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Moliya P, Singh A, Singh N, Kumar V, Sohal A. Insights into gastrointestinal manifestation of human immunodeficiency virus: A narrative review. World J Virol 2025; 14:99249. [PMID: 40134843 PMCID: PMC11612874 DOI: 10.5501/wjv.v14.i1.99249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 10/15/2024] [Accepted: 11/04/2024] [Indexed: 11/28/2024] Open
Abstract
Human immunodeficiency virus (HIV) modifies CD4-positive cells, resulting in immunodeficiency and a wide range of gastrointestinal (GI) manifestations. The burden of HIV-related GI illnesses has significantly evolved with the widespread use of antiretroviral therapy (ART). While ART has effectively reduced the occurrence of opportunistic infections, it has led to an increase in therapy-related GI illnesses. Common esophageal conditions in HIV patients include gastroesophageal reflux disease, idiopathic esophageal ulcers, herpes simplex virus, cytomegalovirus (CMV), and candidal esophagitis. Kaposi's sarcoma, a hallmark of acquired immunodeficiency syndrome, may affect the entire GI system. Gastritis and peptic ulcer disease are also frequently seen in patients with HIV. Diarrhea, often linked to both opportunistic infections and ART, requires careful evaluation. Bloody diarrhea, often a sign of colitis caused by bacterial infections such as Shigella or Clostridium difficile, is prevalent. Small bowel lymphoma, although rare, is increasing in prevalence. Anorectal disorders, including proctitis, fissures, and anal squamous cell carcinoma, are particularly relevant in homosexual men, underlining the importance of timely diagnosis. This review comprehensively explores the epidemiology, pathogenesis, and treatment considerations for the various GI disorders associated with HIV, highlighting the importance of accurate diagnosis and effective treatment to improve outcomes for HIV-infected patients.
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Affiliation(s)
- Pratiksha Moliya
- Department of Transplant Hepatology, University of Nebraska Medical Center, Omaha, NE 69198, United States
| | - Anmol Singh
- Department of Medicine, Tristar Centennial Medical Center, Nashville, TN 37203, United States
| | - Navdeep Singh
- Department of Medicine, Government Medical College, Amritsar 143001, Punjab, India
| | - Vikash Kumar
- Department of Gastroenterology and Hepatology, Creighton University School of Medicine, Phoenix, AZ 85012, United States
| | - Aalam Sohal
- Department of Gastroenterology and Hepatology, Creighton University School of Medicine, Phoenix, AZ 85012, United States
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Hassan MS, Johnson C, Ponna S, Scofield D, Awasthi N, von Holzen U. Inhibition of Insulin-like Growth Factor 1 Receptor/Insulin Receptor Signaling by Small-Molecule Inhibitor BMS-754807 Leads to Improved Survival in Experimental Esophageal Adenocarcinoma. Cancers (Basel) 2024; 16:3175. [PMID: 39335147 PMCID: PMC11430189 DOI: 10.3390/cancers16183175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 09/04/2024] [Accepted: 09/10/2024] [Indexed: 09/30/2024] Open
Abstract
The insulin-like growth factor-1 (IGF-1) and insulin axes are upregulated in obesity and obesity-associated esophageal adenocarcinoma (EAC). Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a contemporary nanotechnology-based paclitaxel (PT) bound to human albumin, ensuring its solubility in water rather than a toxic solvent. Here, we examined the benefits of inhibiting insulin-like growth factor-1 receptor/insulin receptor (IGF-1/IR) signaling and the enhancement of nab-paclitaxel effects by inclusion of the small-molecule inhibitor BMS-754807 using both in vitro and in vivo models of EAC. Using multiple EAC cell lines, BMS-754807 and nab-paclitaxel were evaluated as mono and combination therapies for in vitro effects on cell proliferation, cell death, and cell movement. We then analyzed the in vivo anticancer potency with survival improvement with BMS-754807 and nab-paclitaxel mono and combination therapies. BMS-754807 monotherapy suppressed in vitro cell proliferation and wound healing while increasing apoptosis. BMS-754807, when combined with nab-paclitaxel, enhanced those effects on the inhibition of cell proliferation, increment in cell apoptosis, and inhibition of wound healing. BMS-754807 with nab-paclitaxel produced substantially greater antitumor effects by increasing in vivo apoptosis, leading to increased mice survival compared to those of BMS-754807 or nab-paclitaxel monotherapy. Our outcomes support the use of BMS-754807, alone and in combination with nab-paclitaxel, as an efficient and innovative treatment choice for EAC.
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Affiliation(s)
- Md Sazzad Hassan
- Department of Surgery, Indiana University School of Medicine, South Bend, IN 46617, USA; (N.A.)
- Harper Cancer Research Institute, South Bend, IN 46617, USA
| | - Chloe Johnson
- Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA
| | - Saisantosh Ponna
- Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA
| | - Dimitri Scofield
- Department of Biology, Indiana University, South Bend, IN 47405, USA
| | - Niranjan Awasthi
- Department of Surgery, Indiana University School of Medicine, South Bend, IN 46617, USA; (N.A.)
- Harper Cancer Research Institute, South Bend, IN 46617, USA
| | - Urs von Holzen
- Department of Surgery, Indiana University School of Medicine, South Bend, IN 46617, USA; (N.A.)
- Harper Cancer Research Institute, South Bend, IN 46617, USA
- Goshen Center for Cancer Care, Goshen, IN 46526, USA
- School of Medicine, University of Basel, 4056 Basel, Switzerland
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Qumseya B, Yang S, Guo Y. Trends in prevalence of esophageal adenocarcinoma: Findings from a statewide database of over 6 million patients. Endosc Int Open 2024; 12:E218-E226. [PMID: 38362358 PMCID: PMC10869210 DOI: 10.1055/a-2221-7974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 12/01/2023] [Indexed: 02/17/2024] Open
Abstract
Esophageal cancer (EC) is a leading cause of cancer-related death in the west 1 . Esophageal squamous cell carcinoma (SCC) is the most common type of EC worldwide. However, in Western countries, including the United States, esophageal adenocarcinoma (EAC) is the most common 2 . EAC is most common in the lower esophagus whereas SCC is most common in the middle and upper esophagus 3 . The incidence of EAC has increased dramatically in western countries over the past few decades. 2 3 The exact reason for this rise in EAC has not been clearly understood. However, an increase in the prevalence of EAC risk factors is postulated as a potential explanation 4 . Although there are many identifiable EAC risk factors, including gastroesophageal reflux disease (GERD), obesity, male sex, White race, and smoking 5 6 7 , Barrett's esophagus (BE) remains the major precursor lesion of esophageal adenocarcinoma. BE develops when there is a change in the normal squamous lining of the esophageal mucosa into intestinal metaplasia 8 9 . The incidence has also increased in the population over the past few decades 10 11 . There is a well-described progression within BE from non-dysplastic BE (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), intramucosal carcinoma (IMC), to invasive EAC 12 13 . Recent data suggest that the increased incidence of EAC may have plateaued 1 . However, we questioned whether the prevalence of EAC is still increasing, especially at younger ages in lieu of recent trends showing an increase in the prevalence of colorectal cancer in younger patients. These findings resulted in a lowering of the colorectal cancer screening age cutoff to 45 years from 50 years 14 15 16 . Therefore, we aimed to assess the time trends in the prevalence and incidence of EAC and some of its risk factors in a large population of patients in Florida and to assess these trends based on age categories. We hypothesized that the prevalence of EAC and BE has increased over time at younger age groups.
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Affiliation(s)
- Bashar Qumseya
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, United States
| | - Shuang Yang
- Division of Gastroenterology, University of Florida, GAINESVILLE, United States
| | - Yi Guo
- Department of Health Outcomes and Biomedical Informatics, University of Florida, GAINESVILLE, United States
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Ansari AZ, Bhatia NY, Gharat SA, Godad AP, Doshi GM. Exploring Cytokines as Potential Target in Peptic Ulcer Disease: A Systematic Update. Endocr Metab Immune Disord Drug Targets 2023; 23:21-34. [PMID: 36043736 DOI: 10.2174/1871530322666220829142124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 06/06/2022] [Accepted: 06/15/2022] [Indexed: 11/22/2022]
Abstract
Peptic ulcer disease (PUD) is a widespread condition that affects millions of people each year, with an incidence rate of 0.1%-1.5%, and has a significant impact on human health. A range of stimuli, such as Helicobacter pylori, non-steroidal anti-inflammatory drugs, hyperacidity, stress, alcohol, smoking, and idiopathic disease states, can produce a sore in the gastrointestinal mucosal layer. For individuals infected with H. pylori, 2%-3% remain asymptomatic throughout their life. Although PUD treatments are available, genetic variations occurring in individuals because of geographical dissimilarity and antibiotic resistance pose limitations. Specifically, inflammatory cytokine gene polymorphisms have received immense attention in recent years because they appear to affect the severity and duration of stomach inflammation, which is induced by H. pylori infection, contributing to the initiation of PUD. In such a context, in-depth knowledge of interleukins may aid in the discovery of new targets and provide precautionary approaches for the treatment of PUD. This review aims to give insights into the importance of several interleukins that cognate with PUD and contribute to ulcer progression or healing by activating or dampening the host immunity. Furthermore, the available targets with clinical evidence have been explored in this review.
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Affiliation(s)
- Alveera Zubair Ansari
- Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V. M. Road, Vile Parle (W), Mumbai, India
| | - Nirav Yogesh Bhatia
- Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V. M. Road, Vile Parle (W), Mumbai, India
| | - Sankalp Ashok Gharat
- Department of Pharmaceutics, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V. M. Road, Vile Parle (W), Mumbai, India
| | - Angel Pavalu Godad
- Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V. M. Road, Vile Parle (W), Mumbai, India
| | - Gaurav Mahesh Doshi
- Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V. M. Road, Vile Parle (W), Mumbai, India
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Wang M, Lou E, Xue Z. The role of bile acid in intestinal metaplasia. Front Physiol 2023; 14:1115250. [PMID: 36891144 PMCID: PMC9986488 DOI: 10.3389/fphys.2023.1115250] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Accepted: 02/10/2023] [Indexed: 02/22/2023] Open
Abstract
A precancerous lesion of gastric cancer (GC), intestinal metaplasia (IM) is a pathological transformation of non-intestinal epithelium into an intestinal-like mucosa. It greatly raises the risk of developing the intestinal type of GC, which is frequently observed in the stomach and esophagus. It is understood that esophageal adenocarcinoma's precursor lesion, chronic gastroesophageal reflux disease (GERD), is what causes Barrett's esophagus (BE), an acquired condition. Recently, Bile acids (BAs), which are one of the compositions of gastric and duodenal contents, have been confirmed that it led to the occurrence and development of BE and gastric intestinal metaplasia (GIM). The objective of the current review is to discuss the mechanism of IM induced by bile acids. This review serves as a foundation for further research aimed at improving the way BE and GIM are currently managed.
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Affiliation(s)
- Menglei Wang
- Department of Digestive Diseases, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
| | - Enzhe Lou
- Department of Digestive Diseases, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
| | - Zengfu Xue
- Department of Digestive Diseases, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China
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Mehri-Kakavand G, Pursamimi M, Parwaie W, Ghorbani M, Khosravi M, Hosseini SM, Soleimani Meigooni A. Assessment of Field-in-Field, 3-Field, and 4-Field Treatment Planning Methods for Radiotherapy of Gastro-Esophageal Junction Cancer. J Biomed Phys Eng 2022; 12:439-454. [PMID: 36313414 PMCID: PMC9589079 DOI: 10.31661/jbpe.v0i0.2206-1500] [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: 06/01/2022] [Accepted: 08/17/2022] [Indexed: 11/06/2022]
Abstract
Background Gastro-esophageal (GE) junction cancer is the fastest-growing tumor, particularly in the United States (US). Objective This study aimed to compare dosimetric and radiobiological factors among field-in-field (FIF), three-field (3F), and four-field box (4FB) radiotherapy planning techniques for gastro-esophageal junction cancer. Material and Methods In this experimental study, thirty patients with GE junction cancer were evaluated, and three planning techniques (field-in-field (FIF), three-field (3F), and four-field box (4FB)) were performed for each patient for a 6-MV photon beam. Dose distribution in the target volume, the monitor units (MUs) required, and the dose delivered to organs at risk (OARs) were compared for these techniques using the paired-sample t-test. Results A significant difference was measured between the FIF and 3F techniques with respect to conformity index (CI), dose homogeneity index (HI), and tumor control probability (TCP) for the target organ, as well as the Dmean for the heart, kidneys, and liver. For the spinal cord, the FIF technique showed a slight reduction in the maximum dose compared to the other two techniques. In addition, the V20 Gy of the lungs and the normal tissue complication probability (NTCP) of all OARs were reduced with FIF method. Conclusion The FIF technique showed better performance for treating patients with gastro-esophageal junction tumors, in terms of dose homogeneity in the target, conformity of the radiation field with the target volume, TCP, less dose to healthy organs, and fewer MU.
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Affiliation(s)
- Ghazal Mehri-Kakavand
- MSc, Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohamad Pursamimi
- MSc, Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Wrya Parwaie
- PhD, Department of Medical Physics, Faculty of Paramedical Sciences, Ilam University of Medical Sciences, Ilam, Iran
| | - Mahdi Ghorbani
- PhD, Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Khosravi
- MSc, Vali-e-Asr Radiotherapy and Oncology Center, Qom University of Medical Sciences, Qom, Iran
| | - Seyyed Mohammad Hosseini
- PhD Candidate, Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- PhD Candidate, Research Center for Molecular and Cellular Imaging, Tehran University of Medical Sciences, Tehran, Iran
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Gachara G, Suleiman R, El Kadili S, Ait Barka E, Kilima B, Lahlali R. Drivers of Post-Harvest Aflatoxin Contamination: Evidence Gathered from Knowledge Disparities and Field Surveys of Maize Farmers in the Rift Valley Region of Kenya. Toxins (Basel) 2022; 14:toxins14090618. [PMID: 36136556 PMCID: PMC9500662 DOI: 10.3390/toxins14090618] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 08/23/2022] [Accepted: 09/01/2022] [Indexed: 11/23/2022] Open
Abstract
Maize-dependent populations in sub-Saharan Africa are continually exposed to aflatoxin poisoning owing to their regular consumption of this dietetic cereal. Being a staple in Kenyan households, consumption of maize-based meals is done almost daily, thereby exposing consumers to aflatoxicoses. This study assessed awareness levels, knowledge disparities, and perceptions regarding aflatoxin contamination at the post-harvest phase among farmers in the Rift Valley Region of Kenya. Households were randomly selected using a geographical positioning system (GPS) overlay of the agro-ecological zones within Uasin Gishu and Elgeyo Marakwet counties. Face-to-face interviews were conducted in 212 smallholder and large-scale farms. The study documented the demographic profiles of farmers and knowledge, awareness, and perceptions of aflatoxin contamination using a pre-designed structured questionnaire. Most farmers were familiar with aflatoxins and the adverse effects they present to health (61.32%). Almost all the farmers (94.37%) were aware of storage molds and food-spoilage fungi. However, few farmers adopted good post-harvest practices (PHPs), such as avoiding premature harvests (49.8%), using well-ventilated storage spaces (44.6%), grain sorting (30.5%), proper drying of maize (17.8%), and using hermetic bags for storage (30.5%). Conclusively, intensified farmer education is required to train farmers on good PHPs to protect their maize from aflatoxigenic fungi and aflatoxin accumulation.
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Affiliation(s)
- Grace Gachara
- Department of Food Sciences and Agro-Processing, School of Engineering and Technology, Sokoine University of Agriculture, Morogoro P.O. Box 3006, Tanzania
- Southern Africa Centre of Excellence for Infectious Diseases (SACIDS), SACIDS Foundation for One Health, Sokoine University of Agriculture, Morogoro P.O. Box 3019, Tanzania
- Correspondence: (G.G.); (R.L.); Tel.: +255-725109725 (G.G.); +212-55-30-02-39 (R.L.)
| | - Rashid Suleiman
- Department of Food Sciences and Agro-Processing, School of Engineering and Technology, Sokoine University of Agriculture, Morogoro P.O. Box 3006, Tanzania
| | - Sara El Kadili
- Department of Animal Production, Ecole Nationale d’Agriculture de Meknès, Km10, Rte Haj Kaddour, BP S/40, Meknès 50001, Morocco
| | - Essaid Ait Barka
- Unité de Recherche Résistance Induite et Bio-Protection des Plantes-EA 4707, Université de Reims Champagne-Ardenne, 51100 Reims, France
| | - Beatrice Kilima
- Department of Food Sciences and Agro-Processing, School of Engineering and Technology, Sokoine University of Agriculture, Morogoro P.O. Box 3006, Tanzania
| | - Rachid Lahlali
- Phytopathology Unit, Department of Plant Protection, Ecole Nationale d’Agriculture de Meknès, Km10, Rte Haj Kaddour, BP S/40, Meknès 50001, Morocco
- Correspondence: (G.G.); (R.L.); Tel.: +255-725109725 (G.G.); +212-55-30-02-39 (R.L.)
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Interplays between non-coding RNAs and chemokines in digestive system cancers. Biomed Pharmacother 2022; 152:113237. [PMID: 35716438 DOI: 10.1016/j.biopha.2022.113237] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 06/01/2022] [Accepted: 06/02/2022] [Indexed: 11/24/2022] Open
Abstract
Within tumors, chemokines and their cognate receptors are expressed by infiltrated leukocytes, cancerous cells, and related cells of stroma, like tumor-associated fibroblasts and tumor-associated macrophages. In malignancies, the altered expression of chemokines/chemokine receptors governs leukocyte infiltration and activation, epithelial-mesenchymal transition (EMT), cancer cell proliferation, angiogenesis, and metastasis. Non-coding RNAs (ncRNAs) contribute to multiple physiological and pathophysiological processes. Some miRNAs can exert anti-tumorigenic activity in digestive system malignancies by repressing the expression of tumor-promoting chemokines/chemokine receptors or by upregulating tumor-suppressing chemokines/chemokine receptors. However, many miRNAs exert pro-tumorigenic activity by suppressing the expression of chemokines/chemokine receptors or by upregulating tumor-promoting chemokines/chemokine receptors. LncRNA and circRNAs also exert pro- and anti-tumorigenic effects by targeting downstream miRNAs influencing the expression of tumor-promoting and tumor-suppressor chemokines/chemokine receptors. On the other side, some chemokines influence the expression of ncRNAs affecting tumor formation. The current review explains the communications between ncRNAs and chemokines/chemokine receptors in certain digestive system malignancies, such as gastric, colorectal, and pancreatic cancers and hepatocellular carcinoma to gain better insights into their basic crosstalk as well as possible therapeutic modalities.
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Barragán-Montero A, Bibal A, Dastarac MH, Draguet C, Valdés G, Nguyen D, Willems S, Vandewinckele L, Holmström M, Löfman F, Souris K, Sterpin E, Lee JA. Towards a safe and efficient clinical implementation of machine learning in radiation oncology by exploring model interpretability, explainability and data-model dependency. Phys Med Biol 2022; 67:10.1088/1361-6560/ac678a. [PMID: 35421855 PMCID: PMC9870296 DOI: 10.1088/1361-6560/ac678a] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 04/14/2022] [Indexed: 01/26/2023]
Abstract
The interest in machine learning (ML) has grown tremendously in recent years, partly due to the performance leap that occurred with new techniques of deep learning, convolutional neural networks for images, increased computational power, and wider availability of large datasets. Most fields of medicine follow that popular trend and, notably, radiation oncology is one of those that are at the forefront, with already a long tradition in using digital images and fully computerized workflows. ML models are driven by data, and in contrast with many statistical or physical models, they can be very large and complex, with countless generic parameters. This inevitably raises two questions, namely, the tight dependence between the models and the datasets that feed them, and the interpretability of the models, which scales with its complexity. Any problems in the data used to train the model will be later reflected in their performance. This, together with the low interpretability of ML models, makes their implementation into the clinical workflow particularly difficult. Building tools for risk assessment and quality assurance of ML models must involve then two main points: interpretability and data-model dependency. After a joint introduction of both radiation oncology and ML, this paper reviews the main risks and current solutions when applying the latter to workflows in the former. Risks associated with data and models, as well as their interaction, are detailed. Next, the core concepts of interpretability, explainability, and data-model dependency are formally defined and illustrated with examples. Afterwards, a broad discussion goes through key applications of ML in workflows of radiation oncology as well as vendors' perspectives for the clinical implementation of ML.
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Affiliation(s)
- Ana Barragán-Montero
- Molecular Imaging, Radiation and Oncology (MIRO) Laboratory, Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Belgium
| | - Adrien Bibal
- PReCISE, NaDI Institute, Faculty of Computer Science, UNamur and CENTAL, ILC, UCLouvain, Belgium
| | - Margerie Huet Dastarac
- Molecular Imaging, Radiation and Oncology (MIRO) Laboratory, Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Belgium
| | - Camille Draguet
- Molecular Imaging, Radiation and Oncology (MIRO) Laboratory, Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Belgium
- Department of Oncology, Laboratory of Experimental Radiotherapy, KU Leuven, Belgium
| | - Gilmer Valdés
- Department of Radiation Oncology, Department of Epidemiology and Biostatistics, University of California, San Francisco, United States of America
| | - Dan Nguyen
- Medical Artificial Intelligence and Automation (MAIA) Laboratory, Department of Radiation Oncology, UT Southwestern Medical Center, United States of America
| | - Siri Willems
- ESAT/PSI, KU Leuven Belgium & MIRC, UZ Leuven, Belgium
| | | | | | | | - Kevin Souris
- Molecular Imaging, Radiation and Oncology (MIRO) Laboratory, Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Belgium
| | - Edmond Sterpin
- Molecular Imaging, Radiation and Oncology (MIRO) Laboratory, Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Belgium
- Department of Oncology, Laboratory of Experimental Radiotherapy, KU Leuven, Belgium
| | - John A Lee
- Molecular Imaging, Radiation and Oncology (MIRO) Laboratory, Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Belgium
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Factors associated with access and approach to esophagectomy for cancer: a National Cancer Database study. Surg Endosc 2022; 36:7016-7024. [DOI: 10.1007/s00464-022-09032-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 01/03/2022] [Indexed: 12/24/2022]
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Chang Z, Dang T, Meng X, Chai J. The Role of CCN1 in Esophageal Adenocarcinoma: What We Have Learned From the Lab. Cancer Control 2022; 29:10732748221074734. [PMID: 35291889 PMCID: PMC8935545 DOI: 10.1177/10732748221074734] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background: Esophageal cancer is one of the most common and deadliest cancers in the world, particularly esophageal adenocarcinoma. There has never been a special drug to treat it.Purpose: This article summarizes the work that we have done in our laboratory about the role of CCN1 in esophageal cancer and gives a new perspective of CCN1 biology.Research Design: This is a review article. Study Sample: The work was done using validated cell lines and fixed human tissue slides.Data Collection and Analysis: This is a review article, therefore, no data collection or analysis was involved.Results: CCN1 is a matricellular protein supporting adhesion, migration, and survival in normal cells, but in the esophageal cancer cells, it induces TRAIL-mediated apoptosis. CCN1 promotes TRAIL and its death receptor expression but downregulates the decoy receptors and survivin in a p53-dependant manner. It was thought that CCN1 relies on TNF to induce apoptosis, but our study found that these two molecules antagonize each other. CCN1 promotes TNFR1 cleavage and uses the soluble product to block TNF signaling, while TNF upregulates PGLYRP1 to overcome this obstacle because PGLYRP1 is a secreted protein that competes with TNF for TNFR1 binding. As a result, when CCN1 and TNF are present together in the vicinity of esophageal tumors, they cancel each other out.Conclusions: Based on our laboratory study, CCN1 has much potential to be a candidate for the treatment of esophageal cancer.
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Affiliation(s)
- Zhiheng Chang
- Inner Mongolia Institute of Digestive Diseases, Inner Mongolia Engineering Research Center for Prevention and Treatment of Digestive Diseases, Inner Mongolia University of Science and Technology, 74506The Second Affiliated Hospital of Baotou Medical College, Baotou, China
| | - Tong Dang
- Inner Mongolia Institute of Digestive Diseases, Inner Mongolia Engineering Research Center for Prevention and Treatment of Digestive Diseases, Inner Mongolia University of Science and Technology, 74506The Second Affiliated Hospital of Baotou Medical College, Baotou, China
| | - Xianmei Meng
- Inner Mongolia Institute of Digestive Diseases, Inner Mongolia Engineering Research Center for Prevention and Treatment of Digestive Diseases, Inner Mongolia University of Science and Technology, 74506The Second Affiliated Hospital of Baotou Medical College, Baotou, China
| | - Jianyuan Chai
- Inner Mongolia Institute of Digestive Diseases, Inner Mongolia Engineering Research Center for Prevention and Treatment of Digestive Diseases, Inner Mongolia University of Science and Technology, 74506The Second Affiliated Hospital of Baotou Medical College, Baotou, China.,Laboratory of Gastrointestinal Injury and Cancer, VA Long Beach Healthcare System, Long Beach, CA, USA.,College of Medicine, University of California, Irvine, CA, USA
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12
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Dang T, Chang Z, Meng J, Cui X, Wang P, Chai J. TNF antagonizes CCN1 in apoptosis in esophageal adenocarcinoma. Cytokine 2021; 149:155728. [PMID: 34634651 DOI: 10.1016/j.cyto.2021.155728] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 09/06/2021] [Accepted: 09/27/2021] [Indexed: 12/11/2022]
Abstract
TNF signaling mostly supports cell growth by activating NFκB and only induces cell death when NFκB activation fails. CCN1 is a matricellular protein that has been reported capable to convert TNF from a pro-survival factor into a stimulus for cell death without interfering with NFκB signaling. In this study, we examined the relationship between CCN1 and TNF in the context of esophageal adenocarcinoma and found that CCN1 did not help TNF to induce cell death when they were together, instead, it inhibited TNF expression, as well as TNF-induced JNK activation and apoptosis. CCN1 induced apoptosis in the cancer cells by itself through upregulation of TRAIL and its death receptors. The presence of TNF significantly lowered CCN1 expression and its capability in apoptosis induction. Furthermore, we found that CCN1 boosted ADAM17-mediated cleavage of TNF receptors through ITGA11 and the soluble decoy receptors generated by this action neutralized TNF activity. Taken together, CCN1 and TNF antagonize each other in esophageal cancer cells.
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Affiliation(s)
- Tong Dang
- Inner Mongolia Institute of Digestive Diseases, Inner Mongolia Engineering Research Center for Prevention and Treatment of Digestive Diseases, The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, 30 Hudemulin Rd, Baotou 014030, China
| | - Zhiheng Chang
- Inner Mongolia Institute of Digestive Diseases, Inner Mongolia Engineering Research Center for Prevention and Treatment of Digestive Diseases, The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, 30 Hudemulin Rd, Baotou 014030, China
| | - Jing Meng
- Inner Mongolia Institute of Digestive Diseases, Inner Mongolia Engineering Research Center for Prevention and Treatment of Digestive Diseases, The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, 30 Hudemulin Rd, Baotou 014030, China
| | - Xia Cui
- Inner Mongolia Institute of Digestive Diseases, Inner Mongolia Engineering Research Center for Prevention and Treatment of Digestive Diseases, The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, 30 Hudemulin Rd, Baotou 014030, China
| | - Pei Wang
- Inner Mongolia Institute of Digestive Diseases, Inner Mongolia Engineering Research Center for Prevention and Treatment of Digestive Diseases, The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, 30 Hudemulin Rd, Baotou 014030, China
| | - Jianyuan Chai
- Inner Mongolia Institute of Digestive Diseases, Inner Mongolia Engineering Research Center for Prevention and Treatment of Digestive Diseases, The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, 30 Hudemulin Rd, Baotou 014030, China; Laboratory of Gastrointestinal Injury and Cancer, VA Long Beach Healthcare System, Long Beach, CA 90822, USA.
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13
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Hassan MS, Cwidak N, Johnson C, Däster S, Eppenberger-Castori S, Awasthi N, Li J, Schwarz MA, von Holzen U. Therapeutic Potential of the Cyclin-Dependent Kinase Inhibitor Flavopiridol on c-Myc Overexpressing Esophageal Cancer. Front Pharmacol 2021; 12:746385. [PMID: 34621175 PMCID: PMC8490822 DOI: 10.3389/fphar.2021.746385] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 09/08/2021] [Indexed: 12/14/2022] Open
Abstract
Tumors with elevated c-Myc expression often exhibit a highly aggressive phenotype, and c-Myc amplification has been shown to be frequent in esophageal cancer. Emerging data suggests that synthetic lethal interactions between c-Myc pathway activation and small molecules inhibition involved in cell cycle signaling can be therapeutically exploited to preferentially kill tumor cells. We therefore investigated whether exploiting elevated c-Myc expression is effective in treating esophageal cancer with the CDK inhibitor flavopiridol. We found frequent overexpression of c-Myc in human esophageal cancer cell lines and tissues. c-Myc overexpression correlated with accelerated esophageal cancer subcutaneous xenograft tumor growth. Esophageal cancer cells with elevated c-Myc expression were found preferentially more sensitive to induction of apoptosis by the CDK inhibition flavopiridol compared to esophageal cancer cells with lower c-Myc expression. In addition, we observed that flavopiridol alone or in combination with the chemotherapeutic agent nanoparticle albumin-bound paclitaxel (NPT) or in combinations with the targeted agent BMS-754807 significantly inhibited esophageal cancer cell proliferation and subcutaneous xenograft tumor growth while significantly enhancing overall mice survival. These results indicate that aggressive esophageal cancer cells with elevated c-Myc expression are sensitive to the CDK inhibitor flavopiridol, and that flavopiridol alone or in combination can be a potential therapy for c-Myc overexpressing esophageal cancer.
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Affiliation(s)
- Md Sazzad Hassan
- Department of Surgery, Indiana University School of Medicine, South Bend, IN, United States.,Harper Cancer Research Institute, South Bend, IN, United States
| | - Nicholas Cwidak
- Department of Surgery, Indiana University School of Medicine, South Bend, IN, United States
| | - Chloe Johnson
- University of Notre Dame, Notre Dame, IN, United States
| | | | | | - Niranjan Awasthi
- Department of Surgery, Indiana University School of Medicine, South Bend, IN, United States.,Harper Cancer Research Institute, South Bend, IN, United States
| | - Jun Li
- Harper Cancer Research Institute, South Bend, IN, United States.,University of Notre Dame, Notre Dame, IN, United States
| | - Margaret A Schwarz
- Harper Cancer Research Institute, South Bend, IN, United States.,Department of Pediatrics, Indiana University School of Medicine, South Bend, IN, United States
| | - Urs von Holzen
- Department of Surgery, Indiana University School of Medicine, South Bend, IN, United States.,Harper Cancer Research Institute, South Bend, IN, United States.,University of Basel, Basel, Switzerland.,Goshen Center for Cancer Care, Goshen, IN, United States
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14
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Kitamura Y, Oshikiri T, Takiguchi G, Urakawa N, Hasegawa H, Yamamoto M, Kanaji S, Yamashita K, Matsuda T, Fujino Y, Tominaga M, Nakamura T, Suzuki S, Kakeji Y. Impact of Lymph Node Ratio on Survival Outcome in Esophageal Squamous Cell Carcinoma After Minimally Invasive Esophagectomy. Ann Surg Oncol 2021; 28:4519-4528. [PMID: 33393049 DOI: 10.1245/s10434-020-09451-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 11/11/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Esophageal squamous cell cancer (ESCC) is one of the deadliest cancers in the world. Esophagectomy remains the principal treatment, and minimally invasive esophagectomy (MIE) has been performed worldwide. This study aimed to clarify whether the lymph node ratio (LNR), defined as the ratio of metastatic lymph nodes (LNs) to examined, is a prognostic factor for ESCC after MIE. METHODS This study included 327 MIEs with the patient in the prone position at two institutions from 2010 to 2015. Cox proportional hazards regression analyses using clinicopathologic characteristics and the LNR were performed for the pN1 patients and the whole cohort. RESULTS In the multivariate analysis for all stages, independent prognostic factors were depth of tumor invasion (P < 0.0001), LNR (P = 0.014), operative time (P = 0.003), and pneumonia (P = 0.012). In the analysis of the pN1 subgroup, the optimum LNR cutoff level for overall survival (OS) was 9 based on receiver operation characteristic analysis. The LNR was significantly associated with depth of tumor invasion (P = 0.004) and number of metastatic LNs (P < 0.0001). The OS curve for the group with an LNR of 9 or higher was significantly worse than for the group with an LNR lower than 9 (P < 0.001). Multivariate analyses demonstrated that the LNR is a unique independent prognostic factor for the pN1 subgroup (hazard ratio, 6.811; 95% confidence interval, 2.009-23.087; P = 0.002). CONCLUSIONS The LNR is an independent prognostic factor in ESCC after MIE. Especially for patients with pN1 status, the LNR is more useful than the number of metastatic LNs for predicting survival outcome.
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Affiliation(s)
- Yu Kitamura
- Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan
| | - Taro Oshikiri
- Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan.
| | - Gosuke Takiguchi
- Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan
| | - Naoki Urakawa
- Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan
| | - Hiroshi Hasegawa
- Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan
| | - Masashi Yamamoto
- Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan
| | - Shingo Kanaji
- Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan
| | - Kimihiro Yamashita
- Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan
| | - Takeru Matsuda
- Division of Minimally Invasive Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan
| | - Yasuhiro Fujino
- Department of Gastroenterological Surgery, Hyogo Cancer Center, Akashi, Hyogo, Japan
| | - Masahiro Tominaga
- Department of Gastroenterological Surgery, Hyogo Cancer Center, Akashi, Hyogo, Japan
| | - Tetsu Nakamura
- Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan
| | - Satoshi Suzuki
- Department of Social Community Medicine and Health Science, Division of Community Medicine and Medical Network, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan
| | - Yoshihiro Kakeji
- Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan
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15
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Zhang X, Anandasabapathy S, Abrams J, Othman M, Badr HJ. Lifestyle Risk Factors, Quality of Life, and Intervention Preferences of Barrett's Esophagus Patients: A Prospective Cohort Study. Glob Adv Health Med 2021; 10:21649561211001346. [PMID: 33767920 PMCID: PMC7952842 DOI: 10.1177/21649561211001346] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 01/28/2021] [Accepted: 02/19/2021] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND AND AIMS Lifestyle counseling to achieve a healthy weight, quit smoking, and reduce alcohol is a cornerstone in the management of Barrett's Esophagus (BE). However, little is known about whether patients make these recommended lifestyle changes or the impact of non-adherence on their quality of life (QOL). This study characterized the lifestyle risk factors, QOL, and intervention preferences of BE patients as a first step toward developing lifestyle change interventions for this population. METHODS Patients with a confirmed BE diagnosis (N = 106) completed surveys at a surveillance endoscopy visit (baseline) and at 3- and 6-month follow-ups. Patients reported on lifestyle risk factors, adherence determinants (e.g., perceived benefits/barriers, risk, intentions), QOL, and intervention preferences. RESULTS Most patients (56%) had uncontrolled reflux, were overweight/obese (65.1%), and had low dietary fiber intake (91%). Many (45%) reported poor QOL. Patients' perceived risk of developing esophageal cancer was high, but their behavior change intentions were low. Despite receiving lifestyle counseling from physicians, there were no significant changes in patients' QOL or lifestyle risk factors over time. Nonetheless, patients indicated strong interest in internet (62.6%) and multimedia programs (57.9%) addressing acid reflux and weight control. CONCLUSION BE patients reported uncontrolled reflux, poor QOL, and multiple lifestyle risk factors that did not change over time. Despite low levels of intention for making lifestyle changes, patients were interested receiving more information about controlling acid reflux, suggesting a potential teachable moment and opportunity for web-based and multimedia multiple behavior interventions that seek to control acid reflux symptoms through weight loss and a high fiber diet.
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Affiliation(s)
- Xiaotao Zhang
- Department of Medicine, Section of Epidemiology and Population Science, Baylor College of Medicine, Houston, Texas
| | - Sharmila Anandasabapathy
- Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas
| | - Julian Abrams
- Department of Medicine, Columbia University, New York, New York
| | - Mohamed Othman
- Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas
| | - Hoda J Badr
- Department of Medicine, Section of Epidemiology and Population Science, Baylor College of Medicine, Houston, Texas
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16
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Dang T, Chai J. Molecular Dynamics in Esophageal Adenocarcinoma: Who's in Control? Curr Cancer Drug Targets 2020; 20:789-801. [PMID: 32691711 DOI: 10.2174/1568009620666200720011341] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 06/16/2020] [Accepted: 06/18/2020] [Indexed: 01/01/2023]
Abstract
Esophageal adenocarcinoma (EAC) is one of the fastest-growing cancers in the world. It occurs primarily due to the chronic gastroesophageal reflux disease (GERD), during which the esophageal epithelium is frequently exposed to the acidic fluid coming up from the stomach. This triggers gene mutations in the esophageal cells, which may lead to EAC development. While p53 is activated to get rid of the mutated cells, NFκB orchestrates the remaining cells to heal the wound. However, if the mutations happen to TP53 (a common occasion), the mutant product turns to support tumorigenesis. In this case, NFκB goes along with the mutant p53 to facilitate cancer progression. TRAIL is one of the cytokines produced in response to GERD episodes and it can kill cancer cells selectively, but its clinical use has not been as successful as expected, because some highly sophisticated defense mechanisms against TRAIL have developed during the malignancy. To clear the obstacles for TRAIL action, using a second agent to disarm the cancer cells is required. CCN1 appears to be such a molecule. While supporting normal esophageal cell growth, CCN1 suppresses malignant transformation by inhibiting NFκB and kills the EAC cell through TRAIL-mediated apoptosis.
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Affiliation(s)
- Tong Dang
- Inner Mongolia Institute of Digestive Diseases; Inner Mongolia Engineering Research Center for Prevention and
Treatment of Digestive Diseases; The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, 30 Hudemulin Rd, Baotou, 014030, China
| | - Jianyuan Chai
- Inner Mongolia Institute of Digestive Diseases; Inner Mongolia Engineering Research Center for Prevention and
Treatment of Digestive Diseases; The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, 30 Hudemulin Rd, Baotou, 014030, China,Laboratory of Gastrointestinal Injury and Cancer, VA Long Beach Healthcare System, Long Beach, CA90822, USA,College of Medicine, University of California, Irvine, CA, 92697, USA
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17
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Acid/bile exposure triggers TRAIL-mediated apoptosis in esophageal cancer cells by suppressing the decoy receptors and c-FLIP R. Int J Biochem Cell Biol 2020; 122:105736. [PMID: 32135301 DOI: 10.1016/j.biocel.2020.105736] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 02/28/2020] [Accepted: 03/01/2020] [Indexed: 11/23/2022]
Abstract
Esophageal adenocarcinoma essentially develops from esophageal inflammation caused by chronic GERD. During GERD episodes, the lower esophageal epithelium is repeatedly exposed to stomach acid, which often contains duodenal bile salts that prompt malignant transformation. TRAIL is one of the cytokines produced in response to such insults and targets the transformed cells exclusively. In this study, we simulated GERD episodes in vitro by exposing the cancer cells to acid or acid/bile combination and found that the cancer cells lived through acid attacks by expression of the decoy receptors and c-FLIPR but died of TRAIL-mediated apoptosis when bile salts were present. Further investigation revealed that acid/bile exposure downregulated the decoy receptors and thereby facilitated TRAIL signaling; meantime, it inhibited protein kinase C activity and thus expedited c-FLIPR degradation, allowing apoptosis to take place.
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18
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Banda KJ, Chiu HY, Hu SH, Yeh HC, Lin KC, Huang HC. Associations of dietary carbohydrate and salt consumption with esophageal cancer risk: a systematic review and meta-analysis of observational studies. Nutr Rev 2020; 78:688-698. [DOI: 10.1093/nutrit/nuz097] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Abstract
Context
Evidence has shown that essential nutrients are highly correlated with the occurrence of esophageal cancer (EC). However, findings from observational studies on the associations between dietary carbohydrate, salt consumption, and the risk of EC remain controversial.
Objective
The aim of this study was to conduct a systematic review and meta-analysis to confirm the associations of dietary carbohydrate and salt consumption with EC risk.
Data Source
Various electronic databases (PubMed, MEDLINE, Embase, Google Scholar, Cochrane Library, Chinese Electronic Periodical Services, and China Knowledge Resource Integrated) were searched up until January 31, 2019.
Data Extraction
Data related to patient characteristics and study characteristics were extracted by 2 independent reviewers. The risk ratio reported as relative risk (RR) or odds ratio (OR) was extracted, and random-effects models were performed to estimate the summary risk ratio.
Results
In total, 26 studies were included in this analysis, of which 12 studies, including 11 case-control studies and 1 cohort study, examined dietary carbohydrates, and 18 studies, including 16 case-control studies and 2 cohort studies, examined dietary salt. The pooled OR showed that dietary carbohydrate intake was inversely related to EC risk (OR = 0.62; 95% confidence interval [CI], 0.50–0.77), but positive correlations between dietary salt intake and the risk of EC were supported by the recruited case-control studies (OR = 1.97; 95% CI, 1.50–2.61) and cohort studies (RR = 1.04; 95% CI, 1.00–1.08).
Conclusions
Salt is an essential nutrient for body functions and biochemical processes. Providing health education and management regarding proper use of salt in daily foods and labeling the amount of sodium in manufactured products to reduce the risk of developing EC should be more appropriately performed in the general population.
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Affiliation(s)
- Kondwani-Joseph Banda
- School of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan
- Endoscopy Unit, Surgery Department, Kamuzu Central Hospital, Lilongwe, Malawi
| | - Hsiao-Yean Chiu
- School of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan
| | - Sophia Hueylan Hu
- School of Nursing, College of Nursing, National Yang-Ming University, Taipei, Taiwan
| | - Hsiu-Chun Yeh
- School of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan
| | - Kuan-Chia Lin
- Institute of Hospital and Health Care Administration, Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan
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19
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Hassan MS, Williams F, Awasthi N, Schwarz MA, Schwarz RE, Li J, von Holzen U. Combination effect of lapatinib with foretinib in HER2 and MET co-activated experimental esophageal adenocarcinoma. Sci Rep 2019; 9:17608. [PMID: 31772236 PMCID: PMC6879590 DOI: 10.1038/s41598-019-54129-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 10/08/2019] [Indexed: 01/02/2023] Open
Abstract
Recent studies have demonstrated that HER2 and MET receptor tyrosine kinases are co-overexpressed in a subset esophageal adenocarcinoma (EAC). We therefore studied the usefulness of combining HER2 and MET targeting by small-molecule inhibitors lapatinib and foretinib, respectively, both in in-vitro and in-vivo models of experimental EAC. We characterized MET and HER2 activation in a panel of human EAC cell lines, and the differential susceptibility of these EAC cell lines to single agent or combination of foretinib and lapatinib. We then explored the antitumor efficacy with survival advantage following foretinib and lapatinib monotherapy and in combination in murine subcutaneous xenograft and peritoneal metastatic survival models of human EAC. The OE33 EAC cell line with strong expression of phosphorylated both MET and HER2, demonstrated reduced sensitivity to foretinib and lapatinib when used as a single agent. The co-administration of foretinib and lapatinib effectively inhibited both MET and HER2 phosphorylation, enhanced inhibition of cell proliferation and xenograft tumor growth by inducing apoptosis, and significantly enhanced mouse overall survival, overcoming single agent resistance. In the OE19 EAC cell line with mainly HER2 phosphorylation, and the ESO51 EAC cell line with mainly MET phosphorylation, profound cell growth inhibition with induction of apoptosis was observed in response to single agent with lack of enhanced growth inhibition when the two agents were combined. These data suggest that combination therapy with foretinib and lapatinib should be tested as a treatment option for HER2 positive patients with MET-overexpressing EAC, and could be a novel treatment strategy for specific EAC patients.
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Affiliation(s)
- Md Sazzad Hassan
- Department of Surgery, Indiana University School of Medicine, South Bend, IN, 46617, USA. .,Harper Cancer Research Institute, South Bend, IN, 46617, USA.
| | - Fiona Williams
- Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, 46556, USA
| | - Niranjan Awasthi
- Department of Surgery, Indiana University School of Medicine, South Bend, IN, 46617, USA.,Harper Cancer Research Institute, South Bend, IN, 46617, USA
| | - Margaret A Schwarz
- Harper Cancer Research Institute, South Bend, IN, 46617, USA.,Department of Pediatrics, Indiana University School of Medicine, South Bend, IN, 46617, USA
| | - Roderich E Schwarz
- Department of Surgery, Indiana University School of Medicine, South Bend, IN, 46617, USA.,Harper Cancer Research Institute, South Bend, IN, 46617, USA
| | - Jun Li
- Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN, 46556, USA
| | - Urs von Holzen
- Department of Surgery, Indiana University School of Medicine, South Bend, IN, 46617, USA.,Goshen Center for Cancer Care, Goshen, Goshen, IN, 46526, USA.,Harper Cancer Research Institute, South Bend, IN, 46617, USA.,University of Basel, Basel, Switzerland
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20
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Wang W, Wu D, He X, Hu X, Hu C, Shen Z, Lin J, Pan Z, He Z, Lin H, Wang M. CCL18-induced HOTAIR upregulation promotes malignant progression in esophageal squamous cell carcinoma through the miR-130a-5p-ZEB1 axis. Cancer Lett 2019; 460:18-28. [PMID: 31207321 DOI: 10.1016/j.canlet.2019.06.009] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2018] [Revised: 06/08/2019] [Accepted: 06/12/2019] [Indexed: 12/25/2022]
Abstract
Accumulating evidence indicates that CCL18 and the long non-coding RNA, HOTAIR, have critical roles in cancer progression and metastasis, but the correlation between CCL18 and HOTAIR in esophageal squamous cell carcinoma (ESCC) and their downstream molecular mechanisms remain unclear. Overexpression of CCL18 in ESCC tissues was associated with a worse survival in patients with ESCC. CCL18 enhanced the invasiveness of ESCC cells in a dose-dependent manner, whereas CCL18 knockdown inhibited their invasiveness. In particular, CCL18 expression was positively associated with HOTAIR expression in ESCC tissues. Furthermore, CCL18 upregulated the expression of HOTAIR, and knockdown of HOTAIR alleviated the CCL18-induced invasiveness of ESCC cells. HOTAIR may act as a competing endogenous RNA and could effectively becoming a sponge for miR-130a-5p, thereby modulating the derepression of ZEB1 and promoting epithelial-mesenchymal transition in ESCC. Our study suggests that CCL18 contributes to the malignant progression of esophageal cancer by upregulating HOTAIR expression. HOTAIR overexpression may promote tumor invasiveness and progression in ESCC, given that HOTAIR functions as a miR-130a-5p sponge, positively regulating ZEB1. This provides new therapeutic targets for early diagnosis and treatment of ESCC.
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Affiliation(s)
- Wenjian Wang
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China; Department of Thoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Duoguang Wu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China; Department of Thoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Xiaotian He
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China; Department of Thoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Xueting Hu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China; Department of Thoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Chuwen Hu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China; Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Zhiwen Shen
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China; Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Jiatong Lin
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China; Department of Thoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Zihao Pan
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China; Department of Thoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Zhanghai He
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China; Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Huayue Lin
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China; Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
| | - Minghui Wang
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China; Department of Thoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
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21
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Ma S, Liu T, Xu L, Wang Y, Zhou J, Huang T, Li P, Liu H, Zhang Y, Zhou X, Cui Y, Zang X, Wang Y, Guan F. Histone deacetylases inhibitor MS-275 suppresses human esophageal squamous cell carcinoma cell growth and progression via the PI3K/Akt/mTOR pathway. J Cell Physiol 2019; 234:22400-22410. [PMID: 31120582 DOI: 10.1002/jcp.28805] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Revised: 04/23/2019] [Accepted: 04/24/2019] [Indexed: 12/18/2022]
Abstract
Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with low survival rate, so new therapies are urgently needed. Histone deacetylases (HDACs) play a critical role in tumorigenesis, and HDACs inhibition is a potential therapeutic target in ESSC. In our study, we evaluated the effect and molecular mechanism of MS-275 (an inhibitor of HDACs) on ESCC cells. We found that HDAC1 and HDAC2 were overexpressed in ESCC tissues and related with clinical pathological features of patients with ESCC. MS-275 markedly reduced HDAC1 and HDAC2 expression, whereas increased the level of AcH3 and AcH2B. MS-275 suppressed proliferation and clonogenicity of ESCC cells in a concentration-dependent manner. In addition, MS-275 induced apoptosis, arrested cell cycle, and inhibited migration, epithelial-mesenchymal transition, and sphere-forming ability of ESCC cells in vitro. Moreover, p-Akt1 and p-mTOR were downregulated by MS-275. Finally, MS-275 significantly inhibited tumor growth in vivo. Taken together, HDAC1 and HDAC2 are associated with the progression of ESCC, and MS-275 hinders the progression and stemness of ESCC cells by suppressing the PI3K/Akt/mTOR pathway. Our findings show that MS-275 inhibits ESCC cells growth in vitro and in vivo, which is a potential drug for the ESCC therapy.
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Affiliation(s)
- Shanshan Ma
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Tengfei Liu
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Ling Xu
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China.,Department of Anesthesiology, Shanghai General Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China
| | - Yaping Wang
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Jiankang Zhou
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Tuanjie Huang
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Peng Li
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China.,Clinical Laboratory, Zhumadian Hospital of Traditional Chinese Medicine, Zhumadian, Henan, China
| | - Hongtao Liu
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Yanting Zhang
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Xinkui Zhou
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Yuanbo Cui
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Xingxing Zang
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Yuming Wang
- Henan University People's Hospital, Zhengzhou, Henan, China
| | - Fangxia Guan
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China.,Henan Provincial People's Hospital, Zhengzhou, Henan, China
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22
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van der Sluis PC, Schizas D, Liakakos T, van Hillegersberg R. Minimally Invasive Esophagectomy. Dig Surg 2019; 37:93-100. [PMID: 31096214 DOI: 10.1007/s00464-018-06626-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Accepted: 02/04/2019] [Indexed: 10/27/2022]
Abstract
Minimally invasive esophagectomy (MIE) was introduced in the 1990s with the aim to decrease the rate of respiratory complications associated with thoracotomy, along with the benefits of reduced morbidity and a quicker return to normal activities provided by minimally invasive techniques. However, MIE is not routinely applied as a standard approach for esophageal cancer worldwide, due to the high technical complexity of this minimally invasive procedure. Therefore, the open transthoracic esophagectomy is considered to be the gold standard for resectable esophageal cancer worldwide nowadays. In this article, the current status of conventional MIE and robot-assisted minimally invasive thoraco-laparoscopic esophagectomy will be reviewed.
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Affiliation(s)
| | - Dimitrios Schizas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Theodore Liakakos
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
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23
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Barrett Esophagus Length, Nodularity, and Low-grade Dysplasia are Predictive of Progression to Esophageal Adenocarcinoma. J Clin Gastroenterol 2019; 53:361-365. [PMID: 29608452 DOI: 10.1097/mcg.0000000000001027] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
GOALS To investigate factors predictive of progression from nondysplastic Barrett esophagus (NDBE) or low-grade dysplasia (LGD) to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) using a large, prospective cohort of patients, wherein all esophageal biopsies undergo expert gastrointestinal pathologist review. BACKGROUND Efficacy and cost-effectiveness of endoscopic surveillance to detect incident EAC in the setting of Barrett esophagus (BE), particularly in NDBE patients, is questioned. Previous studies have reported factors predictive of progression to EAC to guide surveillance intervals, but their strength is limited by small sample size and absence of expert gastrointestinal pathologist involvement in esophageal biopsy review. STUDY NDBE and LGD subjects were identified from a prospective registry in a tertiary care center. "Progressors" were BE subjects who developed HGD/EAC>12 months after the initial NDBE or LGD diagnosis. Cox proportional hazards model were used to identify predictors of progression. RESULTS In total, 318 with NDBE and 301 with BE-LGD (mean age, 62.6 y, 85% male) were included. The mean follow-up was 5.3 years. The 7 NDBE and 21 LGD subjects progressed to HGD/EAC. BE length [hazards ratio (HR), 1.16; 95% confidence interval (CI), 1.03-1.29], presence of nodularity (HR, 4.98; 95% CI, 1.80-11.7), and baseline LGD (HR, 2.57; 95% CI, 1.13-6.57) were significant predictors of progression on multivariate analysis. CONCLUSIONS In this well-defined cohort of NDBE and BE-LGD subjects, BE length, presence of LGD, and nodularity were independent predictors of progression to HGD/EAC. These factors may aid in identifying high-risk patients who may benefit from closer endoscopic surveillance/therapy.
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24
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Huber AR, Buscaglia B, Koltz BR, Henry J, McMahon L, Guo J, Hicks DG, Whitney-Miller CL. Impact of Specimen Type and Specimen Number on HER2 Status in Gastroesophageal Junction and Gastric Adenocarcinoma. Am J Clin Pathol 2019; 151:461-468. [PMID: 30624589 DOI: 10.1093/ajcp/aqy166] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
OBJECTIVES Human epidermal growth factor receptor 2 (HER2) is expressed in some gastric and gastroesophageal junction adenocarcinomas. There were two goals: assess the impact of specimen type on HER2 status and evaluate HER2 concordance with multiple specimens. METHODS All cases were evaluated by immunohistochemistry (IHC) for HER2 and interpreted using established criteria. Fluorescence in situ hybridization (FISH) was performed on a subset. RESULTS Of 460 specimens, 83.9% were IHC negative, 5.4% were equivocal, and 10.7% were IHC positive. Of those with FISH testing, 78.5% were FISH negative, and 21.5% were FISH positive. IHC-FISH concordance for biopsy specimens, resections, and metastases was 82%, 84%, and 86%, respectively. With one vs two vs three or more specimens, the HER2-positive rate increased from 10.5% to 18.1% to 24.1%, respectively. CONCLUSIONS HER2 testing may be performed on biopsy specimens with a relatively high concordance rate with resection specimens, and if multiple samples are analyzed from a single patient, the HER2-positive rate increases over twofold.
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Affiliation(s)
- Aaron R Huber
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY
| | - Brandon Buscaglia
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY
| | - Brooke R Koltz
- Department of Pathology, University of Toledo, Toledo, OH
| | - Jill Henry
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY
| | - Loralee McMahon
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY
| | - James Guo
- Northwestern University, Feinberg School of Medicine, Chicago, IL
| | - David G Hicks
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY
| | - Christa L Whitney-Miller
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY
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25
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Overexpression of CCN1 in Het1A cells attenuates bile-induced esophageal metaplasia through suppressing non-canonical NFκB activation. Cytokine 2019; 116:61-69. [PMID: 30685604 DOI: 10.1016/j.cyto.2018.12.020] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Revised: 12/20/2018] [Accepted: 12/24/2018] [Indexed: 01/19/2023]
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26
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Dang T, Modak C, Meng X, Wu J, Narvaez R, Chai J. CCN1 induces apoptosis in esophageal adenocarcinoma through p53-dependent downregulation of survivin. J Cell Biochem 2019; 120:2070-2077. [PMID: 30318638 DOI: 10.1002/jcb.27515] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Accepted: 07/27/2018] [Indexed: 01/24/2023]
Abstract
Many cancer drugs have been developed to control tumor growth by inducing cancer cell apoptosis. However, several intracellular barriers could fail this attempt. One of these barrier is high expression of survivin. Survivin can interfere caspase activation and thereby abort apoptosis. In this study, we found that CCN1 suppressed the survivin expression in tumor cells of esophageal adenocarcinoma (EAC) and thus allowed apoptosis to finish. Furthermore, we demonstrated that this downregulation was dependent on p53 phosphorylation at Ser20, and CCN1 induced EAC cell apoptosis through the activation of p53.
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Affiliation(s)
- Tong Dang
- Inner Mongolia Institute of Digestive Diseases, The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia, China
| | - Cristina Modak
- Laboratory of Gastrointestinal Injury and Cancer, VA Long Beach Healthcare System, Long Beach, California
| | - Xiemei Meng
- Inner Mongolia Institute of Digestive Diseases, The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia, China
| | - Jinbao Wu
- Inner Mongolia Institute of Digestive Diseases, The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia, China
| | - Reinier Narvaez
- Laboratory of Gastrointestinal Injury and Cancer, VA Long Beach Healthcare System, Long Beach, California
| | - Jianyuan Chai
- Inner Mongolia Institute of Digestive Diseases, The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia, China.,Laboratory of Gastrointestinal Injury and Cancer, VA Long Beach Healthcare System, Long Beach, California.,Department of Medicine, College of Medicine, University of California, Irvine, California
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27
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Agzarian J, Visscher SL, Knight AW, Allen MS, Cassivi SD, Nichols FC, Shen KR, Wigle D, Blackmon SH. The cost burden of clinically significant esophageal anastomotic leaks-a steep price to pay. J Thorac Cardiovasc Surg 2018; 157:2086-2092. [PMID: 30558876 DOI: 10.1016/j.jtcvs.2018.10.137] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Revised: 10/08/2018] [Accepted: 10/14/2018] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The purpose of this retrospective cohort study was to evaluate resource consumption of clinically significant esophageal anastomotic leaks. METHODS Between September 1, 2008, to December 31, 2014, a prospectively maintained database was queried to identify patients with grade III to IV anastomotic leaks after esophagectomy for esophageal cancer. Inflation-adjusted standardized costs were applied to billed services related to leak diagnosis and treatment, from time of leak detection to resumption of oral diet. A matched analysis was used to compare average expenditures in patients without vs. those with an anastomotic leak. RESULTS Of 448 patients undergoing esophagectomy after neoadjuvant treatment, 399 patients met inclusion criteria. Twenty-four grade III to IV anastomotic leaks were identified (6% leak rate). Five transhiatal esophagectomies accounted for 20.8% of cases, whereas 9 Ivor Lewis and 10 McKeown esophagectomies accounted for 37.5% and 41.7%, respectively. The median time required to treat an anastomotic leak was 73 days (range 14-701). The additional median standardized cost per leak was $68,296 (mean $119,822). Matched analysis demonstrated that mean treatment costs were 2.6 times greater for patients with an anastomotic leak. This was primarily attributed to prolonged hospitalization, with post-leak detection length of stay ranging from 7 to 73 days. The largest contributors to cost for all patients were intensive care stay (30%), hospital room (17%), pharmacy (16%), and surgical intervention (13%). CONCLUSIONS Grade III to IV esophageal anastomotic leaks more than double the cost of an esophagectomy and have a significant cost burden. Focus should be placed on preventative measures to avoid leaks at the time of the index operation.
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Affiliation(s)
- John Agzarian
- Division of Thoracic Surgery, Department of Surgery, Mayo Clinic, Rochester.
| | - Sue L Visscher
- Mayo Clinic, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minn
| | - Ariel W Knight
- Division of Thoracic Surgery, Department of Surgery, Mayo Clinic, Rochester
| | - Mark S Allen
- Division of Thoracic Surgery, Department of Surgery, Mayo Clinic, Rochester
| | - Stephen D Cassivi
- Division of Thoracic Surgery, Department of Surgery, Mayo Clinic, Rochester
| | - Francis C Nichols
- Division of Thoracic Surgery, Department of Surgery, Mayo Clinic, Rochester
| | - K Robert Shen
- Division of Thoracic Surgery, Department of Surgery, Mayo Clinic, Rochester
| | - Dennis Wigle
- Division of Thoracic Surgery, Department of Surgery, Mayo Clinic, Rochester
| | - Shanda H Blackmon
- Division of Thoracic Surgery, Department of Surgery, Mayo Clinic, Rochester
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28
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Cystic Fibrosis and gastroesophageal reflux disease. J Cyst Fibros 2018; 16 Suppl 2:S2-S13. [PMID: 28986024 DOI: 10.1016/j.jcf.2017.07.007] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Revised: 07/06/2017] [Accepted: 07/06/2017] [Indexed: 12/19/2022]
Abstract
Gastroesophageal reflux is common in children and adults with cystic fibrosis (CF). Pathological gastroesophageal reflux disease (GERD) is also frequent in patients of all ages with CF. This article reviews the pathophysiology, diagnostic work-up, management options, complications, and future directions in the evaluation and management of GERD - unique to and pertinent for - patients with CF in particular.
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29
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Abstract
This relationship between gastroesophageal reflux and airway disorders is complex, possibly bidirectional, and not clearly defined. The tools used to investigate gastroesophageal reflux are mostly informative about involvement of gastroesophageal reflux within the gastrointestinal tract, although they are often utilized to study the relationship between gastroesophageal reflux and airway issues with are suspected to occur in relation to reflux. These modalities often lack specificity for reflux-related airway disorders. Co-incidence of gastroesophageal reflux and airway disorders does not necessarily infer causality. While much of our focus has been on managing acidity, controlling refluxate is an area that has not been traditionally aggressively pursued. Our management approach is based on some of the evidence presented, but also often from a lack of adequate study to provide further guidance.
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Affiliation(s)
- Asim Maqbool
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA.
| | - Matthew J Ryan
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA
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30
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Superior Therapeutic Efficacy of Nanoparticle Albumin Bound Paclitaxel Over Cremophor-Bound Paclitaxel in Experimental Esophageal Adenocarcinoma. Transl Oncol 2018; 11:426-435. [PMID: 29475139 PMCID: PMC5884213 DOI: 10.1016/j.tranon.2018.01.022] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Revised: 01/18/2018] [Accepted: 01/18/2018] [Indexed: 12/18/2022] Open
Abstract
Esophageal adenocarcinoma (EAC) is the fastest growing cancer in the western world and the overall 5 year survival rate of EAC is below 20%. Most patients with EAC present with locally advanced or widespread metastatic disease, where current treatment is largely ineffective. Therefore, new therapeutic approaches are urgently needed. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a novel albumin-stabilized, cremophor-free and water soluble nanoparticle formulation of paclitaxel, and the potential role of nab-paclitaxel has not been tested yet in experimental EAC. Here we tested the antiproliferative and antitumor efficacy with survival advantage of nab-paclitaxel as monotherapy and in combinations in in-vitro, and in murine subcutaneous xenograft and peritoneal metastatic survival models of human EAC. Nab-paclitaxel significantly inhibited in-vitro cell proliferation with higher in-vivo antitumour efficacy and survival benefit compared to paclitaxel or carboplatin treatments both in mono- and combination therapies. Nab-paclitaxel treatment increased expression of mitotic-spindle associated phospho-stathmin, decreased expression of proliferative markers and enhanced apoptosis. This study demonstrates that nab-paclitaxel had stronger antiproliferative and antitumor activity in experimental EAC than the current standard chemotherapeutic agents which supports the rationale for its clinical use in EAC.
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31
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Song L, Wang X, Feng Z. Overexpression of FOXM1 as a target for malignant progression of esophageal squamous cell carcinoma. Oncol Lett 2018; 15:5910-5914. [PMID: 29552222 DOI: 10.3892/ol.2018.8035] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2015] [Accepted: 05/08/2017] [Indexed: 11/05/2022] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is one of the most common types of malignancies globally. Forkhead box M1 (FOXM1) has important functions in cancer progression. However, the function of FOXM1 signaling in ESCC remains unknown. The aim of the present study was to evaluate the expression level and function of FOXM1 in human ESCC. The present study first detected the FOXM1 expression level in 78 cases of primary ESCC tissues and matched normal tissue samples by immunohistochemistry, western blot analysis and reverse transcription-quantitative polymerase chain reaction. Subsequently, the present study investigated the impact of FOXM1 knockdown on the ability of cell proliferation and migration of ESCC cells by MTT, clonogenic and Transwell assays. The results revealed that the mRNA and protein expression levels of FOXM1 were upregulated in a series of ESCC tissue samples. Silencing of FOXM1 inhibited the proliferation and migration of ESCC cells. In conclusion, FOXM1 was significantly increased in cancerous tissue samples of patients with ESCC. It may serve as a selective target for the treatment of ESCC.
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Affiliation(s)
- Liang Song
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
| | - Xiaohang Wang
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
| | - Zhen Feng
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
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32
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Gastroesophageal Reflux Frequency, Severity, Age of Onset, Family History and Acid Suppressive Therapy Predict Barrett Esophagus in a Large Population. J Clin Gastroenterol 2018; 52:873-879. [PMID: 29356784 PMCID: PMC6053338 DOI: 10.1097/mcg.0000000000000983] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
GOALS To identify risk factors associated with Barrett esophagus (BE) for potential improved surveillance and risk reduction. BACKGROUND Gastroesophageal reflux disease (GERD) is a known risk factor for esophageal adenocarcinoma, but the ability of GERD symptom frequency and severity to predict presence of its putative precursor lesion, BE, is less well-defined in large, community-based populations. STUDY We conducted a case-control study within the Kaiser Permanente Northern California population. Cases had new diagnoses of BE. To identify risk factors in the general population, we contrasted cases with population controls; to identify risk factors only among patients with GERD, we contrasted cases with GERD patients who lacked BE. RESULTS We interviewed 953 patients; 320 patients with BE, 316 patients with GERD who lacked BE and 317 population controls. Compared with population controls, BE risk was highest among patients with the most frequent and severe GERD symptoms [odds ratio (OR), 27.00; 95% confidence interval (CI), 14.52-50.21], nocturnal symptoms (OR, 5.40; 95% CI, 3.81-7.72), and family history of GERD (OR, 2.55; 95% CI, 1.80-3.62) or BE (OR, 10.08; 95% CI, 2.83-35.84). Although at least weekly proton pump inhibitor (PPI) use was a risk factor for BE (OR, 9.85; 95% CI, 6.54-14.84), among PPI users in the general population, GERD symptoms were not strongly associated with the risk of BE. Compared with GERD controls, cases were more likely to have onset of GERD symptoms before 30 years of age (OR, 1.93; 95% CI, 1.15-3.22) and a family history of BE (OR, 3.64; 95% CI, 1.50-8.83). CONCLUSIONS Severe and frequent GERD symptoms are strongly associated with increased risk of BE in the general population, especially in the absence of frequent PPI use. Among people with GERD, family history of BE and early age of symptom onset were stronger predictors of BE. These findings may improve identification of patients at highest risk for BE.
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33
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The effect of celecoxib on DNA methylation of CDH13, TFPI2, and FSTL1 in squamous cell carcinoma of the esophagus in vivo. Anticancer Drugs 2017; 27:848-53. [PMID: 27400374 DOI: 10.1097/cad.0000000000000396] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
This study examined the in-vivo effect of the NSAID celecoxib on DNA methylation in the promoter region of the tumor-suppressor genes cadherin 13, tissue factor pathway inhibitor 12, and follistatin-like protein 1, and on apoptosis, in esophageal squamous cell carcinoma (ESCC). Forty-five patients who underwent an esophagectomy for ESCC were allocated to either a treatment group (n=22) or a control group (n=23). Patients in the treatment group were administered 800 mg/day of celecoxib for 14 days before surgery. Patients in the control group did not take any type of NSAID. Biopsies of the tumor were collected before surgery and tissue from the resection specimens after surgery. Methylation-specific PCR was used to measure DNA methylation and apoptosis was measured by flow cytometry. There was no difference in the proportion of patients with methylation for each of the genes between the patient groups before treatment. In those patients with pretreatment methylation, there was a significant reduction in the proportion with methylation and a significant increase in the corresponding messenger RNA expression after treatment with celecoxib. In those tissues in which there was a reduction in methylation following celecoxib treatment, there was a significant increase in the percentage of apoptotic cells, but not in the tissues with no change in methylation. In ESCC, in-vivo treatment with celecoxib is associated with a reduction in DNA methylation and increase in messenger RNA expression of tumor-suppressor genes, and increases in apoptosis.
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34
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CCN1 sensitizes esophageal cancer cells to TRAIL-mediated apoptosis. Exp Cell Res 2017; 361:163-169. [PMID: 29055676 DOI: 10.1016/j.yexcr.2017.10.015] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Revised: 10/11/2017] [Accepted: 10/17/2017] [Indexed: 12/20/2022]
Abstract
TRAIL is one of the best anti-cancer molecules in our body. It kills a variety of cancer cells that are resistant to conventional chemotherapy, without causing much negative impact on normal cells, because its death receptors are almost exclusively found on cancer cells. However, some cancer cells are not sensitive to TRAIL treatment, even though they express its death receptors. A second molecule is needed to help TRAIL to complete its mission. Finding such molecules now becomes a top priority in cancer research. Our study shows that CCN1 is such a molecule. CCN1 was highly expressed in the esophageal epithelium of the patients suffering from gastroesophageal reflux disease, but faded away as the situation worsened towards adenocarcinoma. Treating the tumor cells with CCN1 resulted in apoptosis, while the same treatment to the normal cells only nourished cell growth. It was TRAIL that mediated this process. Apparently, CCN1 altered the expression profile of TRAIL and its receptors in tumor cells, namely, activating TRAIL and its death receptors and shutting down its decoy receptors. CCN1 and TRAIL worked as a team to put the cancer cells to death, as elimination of either one failed apoptosis.
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35
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Saba NF. Refining the predictors of outcome in patients with resectable esophageal cancer. Cancer 2017; 123:4097-4098. [PMID: 28885686 DOI: 10.1002/cncr.30952] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Accepted: 07/09/2017] [Indexed: 01/07/2023]
Affiliation(s)
- Nabil F. Saba
- Department of Hematology and Medical Oncology; Winship Cancer Institute, Emory University; Atlanta Georgia
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36
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Wang W, He X, Zheng Z, Ma X, Hu X, Wu D, Wang M. Serum HOTAIR as a novel diagnostic biomarker for esophageal squamous cell carcinoma. Mol Cancer 2017; 16:75. [PMID: 28376832 PMCID: PMC5379707 DOI: 10.1186/s12943-017-0643-6] [Citation(s) in RCA: 96] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Accepted: 03/27/2017] [Indexed: 12/31/2022] Open
Abstract
Background Early diagnosis of esophageal squamous cell carcinoma (ESCC) is an important issue to improve the prognosis. HOX transcript antisense RNA (HOTAIR), a long noncoding RNA (lncRNA) expressed from the HOXC locus, has been recently revealed as an oncogenic regulator in ESCC. This study aimed to investigate whether serum HOTAIR is involved in the diagnosis of ESCC. Methods In this study, we detected serum HOTAIR expression in 50 patients with ESCC (including 42 tumor resection and 8 without surgery) and 20 healthy volunteers to investigate the role of serum HOTAIR in ESCC using the quantitative real-time polymerase chain reaction (qRT-PCR) method. Results Clinical data indicated that serum HOTAIR were correlated with TNM stage. The expression level of serum HOTAIR (0.189 ± 0.010) was significantly higher in ESCC patients compared with that of healthy controls (0.055 ± 0.008, P < 0.01). The ROC curve analysis yielded an area under the ROC curve (AUC) value of 0.793 (95% CI: 0.692 to 0.895, P < 0.01). Also, the serum HOTAIR expression level decreased obviously in postoperative samples (one month after the surgery) compared to preoperative specimens. Moreover, there was a significant correlation between serum HOTAIR expression and the expression of HOTAIR in ESCC tissue according to Pearson correlation analysis. Conclusions Our study, for the first time, demonstrated that serum HOTAIR might serve as a potential biomarker for the diagnosis of ESCC.
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Affiliation(s)
- Wenjian Wang
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Thoracic surgery, Sun yat-sen memorial hospital, Sun yat-sen University, NO.107 of Yanjiangxi Road, Guangzhou, 510120, China
| | - Xiaotian He
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Thoracic surgery, Sun yat-sen memorial hospital, Sun yat-sen University, NO.107 of Yanjiangxi Road, Guangzhou, 510120, China
| | - Zehua Zheng
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Thoracic surgery, Sun yat-sen memorial hospital, Sun yat-sen University, NO.107 of Yanjiangxi Road, Guangzhou, 510120, China
| | - Xiaofan Ma
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Thoracic surgery, Sun yat-sen memorial hospital, Sun yat-sen University, NO.107 of Yanjiangxi Road, Guangzhou, 510120, China
| | - Xueting Hu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Thoracic surgery, Sun yat-sen memorial hospital, Sun yat-sen University, NO.107 of Yanjiangxi Road, Guangzhou, 510120, China
| | - Duoguang Wu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Thoracic surgery, Sun yat-sen memorial hospital, Sun yat-sen University, NO.107 of Yanjiangxi Road, Guangzhou, 510120, China.
| | - Minghui Wang
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Thoracic surgery, Sun yat-sen memorial hospital, Sun yat-sen University, NO.107 of Yanjiangxi Road, Guangzhou, 510120, China.
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37
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Ma J, Wu K, Zhao Z, Miao R, Xu Z. Special AT-rich sequence binding protein 1 promotes tumor growth and metastasis of esophageal squamous cell carcinoma. Tumour Biol 2017; 39:1010428317694537. [PMID: 28345457 DOI: 10.1177/1010428317694537] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Esophageal squamous cell carcinoma is one of the most aggressive malignancies worldwide. Special AT-rich sequence binding protein 1 is a nuclear matrix attachment region binding protein which participates in higher order chromatin organization and tissue-specific gene expression. However, the role of special AT-rich sequence binding protein 1 in esophageal squamous cell carcinoma remains unknown. In this study, western blot and quantitative real-time polymerase chain reaction analysis were performed to identify differentially expressed special AT-rich sequence binding protein 1 in a series of esophageal squamous cell carcinoma tissue samples. The effects of special AT-rich sequence binding protein 1 silencing by two short-hairpin RNAs on cell proliferation, migration, and invasion were assessed by the CCK-8 assay and transwell assays in esophageal squamous cell carcinoma in vitro. Special AT-rich sequence binding protein 1 was significantly upregulated in esophageal squamous cell carcinoma tissue samples and cell lines. Silencing of special AT-rich sequence binding protein 1 inhibited the proliferation of KYSE450 and EC9706 cells which have a relatively high level of special AT-rich sequence binding protein 1, and the ability of migration and invasion of KYSE450 and EC9706 cells was distinctly suppressed. Special AT-rich sequence binding protein 1 could be a potential target for the treatment of esophageal squamous cell carcinoma and inhibition of special AT-rich sequence binding protein 1 may provide a new strategy for the prevention of esophageal squamous cell carcinoma invasion and metastasis.
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Affiliation(s)
- Jun Ma
- Department of Thoracic Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China
| | - Kaiming Wu
- Department of Colorectal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China
| | - Zhenxian Zhao
- Department of Pancreato-Biliary Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China
| | - Rong Miao
- Operation Centre, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China
| | - Zhe Xu
- Division of Cardiac Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China
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A novel intraperitoneal metastatic xenograft mouse model for survival outcome assessment of esophageal adenocarcinoma. PLoS One 2017; 12:e0171824. [PMID: 28225784 PMCID: PMC5321464 DOI: 10.1371/journal.pone.0171824] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Accepted: 01/26/2017] [Indexed: 01/15/2023] Open
Abstract
Esophageal adenocarcinoma (EAC) has become the dominant type of esophageal cancer in United States. The 5-year survival rate of EAC is below 20% and most patients present with locally advanced or widespread metastatic disease, where current treatment is largely ineffective. Therefore, new therapeutic approaches are urgently needed. Improvement of EAC patient outcome requires well-characterized animal models in which to evaluate novel therapeutics. In this study we aimed to establish a peritoneal dissemination xenograft mouse model of EAC that would support survival outcome analyses. To find the best candidate cell line from 7 human EAC cell lines of different origin named ESO26, OE33, ESO51, SK-GT-2, OE19, OACM5.1C and Flo-1 were injected intraperitoneally/subcutaneously into SCID mice. The peritoneal/xenograft tumor formation and mouse survival were compared among different groups. All cell lines injected subcutaneously formed tumors within 3 months at variable rates. All cell lines except OACM5.1C formed intraperitoneal tumors within 3 months at variable rates. Median animal survival with peritoneal dissemination was 108 days for ESO26 cells (5X106), 65 days for OE33 cells (5X106), 88 days for ESO51 cells (5X106), 76 days for SK-GT-2 cells (5X106), 55 days for OE19 cells (5X106), 45 days for OE19 cells (10X106) and 82 days for Flo-1 cells (5X106). Interestingly, only in the OE19 model all mice (7/7 for 5X106 and 5/5 for10X106) developed bloody ascites with liver metastasis after intraperitoneal injection. The median survival time of these animals was the shortest (45 days for 10X106 cells). In addition, median survival was significantly increased after paclitaxel treatment compared with the control group (57 days versus 45 days, p = 0.0034) along with a significant decrease of the relative subcutaneous tumor volume (p = 0.00011). Thus peritoneal dissemination mouse xenograft model for survival outcome assessment after intraperitoneal injection of OE19 cells will be very useful for the evaluation of cancer therapeutics.
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Palethorpe HM, Drew PA, Smith E. Androgen Signaling in Esophageal Adenocarcinoma Cell Lines In Vitro. Dig Dis Sci 2017; 62:3402-3414. [PMID: 29052817 PMCID: PMC5694516 DOI: 10.1007/s10620-017-4794-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Accepted: 10/06/2017] [Indexed: 01/11/2023]
Abstract
BACKGROUND We showed previously that nuclear localization of the androgen receptor (AR) and expression of the androgen-responsive gene FK506-binding protein 5 (FKBP5) in esophageal adenocarcinoma (EAC) tissues were associated with decreased patient survival, suggesting a role for androgens in this cancer. AIM To investigate the effect of the AR ligand 5α-dihydrotestosterone (DHT) on AR-expressing EAC cell lines in vitro. METHODS AND RESULTS In tissue resection specimens from EAC patients, FKBP5 expression was positively associated with proliferation as measured by Ki-67 expression. We stably transduced AR into three AR-negative EAC cell lines, OE33, JH-EsoAd1, and OE19, to investigate androgen signaling in vitro. In the AR-expressing cell lines, 10 nM DHT, the concentration typically used to study AR signaling, induced changes in the expression of androgen-responsive genes and inhibited proliferation by inducing cell cycle arrest and senescence. At lower DHT concentrations near the half maximal inhibitory concentration (IC50), the AR-expressing cell lines proliferated and there were changes in the expression of androgen-responsive genes. In direct co-culture with cancer-associated fibroblast-like PShTert myofibroblasts, 10 nM DHT induced changes in the expression of androgen-responsive genes but did not inhibit proliferation. CONCLUSIONS This is the first study to show that EAC cell lines respond to androgen in vitro. Proliferation together with the expression of androgen-responsive genes was dependent on the concentration of DHT, or the presence of a permissive microenvironment, consistent with observations in the tissues. These findings are consistent with a role for androgen signaling in EAC.
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Affiliation(s)
- Helen M. Palethorpe
- 0000 0004 1936 7304grid.1010.0Solid Cancer Regulation Group, Discipline of Surgery, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, The University of Adelaide, 28 Woodville Rd, Woodville South, SA 5011 Australia
| | - Paul A. Drew
- 0000 0004 1936 7304grid.1010.0Solid Cancer Regulation Group, Discipline of Surgery, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, The University of Adelaide, 28 Woodville Rd, Woodville South, SA 5011 Australia ,0000 0004 0367 2697grid.1014.4School of Nursing and Midwifery, Flinders University, PO Box 2100, Adelaide, SA 5001 Australia
| | - Eric Smith
- 0000 0004 1936 7304grid.1010.0Solid Cancer Regulation Group, Discipline of Surgery, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, The University of Adelaide, 28 Woodville Rd, Woodville South, SA 5011 Australia ,0000 0004 0486 659Xgrid.278859.9Department of Medical Oncology, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, 28 Woodville Rd, Woodville South, SA 5011 Australia
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Frenkel C, Telem DA, Pryor AD, Altieri MS, Shroyer KR, Regenbogen E. The effect of sleeve gastrectomy on extraesophageal reflux disease. Surg Obes Relat Dis 2016; 12:1263-1269. [DOI: 10.1016/j.soard.2015.11.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2015] [Revised: 11/01/2015] [Accepted: 11/02/2015] [Indexed: 02/08/2023]
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Moro K, Nagahashi M, Ramanathan R, Takabe K, Wakai T. Resolvins and omega three polyunsaturated fatty acids: Clinical implications in inflammatory diseases and cancer. World J Clin Cases 2016; 4:155-164. [PMID: 27458590 PMCID: PMC4945585 DOI: 10.12998/wjcc.v4.i7.155] [Citation(s) in RCA: 72] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2016] [Revised: 03/14/2016] [Accepted: 04/06/2016] [Indexed: 02/06/2023] Open
Abstract
Inflammation is a central process in several disorders and contributes to cancer progression. Inflammation involves a complex cascade of pro-inflammatory and anti-inflammatory signaling events with protein and lipid mediators. Recent advances in lipid detection have revealed the importance of lipid mediators in inflammation. Omega three polyunsaturated fatty acids (ω-3 PUFA) are found naturally in fish oil and have been extensively studied in multiple inflammatory diseases with improved outcomes. Resolvins are thought to be the active metabolites of ω-3 PUFA, and are responsible for facilitating the resolving phase of acute inflammation. Clinically, resolvins have been associated with resolution of acute kidney injury and acute lung injury, micro and macro vascular response to injury, and inhibition of microglia-activated inflammation in neurodegenerative disorders. In addition to inflammatory diseases, ω-3 PUFA and resolvins appear to modulate cancer progression. ω-3 PUFA intake has been associated with reduced inflammation in colorectal cancer, and favorable phenotype in breast cancer. Resolvins offer promising therapeutic potential as they may modulate inflammation with minimal side-effects, in contrast to currently available anti-inflammatory medications. This review describes the roles of ω-3 PUFA and resolvins in the inflammatory cascade, various inflammatory diseases, and specific cancers. Additionally, it will discuss the clinical therapeutic potential of resolvins as targets in inflammatory diseases and cancers.
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Short-term outcomes and one surgeon’s learning curve for thoracoscopic esophagectomy performed with the patient in the prone position. Surg Today 2016; 47:313-319. [DOI: 10.1007/s00595-016-1378-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2016] [Accepted: 06/06/2016] [Indexed: 12/13/2022]
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Li SP, Su HX, Zhao D, Guan QL. Plasma miRNA-506 as a Prognostic Biomarker for Esophageal Squamous Cell Carcinoma. Med Sci Monit 2016; 22:2195-201. [PMID: 27345473 PMCID: PMC4927144 DOI: 10.12659/msm.899377] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Background MicroRNAs (miRNAs) are responsible for regulating proliferation, differentiation, apoptosis, invasion, and metastasis in tumor cells. miRNA-506 is abnormally expressed in multiple tumors, indicating that it might be oncogenic or tumor-suppressive. However, little is known about the association between miRNA-506 expression and esophageal squamous cell carcinoma (ESCC). Material/Methods We examined the expression of miRNA-506 in the plasma of ESCC patients using quantitative real-time polymerase chain reaction (qRT-PCR) to determine the association between miRNA-506 expression and clinicopathological features of ESCC. ROC curves were produced for ESCC diagnosis by plasma miRNA-506 and the area under curve was calculated to explore its diagnostic value. Results Average miRNA-506 expression levels were remarkably higher in the plasma of ESCC patients than in healthy volunteers (P<0.001). The expression of miRNA-506 in the plasma was closely associated with lymph node status (P=0.004), TNM stage (P=0.031), and tumor length (P<0.001). According to ROC curves, the area under the curve for plasma miRNA-506 was 0.835, indicating statistical significance for ESCC diagnosis by plasma miRNA-506 (P<0.001). Kaplan-Meier analysis showed that patients with high miRNA-506 expression had significantly shorter survival time than those with low miRNA-506 expression. Cox regression analysis demonstrated that T stage, N stage, tumor length, and miRNA-506 expression levels were significantly correlated with prognosis in ESCC patients. Conclusions miRNA-506 can serve as an important molecular marker for diagnosis and prognostic prediction of ESCC.
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Affiliation(s)
- Shu-Ping Li
- Department of Radiation Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China (mainland)
| | - Hong-Xin Su
- Department of Radiation Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China (mainland)
| | - Da Zhao
- Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China (mainland)
| | - Quan-Lin Guan
- Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China (mainland)
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Boldrin E, Rumiato E, Fassan M, Rugge M, Cagol M, Marino D, Chiarion-Sileni V, Ruol A, Gusella M, Pasini F, Amadori A, Saggioro D. Genetic risk of subsequent esophageal cancer in lymphoma and breast cancer long-term survival patients: a pilot study. THE PHARMACOGENOMICS JOURNAL 2016; 16:266-271. [PMID: 26054330 DOI: 10.1038/tpj.2015.41] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Revised: 04/22/2015] [Accepted: 04/28/2015] [Indexed: 02/06/2023]
Abstract
The occurrence of a second primary esophageal carcinoma (EC) in long-term cancer survivors may represent a late effect of previous radio-chemotherapeutic treatment. To identify the genetic factors that could increase this risk, we analyzed nine variants within ERCC1, XPD, XRCC1 and XRCC3 DNA repair pathway genes, and GSTP1, TP53 and MDM2 genes in 61 patients who received radio-chemotherapy for a prior lymphoma or breast cancer; 29 of them had a second primary EC. This cohort consists of 22 esophageal squamous cell carcinoma (ESCC) and 7 esophageal adenocarcinoma (EADC) patients. A validation cohort of 154 patients with sporadic EC was also included. The XPD Asp312Asn (rs1799793) was found to be associated with the risk of developing second primary ESCC (P=0.015). The resultant variant was also involved in the onset of sporadic ESCC (P=0.0018). To know in advance who among long-term cancer survivors have an increased risk of EC could lead to a more appropriate follow-up strategy.
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Affiliation(s)
- E Boldrin
- Immunology and Molecular Oncology, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy
| | - E Rumiato
- Immunology and Molecular Oncology, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy
| | - M Fassan
- Department of Medicine, Surgical Pathology and Cytopathology, University of Padova, Padova, Italy
| | - M Rugge
- Department of Medicine, Surgical Pathology and Cytopathology, University of Padova, Padova, Italy
| | - M Cagol
- Oncological Surgery, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy
| | - D Marino
- Medical Oncology, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy
| | - V Chiarion-Sileni
- Medical Oncology, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy
| | - A Ruol
- Department of Surgical Sciences, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - M Gusella
- Department of Oncology, ULSS 18-Rovigo, S. Maria della Misericordia Hospital, Rovigo General Hospital, Rovigo, Italy
| | - F Pasini
- Department of Oncology, ULSS 18-Rovigo, S. Maria della Misericordia Hospital, Rovigo General Hospital, Rovigo, Italy
| | - A Amadori
- Immunology and Molecular Oncology, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy
- Department of Surgical Sciences, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - D Saggioro
- Immunology and Molecular Oncology, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy
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Hu P, Song W, Shan Y, Du M, Huang M, Song C, Zhang L. Lactobacillus paracasei subsp. paracasei M5L induces cell cycle arrest and calreticulin translocation via the generation of reactive oxygen species in HT-29 cell apoptosis. Food Funct 2016; 6:2257-65. [PMID: 26068306 DOI: 10.1039/c5fo00248f] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Lactobacillus paracasei subsp. paracasei M5L (L. paracasei M5L) was isolated and co-cultured with HT-29 colon cancer cells to study its anti-colorectal cancer effects and mechanism. Using the MTT assay we found that L. paracasei M5L significantly inhibits HT-29 cell proliferation. Morphological and biochemical characteristics of apoptosis were observed and confirmed by hematoxylin and eosin (HE) staining and transmission electron microscopy (TEM). Lactobacilli could change the cell cycle distribution and induce calreticulin (CRT) translocation from the endoplasmic reticulum to the surface of the cytomembrane. We also determine that vast reactive oxygen species (ROS) were generated, while the activities of superoxide dismutase (SOD) and catalase (CAT) were noticeably diminished following L. paracasei M5L treatment. This study reveals that L. paracasei M5L induces apoptosis in HT-29 cells through ROS generation followed by CRT accompanied endoplasmic reticulum (ER) stress and S phase arrest. These results provide new insights into the possible molecular mechanism of L. paracasei M5L as a novel probiotic with the potential for further application.
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Affiliation(s)
- Panpan Hu
- Department of Food Science and Engineering, Harbin Institute of Technology, 73# Huanghe road, Nangang District, Harbin, 150090, China.
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Oshikiri T, Yasuda T, Kawasaki K, Harada H, Oyama M, Hasegawa H, Ohara T, Sendo H, Nakamura T, Fujino Y, Tominaga M, Kakeji Y. Hand-assisted laparoscopic surgery (HALS) is associated with less-restrictive ventilatory impairment and less risk for pulmonary complication than open laparotomy in thoracoscopic esophagectomy. Surgery 2016; 159:459-466. [PMID: 26361833 DOI: 10.1016/j.surg.2015.07.026] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2015] [Revised: 06/17/2015] [Accepted: 07/18/2015] [Indexed: 11/29/2022]
Abstract
BACKGROUND Esophagectomy with extended lymphadenectomy improves prognosis but it is associated with high morbidity and mortality. The thoracoscopic approach is associated with fewer pulmonary complications. Abdominal wall injury greatly affects pulmonary function and complication rates during the acute postoperative phase. In this study we aimed to compare the incidence of pulmonary complications and respiratory recovery after thoracoscopic esophagectomy in the prone position with hand-assisted laparoscopic surgery (HALS) versus open laparotomy (OL). METHODS This was a case-matched control study of patients with esophageal cancer who underwent thoracoscopic esophagectomy in the prone position. Thirty-two patients in the HALS group and 32 patients in the OL group were selected by the use of propensity score matching. Operative outcomes and perioperative changes in respiratory function were compared. RESULTS There was no operative mortality in either group. Estimated blood loss was less in the HALS group (P < .001). The incidence of postoperative pneumonia was 6.2% (4/64) overall; it was less in the HALS group (0%) than in the OL group (12.5%) (P = .016). There were no differences in preoperative vital capacity (VC) and percent predicted vital capacity (%VC). Each parameter, including the ratio of the postoperative to preoperative %VC (%VC ratio), reached its nadir on postoperative day 7 in both groups but was greater in the HALS group (VC, 2.91 ± 0.68 L vs 2.53 ± 0.53 L, P = .018; %VC, 90.62 ± 16.92% vs 78.91 ± 16.65%, P = .007; %VC ratio, 80.90 ± 9.87% vs 72.09 ± 11.95%, P = .002). At 1 and 3 months, respiratory recovery was seen in both groups but more so in the HALS group. At 6 months, further respiratory recovery was seen in both groups, without any significant intergroup differences. CONCLUSION During the acute phase after thoracoscopic esophagectomy in the prone position, HALS is associated with less-restrictive ventilatory impairment, fewer subsequent pulmonary complications, and less blood loss than OL. The combination of HALS and thoracoscopic esophagectomy in the prone position is less invasive on respiratory function.
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Affiliation(s)
- Taro Oshikiri
- Department of Gastroenterological Surgery, Hyogo Cancer Center, Hyogo, Japan.
| | - Takashi Yasuda
- Department of Gastroenterological Surgery, Hyogo Cancer Center, Hyogo, Japan
| | - Kentaro Kawasaki
- Department of Gastroenterological Surgery, Hyogo Cancer Center, Hyogo, Japan; Division of Surgery, Kobe Rosai Hospital, Hyogo, Japan
| | - Hitoshi Harada
- Department of Gastroenterological Surgery, Hyogo Cancer Center, Hyogo, Japan
| | - Masato Oyama
- Department of Gastroenterological Surgery, Hyogo Cancer Center, Hyogo, Japan
| | - Hiroshi Hasegawa
- Department of Gastroenterological Surgery, Hyogo Cancer Center, Hyogo, Japan
| | - Tadayuki Ohara
- Department of Gastroenterological Surgery, Hyogo Cancer Center, Hyogo, Japan
| | - Hiroyoshi Sendo
- Department of Gastroenterological Surgery, Hyogo Cancer Center, Hyogo, Japan
| | - Tetsu Nakamura
- Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan
| | - Yasuhiro Fujino
- Department of Gastroenterological Surgery, Hyogo Cancer Center, Hyogo, Japan
| | - Masahiro Tominaga
- Department of Gastroenterological Surgery, Hyogo Cancer Center, Hyogo, Japan
| | - Yoshihiro Kakeji
- Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan
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Zhu X, Zhang Y, Li Q, Yang L, Zhang N, Ma S, Zhang K, Song J, Guan F. β-Carotene Induces Apoptosis in Human Esophageal Squamous Cell Carcinoma Cell Lines via the Cav-1/AKT/NF-κB Signaling Pathway. J Biochem Mol Toxicol 2016; 30:148-57. [PMID: 26733226 DOI: 10.1002/jbt.21773] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2015] [Revised: 09/21/2015] [Accepted: 09/27/2015] [Indexed: 12/24/2022]
Abstract
β-carotene, a type of terpenoid, has many metabolic and physiological functions. In particular, β-carotene has an antitumor effect. However, the efficacy of β-carotene against esophageal squamous cell carcinoma (ESCC) remains unclear. In our study, β-carotene inhibited the growth of ESCC cells and downregulated expression of the Caveolin-1 (Cav-1) protein. Cav-1 protein was expressed only in ESCC cells, not in Het-1A cells. Moreover, β-carotene triggered apoptosis, induced cell cycle G0⁄G1 phase arrest, and inhibited cell migration. To explore the mechanism involved in these processes, we further examined the effect of β-carotene on the Cav-1-mediated AKT/NF-κB pathway. The results showed that the level of AKT and NF-κB phosphorylation was dramatically inhibited, which led to an increase in the Bax/Bcl-2 ratio. Correspondingly, the activity of Caspase-3 was also enhanced. These data suggest that β-carotene has an antiproliferative role in ESCC cells and may be a promising chemotherapeutic agent for use against ESCC cells.
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Affiliation(s)
- Xiangzhan Zhu
- School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, People's Republic of China.
| | - Yanting Zhang
- School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, People's Republic of China
| | - Qinghua Li
- School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, People's Republic of China
| | - Lu Yang
- School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, People's Republic of China
| | - Nannan Zhang
- School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, People's Republic of China.,The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, People's Republic of China
| | - Shanshan Ma
- School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, People's Republic of China
| | - Kun Zhang
- School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, People's Republic of China
| | - Jishi Song
- School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, People's Republic of China
| | - Fangxia Guan
- School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, People's Republic of China.,The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, People's Republic of China
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Yi J, Wang Z, Bai H, Li L, Zhao H, Cheng C, Zhang H, Li J. Polyphenols from pinecones of Pinus koraiensis induce apoptosis in colon cancer cells through the activation of caspase in vitro. RSC Adv 2016. [DOI: 10.1039/c5ra24913a] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The present study reports the antitumor effects of PPP-40 (the purified polyphenols from P. koraiensis pinecones by 40% ethanol) on LOVO cells and revealed its antitumor mechanism, which involved the apoptosis of cells associated with the activation of the caspase pathway.
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Affiliation(s)
- Juanjuan Yi
- School of Chemical Engineering
- Harbin Institute of Technology
- Harbin 150090
- PR China
| | - Zhenyu Wang
- School of Chemical Engineering
- Harbin Institute of Technology
- Harbin 150090
- PR China
| | - Haina Bai
- School of Chemical Engineering
- Harbin Institute of Technology
- Harbin 150090
- PR China
| | - Lu Li
- Northeast Agricultural University
- Harbin 150030
- PR China
| | - Haitian Zhao
- School of Chemical Engineering
- Harbin Institute of Technology
- Harbin 150090
- PR China
| | - Cuilin Cheng
- School of Chemical Engineering
- Harbin Institute of Technology
- Harbin 150090
- PR China
| | - Hua Zhang
- School of Chemical Engineering
- Harbin Institute of Technology
- Harbin 150090
- PR China
| | - Jingtong Li
- School of Chemical Engineering
- Harbin Institute of Technology
- Harbin 150090
- PR China
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49
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Mutiga SK, Hoffmann V, Harvey JW, Milgroom MG, Nelson RJ. Assessment of Aflatoxin and Fumonisin Contamination of Maize in Western Kenya. PHYTOPATHOLOGY 2015; 105:1250-1261. [PMID: 25894319 DOI: 10.1094/phyto-10-14-0269-r] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
We conducted a survey of aflatoxin and fumonisin in maize in western Kenya. In a regional survey of aflatoxin conducted in 2009 across three agroecological zones within three administrative regions, milled maize samples were collected from 985 patrons of 26 hammer mills. Aflatoxin contamination was detected in 49% of samples and was above the regulatory (10 ppb) in 15% of the samples overall; 65% of samples from a drought-prone area were over the limit. In a detailed survey in Bungoma County, we investigated aflatoxin and fumonisin contamination in four popular maize varieties at harvest and after 2 and 4 months of storage. We collected whole-grain samples from farmers' storage sheds and milled samples from patrons of local mills. Mean aflatoxin contamination was identical for storage sheds and mills at 2.3 ppb. In all, 41% of the samples from mills had detectable aflatoxin, with 4% over the regulatory limit, whereas 87% had detectable fumonisin, with 50% over the regulatory limit (1 ppm). Mean contamination levels did not change during storage. Maize varieties differed in fumonisin contamination, with the most popular varieties vulnerable to both mycotoxins and weevils, which are potential factors in exacerbating mycotoxin contamination. Mycotoxin surveillance is important not just in areas known previously for aflatoxin contamination and acute poisoning but also is needed in all maize-producing regions.
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Affiliation(s)
- S K Mutiga
- First, fourth, and fifth authors: School of Integrative Plant Science, Section of Plant Pathology and Plant-Microbe Biology, Cornell University, Ithaca, NY 14853; second author: International Food Policy Research Institute, 2033 K Street NW, Washington DC 20006; and third author: Biosciences Eastern and Central Africa-International Livestock Research Institute (BecA-ILRI) Hub, P.O. Box 30709, Nairobi 00100, Kenya
| | - V Hoffmann
- First, fourth, and fifth authors: School of Integrative Plant Science, Section of Plant Pathology and Plant-Microbe Biology, Cornell University, Ithaca, NY 14853; second author: International Food Policy Research Institute, 2033 K Street NW, Washington DC 20006; and third author: Biosciences Eastern and Central Africa-International Livestock Research Institute (BecA-ILRI) Hub, P.O. Box 30709, Nairobi 00100, Kenya
| | - J W Harvey
- First, fourth, and fifth authors: School of Integrative Plant Science, Section of Plant Pathology and Plant-Microbe Biology, Cornell University, Ithaca, NY 14853; second author: International Food Policy Research Institute, 2033 K Street NW, Washington DC 20006; and third author: Biosciences Eastern and Central Africa-International Livestock Research Institute (BecA-ILRI) Hub, P.O. Box 30709, Nairobi 00100, Kenya
| | - M G Milgroom
- First, fourth, and fifth authors: School of Integrative Plant Science, Section of Plant Pathology and Plant-Microbe Biology, Cornell University, Ithaca, NY 14853; second author: International Food Policy Research Institute, 2033 K Street NW, Washington DC 20006; and third author: Biosciences Eastern and Central Africa-International Livestock Research Institute (BecA-ILRI) Hub, P.O. Box 30709, Nairobi 00100, Kenya
| | - R J Nelson
- First, fourth, and fifth authors: School of Integrative Plant Science, Section of Plant Pathology and Plant-Microbe Biology, Cornell University, Ithaca, NY 14853; second author: International Food Policy Research Institute, 2033 K Street NW, Washington DC 20006; and third author: Biosciences Eastern and Central Africa-International Livestock Research Institute (BecA-ILRI) Hub, P.O. Box 30709, Nairobi 00100, Kenya
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Oshikiri T, Yasuda T, Harada H, Goto H, Oyama M, Hasegawa H, Ohara T, Sendo H, Nakamura T, Fujino Y, Tominaga M, Kakeji Y. A new method (the "Bascule method") for lymphadenectomy along the left recurrent laryngeal nerve during prone esophagectomy for esophageal cancer. Surg Endosc 2015; 29:2442-2450. [PMID: 25303923 DOI: 10.1007/s00464-014-3919-6] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2014] [Accepted: 09/22/2014] [Indexed: 12/18/2022]
Abstract
BACKGROUND In esophageal cancer, lymph nodes along the recurrent laryngeal nerves (RLNs) are thought to be highly involved. Complete dissection of these lymph nodes is recommended but there is limited working space in the left upper mediastinum and advanced dissection skills are required. We present herein a new method for lymphadenectomy along the left RLN, called the Bascule method during prone esophagectomy. METHODS The fundamental concept of this new method is to draw the proximal portion of the divided esophagus and tissue that includes the left RLN and lymph nodes through a gap between the vertebral body and the right scapula. Using this technique, a two-dimensional membrane, similar to the "esophageal mesenteriolum" (lateral pedicle), will be easily recognizable. Identification and reliable cutting of the tracheoesophageal artery and distinguishing the left RLN from the lymph nodes should be easy. This technique was evaluated in 39 consecutive cases of prone esophagectomy for squamous cell cancer. RESULTS There were 18 patients who underwent the new method (Bascule method; Bm) and 21 patients who underwent the conventional method (Cm). The duration of the thoracic procedure and dissection along the left RLN was significantly shorter in Bm group than in Cm group (258 ± 30 vs. 291 ± 39 min; p = 0.007 and 66 ± 9 vs. 75 ± 14 min; p = 0.036, respectively). Estimated blood loss in Bm group was 20 ± 11 g compared to 38 ± 32 g in Cm group (p = 0.028). No intraoperative morbidity related to the left RLN was observed in either group. The hoarseness rate in Bm group was 28 %, which was lower than that in the Cm group (48 %). CONCLUSIONS The Bascule method for lymphadenectomy along the left RLN during prone esophagectomy is technically safe and feasible and reduces operative time and blood loss.
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Affiliation(s)
- Taro Oshikiri
- Department of Gastroenterological Surgery, Hyogo Cancer Center, 13-70, kitaoji-cho, Akashi, Hyogo, 673-8558, Japan,
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