medicine, Sivas, Turkey
| | - Saadettin Kılıçkap
- Department of Medical Oncology, Hacettepe University School of Medicine, Ankara, Turkey
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Satolli MA, Buffoni L, Spadi R, Roato I. Gastric cancer: The times they are a-changin'. World J Gastrointest Oncol 2015; 7:303-16. [PMID: 26600930 PMCID: PMC4644853 DOI: 10.4251/wjgo.v7.i11.303] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Revised: 07/15/2015] [Accepted: 08/13/2015] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer is the third leading cause of cancer death worldwide. Even though during these last decades gastric cancer incidence decreased in Western countries, it remains endemic and with a high incidence in Eastern countries. The survival in advanced and metastatic stage of gastric cancer is still very poor. Recently the Cancer Genoma Atlas Research Network identified four subtypes with different molecular profiles to classify gastric cancer in order to offer the optimal targeted therapies for pre-selected patients. Indeed, the key point is still the selection of patients for the right treatment, on basis of molecular tumor characterization. Since chemotherapy reached a plateau of efficacy for gastric cancer, the combination between cytotoxic therapy and biological agents gets a better prognosis and decreases chemotherapeutic toxicity. Currently, Trastuzumab in combination with platinum and fluorouracil is the only approved targeted therapy in the first line for c-erbB2 positive patients, whereas Ramucirumab is the only approved targeted agent for patients with metastatic gastric cancer. New perspectives for an effective treatment derived from the immunotherapeutic strategies. Here, we report an overview on gastric cancer treatments, with particular attention to recent advances in targeted therapies and in immunotherapeutic approach.
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46
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Tu XP, Qiu QH, Chen LS, Luo XN, Lu ZM, Zhang SY, Chen SH. Preoperative neutrophil-to-lymphocyte ratio is an independent prognostic marker in patients with laryngeal squamous cell carcinoma. BMC Cancer 2015; 15:743. [PMID: 26482899 PMCID: PMC4615885 DOI: 10.1186/s12885-015-1727-6] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2015] [Accepted: 10/08/2015] [Indexed: 01/06/2023] Open
Abstract
Background Neutrophil-lymphocyte ratio (NLR) has been shown to be associated with prognosis in various solid tumors. This study aimed to evaluate the prognostic role of NLR in patients with laryngeal squamous cell carcinoma (LSCC). Methods A total of 141 LSCC patients were retrospectively reviewed. Patients’ demographics were analyzed along with clinical and pathologic data. The optimal cutoff value of NLR was determined using receiver operating characteristic (ROC) curve analysis. The impact of the NLR and other potential prognostic factors on disease-free survival (DFS) and overall survival (OS) was assessed using the Kaplan-Meier method and multivariate Cox regression analysis. Results The optimal cutoff value of the NLR was 2.17. In the NLR ≤ 2.17 group, the 1-, 3-, and 5-year DFS rates were 88.2, 73.9 and 69.1 %, respectively, while in the NLR > 2.17 group, the DFS rates were 83.0, 54.6 and 49.2 %, respectively. Correspondingly, the 1-, 3-, and 5-year OS rates were 98.9, 85.1 and 77.4 % in the NLR ≤ 2.17 group and 97.9, 63.8 and 53.3 % in the NLR > 2.17 group, respectively. The multivariate Cox proportional hazard model analysis showed that NLR > 2.17 was a prognostic factor for both DFS [hazard ratio (HR) = 1.869; 95 % confidence interval (CI) 1.078–3.243; P = 0.026] and OS (HR =2.177; 95 % CI 1.208–3.924; P = 0.010). Conclusion Our results showed that elevated preoperative NLR was an independent predictor of poor prognosis for patients with LSCC after surgical resection.
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Affiliation(s)
- Xiu-Ping Tu
- Department of Otorhinolaryngology, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, P. R. China.
| | - Qian-Hui Qiu
- Department of Otorhinolaryngology, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, P. R. China.
| | - Liang-Si Chen
- Department of Otorhinolaryngology, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, P. R. China.
| | - Xiao-Ning Luo
- Department of Otorhinolaryngology, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, P. R. China.
| | - Zhong-Ming Lu
- Department of Otorhinolaryngology, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, P. R. China.
| | - Si-Yi Zhang
- Department of Otorhinolaryngology, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, P. R. China.
| | - Shao-Hua Chen
- Department of Otorhinolaryngology, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, P. R. China.
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Yildirim M, Kaya V, Demirpence O, Gunduz S, Bozcuk H. Prognostic significance of p53 in gastric cancer: a meta- analysis. Asian Pac J Cancer Prev 2015; 16:327-32. [PMID: 25640374 DOI: 10.7314/apjcp.2015.16.1.327] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Gastric cancer is one of the frequently seen cancers in the world and it is the second most common reason for death due to cancer. The prognostic role of expression of p53 detected by immunohistochemistry in gastric cancer remains controversial. This meta-analysis aimed to explore any association between overexpression and survival outcomes. MATERIALS AND METHODS We systematically searched for studies investigating the relationships between expression of p53 detected by immunohistochemistry and prognosis of gastric cancer patients. Study quality was assessed using the Newcastle-Ottawa Scale. After careful review, survival data were extracted from eligible studies. A meta-analysis was performed to generate combined hazard ratios for overall survival and disease-free survival. RESULTS A total of 4.330 patients from 21 studies were included in the analysis. Our results showed tissue p53 overexpression in patients with gastric cancer to be associated with poor prognosis in terms of overall survival (HR, 1.610; 95% CI, 1.394 -5.235; p: <0.001). Pooled hazard ratio for disease free survival showed that p53 positivity or negativity were not statitistically significant (HR, 1.219; 95%CI, 0.782-1.899; p:0.382). CONCLUSIONS The present meta-analysis indicated overexpression of p53 detected by immunohistochemistry to be associated with a poor prognosis in patients with gastric cancer.
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Affiliation(s)
- Mustafa Yildirim
- Department of Medical Oncology, Ministry of Health Batman Regional Government Hospital, Batman, Turkey E-mail :
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p53 immunoexpression in stepwise progression of cutaneous squamous cell carcinoma and correlation with angiogenesis and cellular proliferation. Pathol Res Pract 2015; 211:782-8. [PMID: 26296918 DOI: 10.1016/j.prp.2015.07.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Revised: 06/05/2015] [Accepted: 07/13/2015] [Indexed: 12/12/2022]
Abstract
Multistep carcinogenesis involves loss of function of tumor suppressor proteins such as p53 and induction of angiogenesis. Such mechanisms contribute to cutaneous squamous cell carcinoma progression and may be interconnected. We aimed to explore p53 immunoexpression in spectral stages of cutaneous squamous cell carcinoma and correlate expression to both neovascularization and cellular proliferation. We estimated the percentages of immunostained cells for p53 and Ki67 (proliferation marker) in three groups: 23 solar keratoses, 28 superficially invasive squamous cell carcinomas and 28 invasive squamous cell carcinomas. The Chalkley method was used to quantify the microvascular area by neoangiogenesis (CD105) immunomarker in each group. There was no significant difference for rate of p53- and Ki67-positive cells between groups. Significant positive correlation was found between the CD105 microvascular area and the rate of p53 positive cells in superficially invasive squamous cell carcinoma as well as between the rate of p53- and Ki67-positive cells in invasive squamous cell carcinoma. p53 and Ki67 immunoexpression did not increase with cutaneous squamous cell carcinoma progression. Neovascularization in the initial stage of invasion and proliferative activity in the frankly invasive stage were both associated with p53 immunoexpression. Loss of p53 tumor suppressor function through progressive steps may be directly involved in skin carcinogenesis.
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Ciliberto D, Staropoli N, Caglioti F, Gualtieri S, Fiorillo L, Chiellino S, De Angelis AM, Mendicino F, Botta C, Caraglia M, Tassone P, Tagliaferri P. A systematic review and meta-analysis of randomized trials on the role of targeted therapy in the management of advanced gastric cancer: Evidence does not translate? Cancer Biol Ther 2015; 16:1148-59. [PMID: 26061272 PMCID: PMC4623405 DOI: 10.1080/15384047.2015.1056415] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2015] [Revised: 05/12/2015] [Accepted: 05/24/2015] [Indexed: 12/15/2022] Open
Abstract
It is still uncertain if targeted therapy-based regimens in advanced gastric cancer actually produce survival benefit. To shed light on this important question, we performed a systematic review and meta-analyses on each relevant targeted-pathway. By searching literature databases and proceedings of major cancer meetings in the time-frame 2005-2014, 22 randomized clinical trials exploring targeted therapy for a total of 7022 advanced gastric cancer patients were selected and included in the final analysis. Benefit was demonstrated for antiangiogenic agents in terms of overall survival (HR 0.759; 95%CI 0.655-0.880; p < 0.001). Conversely no benefit was found for EGFR pathway (HR 1.077; 95%CI 0.847-1.370; p = 0.543). Meta-analysis of HER-2 pathway confirmed improvement in terms of survival outcome, already known for this class of drugs (HR 0.823; 95%CI 0.722-0.939; p = 0.004). Pooled analysis demonstrated a significant survival benefit (OS: HR 0.823; PFS: HR 0.762) with acceptable tolerability profile for targeted-based therapies as compared to conventional treatments. This finding conflicts with the outcome of most individual studies, probably due to poor trial design or patients selection. In conclusion, our findings demonstrate a significant survival benefit for targeted therapy in its whole, which can be ascribed to anti-angiogenic and anti-HER2 agents.
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Key Words
- ADME, absorption, distribution, metabolism, and excretion
- Ab, monoclonal antibody
- BSC, best supportive care
- CHT, chemotherapy
- EGFR, epidermal growth factor receptor
- GC, gastric cancer
- HER2, human epidermal growth factor receptor 2
- HER3, human epidermal growth factor receptor 3
- MET, mesenchymal epithelial transition factor
- NGS, next generation sequencing
- NSCLC, non-small cell lung cancer
- OR, odds-ratio
- OS, overall survival
- PARP, poly ADP ribose polymerase
- PFS, progression free survival
- PI3K, phosphatidylinositide 3-kinases
- PRISMA, preferred reporting items for systematic reviews and meta-analyses
- RAF, rapidly accelerated fibrosarcoma
- RAS, rat sarcoma viral oncogene homolog
- RCTs, randomized clinical trials
- RR, response rate
- TKI, tyrosine kinase inhibitor
- VEGF, vascular endothelial growth factor
- VEGFR: VEGF receptor
- aGC, advanced gastric cancer
- angiogenesis
- gastric cancer
- mTOR, mammalian target of rapamycin
- mTORC, mTOR complex
- meta-analysis
- randomized clinical trials
- systemic chemotherapy
- targeted pathways
- targeted therapy
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Affiliation(s)
- Domenico Ciliberto
- Department of Experimental and Clinical Medicine; Magna Græcia University; Campus Salvatore Venuta; Catanzaro, Italy
| | - Nicoletta Staropoli
- Department of Experimental and Clinical Medicine; Magna Græcia University; Campus Salvatore Venuta; Catanzaro, Italy
| | - Francesca Caglioti
- Department of Experimental and Clinical Medicine; Magna Græcia University; Campus Salvatore Venuta; Catanzaro, Italy
| | - Simona Gualtieri
- Department of Experimental and Clinical Medicine; Magna Græcia University; Campus Salvatore Venuta; Catanzaro, Italy
| | - Lucia Fiorillo
- Department of Experimental and Clinical Medicine; Magna Græcia University; Campus Salvatore Venuta; Catanzaro, Italy
| | - Silvia Chiellino
- Department of Experimental and Clinical Medicine; Magna Græcia University; Campus Salvatore Venuta; Catanzaro, Italy
| | - Antonina Maria De Angelis
- Department of Experimental and Clinical Medicine; Magna Græcia University; Campus Salvatore Venuta; Catanzaro, Italy
| | - Francesco Mendicino
- Department of Experimental and Clinical Medicine; Magna Græcia University; Campus Salvatore Venuta; Catanzaro, Italy
| | - Cirino Botta
- Department of Experimental and Clinical Medicine; Magna Græcia University; Campus Salvatore Venuta; Catanzaro, Italy
| | - Michele Caraglia
- Department of Biochemistry; Biophysics and General Pathology; Second University of Naples; Naples, Italy
- Sbarro Institute for Cancer Research and Molecular Medicine; Center for Biotechnology; College of Science and Technology; Temple University; Philadelphia, PA USA
| | - Pierfrancesco Tassone
- Department of Experimental and Clinical Medicine; Magna Græcia University; Campus Salvatore Venuta; Catanzaro, Italy
- Sbarro Institute for Cancer Research and Molecular Medicine; Center for Biotechnology; College of Science and Technology; Temple University; Philadelphia, PA USA
| | - Pierosandro Tagliaferri
- Department of Experimental and Clinical Medicine; Magna Græcia University; Campus Salvatore Venuta; Catanzaro, Italy
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Wei K, Jiang L, Wei Y, Wang Y, Qian X, Dai Q, Guan Q. The prognostic significance of p53 expression in gastric cancer: a meta-analysis. J Cancer Res Clin Oncol 2015; 141:735-48. [PMID: 25316440 DOI: 10.1007/s00432-014-1844-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2014] [Accepted: 09/26/2014] [Indexed: 12/15/2022]
Abstract
OBJECTIVE This meta-analysis was conducted to quantitatively assess the prognostic significance of p53 expression in gastric cancer patients. METHODS A systematic literature search was conducted to identify eligible studies in PubMed and Embase. The pooled hazard ratios (HRs) or odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were used to estimate the effect sizes. Moreover, meta-regression analysis and subgroup analysis were carried out. RESULTS A total of 34 studies comprising 6,599 patients were subjected to final analysis. Positive/high p53 expression was significantly associated with poorer overall survival (HR 1.56, 95% CI 1.23-1.98) and disease-specific survival (HR 1.52, 95% CI 1.35-1.73). The results also indicated that positive/high p53 expression was significantly associated with gender (OR 1.26, 95% CI 1.09-1.45), Lauren's classification (OR 1.68, 95% CI 1.23-2.29), the depth of invasion (OR 0.68, 95% CI 0.56-0.83), lymph node metastasis (OR 1.56, 95% CI 1.23-1.97), TNM stage (OR 0.57, 95% CI 0.47-0.69), vascular invasion (OR 1.51, 95% CI 1.18-1.92) and lymphatic invasion (OR 1.38, 95% CI 1.11-1.72), but not with Bormann type (OR 1.24, 95% CI 0.91-1.70), grade of differentiation (OR 1.08, 95% CI 0.82-1.44) or distant metastasis (OR 1.37, 95% CI 0.92-2.03). CONCLUSIONS This meta-analysis suggests positive/high p53 expression may be a useful biomarker to predict a poorer prognosis for patients with gastric cancer.
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Affiliation(s)
- Kongkong Wei
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
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