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Wang J, Shao EL, Gao Z. Emerging trends and hotspots of tRNA-derived small RNAs in tumours: a bibliometric analysis via VOSviewer and CiteSpace. Discov Oncol 2025; 16:767. [PMID: 40369221 PMCID: PMC12078907 DOI: 10.1007/s12672-025-02628-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Accepted: 05/08/2025] [Indexed: 05/16/2025] Open
Abstract
INTRODUCTION TRNA-derived small RNAs(tsRNAs) play an important role in many biological processes, and their dysregulation is closely related to the progression of cancer, but the research trend and future direction are not clear. This study aims to identify the leading contributors, collaboration networks, and emerging research trends in tsRNAs and their role in oncology, providing a more comprehensive and intuitive reference for researchers in this field. MATERIALS AND METHODS Related publications related to tsRNA in the field of oncology from 1990 to 2022 were collected from the Science Citation Index Expanded through the Web of Science Core Collection (WOSCC) database on 6 December 2022. RESULTS There were 2,108 publications related to tsRNAs in oncology. The articles came from 69 countries/regions, 2,218 institutions, 11,340 authors, and 200 journals, and included 9,530 keywords. The annual total number of papers and total global citation score increased steadily every year over the study period. Among the articles related to tsRNAs in oncology, the United States had the highest number of publications with 732 articles, and the United States, China, Japan, Canada, and South Korea had the highest number of collaborations. Seoul National University Sun and the journal Nucleic Acids Research had the most publications at 81 and 63 articles, respectively, and the keyword "tRF" was a hotspot. CONCLUSION This study provides an in-depth analysis of the research status and development trends of tsRNAs in the field of cancer from a bibliometric perspective. Offering possible guidance for researchers to explore hot topics and frontiers, select suitable journals, and partners in this field.
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Affiliation(s)
- Junhong Wang
- Department of General Surgery, Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine (The First People's Hospital of Baiyin), Baiyin, China
- First School of Clinical Medicine, Lanzhou University, Lanzhou, China
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China
| | - E-Ling Shao
- Department of Gynecology and Obstetrics, Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine (The First People's Hospital of Baiyin), Baiyin, China
| | - Zhenhua Gao
- Department of General Surgery, Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine (The First People's Hospital of Baiyin), Baiyin, China.
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Wang D, Huang W, Li G. Circular RNA ATP9A Stimulates Non-small Cell Lung Cancer Progression via MicroRNA-582-3p/Ribosomal Protein Large P0 Axis and Activating Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Pathway. Appl Biochem Biotechnol 2025; 197:3166-3183. [PMID: 39832103 DOI: 10.1007/s12010-024-05159-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/24/2024] [Indexed: 01/22/2025]
Abstract
Circular RNAs (circRNAs), along with their pathogenic property in non-small cell lung cancer (NSCLC), require comprehensive analyses and explanations. The study is established with the purpose to elucidate the potential molecular mechanism of circATP9A in NSCLC. CircATP9A and microRNA (miR)-582-3p were evaluated by real-time quantitative polymerase chain reaction, and ribosomal protein large P0 (RPLP0), cleaved caspase-3, cleaved Ki-67, epithelial-to-mesenchymal transition (EMT)-associated proteins (N-cadherin and E-cadherin), and core proteins of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were by Western blot. The processes of proliferation, apoptosis, migration, and invasion were measured by cell counting kit-8, 5-ethynyl-2'deoxyuridine, flow cytometry, and Transwell. Gene interaction was verified by RNA immunoprecipitation and dual luciferase reporter assay. CircATP9A and RPLP0 were abnormally highly expressed in both NSCLC tissues and cell lines, while miR-582-3p was abnormally low. Knockdown of circATP9A reduced NSCLC proliferation, invasion migration, and EMT and promoted apoptosis. This was further validated in nude mouse xenograft experiments. The inhibitory effect of knockdown of circATP9A on NSCLC was reversed by knockdown of miR-582-3p. In addition, the promoting effect of overexpression of circATP9A on NSCLC was reversed by knockdown of RPLP0. Mechanistically, circATP9A acted as a competitive endogenous RNA, sequestering miR-582-3p away from its target, which in turn modulated the expression of RPLP0. CircATP9A activated the miR-582-3p/RPLP0 axis by regulating the PI3K/Akt pathway in NSCLC cells. CircATP9A stimulates NSCLC progression via miR-582-3p/RPLP0 axis and PI3K/AKT cascade activation.
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Affiliation(s)
- Dingxue Wang
- Department of Oncology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No.71 Baoshan North Road, Yunyan District, Guiyang City, 550001, Guizhou Province, China.
| | - Wenqi Huang
- Department of Oncology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No.71 Baoshan North Road, Yunyan District, Guiyang City, 550001, Guizhou Province, China
| | - Gao Li
- Department of Oncology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No.71 Baoshan North Road, Yunyan District, Guiyang City, 550001, Guizhou Province, China
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Kleinlugtenbelt LB, Gorter JW, van Dalen EC, Ketelaar M, Tissing WJE. Integrated care networks in multidisciplinary rehabilitation therapy services for childhood oncology close to home: lessons learned from an international environmental scan. Support Care Cancer 2025; 33:406. [PMID: 40266368 PMCID: PMC12018495 DOI: 10.1007/s00520-025-09421-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 03/29/2025] [Indexed: 04/24/2025]
Abstract
BACKGROUND Integrated care networks (ICNs) close to home have the potential to improve continuity and quality of care for children with cancer and their families during and after treatment. Our goal is to develop such a network for multidisciplinary rehabilitation therapy services (RTS) in The Netherlands, but we lacked a good understanding of an ICN and the factors to make it successful. PURPOSE The aim of the study was to learn from initiatives in ICN's internationally, how are ICN's developed, how does it promote collaboration and what are facilitators and barriers in its development and use? METHODS We performed an environmental scan. First, we performed a systematic literature search (PubMed) focussing on ICNs for childhood oncology. Secondly, we sent a survey regarding development and use of ICNs to international childhood cancer centers. Participating centers were asked to share information about their initiatives in providing care close to home. Data were summarized descriptively and analyzed using content analysis. RESULTS The literature search did not reveal any relevant publications. The results from the survey, including15 countries, provided valuable insights in the understanding of a good ICN, its facilitators and barriers, and the potential added value of developing ICNs close to home to provide continuity and quality of care. CONCLUSIONS Our study highlights the perceived importance of ICNs for multidisciplinary RTS in pediatric oncology and provides valuable information for the formation of such a network. Information about the needs from the perspectives of children and parents is currently missing and essential to develop successful ICNs.
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Affiliation(s)
| | - J W Gorter
- Department of Rehabilitation, Physical Therapy Science and Sports, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands
- Center of Excellence for Rehabilitation Medicine, UMC Utrecht Brain Center, University Medical Center Utrecht, and de Hoogstraat Rehabilitation, Utrecht, the Netherlands
| | - E C van Dalen
- Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
| | - M Ketelaar
- Center of Excellence for Rehabilitation Medicine, UMC Utrecht Brain Center, University Medical Center Utrecht, and de Hoogstraat Rehabilitation, Utrecht, the Netherlands
| | - W J E Tissing
- Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
- Department of Pediatric Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
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Machado GF, Ward LS, Cunha LL. A global perspective of epidemiological trends in oncological emergencies. Curr Opin Oncol 2025:00001622-990000000-00249. [PMID: 40207469 DOI: 10.1097/cco.0000000000001142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/11/2025]
Abstract
PURPOSE OF REVIEW Oncologic emergencies are a critical interface between oncology and acute-care medicine. As global cancer trends evolve and healthcare disparities persist, this review seeks to address the pressing need to understand the epidemiology, predictors of outcomes, and care strategies for oncological emergencies across diverse healthcare contexts. The limited data available in this field underscores the vast knowledge gaps and the potential for significant scientific discovery. RECENT FINDINGS North American research networks have highlighted the variability in emergency department admissions and identified key determinants of outcomes, including functional status and disease staging. European studies have revealed that emergency presentations are frequently linked to advanced disease, whereas data from Asia and Oceania suggest that tumor burden and ethnicity significantly influence emergency care. In resource-limited regions, infection-related malignancies and inadequate healthcare infrastructure exacerbate challenges in managing oncologic emergencies. Despite these regional differences, consistent predictors of clinical outcomes, such as performance status and disease stage, have emerged as universal themes. SUMMARY This review highlights the need for targeted research and innovative interventions to bridge gaps in knowledge and care delivery. Region-specific strategies based on local epidemiological insights can improve patient outcomes and promote equity in oncological emergency management worldwide.
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Affiliation(s)
- Guilherme Falcão Machado
- Division of Emergency Medicine and Evidence-based Medicine, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo
| | - Laura Sterian Ward
- Laboratory of Cancer Molecular Genetics, University of Campinas, São Paulo, Brazil
| | - Lucas Leite Cunha
- Division of Emergency Medicine and Evidence-based Medicine, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo
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Czogalla M, Stöhr J, Gleim N, Papsdorf K, Klagges S, Hambsch P, Kuhnt T, Nägler F, Barrantes-Freer A, Wach J, Nicolay N, Seidel C. Short-term survivors with brain metastases have modest benefits from focal and systemic therapies and remain frequent despite improving treatment landscape. Clin Transl Radiat Oncol 2025; 51:100919. [PMID: 39877301 PMCID: PMC11772985 DOI: 10.1016/j.ctro.2025.100919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 12/22/2024] [Accepted: 01/09/2025] [Indexed: 01/31/2025] Open
Abstract
Purpose Therapeutic options for patients with brain metastases (BM) increase. While these lead to considerable survival effects in subgroups, there is limited knowledge about characteristics, prognosticators and treatment effects in patients with BM and short survival. Methods Patients with a survival time of ≤ 6 months (short-term survivors, STS), diagnosed with BM between 2009-2021 at a large tertiary cancer center were analysed. Clinical and treatment characteristics, pathological data and causes of death were documented. Descriptive statistics, treatment-specific univariate Kaplan-Meier estimator analyses and multivariate Cox regression were performed. Results Among 1248 patients with BM, 480 (38 %) were STS. 256 STS with detailed clinical records were included in this analysis. In univariate and multivariate analysis, Karnofsky Performance Status (KPS) (p < 0.001) and number of BM (p = 0.004) were prognostic. In 75 % of patients, the ds-GPA score predicted short-term survival. Use of resection with focal radiotherapy (p < 0.001) and systemic treatment (p < 0.001) appeared prognostically favourable compared to whole brain radiotherapy (WBRT) alone. However, survival benefits were very modest, with a median gain of 6 weeks following resection and focal radiotherapy compared to whole-brain radiotherapy, and 3 weeks from systemic treatment. Systemic tumor progression was documented as the cause of death in the majority of patients. Over the examined time period, the ratio between STS and other patients remained without significant change. Conclusion Within STS, KPS and number of BM are of prognostic relevance. There is benefit from local and systemic therapy to a limited extent. Shared and carefully discussed individual therapy decisions are necessary.
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Affiliation(s)
- M. Czogalla
- Department of Radiation Oncology, University of Leipzig Medical Center, Stephanstraße 9a, 04103 Leipzig, Germany
- Comprehensive Cancer Center Central Germany, Partner Site Leipzig, Liebigstraße 22, 04103 Leipzig, Germany
| | - J. Stöhr
- Department of Radiation Oncology, University of Leipzig Medical Center, Stephanstraße 9a, 04103 Leipzig, Germany
- Comprehensive Cancer Center Central Germany, Partner Site Leipzig, Liebigstraße 22, 04103 Leipzig, Germany
| | - N. Gleim
- Department of Radiation Oncology, University of Leipzig Medical Center, Stephanstraße 9a, 04103 Leipzig, Germany
- Comprehensive Cancer Center Central Germany, Partner Site Leipzig, Liebigstraße 22, 04103 Leipzig, Germany
| | - K. Papsdorf
- Department of Radiation Oncology, University of Leipzig Medical Center, Stephanstraße 9a, 04103 Leipzig, Germany
- Comprehensive Cancer Center Central Germany, Partner Site Leipzig, Liebigstraße 22, 04103 Leipzig, Germany
| | - S. Klagges
- Clinical Cancer Registry Leipzig, Philipp-Rosenthal-Straße 27b, 04103 Leipzig, Germany
| | - P. Hambsch
- Department of Radiation Oncology, University of Leipzig Medical Center, Stephanstraße 9a, 04103 Leipzig, Germany
- Comprehensive Cancer Center Central Germany, Partner Site Leipzig, Liebigstraße 22, 04103 Leipzig, Germany
| | - T. Kuhnt
- Department of Radiation Oncology, University of Leipzig Medical Center, Stephanstraße 9a, 04103 Leipzig, Germany
- Comprehensive Cancer Center Central Germany, Partner Site Leipzig, Liebigstraße 22, 04103 Leipzig, Germany
| | - F. Nägler
- Department of Radiation Oncology, University of Leipzig Medical Center, Stephanstraße 9a, 04103 Leipzig, Germany
- Comprehensive Cancer Center Central Germany, Partner Site Leipzig, Liebigstraße 22, 04103 Leipzig, Germany
| | - A. Barrantes-Freer
- Department of Neuropathology,University of Leipzig Medical Center, Liebigstraße 26, 04103 Leipzig, Germany
| | - J. Wach
- Department of Neurosurgery, University of Leipzig Medical Center, Liebigstraße 20, 04103 Leipzig, Germany
- Comprehensive Cancer Center Central Germany, Partner Site Leipzig, Liebigstraße 22, 04103 Leipzig, Germany
| | - N.H. Nicolay
- Department of Radiation Oncology, University of Leipzig Medical Center, Stephanstraße 9a, 04103 Leipzig, Germany
- Comprehensive Cancer Center Central Germany, Partner Site Leipzig, Liebigstraße 22, 04103 Leipzig, Germany
| | - C. Seidel
- Department of Radiation Oncology, University of Leipzig Medical Center, Stephanstraße 9a, 04103 Leipzig, Germany
- Comprehensive Cancer Center Central Germany, Partner Site Leipzig, Liebigstraße 22, 04103 Leipzig, Germany
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Mihăileanu F, Cismaru CA, Cordoș AA, Ciocan RA, Chiorescu S, Constantinescu I, Stancu B, Breazu C, Coman H, Berindan Neagoe I, Gherman CD. Specific Quality of Life Questionnaire Validation in Patients with Colorectal Cancer. Diagnostics (Basel) 2024; 14:2481. [PMID: 39594147 PMCID: PMC11592747 DOI: 10.3390/diagnostics14222481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 10/24/2024] [Accepted: 11/03/2024] [Indexed: 11/28/2024] Open
Abstract
(1) Background: The quality of life of cancer patients is not only important for their well-being, but it has great influence on the overall survival and response to therapy, considering the adherence to treatment and follow-up. (2) Methods: This research is a prospective study conducted over a period of 6 months involving patients admitted in the Department of Surgery II, Cluj County Emergency Clinical Hospital. The specific questionnaire designed by us for patients with colorectal cancer contains questions about the quality of life and symptoms such as weight loss, pain, constipation, and diarrhoea. (3) Results: Our prospective study included in the analysis 50 patients with colorectal cancer. The CR 29 questionnaire outlined scores below 30 for sore skin, urinary incontinence, dysuria, faecal incontinence, flatulence, discomfort from bowel movement, sexual dysfunction and hair loss. The CR 30 functioning scale depicted high scores for cognitive (100%, 95% CI [0.91-1]), physical (88%, 95% CI [0.75-0.95]), and functional (88%, 95% CI [0.39-0.68]) domains and low scores (<50) for emotional (98%, 95% CI [0.88-0.99]) and social (100%, 95% CI [0.91-1]) functions. (4) Conclusions: The quality of life of patients with colorectal cancer was influenced by socio-economic status, smoking, surgical procedure, and neoplastic pathology.
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Affiliation(s)
- Florin Mihăileanu
- Department of Surgery—Surgery II, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (F.M.); (S.C.); (I.C.); (B.S.)
| | - Cosmin Andrei Cismaru
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, Romania;
| | - Ariana Anamaria Cordoș
- Department of Surgery—Practical Abilities, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (R.A.C.); (C.D.G.)
- Romanian Society of Medical Informatics, 300222 Timisoara, Romania
| | - Răzvan Alexandru Ciocan
- Department of Surgery—Practical Abilities, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (R.A.C.); (C.D.G.)
| | - Stefan Chiorescu
- Department of Surgery—Surgery II, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (F.M.); (S.C.); (I.C.); (B.S.)
| | - Ioana Constantinescu
- Department of Surgery—Surgery II, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (F.M.); (S.C.); (I.C.); (B.S.)
| | - Bogdan Stancu
- Department of Surgery—Surgery II, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (F.M.); (S.C.); (I.C.); (B.S.)
| | - Caius Breazu
- Department of Surgery—Anaesthetics, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania;
| | - Horațiu Coman
- Vascular Surgery Clinic, Cluj County Emergency Hospital, 400006 Cluj-Napoca, Romania;
| | - Ioana Berindan Neagoe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, Romania;
| | - Claudia Diana Gherman
- Department of Surgery—Practical Abilities, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (R.A.C.); (C.D.G.)
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Carballo‐Muñoz A, Lima G, Llorente L, Remolina‐Bonilla YA, Jaime‐Casas S, Otamendi‐Lopez A, Ortiz‐Guerra RA, Velazquez HE, Atisha‐Fregoso Y, Bourlon MT. Aging-related biomarkers in testicular cancer survivors after different oncologic treatments. Cancer Med 2024; 13:e70200. [PMID: 39300957 PMCID: PMC11413499 DOI: 10.1002/cam4.70200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 08/19/2024] [Accepted: 08/26/2024] [Indexed: 09/22/2024] Open
Abstract
PURPOSE Testicular cancer survivors (TCS) exposed to chemotherapy have an increased expression of CDKN2A/p16INK4a and a lymphocyte phenotype associated with immunosenescence. We seek to define whether the immunosenescent phenotype is associated with chemotherapy. METHODS Case-control study of TCS, disease-free ≥3 months and stratified by primary treatment modality into orchiectomy only, chemotherapy, or bone marrow transplant (BMT). Each group was compared with age-matched healthy controls (HC). We measured the relative proportions of lymphocyte subpopulations using flow cytometry, levels of C-reactive protein, and relative expression of CDKN2A/p16INK4a quantified by qPCR. RESULTS We included 65 patients; 19 were treated with orchiectomy only, 35 received different doses of chemotherapy, and 11 underwent BMT. The chemotherapy and BMT groups had decreased naïve CD4 cells compared to HC. The chemotherapy group showed increased central and effector memory CD4 cells, as well as effector and terminally differentiated CD8 cells, compared to HC. Chemotherapy (chemotherapy 1.84 vs. HC 0.92; p < 0.01) and BMT (BMT 6.96 vs. HC 1.25; p < 0.005) groups had higher expression of CDKN2A/p16INK4a compared to HC. The orchiectomy group showed no significant difference with HC (orchiectomy 1.73 vs. HC 1.01; p = 0.17). CRP levels were higher in all groups when compared with HC; in the orchiectomy group, they were only marginally increased (chemotherapy 0.22 vs. HC 0.06; p < 0.01; BMT 0.26 vs. HC 0.06; p < 0.01; orchiectomy 0.09 vs. HC 0.07; p < 0.01). CONCLUSIONS Among TCS, only patients exposed to cytotoxic agents developed an immunosenescent phenotype. This finding supports the attribution of this alteration to the cytotoxic treatment.
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Affiliation(s)
- A. Carballo‐Muñoz
- Department of Hematology and OncologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico CityTlalpanMexico
| | - G. Lima
- Department of Inmunology and RheumatologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico CityTlalpanMexico
| | - L. Llorente
- Department of Inmunology and RheumatologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico CityTlalpanMexico
| | - Y. A. Remolina‐Bonilla
- Department of Hematology and OncologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico CityTlalpanMexico
| | - S. Jaime‐Casas
- Department of Hematology and OncologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico CityTlalpanMexico
| | - A. Otamendi‐Lopez
- Department of Hematology and OncologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico CityTlalpanMexico
| | - R. A. Ortiz‐Guerra
- Department of Hematology and OncologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico CityTlalpanMexico
| | - Hugo E. Velazquez
- Radiology DepartmentNational Institute of CardiologyMexico CityTlalpanMexico
| | - Y. Atisha‐Fregoso
- Institute of Molecular Medicine, Feinstein Institutes for Medical ResearchNew YorkNew YorkUSA
| | - M. T. Bourlon
- Department of Hematology and OncologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico CityTlalpanMexico
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Didehvar DS, Lanza MR, Atherton MJ, Lenz JA. Malignant transformation and subsequent leptomeningeal carcinomatosis of a gastric polyp in a dog. J Vet Intern Med 2024; 38:1744-1750. [PMID: 38587203 PMCID: PMC11099795 DOI: 10.1111/jvim.17072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 03/27/2024] [Indexed: 04/09/2024] Open
Abstract
Progressive carcinogenesis of a gastric polyp with transformation to gastric adenocarcinoma and subsequent development of leptomeningeal carcinomatosis is described in an adult male Scottish terrier. Presenting clinical signs consisted of vomiting with intermittent hematemesis. Surgical biopsies over the course of 14 months documented the progression from gastric polyp to minimally invasive gastric carcinoma to invasive gastric adenocarcinoma, a pathogenesis not previously documented in veterinary oncology. The patient ultimately developed neurologic pathology and was euthanized, and necropsy evaluation identified widespread carcinomatosis with accompanying leptomeningeal metastasis. As in humans, gastric polyps in dogs rarely have malignant potential.
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Affiliation(s)
- Dillon S. Didehvar
- Department of Clinical Science & Advanced MedicineSchool of Veterinary Medicine, University of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Matthew R. Lanza
- Department of PathobiologySchool of Veterinary Medicine, University of PennsylvaniaPhiladelphiaPennsylvaniaUSA
- Present address:
Department of Comparative Medicine, College of MedicinePennsylvania State UniversityHersheyPennsylvaniaUSA
| | - Matthew J. Atherton
- Department of Clinical Science & Advanced MedicineSchool of Veterinary Medicine, University of PennsylvaniaPhiladelphiaPennsylvaniaUSA
- Department of Biomedical SciencesSchool of Veterinary Medicine, University of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Jennifer A. Lenz
- Department of Clinical Science & Advanced MedicineSchool of Veterinary Medicine, University of PennsylvaniaPhiladelphiaPennsylvaniaUSA
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Fan X, Zhang Q, Qin S, Ju S. CircBRIP1: a plasma diagnostic marker for non-small-cell lung cancer. J Cancer Res Clin Oncol 2024; 150:83. [PMID: 38329551 PMCID: PMC10853360 DOI: 10.1007/s00432-023-05558-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 12/12/2023] [Indexed: 02/09/2024]
Abstract
BACKGROUND Circular RNA (circRNA), which has been demonstrated in studies to be abundantly prevalent in tumor cells and bodily fluids and to play a significant role in tumors, has the potential for biological markers to be used to assist tumor diagnosis. This study mainly discusses the potential of circBRIP1 as a biomarker for diagnosing non-small-cell lung cancer (NSCLC). METHODS First, high-throughput sequencing screened the differentially expressed circBRIP1, and real-time fluorescence quantitative PCR (qRT-PCR) verified its expression in NSCLC. Next, sanger sequencing, agarose gel electrophoresis, RNase R assay, and fluorescence in situ hybridization (FISH) were used to verify its molecular characteristics. The diagnostic value was analyzed by the subject operating characteristic curve (ROC), and the cardinality test was analyzed for correlation with clinicopathological parameters. Finally, we tentatively predicted the downstream miRNA- or RNA-binding protein that may bind to circBRIP1. RESULTS CircBRIP1 is highly expressed in NSCLC tissues, cells and plasma with good specificity and stability. CircBRIP1 not only can well-distinguish NSCLC patients from benign pulmonary diseases (BPD) patients, healthy individuals and small cell lung cancer (SCLC) patients, but it also has some potential for dynamic monitoring. Combined with the analysis of clinicopathological data, the high level of circRNA expression was related to the degree of tumor differentiation, TNM stage, T stage, lymph node metastasis and distal metastasis in NSCLC patients. In addition, circBRIP1 has a high diagnostic value. CONCLUSIONS Plasma circBRIP1 is significantly overexpressed in NSCLC patients. It can be used as a sensitive biomarker with unique value for early diagnosis, tumor development and prognosis detection.
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Affiliation(s)
- Xinfeng Fan
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, Jiangsu, China
- Medical School of Nantong University, Nantong University, Nantong, China
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China
| | - Qi Zhang
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, Jiangsu, China
- Medical School of Nantong University, Nantong University, Nantong, China
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China
| | - Shiyi Qin
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, Jiangsu, China
- Medical School of Nantong University, Nantong University, Nantong, China
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China
| | - Shaoqing Ju
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, Jiangsu, China.
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, No. 20, Xisi Road, Nantong, 226001, Jiangsu, China.
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Medici C, Jørgensen N, Juul A, Albrethsen J, Kreiberg M, Lauritsen J, Wagner T, Rosenvilde J, Daugaard G, Bandak M. Insulin-like Factor 3, Basal and Human Chorionic Gonadotropin-Stimulated Testosterone as Biomarkers to Predict the Effect of Testosterone Replacement in Testicular Cancer Survivors With Mild Leydig Cell Insufficiency. Clin Genitourin Cancer 2024; 22:e106-e112.e4. [PMID: 37673783 DOI: 10.1016/j.clgc.2023.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 08/10/2023] [Indexed: 09/08/2023]
Abstract
INTRODUCTION Mild Leydig cell insufficiency affects a substantial proportion of testicular cancer survivors. Previous studies have not shown a beneficial effect of testosterone replacement therapy, however, with a pronounced interindividual effect. Thus, biomarkers identifying the subgroups that might benefit are wanted. We aimed to determine if insulin-like factor 3 (INSL3), basal and human chorionic gonadotropin (hCG)-stimulated testosterone can predict the effect of testosterone replacement therapy in testicular cancer survivors with mild Leydig cell insufficiency. PATIENTS AND METHODS We randomized adult testicular cancer survivors with mild Leydig cell insufficiency 1:1 to 12 months of transdermal testosterone replacement therapy (Tostran gel 2%) or placebo. INSL3, basal, and hCG-stimulated testosterone were measured at baseline. Outcomes (glucose, insulin, HbA1C, lipids, blood pressure, and body composition) were measured at baseline, 6 and 12 months. We applied a linear mixed-effect model comparing patients receiving testosterone with placebo in subgroups by biomarker. RESULTS We included and randomized 69 patients between October 2016 and February 2018. Patients with INSL3 and hCG-stimulated testosterone concentrations below the median had a -1.7 kg (95% CI: -3.1, -0.4) and -2.0 kg (95% CI: -3.5, -0.6) change in fat mass after 12 months of testosterone replacement therapy compared with placebo. This was not the case in patients with INSL3 and hCG-stimulated testosterone above the median. We did not find any effect of these biomarkers on glucose, insulin, HbA1c, or lipids. CONCLUSION Patients with INSL3 and hCG-stimulated testosterone concentrations below the median had decreased fat mass after 12 months of testosterone replacement therapy compared with placebo. It should be evaluated in larger trials if these biomarkers can be used as predictive markers identifying testicular cancer patients with mild Leydig cell insufficiency who might benefit from testosterone substitution.
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Affiliation(s)
- Clara Medici
- Department of Oncology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
| | - Niels Jørgensen
- Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen Denmark; International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Anders Juul
- Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen Denmark; International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Jakob Albrethsen
- Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen Denmark; International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Michael Kreiberg
- Department of Oncology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Jakob Lauritsen
- Department of Oncology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Thomas Wagner
- Department of Oncology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Josephine Rosenvilde
- Department of Oncology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Gedske Daugaard
- Department of Oncology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Mikkel Bandak
- Department of Oncology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
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Noh H, Anota A, Mongondry R, Meyrand R, Dupuis C, Schiffler C, Marijnen P, Rinaldi S, Lachuer J, Keski-Rahkonen P, Gunter MJ, Fléchon A, Fervers B, Pérol O. Impact of a one-year supervised physical activity program on long-term cancer-related fatigue and mediating effects of the gut microbiota in metastatic testicular cancer patients: protocol of the prospective multicentre, randomized controlled phase-III STARTER trial. BMC Cancer 2024; 24:84. [PMID: 38225551 PMCID: PMC10790440 DOI: 10.1186/s12885-024-11824-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Accepted: 01/02/2024] [Indexed: 01/17/2024] Open
Abstract
BACKGROUND Testicular germ cell tumours (TGCTs) are the most common malignancy in men aged 15-40 years, with increasing incidence worldwide. About 33 ~ 50% of the patients present with metastatic disease at diagnosis. TGCT survivors experience short- and long-term sequelae, including cancer-related fatigue (CRF). Physical activity (PA) has established effects on reducing CRF and other sequelae and improving health-related quality of life (HRQoL). However, its impact on TGCT survivors has so far received little attention. The gut microbiota plays a crucial role in various physiological functions, including cognition and metabolism, and may mediate the effects of PA on CRF and other sequelae, but this has not been investigated in randomized controlled trials. METHODS This national, multicentre, phase-III trial will evaluate the impact of a one-year supervised PA program on CRF and other short- and long-term sequelae in metastatic TGCT patients receiving cisplatin-based chemotherapy combined with etoposide+/-bleomycin. It will also investigate potential mediating effects of the gut microbiota and its metabolites involved in the gut-brain axis on the relationship between PA and CRF and other sequelae. A total of 236 men ≥ 18 years of age with metastatic TGCT (seminoma and non-seminoma) will be enrolled before starting first-line chemotherapy in several French hospitals. The primary (CRF) and secondary (cognitive/psychological/metabolic sequelae, HRQoL, etc.) outcomes and gut microbiota and relevant metabolites will be assessed at inclusion, during and at the end of the one-year intervention, and annually until 10 years since inclusion to assess long-term sequelae, more specifically CRF, cardiovascular toxicities, and second primary cancer occurrence in this population. DISCUSSION This trial will provide comprehensive and novel insights into the effects of a long-term supervised PA program on CRF and other sequelae in metastatic TGCT patients receiving first-line chemotherapy. It will also contribute to understanding the potential role of the gut microbiota and its metabolites in mediating the effects of PA on these outcomes. The findings of this study will help the development of effective PA interventions to improve the health of TGCT survivors and may have implications for other cancer populations as well. TRIAL REGISTRATION The study was registered on ClinicalTrials.gov (NCT05588700) on 20 Oct. 2022.
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Affiliation(s)
- Hwayoung Noh
- Departement of Prevention Cancer Environment, Léon Bérard Cancer Centre, Lyon, France.
- INSERM U1296, Léon Bérard Cancer Centre, Lyon, France.
- Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
| | - Amélie Anota
- Direction of Clinical Research and Innovation, Léon Bérard Cancer Centre, Lyon, France
| | - Rodolf Mongondry
- Departement of Prevention Cancer Environment, Léon Bérard Cancer Centre, Lyon, France
| | - Renaud Meyrand
- Departement of Prevention Cancer Environment, Léon Bérard Cancer Centre, Lyon, France
| | - Carmen Dupuis
- Departement of Prevention Cancer Environment, Léon Bérard Cancer Centre, Lyon, France
| | - Camille Schiffler
- Direction of Clinical Research and Innovation, Léon Bérard Cancer Centre, Lyon, France
| | - Philippe Marijnen
- Departement of Prevention Cancer Environment, Léon Bérard Cancer Centre, Lyon, France
| | - Sabina Rinaldi
- Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Joel Lachuer
- INSERM U1052, Cancer Research Center of Lyon (CRCL), University Lyon 1, Lyon, France
- ProfileXpert, SFR santé Lyon-Est, CNRS UMR-S3453, INSERM US7, Lyon, France
| | - Pekka Keski-Rahkonen
- Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Marc J Gunter
- Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, W2 1PG, London, UK
| | - Aude Fléchon
- Department of Medical Oncology, Léon Bérard Cancer Centre, Lyon, France
| | - Béatrice Fervers
- Departement of Prevention Cancer Environment, Léon Bérard Cancer Centre, Lyon, France
- INSERM U1296, Léon Bérard Cancer Centre, Lyon, France
| | - Olivia Pérol
- Departement of Prevention Cancer Environment, Léon Bérard Cancer Centre, Lyon, France
- INSERM U1296, Léon Bérard Cancer Centre, Lyon, France
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12
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Parra-Mujica F, Roope LS, Abdul-Aziz A, Mustapha F, Ng CW, Rampal S, Lim LL, Dakin H, Clarke P. Health poverty among people with type 2 diabetes mellitus (T2DM) in Malaysia. Soc Sci Med 2024; 340:116426. [PMID: 38016309 DOI: 10.1016/j.socscimed.2023.116426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 11/06/2023] [Accepted: 11/10/2023] [Indexed: 11/30/2023]
Abstract
In the context of the escalating burden of diabetes in low and middle-income countries (LMICs), there is a pressing concern about the widening disparities in care and outcomes across socioeconomic groups. This paper estimates health poverty measures among individuals with type 2 diabetes mellitus (T2DM) in Malaysia. Using data from the National Diabetes Registry between 2009 and 2018, the study linked 932,855 people with T2DM aged 40-75 to death records. Cox proportional hazards models were used to estimate the 5-year survival probabilities for each patient, stratified by age and sex, while controlling for comorbidities and area-based indicators of socio-economic status (SES), such as district-level asset-based indices and night-time luminosity. Measures of health poverty, based on the Foster-Greer-Thorbecke (FGT) measures, were employed to capture excessive risk of premature mortality. Two poverty line thresholds were used, namely a 5% and 10% reduction in survival probability compared to age and sex-adjusted survival probability of the general population. Counterfactual simulations estimated the extent to which comorbidities contribute to health poverty. 43.5% of the sample experienced health poverty using the 5% threshold, and 8.9% were health poor using the 10% threshold. Comorbidities contribute 2.9% for males and 5.4% for females, at the 5% threshold. At the 10% threshold, they contribute 7.4% for males and 3.4% for females. If all patients lived in areas of highest night-light intensity, poverty would fall by 5.8% for males and 4.6% for females at the 5% threshold, and 4.1% for males and 0.8% for females at the 10% threshold. In Malaysia, there is a high incidence of health poverty among people with diabetes, and it is strongly associated with comorbidities and area-based measures of SES. Expanding the application of health poverty measurement, through a combination of clinical registries and open spatial data, can facilitate simulations for health poverty alleviation.
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Affiliation(s)
- Fiorella Parra-Mujica
- Erasmus School of Health Policy and Management (ESHPM), Erasmus, University Rotterdam, the Netherlands; Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; Erasmus Center for Health Economics Rotterdam (EsCHER), the Netherlands.
| | - Laurence Sj Roope
- Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - Alia Abdul-Aziz
- Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Feisul Mustapha
- Non-communicable Disease Section, Disease Control Division, Ministry of Health, Putrajaya, Malaysia
| | - Chiu Wan Ng
- Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Sanjay Rampal
- Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Lee-Ling Lim
- Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Helen Dakin
- Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - Philip Clarke
- Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
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13
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Kleinlugtenbelt LB, Tissing WJE, Solkema WJMPV, van der Torre P, Kollen WJW, Gorter JW. The views of parents of children with cancer and pediatric physical therapists on a network for continuity and optimal quality of care for children with cancer: KinderOncoNet. Support Care Cancer 2023; 32:9. [PMID: 38055083 PMCID: PMC10700193 DOI: 10.1007/s00520-023-08211-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 11/27/2023] [Indexed: 12/07/2023]
Abstract
PURPOSE Children with cancer require specific therapeutic guidance. Parents prefer physical therapy close to home, while pediatric physical therapists (PPTs) working in the community may lack specific knowledge. The aim of this study is to determine the needs of parents of children with cancer and PPTs to inform the design and development of a care network, named "KinderOncoNet." METHODS We explored the perspectives and needs of parents of children with cancer and PPTs in the community, and we investigated the added value that KinderOncoNet could offer. We used an iterative process; data collection consisted of (1) gathering information from parents of children with cancer and PPTs through a survey and (2) co-creation sessions with stakeholders. RESULTS In total, 98 parents and 177 PPTs participated in the survey. Parents (97%) and PPTs (93%) indicated that the care network would bring added value. All but one parent stressed the importance of a local PPT being aware of both the condition and the side and late effects of oncological treatment. Moreover, 40% of PPTs thought they do not have sufficient knowledge to provide high-quality therapy and that they would embrace opportunities for education. Through the co-creation sessions, a prototype of the care network was conceptualized. CONCLUSION KinderOncoNet can contribute to the continuity and quality of physiotherapy care for children with cancer during and after the oncological treatment. Such a network would allow for sharing knowledge, developing skills, and improving accessibility and communication in the Netherlands.
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Affiliation(s)
- L B Kleinlugtenbelt
- Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584, CS, Utrecht, The Netherlands.
| | - W J E Tissing
- Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584, CS, Utrecht, The Netherlands
- Department of pediatric oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | | | - P van der Torre
- Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584, CS, Utrecht, The Netherlands
| | - W J W Kollen
- Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584, CS, Utrecht, The Netherlands
| | - J W Gorter
- Department of Rehabilitation, Physical Therapy Science and Sports, University Medical Center Utrecht, Utrecht, The Netherlands
- UMC Utrecht Brain Center and Center of Excellence for Rehabilitation Medicine, Utrecht University, Utrecht, The Netherlands
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14
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Xu L, Li K, Li J, Xu F, Liang S, Kong Y, Chen B. IL-18 serves as a main effector of CAF-derived METTL3 against immunosuppression of NSCLC via driving NF-κB pathway. Epigenetics 2023; 18:2265625. [PMID: 37871286 PMCID: PMC10595399 DOI: 10.1080/15592294.2023.2265625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 09/07/2023] [Indexed: 10/25/2023] Open
Abstract
Background: N6-methyladenosine (m6A) is the most abundant modification in eukaryotic mRNA. However, its role in non-small cell lung cancer (NSCLC) has not been completely elucidated.Objective: To explore whether methyltransferase like 3 (METTL3) in cancer associated fibroblasts (CAFs) affects the secretion of IL-18, which drives NSCLC cells to regulate PD-L1-mediated immunosuppression via the nuclear factor kappa B (NF-κB) pathway.Methods: Histopathological features of NSCLC tissues were identified by H&E and IHC staining. The levels of m6A writers (METTL3), IL-18 and NF-κB pathway related genes were assessed. The quantity of CD8+ T cells was evaluated by flow cytometry (FCM). The direct binding relationship between METTL3 and IL-18 mRNA was detected by RIP assay and RNA pulldown and confirmed by dual - luciferase reporter assay. The level of RNA m6A was detected by RNA m6A dot blot and meRIP assays. A heterotopic implantation model of NSCLC was established in NOD-SCID mice for further explore the effect of CAF derived METTL3 on immunosuppression of NSCLC in vivo.Results: Our results illustrated that METTL3 was down-regulated in CAFs, and CAF derived METTL3 alleviated PD-L1-mediated immunosuppression of NSCLC through IL-18. Subsequently, we found that IL-18 was main effector of CAF-derived METTL3 against immunosuppression of NSCLC, and IL-18 accelerated immunosuppression of NSCLC by driving NF-κB pathway. In vivo, METTL3 knockdown-derived CAFs accelerated immunosuppression of NSCLC.Conclusion: IL-18 served as a main effector of CAF-derived METTL3 against immunosuppression of NSCLC via driving NF-κB pathway.
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Affiliation(s)
- Li Xu
- The Second Department of Thoracic Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan Province, P.R. China
| | - Kang Li
- The Second Department of Thoracic Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan Province, P.R. China
| | - Jia Li
- The Second Department of Thoracic Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan Province, P.R. China
| | - Fang Xu
- The Second Department of Thoracic Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan Province, P.R. China
| | - Shuzhi Liang
- The Second Department of Thoracic Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan Province, P.R. China
| | - Yi Kong
- The Second Department of Thoracic Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan Province, P.R. China
| | - Bolin Chen
- The Second Department of Thoracic Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan Province, P.R. China
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15
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Zhao P, Ning J, Huang J, Wei B, Wang Z, Huang X. High Expression of MORC2 is Associated with Poor Clinical Outcomes and Immune Infiltrates in Colon Adenocarcinoma. Int J Gen Med 2023; 16:4595-4615. [PMID: 37850194 PMCID: PMC10577261 DOI: 10.2147/ijgm.s420715] [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: 05/20/2023] [Accepted: 09/07/2023] [Indexed: 10/19/2023] Open
Abstract
Purpose Microrchidia 2 (MORC2) is a universally expressed molecule that has recently been identified as a chromatin modulator and elevated in many malignancies. However, its prognostic value and immunological role of MORC2 in colon adenocarcinoma (COAD) have never been illustrated. Methods The clinical parameters and MORC2 expression datasets of COAD patients were obtained from The Cancer Genome Atlas (TCGA). Cancer and adjacent tissue specimens from surgically resected COAD patients were collected, and quantitative real-time PCR was used to detect MORC2 expression. Differentially expressed genes related to MORC2 were discovered and used for functional enrichment analysis. The diagnostic and prognostic values of MORC2 in COAD were conducted using receiver operating characteristics (ROC), Kaplan-Meier survival curve analysis, PrognoScan, Gene Expression Profiling Interactive Analysis (GEPIA) public databases and nomograms. Eventually, the association of MORC2 with tumor microenvironment was analyzed by using TIMER and GSVA package of R (v3.6.3). Results MORC2 expression was upregulated in COAD tissues, and the RT-qPCR results further verified the reliability of our differential analysis at the transcriptional level. Additionally, higher expression of MORC2 was correlated to a poor prognosis for COAD patients. MORC2 was an independent prognostic factor for COAD and could be a diagnostic factor for early COAD. Furthermore, MORC2 expression was positively correlated with immune cells such as NK cells, TFH cells and so on. Conclusion The findings demonstrated that overexpression of MORC2 was correlated with worse prognosis and immune infiltrates of COAD. MORC2 can serve as a reliable diagnostic and prognostic biomarker and a target of immunotherapy for COAD patients.
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Affiliation(s)
- Peizhuang Zhao
- Department of Geriatrics and Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Jiajia Ning
- Department of Geriatrics and Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Jun Huang
- Department of Geriatrics and Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Binqian Wei
- Department of Geriatrics and Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Zhen Wang
- Department of Geriatrics and Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Xue Huang
- Department of Geriatrics and Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
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16
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Shah KV, Carey RM, Prasad A, Panara K, Rajasekaran K, Cannady SB, Brant JA, Brody RM. Postoperative Radiation Therapy Refusal in Major Salivary Gland Cancers. Otolaryngol Head Neck Surg 2023; 169:577-588. [PMID: 36939552 DOI: 10.1002/ohn.285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Revised: 01/11/2023] [Accepted: 01/16/2023] [Indexed: 02/10/2023]
Abstract
OBJECTIVE Major salivary gland cancers (MSGCs) are often treated with primary surgery followed by adjuvant therapy for high-risk pathology. Patients with these cancers may opt out of recommended postoperative radiation therapy (PORT) for many reasons and consequently may suffer worse outcomes. STUDY DESIGN Retrospective cohort study. SETTING National Cancer Database. METHODS Patients diagnosed with MSGC from 2004 to 2016 were identified, and overall survival and risk factors for refusal of recommended PORT were analyzed based on demographic, socioeconomic, and clinical factors. Multivariable logistic regression and a Cox model were used to conduct the analysis. RESULTS 211 out of 4704 qualifying patients (4.5%) refused recommended PORT. Multivariable analysis demonstrated increased PORT refusal for age >74 years (odds ratio OR 4.34, confidence interval [CI] [2.43-7.85]), Asian race (OR 2.25, CI [1.10-4.23]), and certain facility types (comprehensive cancer center, OR 2.39, CI [1.08-6.34]; academic research program, OR 3.29, CI [1.49-8.74]; and integrated network cancer program, OR 2.75, CI [1.14-7.7]). N2 stage was associated with decreased PORT refusal (OR 0.67, CI [0.45-0.98]). The 5-year overall survival for patients who received and refused PORT were significantly different at 65.8% and 53.8%, respectively (p < .001). When controlling for several factors, PORT refusal was independently associated with significantly lower overall survival (HR 1.54, CI [1.21-1.98]). CONCLUSION Patient refusal of recommended PORT in MSGC is rare, associated with various disease and socioeconomic factors, and may decrease overall survival. Our findings can assist clinicians in counseling patients and identifying those who may be more likely to opt out of recommended PORT.
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Affiliation(s)
- Keshav V Shah
- Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Ryan M Carey
- Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Aman Prasad
- Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Kush Panara
- Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Karthik Rajasekaran
- Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Steven B Cannady
- Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Jason A Brant
- Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Otolaryngology, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA
| | - Robert M Brody
- Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Otolaryngology, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA
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17
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Chen JS, Guo X, Sun JY, Wang MX, Gao XZ, Wang Z, Han JL, Sun H, Zhang K, Liu C. Fangchinoline derivatives inhibits PI3K signaling in vitro and in vivo in non-small cell lung cancer. Bioorg Chem 2023; 138:106623. [PMID: 37295240 DOI: 10.1016/j.bioorg.2023.106623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 05/08/2023] [Accepted: 05/21/2023] [Indexed: 06/12/2023]
Abstract
Fangchinoline (Fan) are extracted from the traditional Chinese medicine Stephania tetrandra S., which is a bis-benzyl isoquinoline alkaloids with anti-tumor activity. Therefore, 25 novel Fan derivatives have been synthesized and evaluated for their anti-cancer activity. In CCK-8 assay, these fangchinoline derivatives displayed higher proliferation inhibitory activity on six tumor cell lines than the parental compound. Compared to the parent Fan, compound 2h presented the anticancer activity against most cancer cells, especially A549 cells, with an IC50 value of 0.26 μM, which was 36.38-fold, and 10.61-fold more active than Fan and HCPT, respectively. Encouragingly, compound 2h showed low biotoxicity to the human normal epithelial cell BEAS-2b with an IC50 value of 27.05 μM. The results indicated compound 2h remarkably inhibited the cell migration by decreasing MMP-2 and MMP-9 expression and inhibited the proliferation of A549 cells by arresting the G2/M cell cycle. Meanwhile, compound 2h could also induce A549 cell apoptosis by promoting endogenous pathways of mitochondrial regulation. In nude mice presented that the growth of tumor tissues was markedly inhibited by the consumption of compound 2h in a dose-dependent manner, and it was found that compound 2h could inhibit the mTOR/PI3K/AKT pathway in vivo. In docking analysis, high affinity interaction between 2h and PI3K was responsible for drastic kinase inhibition by the compound. To conclude, this derivative compound may be useful as a potent anti-cancer agent for treatment of NSCLC.
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Affiliation(s)
- Jia-Shu Chen
- Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Key Laboratory of Agro-Products Processing Technology of Shandong Province/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 202 Gongye North Road, Jinan 250100, China
| | - Xu Guo
- Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Key Laboratory of Agro-Products Processing Technology of Shandong Province/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 202 Gongye North Road, Jinan 250100, China
| | - Jin-Yue Sun
- Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Key Laboratory of Agro-Products Processing Technology of Shandong Province/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 202 Gongye North Road, Jinan 250100, China
| | - Mu-Xuan Wang
- Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Key Laboratory of Agro-Products Processing Technology of Shandong Province/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 202 Gongye North Road, Jinan 250100, China
| | - Xiu-Zheng Gao
- Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Key Laboratory of Agro-Products Processing Technology of Shandong Province/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 202 Gongye North Road, Jinan 250100, China
| | - Zhen Wang
- Arura Tibetan Medicine (Shandong) Health Industry Co., Jinan 250100, China
| | - Jin-Long Han
- Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Key Laboratory of Agro-Products Processing Technology of Shandong Province/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 202 Gongye North Road, Jinan 250100, China.
| | - Hui Sun
- Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Key Laboratory of Agro-Products Processing Technology of Shandong Province/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 202 Gongye North Road, Jinan 250100, China.
| | - Kai Zhang
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No.324, JingwuRoad, Jinan, Shandong 250021,China.
| | - Chao Liu
- Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Key Laboratory of Agro-Products Processing Technology of Shandong Province/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 202 Gongye North Road, Jinan 250100, China.
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Data mining combines bioinformatics discover immunoinfiltration-related gene SERPINE1 as a biomarker for diagnosis and prognosis of stomach adenocarcinoma. Sci Rep 2023; 13:1373. [PMID: 36697459 PMCID: PMC9876925 DOI: 10.1038/s41598-023-28234-7] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Accepted: 01/16/2023] [Indexed: 01/27/2023] Open
Abstract
Stomach adenocarcinoma (STAD) is a type of cancer which often at itsadvanced stage apon diagnosis and mortality in clinical practice. Several factors influencethe prognosis of STAD, including the expression and regulation of immune cells in the tumor microenvironment. We here investigated the biomarkers related to the diagnosis and prognosis of gastric cancer, hoping to provide insights for the diagnosis and treatment of gastric cancer in the future. STAD and normal patient RNA sequencing data sets were accessed from the cancer genome atlas (TCGA database). Differential genes were determined and obtained by using the R package DESeq2. The stromal, immune, and ESTIMATE scores are calculated by the ESTIMATE algorithm, followed by the modular genes screening using the R package WGCNA. Subsequently, the intersection between the modular gene and the differential gene was taken and the STRING database was used for PPI network module analysis. The R packages clusterProfiler, enrichplot, and ggplot2 were used for GO and KEGG enrichment analysis. Cox regression analysis was used to screen survival-related genes, and finally, the R package Venn Diagram was used to take the intersection and obtain 7 hub genes. The time-dependent ROC curve and Kaplan-Meier survival curve were used to find the SERPINE1 gene, which plays a critical role in prognosis. Finally, the expression pattern, clinical characteristics, and regulatory mechanism of SERPINE1 were analyzed in STAD. We revealed that the expression of SERPINE1 was significantly increased in the samples from STAD compared with normal samples. Cox regression, time-dependent ROC, and Kaplan-Meier survival analyses demonstrated that SERPINE1 was significantly related to the adverse prognosis of STAD patients. The expression of SERPINE1 increased with the progression of T, N, and M classification of the tumor. In addition, the results of immune infiltration analysis indicated that the immune cells' expression were higher in high SERPINE1 expression group than that in low SERPINE1 expression group, including CD4+ T cells, B cells, CD8+ T cells, macrophages, neutrophils and other immune cells. SERPINE1 was closely related to immune cells in the STAD immune microenvironment and had a synergistic effect with the immune checkpoints PD1 and PD-L1. In conclusion, we proved that SERPINE1 is a promising prognostic and diagnostic biomarker for STAD and a potential target for immunotherapy.
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Zhang C, Xiang Y, Wang J, Yan D. Comparison of the efficacy and safety of third-line treatments for advanced gastric cancer: A systematic review and network meta-analysis. Front Oncol 2023; 13:1118820. [PMID: 36937403 PMCID: PMC10016689 DOI: 10.3389/fonc.2023.1118820] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 02/06/2023] [Indexed: 03/05/2023] Open
Abstract
Background Many options for third-line treatment of advanced gastric cancer (GC) or gastroesophageal junction carcinoma (GEJC) have been developed. Therapies including immunotherapy (nivolumab), chemotherapy (irinotecan, FTD/TPI), targeted therapy (apatinib), and antibody drug conjugates (ADC) have shown to increase the survival rates in patients, but few studies have compared the relative efficacy of these treatments. Here, we compared the efficacies of these regimens using network meta-analysis (NMA) to provide guides in selecting the best regimen and formulating a precise individualized treatment plan. Methods The published RCTs of phase II/III in PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched. The median overall survival (mOS) was the primary outcome of NMA, and the other outcomes were median progression-free survival (mPFS), disease control rate (DCR) (proportion of patients with confirmed CR, PR, or stable disease (SD)) and incidence of grade 3 or above adverse events (≥3AEs). Results Five phase II/III RCTs involving 1674 patients and 7 treatment regimens were analyzed. It showed that Trastuzumab Deruxtecan (DS-8201) prolonged the OS of patients significantly comparing with chemotherapy (HR: 0.59; 95% CI: 0.39-0.89) for the overall population. DS-8201 (HR: 0.27; 95% CI: 0.17-0.42) and chemotherapy (HR: 0.57; 95% CI: 0.47-0.7) improved the PFS significantly over nivolumab. Apatinib (RR: 3.04; 95% CI: 1.65-5.95) and DS-8201 (RR: 2.67; 95% CI: 1.51-4.83) were more effective than nivolumab in improving DCR. DS-8201 achieved greater OS benefits compared to chemotherapy (HR: 0.59; 95% CI: 0.39-0.88) for patients who were HER2-positive. We ranked the Bayesian surface under the cumulative ranking curve according to OS benefit, and showed that ADC ranked first for the general patient population and for patients with a HER2-positive diagnosis, intestinal histopathology, previous gastrectomy history, gastric origination cancer, ages over 65 and ECOG PS=0/1, followed by nivolumab and apatinib. For patients with GEJC, nivolumab ranked first. Conclusions Nivolumab, apatinib, chemotherapy, and ADC all improved the OS of GC/GEJC patients significantly. ADC may be the best option for the overall population of GC, as well as for patients with HER2-overexpression, intestinal histopathology, previous gastrectomy history, gastric origination cancer, ages over 65 and ECOG PS=0/1, followed by nivolumab and apatinib. Nivolumab may be the first treatment option for GEJC patients. Systematic review registration https://www.crd.york.ac.uk/prospero, identifier CRD42022364714.
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20
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The Importance of Repeat Imaging Prior to Treatment Decision-making in Testicular Cancer: Commentary From the Inaugural Global Society of Rare Genitourinary Tumors Summit. Clin Genitourin Cancer 2022; 21:418.e1-418.e6. [PMID: 36624008 DOI: 10.1016/j.clgc.2022.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 12/13/2022] [Accepted: 12/15/2022] [Indexed: 12/24/2022]
Abstract
Testicular cancer is a rare cancer that often affects young and otherwise healthy patients. Imaging plays a critical role in the staging and surveillance of patients with testicular cancer. Indeterminate findings on staging or surveillance imaging, can lead to challenging management decisions for clinicians and patients. In this article, we review the importance of short-interval, repeat imaging for several scenarios faced by patients with testicular cancer and their clinicians. The challenging scenarios and recommendations provided in this article summarize the discussion from the inaugural Global Society of Rare Genitourinary Tumors (GSRGT) Summit held on December 11-12, 2020.
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21
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Sundqvist A, Moberg L, Dickman PW, Högberg T, Borgfeldt C. Time Trends for Incidence and Net Survival of Cervical Cancer in Sweden 1960-2014-A Nationwide Population-Based Study. Cancer Epidemiol Biomarkers Prev 2022; 31:1572-1581. [PMID: 35654420 PMCID: PMC9344906 DOI: 10.1158/1055-9965.epi-21-1323] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 03/24/2022] [Accepted: 05/23/2022] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND The aim was to investigate time trends for incidence and long-term net survival in the morphologic subtypes and stages of cervical cancer in Sweden during the period 1960 to 2014. METHODS Women with invasive cervical cancer were identified through the Swedish Cancer Registry. Incidence and net survival were calculated according to morphology, age at diagnosis, and FIGO stage at diagnosis. RESULTS In total, 29,579 cases of invasive cervical cancer between 1960 and 2014 were included. The age-standardized incidence for squamous cell carcinoma (SCC) decreased until 2000; thereafter, the incidence rate stagnated, and a small increase was found in 2014. The incidence of adenocarcinoma continuously increased. The age-standardized 5-year net survival increased. However, decreasing net survival with increasing age was found. A higher stage at diagnosis showed a worse net survival. SCC and adenocarcinoma did not statistically differ as regards net survival in the last years of the study. CONCLUSIONS Age-standardized 5-year net survival improved between 1960 and 2014. A positive trend for short- and long-term net survival was seen for women ages 18 to 64 years but long-term net survival for women ≥75 years decreased. In this study, age and FIGO stage at diagnosis were found to be important prognostic factors in determining net survival. The morphologies, SCC, and adenocarcinoma did not statistically differ as regards net survival in the last years of the study. IMPACT This study demonstrates longitudinal data on cervical cancer in Sweden for over 50 years with sub analyses on morphology, age, and stage at diagnosis.
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Affiliation(s)
- Avalon Sundqvist
- Department of Obstetrics and Gynecology, Skåne University Hospital Lund, Lund University, Sweden
| | - Louise Moberg
- Department of Obstetrics and Gynecology, Skåne University Hospital Lund, Lund University, Sweden
| | - Paul W. Dickman
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
| | - Thomas Högberg
- Division of Oncology, Department of Clinical Sciences Lund, Lund University, Sweden
| | - Christer Borgfeldt
- Department of Obstetrics and Gynecology, Skåne University Hospital Lund, Lund University, Sweden
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22
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Integrated Bioinformatics Analysis for Identifying the Significant Genes as Poor Prognostic Markers in Gastric Adenocarcinoma. JOURNAL OF ONCOLOGY 2022; 2022:9080460. [PMID: 35726219 PMCID: PMC9206555 DOI: 10.1155/2022/9080460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 05/08/2022] [Accepted: 05/18/2022] [Indexed: 02/05/2023]
Abstract
Gastric adenocarcinoma (GAC) is the most common histological type of gastric cancer and imposes a considerable health burden globally. The purpose of this study was to identify significant genes and key pathways participated in the initiation and progression of GAC. Four datasets (GSE13911, GSE19826, GSE54129, and GSE79973) including 171 GAC and 77 normal tissues from Gene Expression Omnibus (GEO) database were collected and analyzed. Through integrated bioinformatics analysis, we obtained 69 commonly differentially expressed genes (DEGs) among the four datasets, including 20 upregulated and 49 downregulated genes. The prime module in protein-protein interaction network of DEGs, including ADAMTS2, COL10A1, COL1A1, COL1A2, COL8A1, BGN, and SPP1, was enriched in protein digestion and absorption, ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, and amoebiasis. Furthermore, expression and survival analysis found that all seven hub genes were highly expressed in GAC tissues and 6 of them (except for SPP1) were able to predict poor prognosis of GAC. Finally, we verified the 6 high-expressed hub genes in GAC tissues via immunohistochemistry, Western blot, and RNA quantification analysis. Altogether, we identified six significantly upregulated DEGs as poor prognostic markers in GAC based on integrated bioinformatical methods, which could be potential molecular markers and therapeutic targets for GAC patients.
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23
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Song Y, Xu X, Wang N, Zhang T, Hu C. MALDI-TOF-MS analysis in low molecular weight serum peptidome biomarkers for NSCLC. J Clin Lab Anal 2022; 36:e24254. [PMID: 35212031 PMCID: PMC8993654 DOI: 10.1002/jcla.24254] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 01/10/2022] [Accepted: 01/11/2022] [Indexed: 12/20/2022] Open
Abstract
Objects Lung cancer is one of the leading causes of death from cancer in the world. Screening new serum biomarkers is important for the early detection of lung cancer. The purpose of this study was to investigate the serum peptide model between non‐small cell lung cancer (NSCLC) patients and healthy controls, as well as between paired pre‐ and postoperative NSCLC patients, and to find the low molecular weight (LMW) potential tumor markers for NSCLC. Methods 56 serum samples from NSCLC patients, 56 controls, and 20 matched pre‐ and postoperative patients were analyzed using magnetic‐bead (MB)‐based purification technique combined with MALDI‐TOF‐MS. To distinguish NSCLC from cancer‐free controls, three models were established. Finally, comparing the three groups of serum protein fingerprints, nano‐liquid chromatography–electrospray ionization tandem mass spectrometry was used to further identify the differential peptides. Results Among the three models constructed, the GA model had the best diagnostic efficacy. Five differential peaks were screened by combining the case group, healthy controls, and postoperative group analysis, which were up‐regulated in the case group and showed a tendency to return to healthy control values after surgery. The protein matching the mass spectrometry peak m/z 2953.73 was identified as fibrinogen α chain. Conclusion This study shows that the application of MALDI‐TOF‐MS is a promising approach for the identification of potential serum biomarkers for NSCLC, which is potentially valuable for establishing a new diagnostic method for lung cancer. In addition, we found that fibrinogen α chain may be an auxiliary diagnostic indicator for NSCLC.
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Affiliation(s)
- Yufan Song
- Departments of Laboratory Medicine, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, China
| | - Xiaoyu Xu
- Departments of Laboratory Medicine, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, China
| | - Nana Wang
- Departments of Laboratory Medicine, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, China
| | - Ting Zhang
- Departments of Laboratory Medicine, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, China
| | - Chengjin Hu
- Departments of Laboratory Medicine, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, China
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Sharma U, Barwal TS, Murmu M, Acharya V, Pant N, Dey D, Vivek, Gautam A, Bazala S, Singh I, Azzouz F, Bishayee A, Jain A. Clinical potential of long non-coding RNA LINC01133 as a promising biomarker and therapeutic target in cancers. Biomark Med 2022; 16:349-369. [PMID: 35195032 DOI: 10.2217/bmm-2021-0682] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Recently, long intergenic non-protein coding RNA 01133 (LINC01133) was identified as a novel transcript in cancers. It modulates various hallmarks of cancers and acts as oncogenic in some cancers while tumor-suppressive in others. Furthermore, the expression of LINC01133 correlates with tumor size, advanced tumor node metastasis stage and lymphatic node metastasis, Ki-67 levels and overall survival of patients. Herein, the authors provide an in-depth analysis describing how LINC01133 modulates the multiple cancer-associated signaling pathways and the pathogenesis of various malignancies and treatment regimens. Based on the role played by LINC01133, the authors propose LINC01133 as both a potential biomarker and a therapeutic target in cancer.
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Affiliation(s)
- Uttam Sharma
- Department of Zoology, Central University of Punjab, Ghudda, 151 401, Punjab, India
| | - Tushar Singh Barwal
- Department of Zoology, Central University of Punjab, Ghudda, 151 401, Punjab, India
| | - Masang Murmu
- Department of Zoology, Central University of Punjab, Ghudda, 151 401, Punjab, India
| | - Varnali Acharya
- Department of Zoology, Central University of Punjab, Ghudda, 151 401, Punjab, India
| | - Neha Pant
- Department of Zoology, Central University of Punjab, Ghudda, 151 401, Punjab, India
| | - Damayanti Dey
- Department of Zoology, Central University of Punjab, Ghudda, 151 401, Punjab, India
| | - Vivek
- Department of Zoology, Central University of Punjab, Ghudda, 151 401, Punjab, India
| | - Ashima Gautam
- Department of Zoology, Central University of Punjab, Ghudda, 151 401, Punjab, India
| | - Sonali Bazala
- Department of Zoology, Central University of Punjab, Ghudda, 151 401, Punjab, India
| | - Ipsa Singh
- Department of Zoology, Central University of Punjab, Ghudda, 151 401, Punjab, India
| | - Farah Azzouz
- Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
| | - Anupam Bishayee
- Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
| | - Aklank Jain
- Department of Zoology, Central University of Punjab, Ghudda, 151 401, Punjab, India
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Huang Z, Liu X, Wu C, Lu S, Antony S, Zhou W, Zhang J, Wu Z, Tan Y, Fan X, You L, Jing Z, Wu J. A New Strategy to Identify ceRNA-Based CCDC144NL-AS1/SERPINE1 Regulatory Axis as a Novel Prognostic Biomarker for Stomach Adenocarcinoma via High Throughput Transcriptome Data Mining and Computational Verification. Front Oncol 2022; 11:802727. [PMID: 35155200 PMCID: PMC8828946 DOI: 10.3389/fonc.2021.802727] [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: 10/27/2021] [Accepted: 12/27/2021] [Indexed: 11/13/2022] Open
Abstract
Stomach adenocarcinoma (STAD) is one of the most malignant cancers that endanger human health. There is growing evidence that competitive endogenous RNA (ceRNA) regulatory networks play an important role in various human tumors. However, the complexity and behavioral characteristics of the ceRNA network in STAD are still unclear. In this study, we constructed a ceRNA regulatory network to identify the potential prognostic biomarkers associated with STAD. The expression profile of lncRNA, miRNA, and mRNA was downloaded from The Cancer Genome Atlas (TCGA). After performing bioinformatics analysis, the CCDC144NL-AS1/hsa-miR-145-5p/SERPINE1 ceRNA network associated to STAD prognosis of STAD was obtained. The CCDC144NL-AS1/SERPINE1 axis in the ceRNA network was identified by correlation analysis and considered as a clinical prognosis model by Cox regression analysis. In addition, methylation analysis indicated that the abnormal upregulation of CCDC144NL-AS1/SERPINE1 axis might be related to the aberrant methylation of some sites, and immune infiltration analysis suggested that CCDC144NL-AS1/SERPINE1 axis probably influences the alteration of tumor immune microenvironment and the occurrence and development of STAD. In particular, the CCDC144NL-AS1/SERPINE1 axis based on the ceRNA network constructed in the present study might be an important novel factor correlating with the diagnosis and prognosis of STAD.
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Affiliation(s)
- Zhihong Huang
- Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Xinkui Liu
- Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Chao Wu
- Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Shan Lu
- Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Stalin Antony
- Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, China
| | - Wei Zhou
- Pharmacy Department, China-Japan Friendship Hospital, Beijing, China
| | - Jingyuan Zhang
- Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Zhishan Wu
- Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Yingying Tan
- Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Xiaotian Fan
- Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Leiming You
- School of Life Science, Beijing University of Chinese Medicine, Beijing, China
| | - Zhiwei Jing
- Institute of Clinical Basic Medicine of Traditional Chinese Medicine, China Academy of Chinese Medicine Science, Beijing, China
| | - Jiarui Wu
- Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
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Bhurani D, Nair R, Rajappa S, Rao SA, Sridharan N, Boya RR, Raman GS, Menon H, Seshachalam A, Nimmagadda R. Real-World Outcomes of Hodgkin Lymphoma: A Multi-Centric Registry From India. Front Oncol 2022; 11:799948. [PMID: 35223455 PMCID: PMC8881143 DOI: 10.3389/fonc.2021.799948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 12/20/2021] [Indexed: 11/13/2022] Open
Abstract
BackgroundHodgkin’s lymphoma (HL) is one of the most curable malignancies with a 5-year survival of over 80%. Most published literature from low-middle income countries comes from single institute experience.MethodologyThe OncoCollect Lymphoma group registry was set up in 2017 and has 9 major participating sites across India. Data of newly diagnosed classical HL (CHL) patients, treated between 2011 and 2017, were collected using OncoCollect software. The clinical features, subtypes, prognostic stratification, treatment patterns, response to first-line treatment, and 5-year outcomes were analyzed. All statistical analysis was done using Microsoft R Open statistical software linked to OncoCollect software.ResultsThere were 939 newly diagnosed CHL patients with a median age of 38 (range, 18–99) years at presentation. The male-to-female ratio was 2.07:1. Histological subtypes included mixed cellularity, CHL (MC, CHL), nodular sclerosis, CHL (NS, CHL), lymphocyte-rich, CHL (LR, CHL), and lymphocyte-depleted, CHL (LD, CHL), in 60.60%, 26.94%, 9.80%, and 2.66%, respectively. At presentation, 50.43% had B symptoms and 53.35% had advanced disease. 29.71% of advanced-stage patients had high Hodgkin IPI score. 79% and 21% of patients received 1st-line treatment with chemotherapy alone or combined modality treatment with chemotherapy and radiotherapy. The most common first-line chemotherapy was ABVD-based regimen (94.68%). The overall response rate was 93.48%. Complete response rates among early-stage favorable and unfavorable risk groups were 92.73% and 86.79%, and those among advanced-stage low- and high-risk groups were 76.64% and 69.78%, respectively. The median relapse-free follow-up duration was 51 months (IQR 22–69). A significant difference was found in 5-year EFS between the early- and advanced-stage disease 83.53% and 73.55% (p = 0.00087), respectively. Similarly, significant difference was found in EFS among early-stage patients treated with a combination of 4-cycle chemotherapy and radiotherapy vs. chemotherapy alone 88.57% and 66.33% (p = 0.0042), respectively.ConclusionsIn this large cohort from India, survival of patients with HL was comparable to the developed world. With a median follow-up of 51 months, the 5-year EFS and OS of all patients were 78.24% and 83.63%, respectively.
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Affiliation(s)
- Dinesh Bhurani
- Department of Haematology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
- *Correspondence: Dinesh Bhurani,
| | - Reena Nair
- Department of Haematology, Tata Medical Centre, Kolkata, India
| | - Senthil Rajappa
- Department of Medical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, India
| | - Suparna Ajit Rao
- Department of Medical Oncology, P. D. Hinduja Hospital and Medical Research Centre, Mumbai, India
| | | | - Rakesh Reddy Boya
- Department of Medical Oncology, Mahatama Gandhi Cancer Hospital and Research Center, Visakhapatnam, India
| | - Ganapathi S. Raman
- Department of Medical Oncology, Kumaran Hospital Private Ltd., Chennai, India
| | - Hari Menon
- Department of Medical Oncology, CyteCare Cancer Hospitals, Bengaluru, India
| | | | - Ramesh Nimmagadda
- Department of Medical Oncology, Apollo Cancer Institute, Chennai, India
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Campos-Gomez S, Vera-Rodriguez AM, Rivera-Rivera S, Vera-Badillo FE. Treatment Adherence Issues for Adolescents and Young Adults with Testicular Cancer Due to Changes in the Public Health System in Mexico. J Adolesc Young Adult Oncol 2021; 11:540-542. [PMID: 34936493 DOI: 10.1089/jayao.2021.0163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Saul Campos-Gomez
- Departamento de Oncología, Centro Oncológico Estatal, Instituto de Seguridad Social del Estado de México y Municipios, Toluca Estado de México, México
| | - Ana M Vera-Rodriguez
- Departamento de Oncología, Centro Oncológico Estatal, Instituto de Seguridad Social del Estado de México y Municipios, Toluca Estado de México, México
| | - Samuel Rivera-Rivera
- Hospital de Oncología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México
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Stelwagen J, Meuleman AT, Lubberts S, Steursma G, Kruyt LM, Donkerbroek JW, Meijer C, Walenkamp AME, Lefrandt JD, Rakers SE, Huitema RB, de Jong MAA, Wiegman EM, van den Bergh ACM, de Jong IJ, van Rentergem JAA, Schagen SB, Nuver J, Gietema JA. Cognitive Impairment in Long-Term Survivors of Testicular Cancer More Than 20 Years after Treatment. Cancers (Basel) 2021; 13:5675. [PMID: 34830829 PMCID: PMC8616311 DOI: 10.3390/cancers13225675] [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: 10/30/2021] [Revised: 11/05/2021] [Accepted: 11/05/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Impaired cognition can be a late effect after treatment in long-term testicular cancer (TC) survivors, negatively affecting their daily life. However, little data is available beyond 20 years post-treatment. We assessed cognitive impairment in very long-term TC survivors after CT or RT and compared the results with stage I TC survivors and controls. METHODS In this cross-sectional multicenter cohort study, we enrolled TC survivors (treated with orchiectomy followed by CT or RT or orchiectomy only)-with a follow-up duration ≥ 20 years-and age-matched healthy controls. Cognitive testing included the Auditory Verbal Learning Test, Letter Fluency Test, Category Fluency Test, and Trail Making Test. We used fasting blood samples to assess the presence of hypogonadism and measured cardiovascular aging parameters, including carotid pulse wave velocity (c-PWV) and advanced glycation end products (AGEs). RESULTS We included 184 TC survivors (66 CT patients, 53 RT patients, and 65 orchiectomy-only patients) and 70 healthy controls. The median follow-up was 26 years (range: 20-42). TC survivors had a lower combined score of the cognitive tests (mean cumulative Z-score -0.85; 95% CI -1.39 to -0.33) compared to controls (mean 0.67; 95% CI -0.21 to 1.57, p < 0.01). In univariate analysis, the presence of hypogonadism (β -1.50, p < 0.01), high c-PWV (β -0.35, p = 0.09), and high AGEs (β -1.27, p = 0.02) were associated with lower cognitive scores, while only AGEs (β -1.17, p = 0.03) remained a significant predictor in multivariate analysis (Model R2 0.31, p < 0.01). CONCLUSIONS Long-term TC survivors performed worse on cognitive tests compared to controls. Physicians and patients should be informed about timely cardiovascular risk management and testosterone supplementation therapy during follow-up to reduce the risk of cognitive impairment. TRIAL REGISTRATION NCT02572934.
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Affiliation(s)
- Johannes Stelwagen
- Department of Medical Oncology, University Medical Center Groningen and University of Groningen, 9728 NT Groningen, The Netherlands; (J.S.); (A.T.M.); (S.L.); (G.S.); (L.M.K.); (J.W.D.); (C.M.); (A.M.E.W.); (J.N.)
| | - Andrea T. Meuleman
- Department of Medical Oncology, University Medical Center Groningen and University of Groningen, 9728 NT Groningen, The Netherlands; (J.S.); (A.T.M.); (S.L.); (G.S.); (L.M.K.); (J.W.D.); (C.M.); (A.M.E.W.); (J.N.)
| | - Sjoukje Lubberts
- Department of Medical Oncology, University Medical Center Groningen and University of Groningen, 9728 NT Groningen, The Netherlands; (J.S.); (A.T.M.); (S.L.); (G.S.); (L.M.K.); (J.W.D.); (C.M.); (A.M.E.W.); (J.N.)
| | - Gerrie Steursma
- Department of Medical Oncology, University Medical Center Groningen and University of Groningen, 9728 NT Groningen, The Netherlands; (J.S.); (A.T.M.); (S.L.); (G.S.); (L.M.K.); (J.W.D.); (C.M.); (A.M.E.W.); (J.N.)
| | - Lara M. Kruyt
- Department of Medical Oncology, University Medical Center Groningen and University of Groningen, 9728 NT Groningen, The Netherlands; (J.S.); (A.T.M.); (S.L.); (G.S.); (L.M.K.); (J.W.D.); (C.M.); (A.M.E.W.); (J.N.)
| | - Jan W. Donkerbroek
- Department of Medical Oncology, University Medical Center Groningen and University of Groningen, 9728 NT Groningen, The Netherlands; (J.S.); (A.T.M.); (S.L.); (G.S.); (L.M.K.); (J.W.D.); (C.M.); (A.M.E.W.); (J.N.)
| | - Coby Meijer
- Department of Medical Oncology, University Medical Center Groningen and University of Groningen, 9728 NT Groningen, The Netherlands; (J.S.); (A.T.M.); (S.L.); (G.S.); (L.M.K.); (J.W.D.); (C.M.); (A.M.E.W.); (J.N.)
| | - Annemiek M. E. Walenkamp
- Department of Medical Oncology, University Medical Center Groningen and University of Groningen, 9728 NT Groningen, The Netherlands; (J.S.); (A.T.M.); (S.L.); (G.S.); (L.M.K.); (J.W.D.); (C.M.); (A.M.E.W.); (J.N.)
| | - Joop D. Lefrandt
- Department of Internal Medicine, Division of Vascular Medicine, University Medical Center Groningen and University of Groningen, 9728 NT Groningen, The Netherlands;
| | - Sandra E. Rakers
- Department of Neuropsychology, University Medical Center Groningen and University of Groningen, 9728 NT Groningen, The Netherlands; (S.E.R.); (R.B.H.)
| | - Rients B. Huitema
- Department of Neuropsychology, University Medical Center Groningen and University of Groningen, 9728 NT Groningen, The Netherlands; (S.E.R.); (R.B.H.)
| | - Marianne A. A. de Jong
- Department of Radiotherapy, Radiotherapeutic Institute Friesland, 8900 CC Leeuwarden, The Netherlands;
| | - Erwin M. Wiegman
- Department of Radiotherapy, Isala Hospital, 8025 AB Zwolle, The Netherlands;
| | - Alfons C. M. van den Bergh
- Department of Radiotherapy, University Medical Center Groningen and University of Groningen, 9728 NT Groningen, The Netherlands;
| | - Igle J. de Jong
- Department of Urology, University Medical Center Groningen and University of Groningen, 9728 NT Groningen, The Netherlands;
| | - Joost A. Agelink van Rentergem
- Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, 1018 WV Amsterdam, The Netherlands; (J.A.A.v.R.); (S.B.S.)
| | - Sanne B. Schagen
- Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, 1018 WV Amsterdam, The Netherlands; (J.A.A.v.R.); (S.B.S.)
| | - Janine Nuver
- Department of Medical Oncology, University Medical Center Groningen and University of Groningen, 9728 NT Groningen, The Netherlands; (J.S.); (A.T.M.); (S.L.); (G.S.); (L.M.K.); (J.W.D.); (C.M.); (A.M.E.W.); (J.N.)
| | - Jourik A. Gietema
- Department of Medical Oncology, University Medical Center Groningen and University of Groningen, 9728 NT Groningen, The Netherlands; (J.S.); (A.T.M.); (S.L.); (G.S.); (L.M.K.); (J.W.D.); (C.M.); (A.M.E.W.); (J.N.)
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Fung C, Travis LB. Testicular Cancer Survivorship: Looking Back to Move Forward. J Clin Oncol 2021; 39:3531-3534. [PMID: 34591594 PMCID: PMC8577670 DOI: 10.1200/jco.21.01984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 09/08/2021] [Indexed: 11/20/2022] Open
Affiliation(s)
- Chunkit Fung
- Division of Hematology and Oncology, Department of Medicine, University of Rochester School of Medicine and Dentistry, James P. Wilmot Cancer Institute, Rochester, NY
| | - Lois B. Travis
- Department of Medicine, Indiana University School of Medicine, Department of Epidemiology Fairbanks School of Public Health, Indianapolis, IN
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Huang M, Li J, Yu X, Xu Q, Zhang X, Dai X, Li S, Sheng L, Huang K, Liu L. Comparison of Efficacy and Safety of Third-Line Treatments for Advanced Gastric Cancer: A Systematic Review With Bayesian Network Meta-Analysis. Front Oncol 2021; 11:734323. [PMID: 34745955 PMCID: PMC8570109 DOI: 10.3389/fonc.2021.734323] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 10/07/2021] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Although various third-line treatments of advanced gastric cancer (AGC) significantly improved the overall survival, the optimal regimen has not been determined by now. This study aims to evaluate the efficacy and safety of multiple third-line treatments of AGC via integrated analysis and network meta-analysis (NMA) to provide valuable evidence for the optimal third-line systemic therapy for AGC. METHODS By searching the databases of PubMed, Embase and the Cochrane Central Register of Controlled Trials from Jan 01, 2005 to Dec 31, 2020, we included phase II/III randomized clinical trials (RCTs) of the third-line treatments for AGC to perform NMA. The main outcomes for NMA were median overall survival (mOS), median progression-free survival (mPFS), disease control rate (DCR) and adverse events (AEs). We also included phase IB/II non-RCTs and II/III RCTs of the third-line immune checkpoint inhibitors (ICIs) for integrated analysis for pooled mOS (POS), pooled mPFS (PPFS) and other outcomes. RESULTS Eight phase II/III RCTs and 2 ICIs-related phase IB/II non-RCTs were included for analysis, involving 9 treatment regimens and 3012 AGC patients. In terms of mOS, apatinib (hazard ratio [HR] 0.61, 95% credible interval [CrI] 0.48-0.78) and nivolumab (HR 0.62, 95% CrI 0.51-0.76) were the most effective treatments compared with placebo. Apatinib also significantly improved mPFS versus placebo (HR 0.38, 95% CrI 0.29-0.49). Nivolumab ranked first among all regimens for 1-year OS rate and achieved the best OS in patients with HER-2 positive tumor, patients with gastroesophageal junction (GEJ) cancer and patients without gastrectomy history. TAS-102 (OR 7.46, 95% CrI 4.61-12.51) was the most toxic treatment in terms of AEs of grade 3 and higher (≥3 AEs). Pembrolizumab was more likely to cause immune related adverse event. Finally, the POS, pooled 1-year OS rate, pooled ORR and PPFS of AGC patients treated with third-line ICIs were 5.1 months, 25%, 10% and 1.71 months respectively. CONCLUSIONS Apatinib and nivolumab are the most effective treatments for the third-line treatment of AGC in contrast to the third-line chemotherapy. For AGC patients with HER-2 positive tumor, patients with GEJ cancer and patients without gastrectomy history, ICIs could be the optimal third-line treatment choice.
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Affiliation(s)
- Miao Huang
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Jisheng Li
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xuejun Yu
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Qian Xu
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xue Zhang
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Xin Dai
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Medical Oncology, Shandong Provincial Hospital of Traditional Chinese Medicine, Jinan, China
| | - Song Li
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Lei Sheng
- Department of Thyroid Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Kai Huang
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Lian Liu
- Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
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31
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Chen S, Zhou L, Ran R, Huang J, Zheng Y, Xing M, Cai Y. Circ_0016760 accelerates non-small-cell lung cancer progression through miR-646/AKT3 signaling in vivo and in vitro. Thorac Cancer 2021; 12:3223-3235. [PMID: 34658165 PMCID: PMC8636202 DOI: 10.1111/1759-7714.14191] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 09/29/2021] [Accepted: 10/01/2021] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Currently, the prognosis of non-small-cell lung cancer (NSCLC) patients remains dismal due to recurrence and metastasis. The purpose of our study was to explore the role of circular RNA_0016760 (circ_0016760) in NSCLC progression and its associated mechanism. METHODS Quantitative real-time polymerase chain reaction (qRT-PCR) was implemented to measure the expression of circ_0016760, microRNA-646 (miR-646) and AK strain thymoma serine/threonine kinase 3 (AKT3). The protein level of AKT3 was examined by Western blot assay. Cell Counting Kit 8 assay, transwell assays, and flow cytometry were conducted to analyze cell proliferation, metastasis, and apoptosis. Dual-luciferase reporter assay was used to confirm the interactions that were predicted by bioinformatics software (Circular RNA Interactome and TargetScan). A xenograft tumor model was built to investigate the role of circ_0016760 in vivo. RESULTS Circ_0016760 and AKT3 were highly expressed in NSCLC tissue specimens and cell lines. Circ_0016760 interference suppressed cell proliferation, migration, and invasion and promoted the apoptosis of NSCLC cells. Circ_0016760 interacted with miR-646 and negatively regulated its expression. MiR-646 silencing partly counteracted circ_0016760 knockdown-mediated influences in NSCLC cells. MiR-646 bound to the AKT3 3' untranslated region in NSCLC cells, and miR-646 overexpression-induced effects in NSCLC cells were partly overturned by the addition of AKT3 overexpression plasmid. Circ_0016760 silencing reduced the expression of AKT3 through enhancing miR-646 expression. Circ_0016760 knockdown suppressed NSCLC tumor growth in vivo. CONCLUSION Circ_0016760 played an oncogenic role to promote the proliferation, migration, and invasion and restrained the apoptosis of NSCLC cells via miR-646/AKT3 signaling.
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Affiliation(s)
- Shan Chen
- Department of Oncology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China
| | - Long Zhou
- Department of Pulmonary and Critical Care Medicine, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China
| | - Ruizhi Ran
- Department of Oncology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China
| | - Jinqi Huang
- Department of Cardiothoracic Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China
| | - Yong Zheng
- Department of Cardiothoracic Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China
| | - Maohui Xing
- Department of Oncology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China
| | - Yanli Cai
- Department of Cardiothoracic Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China
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Zhou W, Wu C, Zhao C, Huang Z, Lu S, Fan X, Tan Y, Stalin A, You R, Liu X, Zhang J, Wu Z, Wu J. An Advanced Systems Pharmacology Strategy Reveals AKR1B1, MMP2, PTGER3 as Key Genes in the Competing Endogenous RNA Network of Compound Kushen Injection Treating Gastric Carcinoma by Integrated Bioinformatics and Experimental Verification. Front Cell Dev Biol 2021; 9:742421. [PMID: 34646828 PMCID: PMC8502965 DOI: 10.3389/fcell.2021.742421] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 09/06/2021] [Indexed: 12/24/2022] Open
Abstract
Gastric carcinoma (GC) is a severe tumor of the digestive tract with high morbidity and mortality and poor prognosis, for which novel treatment options are urgently needed. Compound Kushen injection (CKI), a classical injection of Chinese medicine, has been widely used to treat various tumors in clinical practice for decades. In recent years, a growing number of studies have confirmed that CKI has a beneficial therapeutic effect on GC, However, there are few reports on the potential molecular mechanism of action. Here, using systems pharmacology combined with proteomics analysis as a core concept, we identified the ceRNA network, key targets and signaling pathways regulated by CKI in the treatment of GC. To further explore the role of these key targets in the development of GC, we performed a meta-analysis to compare the expression differences between GC and normal gastric mucosa tissues. Functional enrichment analysis was further used to understand the biological pathways significantly regulated by the key genes. In addition, we determined the significance of the key genes in the prognosis of GC by survival analysis and immune infiltration analysis. Finally, molecular docking simulation was performed to verify the combination of CKI components and key targets. The anti-gastric cancer effect of CKI and its key targets was verified by in vivo and in vitro experiments. The analysis of ceRNA network of CKI on GC revealed that the potential molecular mechanism of CKI can regulate PI3K/AKT and Toll-like receptor signaling pathways by interfering with hub genes such as AKR1B1, MMP2 and PTGERR3. In conclusion, this study not only partially highlighted the molecular mechanism of CKI in GC therapy but also provided a novel and advanced systems pharmacology strategy to explore the mechanisms of traditional Chinese medicine formulations.
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Affiliation(s)
- Wei Zhou
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.,China-Japan Friendship Hospital, Beijing, China
| | - Chao Wu
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Chongjun Zhao
- Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Zhihong Huang
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Shan Lu
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Xiaotian Fan
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Yingying Tan
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Antony Stalin
- State Key Laboratory of Subtropical Silviculture, Department of Traditional Chinese Medicine, Zhejiang A&F University, Hangzhou, China
| | - Rongli You
- Shanxi Zhendong Pharmaceutical Co., Ltd., Shanxi, China
| | - Xinkui Liu
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Jingyuan Zhang
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Zhishan Wu
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Jiarui Wu
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
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İleri İ, Özsürekci C, Halil MG, Gündoğan K. NRS-2002 and mNUTRIC score: Could we predict mortality of hematological malignancy patients in the ICU? Nutr Clin Pract 2021; 37:1199-1205. [PMID: 34587327 DOI: 10.1002/ncp.10783] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
BACKGROUND Malnutrition is a problem that greatly affects patients with hematological malignancy (HM) throughout the course of illness. Intensity of the malignancy treatment, inadequate energy intake, complex procedures such as hematopoietic stem cell transplantation, and treatment side effects are contributing factors for malnutrition in HM patients. The aim of this study was to compare the accuracy of the modified Nutrition Risk in Critically Ill (mNUTRIC) score and Nutrition Risk Screening 2002 (NRS-2002) in predicting hospital and long-term mortality of HM patients in the intensive care unit (ICU) and to identify effects of malnutrition on ICU mortality. METHODS This prospective observational cohort study was conducted in a university teaching hospital tertiary ICU service. During the study period, 112 HM patients who were >18 years old were admitted to the ICU. We excluded the patients who were discharged or died within 24 h from the statistical analysis. The patients were followed for 3 years after discharge for long-term mortality. RESULTS Twenty-nine patients died within 24 h of admission and were excluded from the study; therefore, statistical analysis was done for 81 patients. Logistic regression analysis demonstrated that high malnutrition risk, according to the NRS-2002 score, was associated with greater odds of ICU mortality (P = 0.002, odds ratio = 19.16). CONCLUSION In this study, we showed that NRS-2002 is superior to mNUTRIC score in predicting ICU mortality in patients with HMs. mNUTRIC score and NRS-2002 were not superior to each other in predicting long-term mortality.
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Affiliation(s)
- İbrahim İleri
- Internal Medicine Department, Division of Geriatrics, Hacettepe University School of Medicine, Ankara, Turkey
| | - Cemile Özsürekci
- Internal Medicine Department, Division of Geriatrics, Hacettepe University School of Medicine, Ankara, Turkey
| | - Meltem Gülhan Halil
- Internal Medicine Department, Division of Geriatrics, Hacettepe University School of Medicine, Ankara, Turkey
| | - Kürşat Gündoğan
- Internal Medicine Department, Division of Medical Intensive Care, Erciyes University School of Medicine, Kayseri, Turkey
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Fernández-Rodríguez C, González-Fernández S, Coto-Lesmes R, Pedrosa I. Behavioral Activation and Acceptance and Commitment Therapy in the Treatment of Anxiety and Depression in Cancer Survivors: A Randomized Clinical Trial. Behav Modif 2021; 45:822-859. [PMID: 32316765 DOI: 10.1177/0145445520916441] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2024]
Abstract
Behavioural Activation (BA) and Acceptance and Commitment Therapy (ACT) aim to reduce the inflexible avoidance of painful thoughts, feelings and memories and to encourage involvement in relevant activities, objectives which are clearly relevant to the situation of cancer survivors with emotional problems. With a view to evaluating and comparing the efficacy of both therapies, applied on a group basis, a randomized controlled trial was developed. Cancer survivors (age 18-65 years) with anxiety and/or depression were assigned at random to two experimental groups (BA; ACT) and a waiting list control group (WL). Of the 66 cancer survivors randomized to trial (intention-to-treat sample), 46 participants (M = 51.49; SD = 6.88) completed the intervention (BA, n = 17; ACT, n = 12; WL, n = 17) (per-protocol sample). The emotional state, experiential avoidance and behavioural activation of the participants was evaluated in the pre- and post-treatment and in a 3-month follow-up using standardized instruments. Both treatment groups showed statistically significant changes, indicating an improvement in all the result variables in the post-treatment and follow-up as compared to the pre-treatment. BA showed better results than ACT regarding impact on anxiety and activation. This greater efficacy may have been due to factors such as the emphasis placed in BA on behavioural activation and the central role played in it by functional analysis. The key role played by experiential avoidance and behavioral activation in the maintenance and treatment of emotional problems in cancer survivors is discussed. Raw data are available online (http://dx.doi.org/10.17632/m7w688khs8.1).
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35
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Research updates on the clinical implication of long noncoding RNA in digestive system cancers and chemoresistance. 3 Biotech 2021; 11:423. [PMID: 34603923 DOI: 10.1007/s13205-021-02971-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Accepted: 08/19/2021] [Indexed: 10/20/2022] Open
Abstract
Long noncoding RNAs (lncRNAs) are implicated in various biological processes, such as cell proliferation, differentiation, apoptosis, migration, and invasion. They are also key players in various biological pathways. LncRNA was considered as 'translational noise' before 1980s. It has been reported that lncRNAs are aberrantly expressed in different cancers, either as oncogene or tumor suppressor gene. Therefore, more and more lncRNAs are recognized as potential diagnostic biomarkers and/or therapeutic targets. As competitive endogenous RNA, lncRNAs can interact with microRNA to alter the expression of target genes, which may have extensive clinical implications in cancers, including diagnosis, treatment, prognosis, and chemoresistance. This review comprehensively summarizes the functions and clinical relevance of lncRNAs in digestive system cancers, especially as a potential tool to overcome chemoresistance.
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36
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Kirk JA, Cheung JY, Feldman AM. Therapeutic targeting of BAG3: considering its complexity in cancer and heart disease. J Clin Invest 2021; 131:e149415. [PMID: 34396980 DOI: 10.1172/jci149415] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Bcl2-associated athanogene-3 (BAG3) is expressed ubiquitously in humans, but its levels are highest in the heart, the skeletal muscle, and the central nervous system; it is also elevated in many cancers. BAG3's diverse functions are supported by its multiple protein-protein binding domains, which couple with small and large heat shock proteins, members of the Bcl2 family, other antiapoptotic proteins, and various sarcomere proteins. In the heart, BAG3 inhibits apoptosis, promotes autophagy, couples the β-adrenergic receptor with the L-type Ca2+ channel, and maintains the structure of the sarcomere. In cancer cells, BAG3 binds to and supports an identical array of prosurvival proteins, and it may represent a therapeutic target. However, the development of strategies to block BAG3 function in cancer cells may be challenging, as they are likely to interfere with the essential roles of BAG3 in the heart. In this Review, we present the current knowledge regarding the biology of this complex protein in the heart and in cancer and suggest several therapeutic options.
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Affiliation(s)
- Jonathan A Kirk
- Department of Cell and Molecular Physiology, Loyola University Chicago, Chicago, Illinois, USA
| | - Joseph Y Cheung
- Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Arthur M Feldman
- Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA
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37
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Mao R, Liu K, Zhao N, Guo P, Wu Y, Wang Z, Liu Y, Zhang T. Clinical significance and prognostic role of an immune-related gene signature in gastric adenocarcinoma. Aging (Albany NY) 2021; 13:17734-17767. [PMID: 34247148 PMCID: PMC8312416 DOI: 10.18632/aging.203266] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 05/11/2021] [Indexed: 12/13/2022]
Abstract
Limited progress has been made in the treatment of gastric adenocarcinoma (GAC) in recent years, but the potential of immunotherapy in GAC is worthy of consideration. The purpose of this study was to develop a reliable, personalized signature based on immune genes to predict the prognosis of GAC. Here, we identified two groups of patients with significantly different prognoses by performing unsupervised clustering analysis of The Cancer Genome Atlas (TCGA) database based on 881 immune genes. The immune signature was constructed with a training set composed of 350 GAC samples from the TCGA and subsequently validated with 431 samples from GSE84437, 432 samples from GSE26253, and 145 GAC samples from real-time quantitative reverse transcription polymerase chain reaction data. This classification system can also be used to predict prognosis in different clinical subgroups. Further analysis suggested that high-risk patients were characterized by low immune scores, distinctive immune cell proportions, different immune checkpoint profiles, and a low tumor mutational burden. Ultimately, the signature was identified as an independent prognostic factor. In general, the signature can accurately predict recurrence and overall survival in patients with GAC and may serve as a powerful prognostic tool to further optimize cancer immunotherapy.
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Affiliation(s)
- Rui Mao
- Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University and The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu 610031, China.,Affiliated Hospital of Southwest Jiaotong University, Chengdu 610036, China
| | - Kehao Liu
- Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University and The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu 610031, China
| | - Nana Zhao
- Department of Operating Room, The Third People's Hospital of Chengdu, Chengdu 610031, China
| | - Pengsen Guo
- Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University and The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu 610031, China
| | - Yingxin Wu
- Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University and The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu 610031, China
| | - Zheng Wang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yanjun Liu
- Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University and The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu 610031, China.,Affiliated Hospital of Southwest Jiaotong University, Chengdu 610036, China
| | - Tongtong Zhang
- Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University and The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu 610031, China.,Affiliated Hospital of Southwest Jiaotong University, Chengdu 610036, China.,Medical Research Center, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, The Second Chengdu Hospital Affiliated to Chongqing Medical University, Chengdu 610031, China
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Amiri A, Chovanec M, Oliva V, Sedliak M, Mego M, Ukropec J, Ukropcová B. Chemotherapy-induced toxicity in patients with testicular germ cell tumors: The impact of physical fitness and regular exercise. Andrology 2021; 9:1879-1892. [PMID: 34245663 DOI: 10.1111/andr.13078] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 07/04/2021] [Accepted: 07/07/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Testicular germ cell tumors (TGCTs) represent ∼95% of testicular malignancies and are the most common type of malignancy in young male adults. While the incidence of TGCTs has increased during the last decades, the advances in treatment, namely introducing cisplatin into the chemotherapy regimen, have made TGCTs highly curable with the 10-year survival rate exceeding 95%. However, in parallel with increased cure rates, survivors may experience acute and late adverse effects of treatment, which increase morbidity, reduce the quality of life, and can be potentially life-threatening. Chemotherapy-related toxicities include cardiovascular and metabolic diseases, secondary cancer, avascular necrosis, cognitive impairment, cancer-related fatigue, poor mental health-related quality of life, nephrotoxicity, hypogonadism, neurotoxicity, pulmonary toxicity, anxiety, and depression. These treatment-related adverse effects have emerged as important survivorship dilemmas in TGCT cancer survivors. Recently, regular physical exercise has increasingly attracted research and clinical attention as an adjunct therapy for cancer patients. PURPOSE Herein, we review the most common chemotherapy-related adverse effects in TGCT survivors and clinical relevance of exercise and increased cardio-respiratory fitness in modulating chemotherapy-related toxicity and quality of life in this population. RESULTS AND CONCLUSION Exercise has positive effects on a spectrum of physical and psychosocial outcomes during and after cancer treatment, and current guidelines on exercise prescription in chronic diseases define the recommended dose (volume and intensity) of regular exercise for cancer survivors, highlighting regular, sufficiently intensive physical activity as an essential part of patients' care.
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Affiliation(s)
- Ali Amiri
- Department of Metabolic Disease Research & Center of Physical Activity Research, Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Michal Chovanec
- 2nd, Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia
| | - Viktor Oliva
- Faculty of Physical Education and Sports, Comenius University, Bratislava, Slovakia
| | - Milan Sedliak
- Faculty of Physical Education and Sports, Comenius University, Bratislava, Slovakia
| | - Michal Mego
- 2nd, Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia
| | - Jozef Ukropec
- Department of Metabolic Disease Research & Center of Physical Activity Research, Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Barbara Ukropcová
- Department of Metabolic Disease Research & Center of Physical Activity Research, Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.,Institute of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia
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Altena R, Hubbert L, Kiani NA, Wengström Y, Bergh J, Hedayati E. Evidence-based prediction and prevention of cardiovascular morbidity in adults treated for cancer. CARDIO-ONCOLOGY (LONDON, ENGLAND) 2021; 7:20. [PMID: 34049593 PMCID: PMC8161987 DOI: 10.1186/s40959-021-00105-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 05/04/2021] [Indexed: 12/22/2022]
Abstract
BACKGROUND Cancer treatment-related morbidity relevantly compromises health status in cancer survivors, and efforts to optimise health-related outcomes in this population are vital to maximising healthy survivorship. A pre-treatment assessment - and possibly preventive management strategies - of cancer patients at increased risk for cardiovascular disease (CVD) seems a rational approach in this regard. Definitive evidence for such strategies is largely lacking, thereby impeding the formulation of firm recommendations. RESULTS The current scoping review aims to summarise and grade the evidence regarding strategies for prediction and prevention of CVD in adults in relation to oncological treatments. We conducted a scoping literature search for different strategies for primary prevention, such as medical and lifestyle interventions, as well as the use of predictive risk scores. We identified studies with moderate to good strength and up to now limited evidence to recommend primary preventive strategies in unselected patients treated with potentially cardiotoxic oncologic therapies. CONCLUSION Efforts to minimize the CVD burden in cancer survivors are needed to accomplish healthy survivorship. This can be done by means of robust models predictive for CVD events or application of interventions during or after oncological treatments. Up to now there is insufficient evidence to implement preventive strategies in an unselected group of patients treated with potential cardiotoxic oncological treatments. We conclude that randomised controlled trials are needed that evaluate medical and lifestyle interventions in groups at increased risk for complications, in order to be able to influence chronic illness risks, such as cardiovascular complications, for cancer survivors.
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Affiliation(s)
- Renske Altena
- Department of Oncology and Pathology Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden.
- Medical Unit breast, endocrine tumours and sarcoma, Theme Cancer, Karolinska University Hospital Stockholm, Solna, Sweden.
| | - Laila Hubbert
- Department of Cardiology and Department of Health, Medicine and Caring Sciences, Linköping University, Norrköping, Sweden
| | - Narsis A Kiani
- Department of Oncology and Pathology Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
| | - Yvonne Wengström
- Department of Neurobiology, Care Sciences and Society, Division of Nursing, Karolinska Institutet, Stockholm, Sweden
| | - Jonas Bergh
- Department of Oncology and Pathology Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
- Medical Unit breast, endocrine tumours and sarcoma, Theme Cancer, Karolinska University Hospital Stockholm, Solna, Sweden
| | - Elham Hedayati
- Department of Oncology and Pathology Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
- Medical Unit breast, endocrine tumours and sarcoma, Theme Cancer, Karolinska University Hospital Stockholm, Solna, Sweden
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40
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Circulating Biomarkers of Colorectal Cancer (CRC)-Their Utility in Diagnosis and Prognosis. J Clin Med 2021; 10:jcm10112391. [PMID: 34071492 PMCID: PMC8199026 DOI: 10.3390/jcm10112391] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 05/25/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
The global burden of colorectal cancer (CRC) is expected to increase, with 2.2 million new cases and 1.1 million annual deaths by 2030. Therefore, the establishment of novel biomarkers useful in the early diagnosis of CRC is of utmost importance. A number of publications have documented the significance of the overexpression of several specific proteins, such as inflammatory mediators, in CRC progression. However, little is known about the potential utility of these proteins as circulating blood tumor biomarkers of CRC. Therefore, in the present review we report the results of our previous original studies as well as the findings of other authors who investigated whether inflammatory mediators might be used as novel biomarkers in the diagnosis and prognosis of CRC. Our study revealed that among all of the tested proteins, serum M-CSF, CXCL-8, IL-6 and TIMP-1 have the greatest value in the diagnosis and progression of CRC. Serum TIMP-1 is useful in differentiating between CRC and colorectal adenomas, whereas M-CSF and CRP are independent prognostic factors for the survival of patients with CRC. This review confirms the promising significance of these proteins as circulating biomarkers for CRC. However, due to their non-specific nature, further validation of their sensitivity and specificity is required.
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Janssen TL, de Vries J, Lodder P, Faes MC, Ho GH, Gobardhan PD, van der Laan L. The effects of elective aortic repair, colorectal cancer surgery and subsequent postoperative delirium on long-term quality of life, cognitive functioning and depressive symptoms in older patients. Aging Ment Health 2021; 25:896-905. [PMID: 32054299 DOI: 10.1080/13607863.2020.1725807] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Objectives: This study aimed to demonstrate the impact of elective major abdominal surgery and subsequent postoperative delirium on quality of life (QOL; primary outcome), cognitive functioning and depressive symptoms (secondary outcomes) in older surgical patients.Method: A single-centre, longitudinal prospective cohort study was conducted between November 2015 and June 2018, including patients ≥70 years old who underwent surgery for colorectal cancer or an abdominal aortic aneurysm. They were followed-up at discharge and at 6 and 12 months postoperatively until June 2019. QOL was assessed with the World Health Organization Quality of Life-BREF questionnaire (WHOQOL-BREF). Cognitive functioning was measured with the Mini-Mental State Examination and depressive symptoms with the CES-D 16.Results: In all patients (n = 265), physical and psychological health were significantly lower at discharge compared to baseline (p < 0.001 for both domains). Physical health restored after 6 months, but psychological health remained decreased for the complete study period. Psychological, social and environmental QOL were significantly worse in patients with delirium compared to patients without (p = 0.001, p = 0.006 and p = 0.001 respectively). The cognitive functioning score was significantly lower at baseline in patients with delirium compared to those without (p = 0.006). Patients with delirium had a significantly higher CES-D 16 score compared to those without after 12 months (p = 0.027).Conclusion: Physical and psychological QOL were decreased in the early postoperative period. While physical health was restored after 6 and 12 months, psychological health remained decreased. After 12 months, postoperative delirium resulted in worse psychological, social and environmental QOL and more depressive symptoms. Decreased cognitive functioning may be a risk factor for delirium.
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Affiliation(s)
- Ties L Janssen
- Department of Surgery, Amphia Hospital, Breda, the Netherlands
| | - Jolanda de Vries
- Department of Medical Psychology, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands.,Department of Medical and Clinical Psychology, Tilburg University, Tilburg, The Netherlands
| | - Paul Lodder
- Department of Medical and Clinical Psychology, Tilburg University, Tilburg, The Netherlands.,Department of Methodology and Statistics, Tilburg University, Tilburg, The Netherlands
| | - Miriam C Faes
- Department of Geriatrics, Amphia Hospital, Breda, the Netherlands
| | - Gwan H Ho
- Department of Surgery, Amphia Hospital, Breda, the Netherlands
| | | | - Lijckle van der Laan
- Department of Surgery, Amphia Hospital, Breda, the Netherlands.,Department of Cardiovascular Science, UZ Leuven, Leuven, Belgium
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Kamphuis JAM, Linschoten M, Cramer MJ, Alsemgeest F, van Kessel DJW, Urgel K, Post MC, Manintveld OC, Hassing HC, Liesting C, Wardeh AJ, Olde Bijvank EGM, Schaap J, Stevense-den Boer AM, Doevendans PA, Asselbergs FW, Teske AJ. ONCOR: design of the Dutch cardio-oncology registry. Neth Heart J 2021; 29:288-294. [PMID: 33201485 PMCID: PMC8062648 DOI: 10.1007/s12471-020-01517-8] [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] [Accepted: 10/20/2020] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND The relative new subspecialty 'cardio-oncology' was established to meet the growing demand for an interdisciplinary approach to the management of cancer therapy-related cardiovascular adverse events. In recent years, specialised cardio-oncology services have been implemented worldwide, which all strive to improve the cardiovascular health of cancer patients. However, limited data are currently available on the outcomes and experiences of these specialised services, and optimal strategies for cardio-oncological care have not been established. AIM The ONCOR registry has been created for prospective data collection and evaluation of cardio-oncological care in daily practice. METHODS Dutch hospitals using a standardised cardio-oncology care pathway are included in this national, multicentre, observational cohort study. All patients visiting these cardio-oncology services are eligible for study inclusion. Data collection at baseline consists of the (planned) cancer treatment and the cardiovascular risk profile, which are used to estimate the cardiotoxic risk. Information regarding invasive and noninvasive tests is collected during the time patients receive cardio-oncological care. Outcome data consist of the incidence of cardiovascular complications and major adverse cardiac events, and the impact of these events on the oncological treatment. DISCUSSION Outcomes of the ONCOR registry may aid in gaining more insight into the incidence of cancer therapy-related cardiovascular complications. The registry facilitates research on mechanisms of cardiovascular complications and on diagnostic, prognostic and therapeutic strategies. In addition, it provides a platform for future (interventional) studies. Centres with cardio-oncology services that are interested in contributing to the ONCOR registry are hereby invited to participate.
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Affiliation(s)
- J A M Kamphuis
- Department of Cardiology, Division of Heart and Lungs, University Medical Centre Utrecht, University of Utrecht, Utrecht, The Netherlands
| | - M Linschoten
- Department of Cardiology, Division of Heart and Lungs, University Medical Centre Utrecht, University of Utrecht, Utrecht, The Netherlands
| | - M J Cramer
- Department of Cardiology, Division of Heart and Lungs, University Medical Centre Utrecht, University of Utrecht, Utrecht, The Netherlands
| | - F Alsemgeest
- Department of Cardiology, St Jansdal Hospital, Harderwijk, The Netherlands
| | - D J W van Kessel
- Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands
| | - K Urgel
- Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands
| | - M C Post
- Department of Cardiology, Division of Heart and Lungs, University Medical Centre Utrecht, University of Utrecht, Utrecht, The Netherlands
- Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands
| | - O C Manintveld
- Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - H C Hassing
- Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - C Liesting
- Department of Cardiology, Albert Schweitzer Hospital, Dordrecht, The Netherlands
| | - A J Wardeh
- Department of Cardiology, Haaglanden Medical Center, The Hague, The Netherlands
| | - E G M Olde Bijvank
- Department of Cardiology, Haaglanden Medical Center, The Hague, The Netherlands
| | - J Schaap
- Department of Cardiology, Amphia Hospital, Breda, The Netherlands
| | | | - P A Doevendans
- Department of Cardiology, Division of Heart and Lungs, University Medical Centre Utrecht, University of Utrecht, Utrecht, The Netherlands
- Central Military Hospital, Utrecht, The Netherlands
- Netherlands Heart Institute, Utrecht, The Netherlands
| | - F W Asselbergs
- Department of Cardiology, Division of Heart and Lungs, University Medical Centre Utrecht, University of Utrecht, Utrecht, The Netherlands
- Netherlands Heart Institute, Utrecht, The Netherlands
- Health Data Research UK, Institute of Health Informatics and Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, UK
| | - A J Teske
- Department of Cardiology, Division of Heart and Lungs, University Medical Centre Utrecht, University of Utrecht, Utrecht, The Netherlands.
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Endo M. How do gynecologists face to social problems among women cancer survivors? J Obstet Gynaecol Res 2021; 47:1651-1653. [PMID: 33763951 DOI: 10.1111/jog.14703] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Revised: 01/18/2021] [Accepted: 01/30/2021] [Indexed: 12/28/2022]
Abstract
In recent decades, surgical techniques, new anticancer drugs' development, and radiation equipment have led to continuous improvements in cancer survival rates and quality of life of cancer survivors (CSs). While 61.0% of gynecological cancer survivors (GCS) in Japan belonged to a working-age group (20-64 years old), the number of working GCS within the working-age population has increased. In Japan, it seems that there has been more interest in striking a balance between cancer treatment and work, especially since 2016 when the Cancer Control Act was amended and national guidelines for working CSs were published. Maintaining employment after gynecological cancer diagnosis remains an important issue for not only GCS and their families but also employers and society. GCS suffered from various symptoms including cancer-related fatigue, pain, menopausal symptoms, lymphedema, and psychological distress, which made maintaining employment difficult for them. Full return to work (RTW) rate at 365 days after the initial days of sick leave among was 77.6% and median time to full RTW among GCSs was 172 days. Five-year work continuance rate after RTW among GCSs was 63.4%. It is better for gynecologists to write a certificate for workplace in words of not "symptoms," but "caseness words (such as, workable as long as it is sedentary or clerical work. Partial RTW (4-h work, 6-h work) might be desirable for a while after RTW," in order to support GCSs' maintaining employment.
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Affiliation(s)
- Motoki Endo
- Department of Public Health, Juntendo University Faculty of Medicine, Tokyo, Japan
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Gómez-Salgado J, Fagundo-Rivera J, Ortega-Moreno M, Allande-Cussó R, Ayuso-Murillo D, Ruiz-Frutos C. Night Work and Breast Cancer Risk in Nurses: Multifactorial Risk Analysis. Cancers (Basel) 2021; 13:1470. [PMID: 33806956 PMCID: PMC8004617 DOI: 10.3390/cancers13061470] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 03/15/2021] [Accepted: 03/19/2021] [Indexed: 02/07/2023] Open
Abstract
Night work has been highlighted by the International Agency for Research on Cancer (IARC) as a likely carcinogenic factor for humans, associated with breast cancer and professions that require continuity of work. Knowing the impact that short and long-term night work has on the nurses' collective seems a priority, therefore, this study aims to analyse the relationship between night work and the development of breast cancer risk factors in nurses. For this, a cross-sectional study through an online questionnaire on breast cancer risk variables and working life was designed. The study was conducted in Spain and the sample consisted of 966 nurses, of whom 502 were healthy participants and 56 were breast cancer patients. These two groups were compared in the analyses. A descriptive analysis was performed, and the relationship was tested using χ2 independence test and OR calculation. The CHAID (Chi Square Automatic Interaction Detection) data mining method allowed for the creation of a segmentation tree for the main risk variables. The most significant risk variables related to working life have been the number of years worked, nights worked throughout life, and years working more than 3 nights per month. Exceeding 16 years of work has been significant for women and men. When the time worked is less than 16 years, the number of cases increases if there is a family history of cancer and if there have been more than 500 nights of work. High-intensity night work seems more harmful at an early age. The accumulation of years and nights worked increase the risk of breast cancer when factors such as sleep disturbance, physical stress, or family responsibilities come together.
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Affiliation(s)
- Juan Gómez-Salgado
- Department of Sociology, Social Work and Public Health, Faculty of Labour Sciences, University of Huelva, 21007 Huelva, Spain;
- Safety and Health Postgraduate Programme, Universidad Espíritu Santo, Guayaquil 092301, Ecuador
| | - Javier Fagundo-Rivera
- Health Sciences Doctorate School, University of Huelva, 21071 Huelva, Spain;
- Centro Universitario de Enfermería Cruz Roja, University of Seville, 41009 Seville, Spain
- Escola Superior de Saúde, Universidade Atlântica, 2730-036 Barcarena, Portugal
| | - Mónica Ortega-Moreno
- Department of Economy, Faculty of Labour Sciences, University of Huelva, 21007 Huelva, Spain;
| | | | | | - Carlos Ruiz-Frutos
- Department of Sociology, Social Work and Public Health, Faculty of Labour Sciences, University of Huelva, 21007 Huelva, Spain;
- Safety and Health Postgraduate Programme, Universidad Espíritu Santo, Guayaquil 092301, Ecuador
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Bresesti C, Vezzoli V, Cangiano B, Bonomi M. Long Non-Coding RNAs: Role in Testicular Cancers. Front Oncol 2021; 11:605606. [PMID: 33767982 PMCID: PMC7986848 DOI: 10.3389/fonc.2021.605606] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2020] [Accepted: 01/05/2021] [Indexed: 12/13/2022] Open
Abstract
In the last few years lncRNAs have gained increasing attention among the scientific community, thanks to the discovery of their implication in many physio-pathological processes. In particular, their contribution to tumor initiation, progression, and response to treatment has attracted the interest of experts in the oncologic field for their potential clinical application. Testicular cancer is one of the tumors in which lncRNAs role is emerging. Said malignancies already have very effective treatments, which although lead to the development of quite serious treatment-related conditions, such as secondary tumors, infertility, and cardiovascular diseases. It is therefore important to study the impact of lncRNAs in the tumorigenesis of testicular cancer in order to learn how to exploit them in a clinical setting and to substitute more toxic treatments. Eventually, the use of lncRNAs as biomarkers, drug targets, or therapeutics for testicular cancer may represent a valid alternative to that of conventional tools, leading to a better management of this malignancy and its related conditions, and possibly even to the treatment of poor prognosis cases.
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Affiliation(s)
- Chiara Bresesti
- Department of Endocrine and Metabolic Medicine, IRCCS Istituto Auxologico Italiano, Milan, Italy
- Lab of Endocrine and Metabolic Researches, IRCCS Istituto Auxologico Italiano, Cusano Milanino, Italy
| | - Valeria Vezzoli
- Department of Endocrine and Metabolic Medicine, IRCCS Istituto Auxologico Italiano, Milan, Italy
- Lab of Endocrine and Metabolic Researches, IRCCS Istituto Auxologico Italiano, Cusano Milanino, Italy
| | - Biagio Cangiano
- Department of Endocrine and Metabolic Medicine, IRCCS Istituto Auxologico Italiano, Milan, Italy
- Lab of Endocrine and Metabolic Researches, IRCCS Istituto Auxologico Italiano, Cusano Milanino, Italy
- Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
| | - Marco Bonomi
- Department of Endocrine and Metabolic Medicine, IRCCS Istituto Auxologico Italiano, Milan, Italy
- Lab of Endocrine and Metabolic Researches, IRCCS Istituto Auxologico Italiano, Cusano Milanino, Italy
- Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
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Huang Y, Zhong L, Nie K, Li L, Song S, Liu F, Li P, Cao D, Liu Y. Identification of LINC00665-miR-let-7b-CCNA2 competing endogenous RNA network associated with prognosis of lung adenocarcinoma. Sci Rep 2021; 11:4434. [PMID: 33627711 PMCID: PMC7904782 DOI: 10.1038/s41598-020-80662-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Accepted: 08/26/2020] [Indexed: 02/07/2023] Open
Abstract
Prognosis of patients with lung cancer remains extremely poor; thus, we sought to unearth novel competing endogenous RNA (ceRNA) networks associated with the prognosis of lung adenocarcinoma (LUAD). Aberrant mRNAs were identified from the intersection of three Gene Expression Omnibus (GEO) datasets. A protein-protein interaction (PPI) network was constructed, and miRNAs and long noncoding RNAs (lncRNAs) upstream of mRNAs were predicted. In the present study, 402 upregulated and 638 downregulated genes in lung cancer tissues were identified. Functional analysis showed significant enrichment of cancer pathways. In these top hub genes, 10 upregulated and 7 downregulated genes had substantial prognostic values in LUAD. Thirty-seven miRNAs were predicted to target 17 key genes, and only five miRNAs exhibited prognostic correlation. Through stepwise reverse prediction and validation from miRNA to lncRNA, four key lncRNAs were identified using expression and survival analysis. Ultimately, the co-expression analysis identified LINC00665-miR-let-7b-CCNA2 as the key ceRNA network associated with the prognosis of LUAD. We successfully constructed a novel ceRNA network wherein each component was significantly associated with the prognosis of LUAD. Hence, we propose that this network may provide key biomarkers or potential therapeutic targets for LUAD prognosis.
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Affiliation(s)
- Yusheng Huang
- Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 12 Airport Road, Baiyun District, Guangzhou, 510407, China
| | - Limei Zhong
- Department of Laboratory Medicine, Guangdong Second Provincial General Hospital, Guangzhou, 510317, China
| | - Kechao Nie
- Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 12 Airport Road, Baiyun District, Guangzhou, 510407, China
| | - Lijuan Li
- Department of Laboratory Medicine, Guangdong Second Provincial General Hospital, Guangzhou, 510317, China
| | - Shaohua Song
- Department of Laboratory Medicine, Guangdong Second Provincial General Hospital, Guangzhou, 510317, China
| | - Fengbin Liu
- Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 12 Airport Road, Baiyun District, Guangzhou, 510407, China
| | - Peiwu Li
- Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 12 Airport Road, Baiyun District, Guangzhou, 510407, China
| | - Donglin Cao
- Department of Laboratory Medicine, Guangdong Second Provincial General Hospital, Guangzhou, 510317, China.
| | - Yufeng Liu
- Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 12 Airport Road, Baiyun District, Guangzhou, 510407, China.
- Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510407, China.
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Ykema BLM, Bisseling TM, Spaander MCW, Moons LMG, van der Biessen-van Beek D, Saveur L, Kerst M, Mulder SF, de Wit R, Zweers D, Meijer GA, Beijnen JH, Lansdorp-Vogelaar I, van Leeuwen FE, Snaebjornsson P, van Leerdam ME. Diagnostic yield of colonoscopy surveillance in testicular cancer survivors treated with platinum-based chemotherapy: study protocol of a prospective cross-sectional cohort study. BMC Gastroenterol 2021; 21:67. [PMID: 33579196 PMCID: PMC7881638 DOI: 10.1186/s12876-021-01639-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 02/02/2021] [Indexed: 01/01/2023] Open
Abstract
Background Testicular cancer (TC) survivors have an increased risk of various second primary malignancies. A recent cohort study detected an increased risk of colorectal cancer (CRC) in TC survivors treated with platinum-based chemotherapy with a hazard ratio of 3.9. CRC risk increased with higher cisplatin-dose. We know that colonoscopy surveillance in high-risk populations results in reduced incidence and mortality of CRC. TC survivors treated with platinum-based chemotherapy can potentially benefit from colonoscopy surveillance; however, to which extent is unknown. Furthermore, the pathogenesis of these secondary CRCs is unknown, and better insights into the carcinogenesis may affect surveillance decisions. Methods This prospective multicenter study will be performed in four Dutch hospitals. TC survivors are eligible if treated with ≥ 3 cycles of cisplatin before age 50. Colonoscopy will be performed ≥ 8 years after initial treatment (minimum and maximum ages at colonoscopy, 35 and 75 years, respectively). The primary aim of the study is the diagnostic yield of advanced neoplasia detected during colonoscopy. As secondary aim, we will evaluate the molecular profile of advanced colorectal neoplasia and will assess current platinum levels in blood and urine and correlate blood-platinum levels with prevalence of colorectal lesions. Furthermore, we will investigate effectiveness of fecal immunochemical testing (FIT) and burden of colonoscopy by two questionnaires. Demographic data, previous history, results of colonoscopy, hemoglobin level of FIT and results of molecular and platinum levels will be obtained. Yield of colonoscopy will be determined by detection rate of adenoma and serrated lesions, advanced adenoma detection rate and CRC detection rate. The MISCAN model will be used for cost-effectiveness analyses of CRC surveillance. With 234 participants undergoing colonoscopy, we can detect an absolute difference of 6% of advanced neoplasia with 80% power. Discussion TC survivors treated with cisplatin-based chemotherapy can benefit from CRC surveillance. Evaluation of the diagnostic performance and patient acceptance of CRC surveillance is of importance to develop surveillance recommendations. Insight into the carcinogenesis of cisplatin-related advanced colorectal lesions will contribute to CRC prevention in the increasing number of TC survivors. The results may also be important for the many other cancer survivors treated with platinum-based chemotherapy. Trial registration Clinical Trials: NCT04180033, November 27, 2019, https://clinicaltrials.gov/ct2/show/NCT04180033.
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Affiliation(s)
- Berbel L M Ykema
- Department of Gastroenterology and Hepatology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
| | - Tanya M Bisseling
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Manon C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Leon M G Moons
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | | | - Lisette Saveur
- Department of Gastroenterology and Hepatology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - Martijn Kerst
- Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Sasja F Mulder
- Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Ronald de Wit
- Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Danielle Zweers
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Gerrit A Meijer
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Jos H Beijnen
- Department of Pharmacy and Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Iris Lansdorp-Vogelaar
- Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Flora E van Leeuwen
- Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Petur Snaebjornsson
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Monique E van Leerdam
- Department of Gastroenterology and Hepatology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.,Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
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Wells MB, Delilovic S, Gunnarsson M, Dervish J, von Knorring M, Hasson H. Primary care physicians' views of standardised care pathways in cancer care: A Swedish qualitative study on implementation experiences. Eur J Cancer Care (Engl) 2021; 30:e13426. [PMID: 33559330 DOI: 10.1111/ecc.13426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 11/16/2020] [Accepted: 01/11/2021] [Indexed: 12/09/2022]
Abstract
OBJECTIVE Primary care physicians (PCPs) recently started using standardised care pathways (PCPs) to refer patients to specialists for diagnostics in Sweden. The aim of the current study is therefore to examine PCPs views of implementing standardised care pathways (SCPs) in cancer care. METHOD In total, 27 semi-structured interviews (17 individual and 10 group interviews) were conducted within 24 primary care units, including 61 physicians representing the public and private sectors. Interviews were conducted during 2017 and 2018. Data were analysed using a thematic analysis approach. RESULTS Eight themes, including both perceived opportunities and challenges with the SCPs, were identified in the analysis. Most PCPs valued the SCPs, citing that they expedited the referral system and decreased patient waiting time. However, the guidelines were not completely clear leaving PCPs to wonder what constituted an SCP referral, who should initiate the referral, and how PCPs should communicate and collaborate with specialists. CONCLUSION SCPs were a welcomed organisational change by PCPs, where PCPs thought that the SCPs could help in providing better patient care to potential cancer patients. However, updated guidelines and clarifications within the SCPs are warranted to have increased services for both the patients and medical personnel.
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Affiliation(s)
- Michael B Wells
- Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
| | - Sara Delilovic
- Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden.,Center for Epidemiology and Community Medicine, Region Stockholm, Stockholm, Sweden
| | - Malin Gunnarsson
- Center for Epidemiology and Community Medicine, Region Stockholm, Stockholm, Sweden
| | - Jessica Dervish
- Center for Epidemiology and Community Medicine, Region Stockholm, Stockholm, Sweden
| | - Mia von Knorring
- Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden
| | - Henna Hasson
- Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden.,Center for Epidemiology and Community Medicine, Region Stockholm, Stockholm, Sweden
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Siddiqui SS, Prabu NR, Chaudhari HK, Narkhede AM, Sarode SV, Dhundi U, Divatia JV, Kulkarni AP. Epidemiology, Clinical Characteristics, and Prognostic Factors in Critically Ill Patients with Hematolymphoid Malignancy. Indian J Crit Care Med 2021; 25:56-61. [PMID: 33603303 PMCID: PMC7874294 DOI: 10.5005/jp-journals-10071-23469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Objective Despite advances in the field of oncology and intensive care, the outcomes of hematolymphoid malignancy (HLM) patients admitted to ICU are poor. This study was carried out to look at the demographic data, clinical features, and predictors of hospital mortality in these patients. Materials and methods We prospectively studied 101 adult critically ill patients with HLM admitted to the 14-bedded mixed medical surgical ICU of a tertiary care cancer center. Out of 101 patients, end-of-life care decisions were taken in 7 patients, who were excluded from the outcome analysis. Predictors of in-hospital mortality were evaluated using univariate and multivariate analysis. Results The ICU and in-hospital mortality recorded in our study were 48.9 and 54.3%, respectively. Neutropenia at ICU admission, Simplified Acute Physiology Score III (SAPS III) score, and mechanical ventilation (MV) within 24 hours of ICU admission were associated with in-hospital mortality on univariate analysis. On multivariate logistic regression analysis, neutropenia at ICU admission (OR 4.621; 95% CI, 1.2–17.357) and MV within 24 hours of ICU admission (OR 2.728; 95% CI, 1.077–6.912) were independent predictors of in-hospital mortality. Conclusion The HLM patients needing critical care have high acuity of illness, and acute respiratory failure is the commonest reason for ICU admission in these patients. In our study, the ICU survival was more than 50% and more than 45% patients were discharged alive from the hospital. We found a need for MV within 24 hours of ICU admission and presence of neutropenia at ICU admission to be independent predictors of hospital mortality in our study. How to cite this article Siddiqui SS, Prabu NR, Chaudhari HK, Narkhede AM, Sarode SV, Dhundi U, et al. Epidemiology, Clinical Characteristics, and Prognostic Factors in Critically Ill Patients with Hematolymphoid Malignancy. Indian J Crit Care Med 2021;25(1):56–61.
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Affiliation(s)
- Suhail S Siddiqui
- Department of Critical Care Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
| | - Natesh R Prabu
- Department of Critical Care Medicine, St John's Medical College, Bengaluru, Karnataka, India
| | | | - Amit M Narkhede
- Department of Critical Care, Jupiter Hospital, Thane, Maharashtra, India
| | - Satish V Sarode
- Vishwaraj Super Speciality Hospital, Pune, Maharashtra, India
| | - Ujwal Dhundi
- Department of Critical Care and Emergency Medicine, Deenanath Mangeshkar Hospital and Research Center, Pune, Maharashtra, India
| | - Jigeeshu V Divatia
- Department of Anaesthesia, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai, Maharashtra, India
| | - Atul P Kulkarni
- Division of Critical Care Medicine, Department of Anaesthesia, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
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Pu R, Pu M, Huang H, Cui Y. MicroRNA 144 inhibits cell migration and invasion and regulates inflammatory cytokine secretion through targeting toll like receptor 2 in non-small cell lung cancer. Arch Med Sci 2021; 17:1028-1037. [PMID: 34336030 PMCID: PMC8314413 DOI: 10.5114/aoms.2020.93084] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2018] [Accepted: 06/14/2018] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION MicroRNAs (miRNAs) are endogenous small noncoding RNA molecules involved in modulation of cancer progression. Here, we investigated the possible role of miR-144 in non-small cell lung cancer (NSCLC) development. MATERIAL AND METHODS The expression of miR-144 and TLR2 in NSCLC tissue and cell lines was determined by quantitative real-time PCR (qPCR). The TargetScan database was used to predict potential target genes of miR-144. Luciferase assay was used to verify the interaction between TLR2 and miR-144. TLR2 protein expression was measured by western blot. The secretion of interleukin (IL)-1β, IL-6 and IL-8 in A549 cells was detected by an ELISA kit. Cell migration and invasion were evaluated by wound healing assay and transwell assay, respectively. RESULTS Our results showed that miR-144 was downregulated in NSCLC tissue and cell lines when compared with the normal tissues and cell line (p < 0.05). The protein level of TLR2 in NSCLC tissue and cell lines was significantly higher than that in normal lung tissues. Dual luciferase reporter gene assay showed that miR-144 could bind to the 3'UTR of TLR2 specifically. Up-regulation of miR-144 significantly decreased the expression of TLR2. Up-regulation of miR-144 or down-regulation of TLR2 could decrease cell migration, invasion and secretion of IL-1β, IL-6 and IL-8 in A549 cells. Moreover, overexpression of TLR2 rescued the inhibitory effects of miR-144 on migration, invasion and inflammatory factor secretion of A549 cells. CONCLUSIONS miR-144 could inhibit the migration, invasion and secretion of IL-1β, IL-6 and IL-8 through downregulation of TLR2 expression in A549 cells.
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Affiliation(s)
- Rong Pu
- Department of Laboratory, The Third People’s Hospital of Dongguan, Dongguan, Guangdong, China
| | - Meicen Pu
- Department of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, China
| | - Haohai Huang
- Department of Education and Science, The Third People’s Hospital of Dongguan, Dongguan, Guangdong, China
| | - Yejia Cui
- Department of Laboratory, The Third People’s Hospital of Dongguan, Dongguan, Guangdong, China
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