1
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Drabke S, Kaufmann J, Schmidberger H. [Neoadjuvant therapy of locally advanced squamous cell carcinoma of the esophagus : Radiochemotherapy vs. doublet or triplet chemotherapy alone]. Strahlenther Onkol 2024; 200:1100-1102. [PMID: 39402378 DOI: 10.1007/s00066-024-02310-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/23/2024] [Indexed: 11/26/2024]
Affiliation(s)
- Sophia Drabke
- Klinik und Poliklinik für Radioonkologie und Strahlentherapie, Universitätsmedizin Mainz, Langenbeckstraße 1, 55131, Mainz, Deutschland.
- Arbeitsgruppe junge DEGRO der Deutschen Gesellschaft für Radioonkologie e. V. (DEGRO), Berlin, Deutschland.
| | - Justus Kaufmann
- Klinik und Poliklinik für Radioonkologie und Strahlentherapie, Universitätsmedizin Mainz, Langenbeckstraße 1, 55131, Mainz, Deutschland
- Arbeitsgruppe junge DEGRO der Deutschen Gesellschaft für Radioonkologie e. V. (DEGRO), Berlin, Deutschland
| | - Heinz Schmidberger
- Klinik und Poliklinik für Radioonkologie und Strahlentherapie, Universitätsmedizin Mainz, Langenbeckstraße 1, 55131, Mainz, Deutschland
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2
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Huang Y, Guan Y, Zhang X. METTL3-Mediated Maturation of miR-99a-5p Promotes Cell Migration and Invasion in Oral Squamous Cell Carcinoma by Targeting ZBTB7A. Mol Biotechnol 2024; 66:1942-1953. [PMID: 37498409 DOI: 10.1007/s12033-023-00815-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 06/29/2023] [Indexed: 07/28/2023]
Abstract
METTL3 is an important methyltransferase in N(6)-methyladenosine (m6A) modification. Recently, METTL3 mediates methylation of pri-microRNA (miRNA) to accelerate miRNA maturation, regulating tumor development. This study explored whether METTL3 mediated miR-99a-5p to influence oral squamous cell carcinoma (OSCC) cell metastasis. MiR-99a-5p, ZBTB7A, and MATTL3 expression was measured using quantitative real-time PCR. Biological behaviors were assessed using cell counting kit-8, flow cytometry, Transwell assay, as well as western blot. Luciferase reporter assay evaluated the interaction between miR-99a-5p and ZBTB7A. METTL3-regulated pri-miR-99a-5p processing was determined by RNA binding protein immunoprecipitation (RIP) and methylated RNA immunoprecipitation (MeRIP) assays. The consequences clarified that miR-99a-5p was upregulated in OSCC cells. Downregulation of miR-99a-5p suppressed cellular viability, migration, invasion, and epithelial-mesenchymal transition (EMT), and induced apoptosis. ZBTB7A acted as a miR-99a-5p target and reversed the effects on cellular behaviors induced by miR-99a-5p inhibitor. m6A content and METTL3 expression were increased in OSCC cells. METTL3 promoted the m6A modification of pri-miR-99a-5p and thereby facilitated miR-99a-5p processing. Moreover, knockdown of METTL3 inhibited OSCC metastasis by downregulating miR-99a-5p. Taken together, METTL3 promoted miR-99a-5p maturation in an m6A-dependent manner, which further targets ZBTB7A to accelerate the progression of OSCC. These findings suggest potential targets for OSCC therapy.
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Affiliation(s)
- Yuhua Huang
- Department of stomatology, The Second Affiliated Hospital of Guangzhou, University of Chinese Medicine, 6/F, East Zone, No. 111, Dade Road, Yuexiu District, Guangzhou, 510000, Guangdong, China
| | - Yun Guan
- Department of stomatology, The Second Affiliated Hospital of Guangzhou, University of Chinese Medicine, 6/F, East Zone, No. 111, Dade Road, Yuexiu District, Guangzhou, 510000, Guangdong, China
| | - Xing Zhang
- Department of stomatology, The Second Affiliated Hospital of Guangzhou, University of Chinese Medicine, 6/F, East Zone, No. 111, Dade Road, Yuexiu District, Guangzhou, 510000, Guangdong, China.
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3
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Ebert MP, Fischbach W, Hollerbach S, Höppner J, Lorenz D, Stahl M, Stuschke M, Pech O, Vanhoefer U, Porschen R. S3-Leitlinie Diagnostik und Therapie der Plattenepithelkarzinome und Adenokarzinome des Ösophagus. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:535-642. [PMID: 38599580 DOI: 10.1055/a-2239-9802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/12/2024]
Affiliation(s)
- Matthias P Ebert
- II. Medizinische Klinik, Medizinische Fakultät Mannheim, Universitätsmedizin, Universität Heidelberg, Mannheim
- DKFZ-Hector Krebsinstitut an der Universitätsmedizin Mannheim, Mannheim
- Molecular Medicine Partnership Unit, EMBL, Heidelberg
| | - Wolfgang Fischbach
- Deutsche Gesellschaft zur Bekämpfung der Krankheiten von Magen, Darm und Leber sowie von Störungen des Stoffwechsels und der Ernährung (Gastro-Liga) e. V., Giessen
| | | | - Jens Höppner
- Klinik für Allgemeine Chirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck
| | - Dietmar Lorenz
- Chirurgische Klinik I, Allgemein-, Viszeral- und Thoraxchirurgie, Klinikum Darmstadt, Darmstadt
| | - Michael Stahl
- Klinik für Internistische Onkologie und onkologische Palliativmedizin, Evang. Huyssensstiftung, Evang. Kliniken Essen-Mitte, Essen
| | - Martin Stuschke
- Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Essen, Essen
| | - Oliver Pech
- Klinik für Gastroenterologie und Interventionelle Endoskopie, Krankenhaus Barmherzige Brüder, Regensburg
| | - Udo Vanhoefer
- Klinik für Hämatologie und Onkologie, Katholisches Marienkrankenhaus, Hamburg
| | - Rainer Porschen
- Gastroenterologische Praxis am Kreiskrankenhaus Osterholz, Osterholz-Scharmbeck
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4
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Porschen R, Fischbach W, Gockel I, Hollerbach S, Hölscher A, Jansen PL, Miehlke S, Pech O, Stahl M, Vanhoefer U, Ebert MPA. Updated German guideline on diagnosis and treatment of squamous cell carcinoma and adenocarcinoma of the esophagus. United European Gastroenterol J 2024; 12:399-411. [PMID: 38284661 PMCID: PMC11017771 DOI: 10.1002/ueg2.12523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 11/21/2023] [Indexed: 01/30/2024] Open
Abstract
Diagnosis and therapy of esophageal carcinoma is challenging and requires a multidisciplinary approach. The purpose of the updated German guideline "Diagnosis and Treatment of Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus-version 3.1" is to provide practical and evidence-based advice for the management of patients with esophageal cancer. Recommendations were developed by a multidisciplinary expert panel based on an extensive and systematic evaluation of the published medical literature and the application of well-established methodologies (e.g. Oxford evidence grading scheme, grading of recommendations). Accurate diagnostic evaluation of the primary tumor as well as lymph node and distant metastases is required in order to guide patients to a stage-appropriate therapy after the initial diagnosis of esophageal cancer. In high-grade intraepithelial neoplasia or mucosal carcinoma endoscopic resection shall be performed. Whether endoscopic resection is the definitive therapeutic measure depends on the histopathological evaluation of the resection specimen. Esophagectomy should be performed minimally invasive or in combination with open procedures (hybrid technique). Because the prognosis in locally advanced esophageal carcinoma is poor with surgery alone, multimodality therapy is recommended. In locally advanced adenocarcinomas of the esophagus or esophagogastric junction, perioperative chemotherapy or preoperative radiochemotherapy should be administered. In locally advanced squamous cell carcinomas of the esophagus, preoperative radiochemotherapy followed by complete resection or definitive radiochemotherapy without surgery should be performed. In the case of residual tumor in the resection specimen after neoadjuvant radiochemotherapy and R0 resection of squamous cell carcinoma or adenocarcinoma, adjuvant immunotherapy with nivolumab should be given. Systemic palliative treatment options (chemotherapy, chemotherapy plus immunotherapy, immunotherapy alone) in unresectable or metastastic esophageal cancer depend on histology and are stratified according to PD-L1 and/or Her2 expression.
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Affiliation(s)
- Rainer Porschen
- Gastroenterologische Praxis am Kreiskrankenhaus OsterholzOsterholz‐ScharmbeckGermany
| | - Wolfgang Fischbach
- Deutsche Gesellschaft zur Bekämpfung der Krankheiten von MagenDarm und Leber sowie von Störungen des Stoffwechsels und der Ernährung (Gastro‐Liga) e. V.GiessenGermany
| | - Ines Gockel
- Klinik für Viszeral‐, Transplantations‐, Thorax‐ und GefäßchirurgieLeipzigGermany
| | | | - Arnulf Hölscher
- Contilia Zentrum für SpeiseröhrenerkrankungenElisabeth Krankenhaus EssenEssenGermany
| | - Petra Lynen Jansen
- Deutsche Gesellschaft für GastroenterologieVerdauungs‐ und StoffwechselkrankheitenBerlinGermany
| | | | - Oliver Pech
- Klinik für Gastroenterologie und Interventionelle EndoskopieKrankenhaus Barmherzige BrüderRegensburgGermany
| | - Michael Stahl
- Klinik für Internistische Onkologie & Onkologische PalliativmedizinEvang. Kliniken Essen‐MitteEssenGermany
| | - Udo Vanhoefer
- Klinik für Hämatologie und OnkologieKath. MarienkrankenhausHamburgGermany
| | - Matthias P. A. Ebert
- Medizinische Fakultät MannheimII. Medizinische KlinikUniversitätsmedizinUniversität HeidelbergMannheimGermany
- DKFZ‐Hector Krebsinstitut an der Universitätsmedizin MannheimMannheimGermany
- Molecular Medicine Partnership UnitEMBLHeidelbergGermany
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5
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Yuan MX, Cai QG, Zhang ZY, Zhou JZ, Lan CY, Lin JB. Application of neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in curative surgery for esophageal cancer: A meta-analysis. World J Gastrointest Oncol 2024; 16:214-233. [PMID: 38292844 PMCID: PMC10824113 DOI: 10.4251/wjgo.v16.i1.214] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 10/20/2023] [Accepted: 12/04/2023] [Indexed: 01/11/2024] Open
Abstract
BACKGROUND The effectiveness of neoadjuvant therapy in esophageal cancer (EC) treatment is still a subject of debate. AIM To compare the clinical efficacy and toxic side effects between neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemotherapy (nCT) for locally advanced EC (LAEC). METHODS A comprehensive search was conducted using multiple databases, including PubMed, EMBASE, MEDLINE, Science Direct, The Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Journal Database, and Chinese Biomedical Literature Database Article. Studies up to December 2022 comparing nCRT and nCT in patients with EC were selected. RESULTS The analysis revealed significant differences between nCRT and nCT in terms of disease-free survival. The results indicated that nCRT provided better outcomes in terms of the 3-year overall survival rate (OSR) [odds ratio (OR) = 0.95], complete response rate (OR = 3.15), and R0 clearance rate (CR) (OR = 2.25). However, nCT demonstrated a better 5-year OSR (OR = 1.02) than nCRT. Moreover, when compared to nCRT, nCT showed reduced risks of cardiac complications (OR = 1.15) and pulmonary complications (OR = 1.30). CONCLUSION Overall, both nCRT and nCT were effective in terms of survival outcomes for LAEC. However, nCT exhibited better performance in terms of postoperative complications.
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Affiliation(s)
- Mao-Xiu Yuan
- The Graduate School, Fujian Medical University, Fuzhou 350000, Fujian Province, China
- Department of Thoracic Surgery, Affiliated Hospital of Jinggangshan University, Ji’an 343000, Jiangxi Province, China
| | - Qi-Gui Cai
- Department of Thoracic Surgery, Affiliated Hospital of Jinggangshan University, Ji’an 343000, Jiangxi Province, China
| | - Zhen-Yang Zhang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou 350000, Fujian Province, China
| | - Jian-Zhong Zhou
- Department of Thoracic Surgery, Affiliated Hospital of Jinggangshan University, Ji’an 343000, Jiangxi Province, China
| | - Cai-Yun Lan
- Department of Thoracic Surgery, Affiliated Hospital of Jinggangshan University, Ji’an 343000, Jiangxi Province, China
| | - Jiang-Bo Lin
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou 350000, Fujian Province, China
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Worrell SG, Goodman KA, Altorki NK, Ashman JB, Crabtree TD, Dorth J, Firestone S, Harpole DH, Hofstetter WL, Hong TS, Kissoon K, Ku GY, Molena D, Tepper JE, Watson TJ, Williams T, Willett C. The Society of Thoracic Surgeons/American Society for Radiation Oncology Updated Clinical Practice Guidelines on Multimodality Therapy for Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction. Pract Radiat Oncol 2024; 14:28-46. [PMID: 37921736 DOI: 10.1016/j.prro.2023.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/05/2023] [Indexed: 11/04/2023]
Abstract
Outcomes for patients with esophageal cancer have improved over the last decade with the implementation of multimodality therapy. There are currently no comprehensive guidelines addressing multidisciplinary management of esophageal cancer that have incorporated the input of surgeons, radiation oncologists, and medical oncologists. To address the need for multidisciplinary input in the management of esophageal cancer and to meet current best practices for clinical practice guidelines, the current guidelines were created as a collaboration between The Society of Thoracic Surgeons (STS), American Society for Radiation Oncology (ASTRO), and the American Society of Clinical Oncology (ASCO). Physician representatives chose 8 key clinical questions pertinent to the care of patients with locally advanced, resectable thoracic esophageal cancer (excluding cervical location). A comprehensive literature review was performed identifying 227 articles that met the inclusion criteria covering the use of induction chemotherapy, chemotherapy vs chemoradiotherapy before surgery, optimal radiation dose, the value of esophagectomy, timing of esophagectomy, the approach and extent of lymphadenectomy, the use of minimally invasive esophagectomy, and the value of adjuvant therapy after resection. The relevant data were reviewed and voted on by the panel with 80% of the authors, with 75% agreement on class and level of evidence. These data were then complied into the guidelines document.
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Affiliation(s)
- Stephanie G Worrell
- Section of Thoracic Surgery, Department of Surgery, University of Arizona College of Medicine, Tucson, Arizona.
| | - Karyn A Goodman
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Nasser K Altorki
- Division of Thoracic Surgery, Weill Cornell Medicine, NewYork-Presbyterian Hospital, New York, New York
| | | | - Traves D Crabtree
- Division of Cardiothoracic Surgery, Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois
| | - Jennifer Dorth
- Department of Radiation Oncology, Seidman Cancer Center, University Hospitals, Cleveland, Ohio
| | | | - David H Harpole
- Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina
| | - Wayne L Hofstetter
- Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | | | - Geoffrey Y Ku
- Gastrointestinal Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Daniela Molena
- Division of Thoracic Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Joel E Tepper
- Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina
| | - Thomas J Watson
- Thoracic Surgery Group, Beaumont Health, Royal Oak, Michigan
| | - Terence Williams
- Department of Radiation Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California
| | - Christopher Willett
- Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina
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7
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Worrell SG, Goodman KA, Altorki NK, Ashman JB, Crabtree TD, Dorth J, Firestone S, Harpole DH, Hofstetter WL, Hong TS, Kissoon K, Ku GY, Molena D, Tepper JE, Watson TJ, Williams T, Willett C. The Society of Thoracic Surgeons/American Society for Radiation Oncology Updated Clinical Practice Guidelines on Multimodality Therapy for Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction. Ann Thorac Surg 2024; 117:15-32. [PMID: 37921794 DOI: 10.1016/j.athoracsur.2023.09.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 08/23/2023] [Accepted: 09/05/2023] [Indexed: 11/04/2023]
Abstract
Outcomes for patients with esophageal cancer have improved over the last decade with the implementation of multimodality therapy. There are currently no comprehensive guidelines addressing multidisciplinary management of esophageal cancer that have incorporated the input of surgeons, radiation oncologists, and medical oncologists. To address the need for multidisciplinary input in the management of esophageal cancer and to meet current best practices for clinical practice guidelines, the current guidelines were created as a collaboration between The Society of Thoracic Surgeons (STS), American Society for Radiation Oncology (ASTRO), and the American Society of Clinical Oncology (ASCO). Physician representatives chose 8 key clinical questions pertinent to the care of patients with locally advanced, resectable thoracic esophageal cancer (excluding cervical location). A comprehensive literature review was performed identifying 227 articles that met the inclusion criteria covering the use of induction chemotherapy, chemotherapy vs chemoradiotherapy before surgery, optimal radiation dose, the value of esophagectomy, timing of esophagectomy, the approach and extent of lymphadenectomy, the use of minimally invasive esophagectomy, and the value of adjuvant therapy after resection. The relevant data were reviewed and voted on by the panel with 80% of the authors, with 75% agreement on class and level of evidence. These data were then complied into the guidelines document.
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Affiliation(s)
- Stephanie G Worrell
- Section of Thoracic Surgery, Department of Surgery, University of Arizona College of Medicine, Tucson, Arizona.
| | - Karyn A Goodman
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Nasser K Altorki
- Division of Thoracic Surgery, Weill Cornell Medicine, NewYork-Presbyterian Hospital, New York, New York
| | | | - Traves D Crabtree
- Division of Cardiothoracic Surgery, Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois
| | - Jennifer Dorth
- Department of Radiation Oncology, Seidman Cancer Center, University Hospitals, Cleveland, Ohio
| | | | - David H Harpole
- Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina
| | - Wayne L Hofstetter
- Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | | | - Geoffrey Y Ku
- Gastrointestinal Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Daniela Molena
- Division of Thoracic Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Joel E Tepper
- Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina
| | - Thomas J Watson
- Thoracic Surgery Group, Beaumont Health, Royal Oak, Michigan
| | - Terence Williams
- Department of Radiation Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California
| | - Christopher Willett
- Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina
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8
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Xue M, Tong Y, Xiong Y, Yu C. Role of cancer-associated fibroblasts in the progression, therapeutic resistance and targeted therapy of oesophageal squamous cell carcinoma. Front Oncol 2023; 13:1257266. [PMID: 37927475 PMCID: PMC10623436 DOI: 10.3389/fonc.2023.1257266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 09/11/2023] [Indexed: 11/07/2023] Open
Abstract
Oesophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumours with high morbidity and mortality. Although surgery, radiotherapy and chemotherapy are common treatment options available for oesophageal cancer, the 5-year survival rate remains low after treatment. On the one hand, many oesophageal cancers are are discovered at an advanced stage and, on the other hand, treatment resistance is a major obstacle to treating locally advanced ESCC. Cancer-associated fibroblasts (CAFs), the main type of stromal cell in the tumour microenvironment, enhance tumour progression and treatment resistance and have emerged as a major focus of study on targeted therapy of oesophageal cancer.With the aim of providing potential, prospective targets for improving therapeutic efficacy, this review summarises the origin and activation of CAFs and their specific role in regulating tumour progression and treatment resistance in ESCC. We also emphasize the clinical potential and emerging trends of ESCC CAFs-targeted treatments.
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Affiliation(s)
| | | | | | - Changhua Yu
- Department of Radiotherapy, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, China
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9
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Authors, und die Mitarbeiter der Leitlinienkommission, Collaborators:. S3-Leitlinie Diagnostik und Therapie der Plattenepithelkarzinome und Adenokarzinome des Ösophagus. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:701-745. [PMID: 37285870 DOI: 10.1055/a-1771-7087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
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10
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Authors, und die Mitarbeiter der Leitlinienkommission, Collaborators:. S3-Leitlinie Diagnostik und Therapie der Plattenepithelkarzinome und Adenokarzinome des Ösophagus. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:e209-e307. [PMID: 37285869 DOI: 10.1055/a-1771-6953] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
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11
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Alwahsh M, Farhat J, Talhouni S, Hamadneh L, Hergenröder R. Bortezomib advanced mechanisms of action in multiple myeloma, solid and liquid tumors along with its novel therapeutic applications. EXCLI JOURNAL 2023; 22:146-168. [PMID: 36998701 PMCID: PMC10043448 DOI: 10.17179/excli2022-5653] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 01/12/2023] [Indexed: 04/01/2023]
Abstract
Bortezomib (BTZ) is a first-in-class reversible and selective proteasome inhibitor. It inhibits the ubiquitin proteasome pathway that leads to the degradation of many intracellular proteins. Initially, BTZ was FDA approved for the treatment of refractory or relapsed multiple myeloma (MM) in 2003. Later, its usage was approved for patients with previously untreated MM. In 2006, BTZ was approved for the treatment of relapsed or refractory Mantle Cell Lymphoma (MCL) and, in 2014, for previously untreated MCL. BTZ has been extensively studied either alone or in combination with other drugs for the treatment of different liquid tumors especially in MM. However, limited data evaluated the efficacy and safety of using BTZ in patients with solid tumors. In this review, we will discuss the advanced and novel mechanisms of action of BTZ documented in MM, solid tumors and liquid tumors. Moreover, we will shed the light on the newly discovered pharmacological effects of BTZ in other prevalent diseases.
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Affiliation(s)
- Mohammad Alwahsh
- Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan
- Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V., 44139 Dortmund, Germany
- Institute of Pathology and Medical Research Center (ZMF), University Medical Center Mannheim, Heidelberg University, 68167 Mannheim, Germany
- *To whom correspondence should be addressed: Mohammad Alwahsh, Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan, E-mail:
| | - Joviana Farhat
- Department of Epidemiology and Population Health, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, PO Box 127788, United Arab Emirates
| | - Shahd Talhouni
- Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan
| | - Lama Hamadneh
- Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan
| | - Roland Hergenröder
- Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V., 44139 Dortmund, Germany
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12
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The Impact of Radiation Dose on Preoperative Neoadjuvant Chemoradiotherapy Effects for Patients with Locally Advanced Squamous Cell Esophageal Carcinoma: A Propensity Score-Matched Retrospective Study. J Immunol Res 2022; 2022:7581799. [PMID: 36285181 PMCID: PMC9588370 DOI: 10.1155/2022/7581799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 08/08/2022] [Accepted: 08/16/2022] [Indexed: 12/24/2022] Open
Abstract
Objective To explore the impact of radiation dose on preoperative neoadjuvant chemoradiotherapy effects for patients with locally advanced squamous cell esophageal carcinoma (LASCEC) with long-term follow-up data. Methods The patients with LASCEC received either low dose radiotherapy (50.4Gy/23f/1.8Gy) or a high dose (64.8Gy/25f/1.8Gy) followed by neoadjuvant chemotherapy preoperatively were included in this study. To balance potential bias, 1 : 1 propensity score matching (PSM) with a caliper of 0.1 was used. The two groups were compared in terms of radical resection, post-radiation adverse event rates, perioperative mortality, postoperative adverse event rates, overall survival (OS), local recurrence rate, and distant metastatic rate. Results Forty-two patients were enrolled in this study, with 21 patients in each group after PSM. There was no difference in baseline characteristics between the two groups (all p >0.05). The rates of radical resection (71.4% vs 57.1%, P =0.334), perioperative mortality (9.5% vs 4.8%, P =0.549), and postoperative adverse event rates (76.2% vs 90.5%, P =0.410) did not differ significantly between the two groups. The 5-year OS rate was statistically higher in the group with a high dose (66.7% vs. 28.6%, P =0.013). Meanwhile, the local recurrence rate was statistically lower in the high dose group (14.3% vs 47.6%, P =0.019 for 3 years; 33.3% vs 66.6%, P =0.031 for 5 years). Moreover, the 3-year distant metastasis rate was statistically lower in the group with a high dose (9.5% vs 38.1%, P = 0.03). Conclusion Patients with LASCEC may benefit from preoperative neoadjuvant chemoradiotherapy with a high radiation dosage (64.8Gy/25f/1.8Gy).
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13
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Waters JK, Reznik SI. Update on Management of Squamous Cell Esophageal Cancer. Curr Oncol Rep 2022; 24:375-385. [PMID: 35142974 DOI: 10.1007/s11912-021-01153-4] [Citation(s) in RCA: 101] [Impact Index Per Article: 33.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/12/2021] [Indexed: 12/26/2022]
Abstract
PURPOSE OF THE REVIEW Esophageal cancer is the sixth most common cause of cancer death globally. Squamous cell carcinoma of the esophagus (ESCC) is the predominant histologic type in the world. Treatment strategies have evolved in the last decade and new paradigms are replacing traditional approaches at all stages of cancer. This review will summarize the epidemiology, diagnosis, staging, and treatment of esophageal squamous cell carcinoma. RECENT FINDINGS Novel approaches to screening may be cost-effective in regions with a high incidence of ESCC. Multi-disciplinary evaluation and treatment has become the standard of care. Endoscopic resection may be an option for early stage ESCC. Minimally invasive esophagectomy can be performed safely as a primary therapy or after-induction chemoradiation. Several recent studies have found a survival benefit to immunotherapy for patients with metastatic or persistent disease. Multi-disciplinary evaluation and multi-modal therapy including cytotoxic chemotherapy, radiation, surgery, and immunotherapy have improved survival compared to surgery alone.
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Affiliation(s)
- John K Waters
- Division of Thoracic Surgery, Department of Cardiovascular and Thoracic Surgery, 5323 Harry Hines Boulevard, MC 8879, Dallas, TX, 75390-8879, USA
| | - Scott I Reznik
- Division of Thoracic Surgery, Department of Cardiovascular and Thoracic Surgery, 5323 Harry Hines Boulevard, MC 8879, Dallas, TX, 75390-8879, USA.
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Liu P, Wang GF, Peng H, Zhang L, Li XY, Zeng QM, Li Q, Zhou JH. Effectiveness and Safety of Targeted Agents Combined With Chemoradiotherapy for the Treatment of Esophageal Cancer: A Network Meta-Analysis. Front Oncol 2021; 11:621917. [PMID: 34912696 PMCID: PMC8666421 DOI: 10.3389/fonc.2021.621917] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 11/05/2021] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Concurrent chemoradiotherapy (CRT) is the preferred treatment strategy for inoperable esophageal cancer (EC). However, the effect of CRT needs to be improved. METHODS This study comprehensively analyzed targeted agents combined with CRT for the treatment of EC by a network meta-analysis. The search was performed in public databases from incipient to 5 August 2021. Randomized controlled trials comparing the effect of targeted agents combined with CRT and CRT alone on EC patients were included. RESULTS Ten studies were included. For progression-free survival (PFS), nivolumab (67.4%) and erlotinib (64.6%) had advantages based on Cox analysis. Regarding the frequency of PFS, cetuximab (OR: 1.39; 95% CI: 1.01, 1.91; p=0.042) and nivolumab (OR: 1.81; 95% CI: 1.34, 2.44; p<0.01) were significantly superior to the control. For overall survival (OS), nivolumab (71.6%) in Cox analysis and nimotuzumab (69.7%) in frequency analysis were found to have relative advantages. Nimotuzumab combined with CRT was significantly better than the control with regard to endoscopic and the pathologic complete response (epCR; OR: 2.81; 95% CI: 1.28, 6.14; p=0.011) and objective response rate (ORR; 4.71; 95% CI: 1.45, 15.29; p=0.008). The targeted drugs were not associated with significant SEA risk. CONCLUSION In conclusion, compared to CRT alone, cetuximab and nivolumab combined with CRT were found to significantly improve the PFS rate only based on the frequency results. However, there was no benefit in terms of OS. For epCR and ORR, nimotuzumab was better than the blank control. Considering the limitations in this study, more well-designed RCTs are needed in the future to validate the results.
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Affiliation(s)
- Peng Liu
- Intensive Care Unit of Cardiovascular Surgery Department, Xiangya Hospital Central South University, Changsha, China
| | - Guo-Fei Wang
- Intensive Care Unit of Cardiovascular Surgery Department, Xiangya Hospital Central South University, Changsha, China
| | - Hua Peng
- Department of Nursing, Xiangya Hospital Central South University, Changsha, China
| | - Lei Zhang
- Intensive Care Unit of Cardiovascular Surgery Department, Xiangya Hospital Central South University, Changsha, China
| | - Xiao-Yan Li
- Department of Thoracic Surgery, Xiangya Hospital Central South University, Changsha, China
| | - Qiao-Miao Zeng
- Department of Oncological Radiotherapy, Xiangya Hospital Central South University, Changsha, China
| | - Qian Li
- Intensive Care Unit of Cardiovascular Surgery Department, Xiangya Hospital Central South University, Changsha, China
| | - Jian-Hui Zhou
- Department of Nursing, Xiangya Hospital Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China
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15
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Ma Z, Yuan M, Bao Y, Wang Y, Men Y, Hui Z. Survival of Neoadjuvant and Adjuvant Therapy Compared With Surgery Alone for Resectable Esophageal Squamous Cell Carcinoma: A Systemic Review and Network Meta-Analysis. Front Oncol 2021; 11:728185. [PMID: 34745950 PMCID: PMC8564474 DOI: 10.3389/fonc.2021.728185] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 09/23/2021] [Indexed: 01/02/2023] Open
Abstract
Objective The optimal treatment for resectable esophageal squamous cell carcinoma (ESCC) remains controversial. Surgery is the primary treatment but with poor results. Attempts to improve patient survival have been made by introducing chemotherapy, radiotherapy, or both. However, randomized comparisons for all these strategies are not always available. This network meta-analysis compared the overall survival of neoadjuvant and adjuvant therapy with surgery alone to identify the most effective approach. Methods We systematically searched electronic databases (PubMed, Embase, and Cochrane Library) for relevant studies published before April 2021. Only phase II and III randomized controlled trials comparing the following treatments were included: surgery alone, neoadjuvant chemotherapy (NCT), radiotherapy (NRT) or chemoradiotherapy (NCRT), adjuvant chemotherapy (ACT), radiotherapy (ART), or chemoradiotherapy (ACRT). The hazard ratios (HR) and 95% confidence intervals (CIs) of overall survival (OS) was identified as the measurement of effectiveness. A network meta-analysis was conducted to synthesize the evidence under the Bayesian framework, and the relative effects of all possible comparisons were made. The ranking analysis was performed to support the decision in clinical practice. Results A total of 19 relevant trials with 3,749 patients were identified. Compared with surgery alone, NCRT (HR 0.76, 95% CI 0.65–0.89) and NCT (HR 0.81, 95% CI 0.70–0.94) significantly improved OS, while other treatments, including NRT (HR 0.86, 95% CI 0.66–1.08), ACRT (HR 0.73, 95% CI 0.49–1.08), ACT (HR 0.96, 95% CI 0.75–1.21), and ART (HR 0.86, 95% CI 0.66–1.14), provided no significant survival advantage. None of the neoadjuvant and adjuvant treatments showed a statistically significant difference in OS to each other when compared in pairs. Conclusion For resectable esophageal squamous cell carcinoma, this network meta-analysis showed that NCRT may be the optimal strategy, NCT may be the second choice, while other multimodality treatments could not improve OS compared with surgery alone. It remains unclear whether ESCC will benefit from adding radiotherapy into the neoadjuvant treatment. Systematic Review Registration We registered this meta-analysis protocol at the prospective register of systematic reviews, PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=172745 (Identification code: CRD42020172745).
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Affiliation(s)
- Zeliang Ma
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Meng Yuan
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yongxing Bao
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yang Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yu Men
- Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhouguang Hui
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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16
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Zhao Y, Wang Y, Shan L, Peng C, Zhang W, Zhao X. A network meta-analysis for neoadjuvant and adjuvant treatments for resectable squamous cell carcinoma of esophagus. Sci Rep 2021; 11:6800. [PMID: 33762694 PMCID: PMC7990939 DOI: 10.1038/s41598-021-86102-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Accepted: 03/03/2021] [Indexed: 02/07/2023] Open
Abstract
The optimal treatment for resectable esophageal squamous cell carcinoma (ESCC) is still a debatable point; however, randomized trials for strategies including neoadjuvant or adjuvant chemotherapy (CT), radiotherapy, or chemoradiotherapy (CRT) are not always available. This network meta-analysis aimed to identify an effective approach through indirect comparisons. An extensive literature search comparing multimodality treatment and surgery was performed, and a network meta-analysis was conducted with the frequentist method. Twenty-three trials including a total of 3636 ESCC patients were included. Neoadjuvant CRT and neoadjuvant CT, which were recommended by most guidelines for esophageal cancer, were associated with an overall survival advantage compared with surgery alone (HR = 0.43, 95% CI 0.26-0.73; HR = 0.71, 95% CI 0.32-1.59). A statistically significant survival benefit from neoadjuvant CRT compared with neoadjuvant CT could not be demonstrated in our study (HR = 0.61, 95% CI 0.32-1.17, P = 0.08). Our network meta-analysis showed that both neoadjuvant CRT and neoadjuvant CT were effective in improving the survival of patients with ESCC. Individual clinical decisions need further study in the future.
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Affiliation(s)
- Yunpeng Zhao
- Department of Thoracic Surgery, The Second Hospital of Shandong University, Jinan, Shandong Province, China
| | - Yongqiang Wang
- Department of Thoracic Surgery, The Second Hospital of Shandong University, Jinan, Shandong Province, China
| | - Lei Shan
- Department of Thoracic Surgery, The Second Hospital of Shandong University, Jinan, Shandong Province, China
| | - Chuanliang Peng
- Department of Thoracic Surgery, The Second Hospital of Shandong University, Jinan, Shandong Province, China
| | - Wenhao Zhang
- Department of Thoracic Surgery, The Second Hospital of Shandong University, Jinan, Shandong Province, China
| | - Xiaogang Zhao
- Department of Thoracic Surgery, The Second Hospital of Shandong University, Jinan, Shandong Province, China.
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17
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Wang Y, Jia RZ, Diao S, He J, Jia L. miRNA-101 Targets TGF-βR1 to Retard the Progression of Oral Squamous Cell Carcinoma. Oncol Res 2019; 28:203-212. [PMID: 31831099 PMCID: PMC7851522 DOI: 10.3727/096504019x15761480623959] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Despite the considerable knowledge on the involvement of microRNA-101 (miR-101) in the evolution of oral squamous cell carcinoma (OSCC), the underlying mechanisms remain obscure. In this study, miR-101 expression was markedly downregulated in the OSCC cell lines and tissues. Cell counting kit-8 (CCK-8), ethynyl deoxyuridine (EdU), and colony formation assays showed that miR-101 inhibited the proliferation of OSCC cells. Flow cytometry and caspase 3 activity assays indicated that miR-101 induced OSCC cell apoptosis. Transwell assays demonstrated that this miRNA also repressed OSCC cell migration and invasion. Moreover, tube formation assay showed that miR-101 abated the proangiogenesis of OSCC cells. Dual-luciferase reporter assay confirmed that miR-101 directly targeted transforming growth factor-β receptor 1 (TGF-βR1) in OSCC. Ectopic expression of TGF-βR1 counteracted the effects of miR-101 on the OSCC cell characteristics. Thus, miR-101 significantly abolished the proliferation, motility, and proangiogenesis of OSCC cells and induced their apoptosis by targeting TGF-βR1. These results imply the potential application of miR-101 in OSCC treatment.
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Affiliation(s)
- Yong Wang
- Department of Pediatric Dentistry, Beijing Stomatological Hospital & School of Stomatology, Capital Medical UniversityBeijingChina
| | - Rui-Zhi Jia
- Department of Pediatric Dentistry, Beijing Stomatological Hospital & School of Stomatology, Capital Medical UniversityBeijingChina
| | - Shu Diao
- Department of Pediatric Dentistry, Beijing Stomatological Hospital & School of Stomatology, Capital Medical UniversityBeijingChina
| | - Jun He
- Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention of PLABeijingChina
| | - Li Jia
- Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention of PLABeijingChina
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18
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Chung TR, Kim JH, Lee IJ, Cho Y, Kim JW, Lee CG, Jung DH, Park JJ, Youn YH, Park H. Different prognosis of patients with esophageal carcinoma with M1a and regional node involvement. Dig Liver Dis 2019; 51:1610-1616. [PMID: 31175014 DOI: 10.1016/j.dld.2019.05.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 05/04/2019] [Accepted: 05/09/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND PURPOSE Based on the 6th edition of the American Joint Commission on Cancer (AJCC) staging system for esophageal squamous cell carcinoma (ESCC), M1a node involvement was classified as regional node involvement in the revised 7th/8th edition. However, the clinical significance of M1a node involvement is unclear. Thus, we analyzed the prognostic value of M1a node involvement in patients with ESCC after definitive concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS In total, 188 patients with ESCC had M0 disease according to the 7th/8th edition AJCC. We reclassified 31 (16.5%) of these patients as having M1a disease according to the 6th edition. After definitive CCRT, we compared baseline characteristics between the two groups and analyzed the rates of responders and recurrence. Finally, we compared prognoses according to overall survival (OS), disease-specific OS, and disease-free survival (DFS). RESULTS Among 31 patients reclassified to have M1a disease, 21 (67.7%) had supraclavicular lymph node metastasis and 10 (32.3%) had celiac lymph node metastasis. The number of responders was significantly lower for M1a disease based on univariate (p = 0.004) and multivariate (p = 0.011) analyses. Significantly lower survival rates were observed in individuals with M1a disease (median OS, 16.4 vs. 42.7 months; 5-year OS, 10.8% vs. 41.2%). CONCLUSIONS M1a node involvement should be differentiated from regional node involvement.
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Affiliation(s)
- Tae Ryong Chung
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jie-Hyun Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
| | - Ik Jae Lee
- Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea; Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
| | - Yeona Cho
- Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea; Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jun Won Kim
- Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea; Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Chang Geol Lee
- Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Da Hyun Jung
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jae Jun Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Young Hoon Youn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyojin Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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Cordycepin Enhances Radiosensitivity in Oral Squamous Carcinoma Cells by Inducing Autophagy and Apoptosis Through Cell Cycle Arrest. Int J Mol Sci 2019; 20:ijms20215366. [PMID: 31661901 PMCID: PMC6862293 DOI: 10.3390/ijms20215366] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 10/23/2019] [Accepted: 10/24/2019] [Indexed: 01/16/2023] Open
Abstract
Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide and accounts for over 90% of malignant neoplasms of the oral cavity, with a 5-year survival rate of less than 50%. The long-term survival rate of OSCC patients has not markedly improved in recent decades due to its heterogeneous etiology and treatment outcomes. We investigated the anticancer effect of the combination of irradiation (IR) and cordycepin in the treatment of human OSCC cells in vitro. The type of cell death, especially autophagy and apoptosis, and the underlying mechanisms were examined. We found synergistic effects of cordycepin and IR on the viability of human oral cancer cells. The combination of cordycepin and IR treatment induced apoptosis, cell cycle arrest, and autophagic cell death. Furthermore, cordycepin induced S-phase arrest and prolonged G2/M arrest in the cells that received the combination treatment compared with those that received irradiation alone. Combined treatment induced the upregulation of ATG5 and p21 in an autophagy cascade-dependent manner, arrested the cell cycle in the G2/M phase, and repressed cell proliferation. Thus, we conclude that the combination of cordycepin and IR treatment could be a potential therapeutic strategy for OSCC.
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20
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Radiation With Neoadjuvant Chemotherapy Does Not Improve Outcomes in Esophageal Squamous Cell Cancer. J Surg Res 2019; 236:259-265. [PMID: 30694764 PMCID: PMC10005325 DOI: 10.1016/j.jss.2018.11.052] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2018] [Revised: 10/25/2018] [Accepted: 11/26/2018] [Indexed: 01/26/2023]
Abstract
BACKGROUND Neoadjuvant treatment improves survival for patients undergoing esophagectomy for esophageal cancer. Recent evidence suggests that neoadjuvant chemoradiation offers no advantage over chemotherapy alone before surgical resection for adenocarcinoma histology. We sought to examine if this applies to patients with squamous cell histology. MATERIALS AND METHODS The National Cancer Database was queried for patients who underwent treatment for squamous cell carcinoma of the esophagus from 2004 to 2012. Patients who underwent neoadjuvant chemotherapy before esophagectomy were compared with those undergoing chemotherapy and radiation before surgical resection. Associations between potential covariates and treatment were analyzed using the Pearson chi-square test for categorical variables and Wilcoxon rank sum test for continuous variables. Univariate and multivariate proportional hazards modeling results were used to assess the effect of treatment on overall survival. Relative prognosis was summarized using estimates and 95% confidence limits for the hazard ratio. Unadjusted differences in overall survival and disease-specific survival between the treatment are shown using Kaplan-Meier methods. RESULTS A total of 902 patients underwent neoadjuvant therapy before surgical resection during the study period, with 827 receiving chemotherapy and radiation, and 75 receiving chemotherapy alone preoperatively. The 30- and 90-d mortality for patients undergoing neoadjuvant chemotherapy and radiation followed by surgery were 5.4% and 10.4% compared to 5.5% and 11.1% for patients who received chemotherapy alone preoperatively (P = 0.963 and P = 0.856), respectively. Median overall survival for patients receiving chemotherapy and radiation was 36.0 mo versus 40.8 mo for chemotherapy alone. The 5-y survival was 39% for the chemotherapy and radiation group and 43% for the chemotherapy group (logrank P = 0.7212). CONCLUSIONS For patients undergoing neoadjuvant treatment before planned surgical resection of squamous cell carcinoma of the esophagus, the addition of radiation to neoadjuvant chemotherapy did not improve long-term survival and did not appear to impact short-term outcomes postoperatively. Further study with a randomized phase III trial is needed.
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Krishnamurthy A, Mohanraj N, Radhakrishnan V, John A, Selvaluxmy G. Neoadjuvant chemoradiation for locally advanced resectable carcinoma of the esophagus: A single-center experience from India with a brief review of the literature. Indian J Cancer 2018; 54:646-651. [PMID: 30082551 DOI: 10.4103/ijc.ijc_452_17] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
BACKGROUND The management of locally advanced carcinomas of the esophagus and esophagogastric junction has undergone a major evolution over the past two decades with the widespread use of combined modality therapy. Although many Indian centers practice the combined modality therapy with neoadjuvant chemoradiation (nCRT), published data are sparse. OBJECTIVES The objective of this study was to study the safety and efficacy of nCRT in patients with locally advanced resectable carcinoma of the esophagus. MATERIALS AND METHODS Prospective single-arm study of the first fifty patients enrolled over 3 years (2014-2016). RESULTS The median age was 51 years (M:F = 3:2), 90% of the patients had squamous cell carcinomas, and 69% had lower-third lesions. All accrued patients completed the intended dose of radiation; however, approximately 20% had a treatment delay, which was duly gap corrected. Importantly, there were no treatment-related toxic deaths. Eleven patients could not undergo surgery following nCRT (two patients defaulted, two were deemed medically unfit, and seven (14%) patients had disease progression on imaging). Thirty-nine (78%) patients were planned for definitive surgery; however, a further 7 (14%) were found to be inoperable intraoperatively. Thirty-two patients successfully completed their definitive surgical procedures with R0 resections, of which 19 patients (38%) had a pathological complete response (pCR). There was no postoperative 90-day mortality in our study cohort. Analysis of prognostic factors that predicted a response showed that patients who had adenocarcinoma and with circumferential lesions responded poorly. CONCLUSION nCRT appears to be a safe and a reasonably well-tolerated option in carefully selected patients with resectable locally advanced esophageal cancers. Although our data are not mature to analyze the survival outcomes with a pCR rate of 38%, it suggests nCRT to be a promising option in the management of locally advanced resectable esophageal cancers.
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Affiliation(s)
- Arvind Krishnamurthy
- Department of Surgical Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India
| | - N Mohanraj
- Department of Surgical Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India
| | | | - Alexander John
- Department of Radiation Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India
| | - G Selvaluxmy
- Department of Radiation Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India
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22
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Liu T, Liu W, Zhang H, Ren C, Chen J, Dang J. The role of postoperative radiotherapy for radically resected esophageal squamous cell carcinoma: a systemic review and meta-analysis. J Thorac Dis 2018; 10:4403-4412. [PMID: 30174889 PMCID: PMC6105941 DOI: 10.21037/jtd.2018.06.65] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Accepted: 06/06/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND The role of postoperative radiotherapy (PORT) for radical resected esophageal squamous cell carcinoma (ESCC) remains controversial. This meta-analysis aims to determine whether PORT achieves survival benefit compared with surgery alone (S alone) for radically resected ESCC. METHODS The PubMed, EMBASE, Web of Science, and Cochrane Library were searched for relevant articles. The primary endpoints were overall survival (OS) and disease-free survival (DFS), reported as hazard ratios (HR) and 95% confidence intervals (CIs). RESULTS Six randomized trials and 13 retrospective studies that included a total of 8,198 patients were eligible. PORT provided significant OS benefit compared with S alone in retrospective studies (HR =0.75, 95% CI: 0.65-0.85), but not in randomized controlled trials (RCTs) (HR =0.94, 95% CI: 0.81-1.09). PORT was associated with significantly improved DFS and obvious reduction in the risk of locoregional recurrence compared to S alone in either retrospective studies or RCTs. In the subgroup analysis for retrospective studies, PORT gained superior OS in patients with lymph node-positive (pN+), patients with lymph node-negative (pN0) or pT2-3N0, PORT with three-dimensional radiotherapy (3D-RT), PORT with chemotherapy, and patients with R0 resection, respectively. CONCLUSIONS The present study shows that PORT can improve DFS and decrease risk of locoregional recurrence in patients with radically resected ESCC, and PORT using 3D-RT or in combination with chemotherapy is likely to be more useful. Further well-designed, prospective studies are needed to confirm the effect of PORT on OS.
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Affiliation(s)
- Tingting Liu
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang 110001, China
| | - Wen Liu
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang 110001, China
| | - Hongwei Zhang
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang 110001, China
| | - Chengbo Ren
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang 110001, China
| | - Jun Chen
- Department of Radiation Oncology, Shenyang Chest Hospital, Shenyang 110044, China
| | - Jun Dang
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang 110001, China
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23
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Wu YH, Wu WS, Lin LC, Liu CS, Ho SY, Wang BJ, Huang BM, Yeh YL, Chiu HW, Yang WL, Wang YJ. Bortezomib enhances radiosensitivity in oral cancer through inducing autophagy-mediated TRAF6 oncoprotein degradation. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2018; 37:91. [PMID: 29703234 PMCID: PMC5921410 DOI: 10.1186/s13046-018-0760-0] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 04/11/2018] [Indexed: 12/14/2022]
Abstract
Background Oral squamous cell carcinoma (OSCC) is a malignant tumor that may occur anywhere within the oral cavity. The survival rate of OSCC patients has not improved over the past decades due to its heterogeneous etiology, genetic aberrations, and treatment outcomes. We investigated the role of tumor necrosis factor receptor-associated factor 6 (TRAF6) in OSCC cells treated with bortezomib (a proteasome inhibitor) combined with irradiation (IR) treatment. Methods The effects of combined treatment in OSCC cells were investigated using assays of cell viability, autophagy, apoptosis, western blotting, and immunofluorescence staining. The ubiquitination of proteins was analyzed by immunoprecipitation. Stable knockdown of TRAF6 in OSCC cells was constructed with lentivirus. The xenograft murine models were used to observe tumor growth. Results We found synergistic effects of bortezomib and IR on the viability of human oral cancer cells. The combination of bortezomib and IR treatment induced autophagic cell death. Furthermore, bortezomib inhibited IR-induced TRAF6 ubiquitination and inhibited TRAF6-mediated Akt activation. Bortezomib reduced TRAF6 protein expression through autophagy-mediated lysosomal degradation. TRAF6 played an oncogenic role in tumorigenesis of human oral cancer cells and oral tumor growth was suppressed by bortezomib and IR treatment. In addition, OSCC patients with expression of TRAF6 showed a trend towards poorer cancer-specific survival when compared with patients without TRAF6 expression. Conclusions A combination of a proteasome inhibitor, IR treatment and TRAF6 inhibition could be a novel therapeutic strategy in OSCC. Electronic supplementary material The online version of this article (10.1186/s13046-018-0760-0) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yuan-Hua Wu
- Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.,Department of Radiation Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wun-Syuan Wu
- Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Li-Ching Lin
- Department of Radiation Oncology, Chi Mei Medical Center, Tainan, Taiwan.,School of Medicine, Taipei Medical University, Taipei, Taiwan.,Chung Hwa University of Medical Technology, Tainan, Taiwan
| | - Chiang-Shin Liu
- Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Sheng-Yow Ho
- Department of Radiation Oncology, Chi Mei Medical Center, Liouying, Tainan, Taiwan.,Chang Jung Christian University, Tainan, Taiwan
| | - Bour-Jr Wang
- Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.,Department of Cosmetic Science and Institute of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Bu-Miin Huang
- Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ya-Ling Yeh
- Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hui-Wen Chiu
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan
| | - Wei-Lei Yang
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
| | - Ying-Jan Wang
- Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. .,Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. .,Department of Biomedical Informatics, Asia University, Taichung, Taiwan. .,Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
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24
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Tu CC, Hsu PK. The frontline of esophageal cancer treatment: questions to be asked and answered. ANNALS OF TRANSLATIONAL MEDICINE 2018; 6:83. [PMID: 29666806 DOI: 10.21037/atm.2017.10.31] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Achieving a good treatment for esophageal cancer is a great challenge. For early stage cancer, endoscopic treatment is considered the first line and a possible curative therapy. Chemotherapy, radiotherapy, and surgery are all used for the treatment of locally advanced esophageal cancer, administered either alone or combined. Some combinations have proven to be feasible, effective, and superior, such as neoadjuvant chemoradiation (CRT) plus surgery in the Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) trial. However, other strategies such as perioperative chemotherapy or definitive chemoradiation also have demonstrated substantial effectiveness. The current article addresses the following questions: (I) how can a choice between different multi-modality treatments be made; (II) is there enough evidence to compare the merits of the different strategies; and (III) is there any new evidence to improve the current practice. Moreover, in this article, existing evidence for treatment strategies for locally advanced esophageal cancer have been reviewed.
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Affiliation(s)
- Cheng-Che Tu
- Division of Thoracic Surgery, Department of Surgery, Chang Bing Show Chwan Memorial Hospital, Changhua
| | - Po-Kuei Hsu
- Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital and School of Medicine, National Yang-Ming University, Taipei
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