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  • Gastric Cancer
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  • 1
    Language: English
    In: International Journal of Cancer, 01 September 2010, Vol.127(5), pp.1197-1208
    Description: The receptor tyrosine kinases (RTKs), epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 1‐3 (VEGFR1‐3), are frequently expressed in gastric cancer and are putative therapeutic targets in this disease. We have investigated the anti‐proliferative and chemosensitizing properties of the multitargeted small‐molecule RTK inhibitors sunitinib and vandetanib in a panel of 4 human gastric and esophageal cancer cell lines. In the 1st instance, the expression of potential targets of these small‐molecule inhibitors was examined by reverse transcriptase‐polymerase chain reaction, western blotting, and flow cytometry. EGFR mRNA and protein was detected in all cases, with VEGFR2 expression noted in all but 1 line. Both EGF and VEGF were shown to stimulate tumor cell growth, and both sunitinib and vandetanib were found to be associated with significant dose‐dependent inhibition of proliferation and an enhancement of apoptosis, as determined by MTT and propidium iodide/Annexin V labeling assays, respectively. The addition of sunitinib to VEGF‐stimulated NCI‐N87 cells was associated with a reduction in MAPK phosphorylation (pMAPK) but not Akt phosphorylation (pAkt), whereas the addition of vandetanib was associated with reductions in both VEGF‐ and EGF‐mediated VEGFR2 phosphorylation, pMAPK and pAkt. Co‐administration of sunitinib significantly enhanced the sensitivity of MKN‐45 cells to cisplatin and irinotecan. In addition, vandetanib synergistically enhanced the sunitinib‐associated inhibition of gastric cancer cell growth. In conclusion, these preliminary data confirm the importance of EGFR and VEGFR signaling in gastric cancer and suggest that the simultaneous inhibition of RTK‐pathways through sunitinib and vandetanib may provide therapeutic benefit in this disease.
    Keywords: Sunitinib ; Rtk ; Gastric Cancer ; Vandetanib ; Chemotherapy
    ISSN: 0020-7136
    E-ISSN: 1097-0215
    Source: John Wiley & Sons, Inc.
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  • 2
    Language: English
    In: Gastric Cancer, 2015, Vol.18(3), pp.550-563
    Description: Byline: Markus Moehler (1,17), Christoph T. H. Baltin (5), Matthias Ebert (2), Wolfgang Fischbach (3), Ines Gockel (1), Lars Grenacher (4), Arnulf H. Holscher (5), Florian Lordick (6), Peter Malfertheiner (7), Helmut Messmann (8), Hans-Joachim Meyer (9), Anne Palmqvist (1), Christoph Rocken (10), Christoph Schuhmacher (11), Michael Stahl (12), Martin Stuschke (13), Michael Vieth (14), Christian Wittekind (15), Dorothea Wagner (16), Stefan P. Monig (5) Keywords: Guidelines; Esophageal cancer; Gastric cancer; Perioperative therapy; Diagnosis Abstract: Background Clinical guidelines are essential in implementing and maintaining nationwide stage-specific diagnostic and therapeutic standards. In 2011, the first German expert consensus guideline defined the evidence for diagnosis and treatment of early and locally advanced esophagogastric cancers. Here, we compare this guideline with other national guidelines as well as current literature. Methods The German S3-guideline used an approved development process with de novo literature research, international guideline adaptation, or good clinical practice. Other recent evidence-based national guidelines and current references were compared with German recommendations. Results In the German S3 and other Western guidelines, adenocarcinomas of the esophagogastric junction (AEG) are classified according to formerly defined AEG I--III subgroups due to the high surgical impact. To stage local disease, computed tomography of the chest and abdomen and endosonography are reinforced. In contrast, laparoscopy is optional for staging. Mucosal cancers (T1a) should be endoscopically resected "en-bloc" to allow complete histological evaluation of lateral and basal margins. For locally advanced cancers of the stomach or esophagogastric junction (a[yen]T3N+), preferred treatment is preoperative and postoperative chemotherapy. Preoperative radiochemotherapy is an evidence-based alternative for large AEG type I--II tumors (a[yen]T3N+). Additionally, some experts recommend treating T2 tumors with a similar approach, mainly because pretherapeutic staging is often considered to be unreliable. Conclusions The German S3 guideline represents an up-to-date European position with regard to diagnosis, staging, and treatment recommendations for patients with locally advanced esophagogastric cancer. Effects of perioperative chemotherapy versus chemoradiotherapy are still to be investigated for adenocarcinoma of the cardia and the lower esophagus. Author Affiliation: (1) University Medical Center Mainz, Mainz, Germany (2) University Medical Center Mannheim, Mannheim, Germany (3) Klinikum Aschaffenburg, Aschaffenburg, Germany (4) Heidelberg University Hospital, Heidelberg, Germany (5) University Hospital of Cologne, Cologne, Germany (6) Klinikum Braunschweig, Braunschweig, Germany (7) University Clinic Magdeburg, Magdeburg, Germany (8) Klinikum Augsburg, Augsburg, Germany (9) Stadtisches Klinikum Solingen, Solingen, Germany (10) Charite Universitatsmedizin Berlin, Berlin, Germany (11) University Hospital Klinikum Rechts der Isar, Munich, Germany (12) Kliniken Essen-Mitte, Essen, Germany (13) Essen University Hospital, Essen, Germany (14) Klinikum Bayreuth, Bayreuth, Germany (15) Universitatsmedizin Leipzig, Leipzig, Germany (16) Center Hospitalier Universitaire Vaudois, Lausanne, Switzerland (17) Medizinische Klinik und Poliklinik, Johannes-Gutenberg-Universitat, Langenbeckstra[sz]e, 155101, Mainz, Germany Article History: Registration Date: 16/07/2014 Received Date: 07/10/2013 Accepted Date: 13/07/2014 Online Date: 07/09/2014 Article note: M. Moehler and C.T.H. Baltin contributed equally. Electronic supplementary material The online version of this article (doi: 10.1007/s10120-014-0403-x) contains supplementary material, which is available to authorized users.
    Keywords: Guidelines ; Esophageal cancer ; Gastric cancer ; Perioperative therapy ; Diagnosis
    ISSN: 1436-3291
    E-ISSN: 1436-3305
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  • 3
    Language: English
    In: Oncology Research and Treatment, February 2018, Vol.41(3), pp.122-128
    Description: Background: Despite the announcement of the 8th edition of TNM classification, the 7th edition (2010) is still being used for prognostic assessment in gastric cancer patients. A proposed new staging system (termed as the Kiel proposal) claims to offer a better prognostic stratification. Our objective was to retrospectively evaluate the Kiel proposal and compare it with the 6th and 7th TNM editions on a collected database. Methods: We retrospectively analyzed gastric cancer patients who had undergone surgical resection without any previous treatment from selected randomized trials and from a cohort of patients operated at the University Hospital of Mainz, Germany. All patients were restaged using the 3 staging systems and overall survival was estimated and compared. Results: A study population of 491 patients was identified. Relevant changes in stage distribution between the 6th and 7th TNM and the Kiel staging systems were observed. The 6th classification appears to display the best discriminatory measures. The Kiel staging system is slightly less prognostic than the TNM editions, but provides clearly separated strata as with the 6th edition. Conclusions: The Kiel staging system for gastric cancer appears promising in terms of simplicity, predictability and applicability and should be taken into consideration in future TNM revisions.
    Keywords: Research Article ; Gastric Cancer ; Staging System ; Prognosis ; Medicine
    ISSN: 2296-5270
    E-ISSN: 2296-5262
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  • 4
    Language: English
    In: International journal of cancer, 01 September 2010, Vol.127(5), pp.1197-208
    Description: The receptor tyrosine kinases (RTKs), epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 1-3 (VEGFR1-3), are frequently expressed in gastric cancer and are putative therapeutic targets in this disease. We have investigated the anti-proliferative and chemosensitizing properties of the multitargeted small-molecule RTK inhibitors sunitinib and vandetanib in a panel of 4 human gastric and esophageal cancer cell lines. In the 1st instance, the expression of potential targets of these small-molecule inhibitors was examined by reverse transcriptase-polymerase chain reaction, western blotting, and flow cytometry. EGFR mRNA and protein was detected in all cases, with VEGFR2 expression noted in all but 1 line. Both EGF and VEGF were shown to stimulate tumor cell growth, and both sunitinib and vandetanib were found to be associated with significant dose-dependent inhibition of proliferation and an enhancement of apoptosis, as determined by MTT and propidium iodide/Annexin V labeling assays, respectively. The addition of sunitinib to VEGF-stimulated NCI-N87 cells was associated with a reduction in MAPK phosphorylation (pMAPK) but not Akt phosphorylation (pAkt), whereas the addition of vandetanib was associated with reductions in both VEGF- and EGF-mediated VEGFR2 phosphorylation, pMAPK and pAkt. Co-administration of sunitinib significantly enhanced the sensitivity of MKN-45 cells to cisplatin and irinotecan. In addition, vandetanib synergistically enhanced the sunitinib-associated inhibition of gastric cancer cell growth. In conclusion, these preliminary data confirm the importance of EGFR and VEGFR signaling in gastric cancer and suggest that the simultaneous inhibition of RTK-pathways through sunitinib and vandetanib may provide therapeutic benefit in this disease.
    Keywords: Cell Proliferation -- Drug Effects ; Esophageal Neoplasms -- Drug Therapy ; Indoles -- Pharmacology ; Piperidines -- Pharmacology ; Pyrroles -- Pharmacology ; Quinazolines -- Pharmacology ; Signal Transduction -- Drug Effects ; Stomach Neoplasms -- Drug Therapy
    E-ISSN: 1097-0215
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  • 5
    Language: English
    In: Journal of gastric cancer, December 2018, Vol.18(4), pp.379-391
    Description: Gastric cancer (GC) patients with peritoneal metastasis (PM) have poor prognosis. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in combination with systemic chemotherapy is a novel treatment option for patients in stage IV of the disease. Between November 2015 and June 2018, prospective data collection was performed in 24 patients with GC and PM (median age, 57; range, 44-75 years). These patients underwent 46 PIPAC procedures with a median number of 2 interventions per patient (range, 1-6). A laparoscopic access was used and a combined therapy of cisplatin and doxorubicin aerosol was administered. The median peritoneal carcinomatosis index before the 1st PIPAC was 14 (range, 2-36), and the median ascites volume in patients before the 1st PIPAC was 100 mL (range, 0-6 mL, 300 mL). Eleven patients, who received 2 or more PIPAC procedures, had decreased and stable volumes of ascites, while only 3 patients displayed increasing volume of ascites. The median overall survival was 121 days (range, 66-625 days) after the 1st PIPAC procedure, while 8 patients who received more than 3 PIPAC procedures had a median survival of 450 days (range, 206-481 days) (P=0.0376). Our data show that PIPAC is safe and well tolerated, and that the production of ascites can be controlled by PIPAC in GC patients. Patients, who received 2 or more PIPAC procedures, reported a stable overall quality of life. Further studies are required to document the significance of PIPAC as a palliative multimodal therapy. ClinicalTrials.gov Identifier: NCT03100708.
    Keywords: Gastric Cancer ; Pipac ; Palliative Chemotherapy ; Peritoneal Metastasis
    ISSN: 2093-582X
    E-ISSN: 20935641
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  • 6
    In: 世界胃肠病学杂志:英文版 - World Journal of Gastroenterology, 2008, Vol.14(24), pp.3773-3780
    Description: Carcinomas of the stomach and gastroesophageal junction are among the five top leading cancer types worldwide. In spite of radical surgical R0 resections being the basis of cure of gastric cancer, surgery alone provides long-term survival in only 30% of patients with advanced International Union Against Cancer (UICC) stages in Western countries because of the high risk of recurrence and metachronous metastases. However, recent large phase-Ⅲ studies improved the diagnostic and therapeutic options in gastric cancers, indicating a more multidisciplinary management of the disease. Multimodal strategies combining different neoadjuvant and/or adjuvant protocols have clearly improved the gastric cancer prognosis when combined with surgery with curative intention. In particular, the perioperative (neoadjuvant, adjuvant) chemotherapy is now a well-established new standard of care for advanced tumors. Adjuvant therapy alone should be carefully discussed after surgical resection, mainly in individual patients with large lymph node positive tumors when neoadjuvant therapy could not be done. The palliative treatment options have also been remarkably improved with new chemotherapeutic agents and will further be enhanced with targeted therapies such as different monoclonal antibodies. This article reviews the most relevant literature on the multidisciplinary management of gastric and gastroesophageal cancer, and discusses future strategies toimprove Iocoregional failures.
    Keywords: 胃癌 ; 化疗 ; 辅助剂 ; 胃食管癌 ; Gastric Cancer; Chemotherapy; Chemoradiation; Adjuvant; Neoadjuvant
    ISSN: 1007-9327
    E-ISSN: 22192840
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  • 7
    Language: English
    In: Digestive Diseases, April 2005, Vol.22(4), pp.345-350
    Description: Despite surgical R0 resections, patients with gastric cancer stage UICC II–III have a high risk of recurrence and metachronic metastases. Preliminary evidence exists that adjuvant chemotherapy or neoadjuvant chemo(radio)therapy protocols may improve the prognosis of these patients undergoing surgery of gastric cancer with curative intention. As for palliative regimens, 5-fluorouracil and cisplatin are integral components of such (neo)adjuvant strategies. Upcoming cytostatic agents, i.e. irinotecan, docetaxel, oxaliplatin, and oral fluoropyridines are currently under investigation in new multimodality treatment regimens and may further increase R0 resection rates and may prolong disease-free and overall survival in the treatment of advanced localized gastric cancer.
    Keywords: Review Article ; Gastric Cancer ; Chemotherapy ; Adjuvant/Neoadjuvant Therapy ; Chemoradiation ; Taxanes ; Irinotecan ; Oxaliplatin ; Docetaxel ; Medicine
    ISBN: 9783805579230
    ISBN: 3805579233
    ISSN: 0257-2753
    E-ISSN: 1421-9875
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  • 8
    In: Cancer Medicine, October 2018, Vol.7(10), pp.5057-5065
    Description: Genetic associations between variants on chromosome 5p13 and 8q24 and gastric cancer () have been previously reported in the Asian population. We aimed to replicate these findings and to characterize the associations at the genome and transcriptome level. We performed a fine‐mapping association study in 1926 patients and 2012 controls of European descent using high dense marker sets on both chromosomal regions. Next, we performed expression quantitative trait locus () analyses using gastric transcriptome data from 143 individuals focusing on the associated variants. On chromosome 5p13 the strongest association was observed at rs6872282 ( = 2.53 × 10) and on chromosome 8q24 at rs2585176 ( = 1.09 × 10). On chromosome 5p13 we found cis‐ effects with an upregulation of 4 expression in risk allele carrier ( = 9.27 × 10). On chromosome 8q24 we observed cis‐ effects with an upregulation of expression in risk allele carrier ( = 2.17 × 10). In addition, we found trans‐ effects for the same variants on 8q24 with a downregulation of 7 expression in risk allele carrier ( = 3.11 × 10). In summary, we confirmed and refined the previously reported associations at both chromosomal regions. Our data point to shared etiological factors between Asians and Europeans. Furthermore, our data imply an upregulated expression of 4 and as well as a downregulated expression of 7 in gastric tissue as risk‐conferring pathomechanisms. Genetic variants at chromosome 5p13 and 8q24 contribute to gastric cancer (GC) risk. Expression quantitative trait loci (eQTLs) involving PTGER4 (5p13), PSCA (8q24), and MBOAT7 may act as underlying pathomechanisms.
    Keywords: Eqtl Study ; Gene Expression ; Genetic Association Study ; Stomach Neoplasms
    ISSN: 2045-7634
    E-ISSN: 2045-7634
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  • 9
    Language: English
    In: Langenbeck's Archives of Surgery, 2005, Vol.390(2), pp.148-155
    Description: Against the background of the continuing controversy as to the surgical procedure of choice for gastric cancer, the aim of the present study was to evaluate perioperative morbidity, prognostic factors of survival, and long-term survival after subtotal, abdominal and abdominothoracic gastrectomy in patients with gastric cancer. Between January 1993 and December 2002, 338 consecutive patients underwent surgery for adenocarcinoma of the stomach. Subtotal gastrectomy was carried out in 80 (23.7%) patients; 240 (71.0%) patients had abdominal gastrectomy, and 18 (5.3%) underwent abdominothoracic gastrectomy. At an overall 30-day mortality of 3.6% (hospital mortality, 5.2%), the total complication rate was 16.3%. The estimated 5-year survival rate was 43% in patients after subtotal gastrectomy, 39% in patients with abdominal gastrectomy, and 28% in patients with abdominothoracic gastrectomy after complete tumour clearance, without significant differences between the groups. Patients who underwent left pancreatectomy and had a higher ratio of metastatic/dissected lymph nodes were characterised by a significantly poorer prognosis. The lower morbidity and mortality rate with a nearly identical long-term survival yielded by subtotal gastrectomy compared with total gastrectomy leads us to justify subtotal gastrectomy, especially in elderly patients with comorbidity and a high operative risk, on the condition that its performance is radical from an oncological point of view.
    Keywords: Gastric cancer ; Perioperative morbidity ; Prognosis ; Subtotal ; Total gastrectomy
    ISSN: 1435-2443
    E-ISSN: 1435-2451
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  • 10
    In: Oncotarget, 2019, Vol.10(46), p.4731-4742
    Description: Purpose: Presence of tumor-associated macrophages (TAM) and high levels of ferritin and lipocalin 2 (Lcn2) in the tumor microenvironment are associated with poor prognosis in many types of cancer. Here we investigate whether iron deprivation influences TAM phenotype and chemotherapy resistance in tumor slice cultures (TSC) of gastric cancer. Results: TAM remained morphologically and functionally stable for four DIV. DFO treatment for 72 h decreased ferritin expression in TAM and in the tumor stroma but did not alter Lcn2 expression. TAM phenotype was altered after 72 h of cisplatin or DFO treatment compared with control conditions. Single DFO treatment and combined treatment with cytotoxic drugs significantly increased tumor cell apoptosis in TSC of gastric cancer. Methods: TSC were manufactured by cutting tissue of gastric cancer resection specimens in 350 μm thick slices and cultivating them under standard conditions on a filter membrane, at an air-liquid interface. After 24 h ex vivo , TSC were treated with irinotecan (100 nM) or cisplatin (10 μM) alone and in combination with deferoxamine (DFO; 10 μM, 100 μM), respectively, for 72 h. After four days in vitro (DIV) the TSC were fixated with paraformaldehyde, paraffin embedded and analyzed by immunohistochemistry for apoptosis (cPARP), proliferation (Ki67), TAM (CD68, CD163), ferritin, and Lcn2 expression. Conclusions: TAM are well preserved and can be studied in TSC of gastric cancer. Iron deprivation significantly increased tumor cell apoptosis.
    Keywords: Research Paper ; Tumor-Associated Macrophages ; Tumor Slice Cultures ; Deferoxamine ; Gastric Cancer ; Iron
    E-ISSN: 1949-2553
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