Receptor tyrosine kinases (RTKs) such as the epidermal growth factor receptor family participate in several steps of tumor formation including proliferation and metastatic spread. Several known RTKs are upregulated ...Receptor tyrosine kinases (RTKs) such as the epidermal growth factor receptor family participate in several steps of tumor formation including proliferation and metastatic spread. Several known RTKs are upregulated in gastric cancer being prime targets of a tailored therapy. Only preliminary data exist, however, on the use of the currently clinically available drugs such as trastuzumab, cetuximab, bevacizumab, gefitinib, erlotinib, and imatinib in the setting of gastric cancer. Preclinical data suggest a potential benefit of their use, especially in combination with "conventional" cytostatic therapy. This review summarizes the current knowledge about their use in cancer therapy as well as new approaches and drugs to optimize treatment success.展开更多
AIM: To investigate the therapeutic effects of DA-9601 on sodium taurocholate (TCA)-induced chronic reflux gastritis in SD rats.METHODS: In this study, we have investigated the therapeutic effects of DA-9601 on chroni...AIM: To investigate the therapeutic effects of DA-9601 on sodium taurocholate (TCA)-induced chronic reflux gastritis in SD rats.METHODS: In this study, we have investigated the therapeutic effects of DA-9601 on chronic erosive and atrophic gastritis induced by 6 mo of TCA administration (5 mmol/L in drinking water) in SD rats. RESULTS: Four weeks of DA-9601 administration (0.065%, 0.216% in rat chow), following the withdrawal of TCA treatment, resulted in a significant decrease in total length of erosions in rats in a dose-dependent manner. Furthermore, the indicators of atrophic gastritis, such as reduced mucosal thickness and reduction in the number of parietal cells, were improved by the administration of DA-9601 in a dose-related manner. DA-9601 also attenuated inflammatory cell infiltration and the proliferation of collagenous fiber in the gastric mucosa. The improvement in the reduction of the gastric mucus was observed in the rats receiving a high dose of DA-9601 (0.216%). The therapeutic effect of DA-9601 on experimental chronic erosive gastritis was superior to that of rebamipide (1.08% in rat chow). Biochemical analyses showed increased mucosal prostaglandin E2 and reduced glutathione levels by DA-9601 treatment. CONCLUSION: We suggest that DA-9601 is apromising agent for the treatment of chronic erosive and atrophic gastritis with an etiological factor of bile reflux. Increasedmucosal prostaglandin E2 and reduced glutathione by DA-9601 treatment may be therapeutic mechanisms for chronic erosive and atrophic gastritis.展开更多
AIM: To investigate the prognostic role of thymidylate synthase (TS) and thymidine phosphorylase (TP) mRNA levels in T3 or T4 gastric cancer treated with 5-fluorouraci-based adjuvant chemotherapy. METHODS: Fifty...AIM: To investigate the prognostic role of thymidylate synthase (TS) and thymidine phosphorylase (TP) mRNA levels in T3 or T4 gastric cancer treated with 5-fluorouraci-based adjuvant chemotherapy. METHODS: Fifty-one patients with T3 or T4 gastric cancer received systemic 5-fluorouraci-based adjuvant chemotherapy, and intratumoral expression of TS and TP in 51 gastric cancer tissue samples was tested by realtime quantitative PCR.RESULTS: The median disease-free survival (DFS) time was 10.2 mo in the patients. There were no significant differences in DFS between the groups with high and low levels of TP. However, the group with low level of TS had a longer DFS (14.4 mo vs 8.3 mo, P = 0.017). The median overall survival (OS) time was 18.5 mo, and there were significant differences in OS between the groups with high and low levels of TS or TP (for TS, 17.0 mo vs 21.3 mo, P = 0.010; for TP, 16.6 mo vs 22.5 too, P = 0.009). Moreover, the coupled low expression of these two genes was strongly associated with a longer survival time of patients as compared with that of a single gene.CONCLUSION: Expression of TS and TP mRNA is a useful predictive parameter for the survival of postoperative gastric cancer patients after 5-fluorouracilbased adjuvant chemotherapy.展开更多
AIM: Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoforms of kit kinase or platelet-derived growth factor receptor alpha (PDGFRA), which are potential therapeutic targets ...AIM: Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoforms of kit kinase or platelet-derived growth factor receptor alpha (PDGFRA), which are potential therapeutic targets for imatinib mesylate (Glivec). Partial response occurred in almost two thirds of GIST patients treated with Glivec. However, complete response (CR) after Glivec therapy was sporadically reported. Here we illustrated advanced GIST patients with CR after Glivec treatment. METHODS: Between January 2001 and June 2005, 42 advanced GIST patients were treated with Glivec. Patients were administered 400 mg of Glivec in 100-mg capsules, taken orally daily with food. The response of the tumor to Glivec was evaluated after one month, three months, and every three months thereafter or whenever medical need was indicated. Each tumor of patients was investigated for mutations of kit or PDGFRA. RESULTS: The median follow-up time of the 42 ad-vanced GIST patients treated with Glivec was 16.9 months (range, 1.0- 47.0 months). Overall, 3 patients had complete response CR (7.1%), 26 partial response (67.8%), 5 stationary disease (11.9%), and 3 progressive disease (11.9%). The median duration of Glivec administration for the three patients was 36 months (range, 23-36 months). The median time to CR after Glivec treatment was 20 months (range, 9-26 months). Deletion and insertion mutations of c-kit exon 11 and insertion mutation of c-kit exon 9 were found in two cases and one case, respectively. CONCLUSION: Complete response (CR) can be achieved in selected advanced GIST patients treated with Glivec. The median time to CR after Glivec treatment was 20 months. Deletion and insertion mutations of kit exon 11 and insertion mutation of kit exon 9 contribute to the genetic features in these selected cases.展开更多
OBJECTIVE To examine the therapeutic effects and toxicity of high-dose-folinic acid plus a 5-fluorouracil(5-FU)bolus and continuous infusion with 5-FU combined with locally produced oxaliplatin(L-HOP)in treating advan...OBJECTIVE To examine the therapeutic effects and toxicity of high-dose-folinic acid plus a 5-fluorouracil(5-FU)bolus and continuous infusion with 5-FU combined with locally produced oxaliplatin(L-HOP)in treating advanced gastric carcinoma patients. METHODS Sixty-five patients with advanced gastric carcinoma were treated with high-dose-folinic acid plus a 5-FU bolus and a 48-h continuous infusion of 5-FU combined with oxaliplatin.The effects of treatment and toxicity were observed. RESULTS There were 4 complete responses,26 partial responses, 30 with no change and 5 with progressive disease.The overall effective response rate was 46.2%(30/65).The median duration was 7 months,with the main side effects including nausea and vomiting,peripheral phlebitis,alopecia,leukopenia,dental ulcers, peripheral neuritis and diarrhea.All the side effects were tolerated and minimal. CONCLUSION The results showed that high-dose folinic acid plus a 5-FU bolus and continuous infusion of 5-FU combined with oxaliplatin appears to be a safe and effective therapy for patients with advanced gastric carcinoma.This therapeutic regimen is of value for these patients.展开更多
In this article, we have reviewed the main therapeutic measures for the treatment of Zollinger-Ellison syndrome (ZES). Review of the literature was based on computer searches (Pub-Med, Index Medicus) and personal ...In this article, we have reviewed the main therapeutic measures for the treatment of Zollinger-Ellison syndrome (ZES). Review of the literature was based on computer searches (Pub-Med, Index Medicus) and personal experiences. We have evaluated all the measures now available for treating patients with sporadic gastrinomas or gastrinomas associated with Multiple Endocrine Neoplasia Type 1, (MEN 1) including medical therapy such as antisecretory drugs and somatostatin analogs (SST), chemotherapy and chemoembolization, and surgical procedures. In ZES patients, the best therapeutic procedure is surgery which, if radical, can be curative. Medical treatment can be the best palliative therapy and should be used, when possible, in association with surgery, in a multimodal therapeutic approach.展开更多
Gastrointestinal stromal tumors (GIST) are rare mesenchymal smooth muscle sarcomas that can arise anywhere within the gastrointestinal tract. Sporadic mutations within the tyrosine kinase receptors of the interstitial...Gastrointestinal stromal tumors (GIST) are rare mesenchymal smooth muscle sarcomas that can arise anywhere within the gastrointestinal tract. Sporadic mutations within the tyrosine kinase receptors of the interstitial cells of Cajal have been identified as the key molecular step in GIST carcinogenesis. Although many patients are asymptomatic, the most common associated symptoms include: abdominal pain, dyspepsia, gastric outlet obstruction, and anorexia. Rarely, GIST can perforate causing life-threatening hemoperitoneum. Most are ultimately diagnosed on cross-sectional imaging studies (i.e., computed tomography and/or magnetic resonance imaging in combination with upper endoscopy. Endoscopic ultrasonographic localization of these tumors within the smooth muscle layer and acquisition of neoplastic spindle cells harboring mutations in the c-KIT gene is pathognomonic. Curative treatment requires a complete gross resection of the tumor. Both open and minimally invasive operations have been shown to reduce recurrence rates and improve long-term survival. While there is considerable debate over whether GIST can be benign neoplasms, we believe that all GIST have malignant potential, but vary in their propensity to recur after resection and metastasize to distant organ sites. Prognostic factors include location, size (i.e., > 5 cm), grade (> 5-10 mitoses per 50 high power fields and specific mutational events that are still being defined. Adjuvant therapy with tyrosine kinase inhibitors, such as imatinib mesylate, has been shown to reduce the risk of recurrence after one year of therapy. Treatment of locally-advanced or borderline resectable gastric GIST with neoadjuvant imatinib has been shown to induce regression in a minority of patients and stabilization in the majority of cases. This treatment strategy potentially reduces the need for more extensive surgical resections and increases the number of patients eligible for curative therapy. The modern surgical treatment of gastric GIST combines the novel use of targeted therapy and aggressive minimally invasive surgical procedures to provide effective treatment for this lethal, but rare gastrointestinal malignancy.展开更多
The Clinical Practice Guideline on Acupuncture and Moxibustion:Gastroesophageal Reflux Disease(GERD)(WFAS 007.9-2023),officially released by the World Federation of Acupuncture-Moxibustion Societies(WFAS)on October 9,...The Clinical Practice Guideline on Acupuncture and Moxibustion:Gastroesophageal Reflux Disease(GERD)(WFAS 007.9-2023),officially released by the World Federation of Acupuncture-Moxibustion Societies(WFAS)on October 9,2023,represents the inaugural acupuncture and moxibustion clinical practice guideline dedicated to GERD globally.This guideline outlines its purpose,scope,target audience,and relevant environments,along with detailing the acupuncture and moxibustion treatment methodology for GERD,as well as the guideline development process and recommendations.This article specifically emphasizes the recommendations of the guideline,highlighting the crucial importance of both the dissemination and adherence to this guideline to standardize acupuncture and moxibustion treatments for GERD.Such standardization plays a pivotal role in the advancement and widespread utilization of acupuncture and moxibustion in the management of GERD.展开更多
Gastric cancer imposes a considerable health burden worldwide, and its mortality ranks as the second highest for all types of cancers. The limited knowledge of the molecular mechanisms underlying gastric cancer tumori...Gastric cancer imposes a considerable health burden worldwide, and its mortality ranks as the second highest for all types of cancers. The limited knowledge of the molecular mechanisms underlying gastric cancer tumorigenesis hinders the development of therapeutic strategies. However, ongoing collaborative sequencing efforts facilitate molecular classification and unveil the genomic landscape of gastric cancer. Several new drivers and tumorigenic pathways in gastric cancer, including chromatin remodeling genes, Rho A-related pathways, TP53 dysregulation, activation of receptor tyrosine kinases, stem cell pathways and abnormal DNA methylation, have been revealed. These newly identified genomic alterations await translation into clinical diagnosis and targeted therapies. Considering that loss-of-function mutations are intractable, synthetic lethality could be employed when discussing feasible therapeutic strategies. Although many challenges remain to be tackled, we are optimistic regarding improvements in the prognosis and treatment of gastric cancer in the near future.展开更多
基金Supported by a grant from the IMF (innovative medical research fund), No. PO210205, University of Munster, Germany
文摘Receptor tyrosine kinases (RTKs) such as the epidermal growth factor receptor family participate in several steps of tumor formation including proliferation and metastatic spread. Several known RTKs are upregulated in gastric cancer being prime targets of a tailored therapy. Only preliminary data exist, however, on the use of the currently clinically available drugs such as trastuzumab, cetuximab, bevacizumab, gefitinib, erlotinib, and imatinib in the setting of gastric cancer. Preclinical data suggest a potential benefit of their use, especially in combination with "conventional" cytostatic therapy. This review summarizes the current knowledge about their use in cancer therapy as well as new approaches and drugs to optimize treatment success.
基金Supported by the grant from Korean Ministry of Health and Welfare, HMP-98-D-1-0007
文摘AIM: To investigate the therapeutic effects of DA-9601 on sodium taurocholate (TCA)-induced chronic reflux gastritis in SD rats.METHODS: In this study, we have investigated the therapeutic effects of DA-9601 on chronic erosive and atrophic gastritis induced by 6 mo of TCA administration (5 mmol/L in drinking water) in SD rats. RESULTS: Four weeks of DA-9601 administration (0.065%, 0.216% in rat chow), following the withdrawal of TCA treatment, resulted in a significant decrease in total length of erosions in rats in a dose-dependent manner. Furthermore, the indicators of atrophic gastritis, such as reduced mucosal thickness and reduction in the number of parietal cells, were improved by the administration of DA-9601 in a dose-related manner. DA-9601 also attenuated inflammatory cell infiltration and the proliferation of collagenous fiber in the gastric mucosa. The improvement in the reduction of the gastric mucus was observed in the rats receiving a high dose of DA-9601 (0.216%). The therapeutic effect of DA-9601 on experimental chronic erosive gastritis was superior to that of rebamipide (1.08% in rat chow). Biochemical analyses showed increased mucosal prostaglandin E2 and reduced glutathione levels by DA-9601 treatment. CONCLUSION: We suggest that DA-9601 is apromising agent for the treatment of chronic erosive and atrophic gastritis with an etiological factor of bile reflux. Increasedmucosal prostaglandin E2 and reduced glutathione by DA-9601 treatment may be therapeutic mechanisms for chronic erosive and atrophic gastritis.
文摘AIM: To investigate the prognostic role of thymidylate synthase (TS) and thymidine phosphorylase (TP) mRNA levels in T3 or T4 gastric cancer treated with 5-fluorouraci-based adjuvant chemotherapy. METHODS: Fifty-one patients with T3 or T4 gastric cancer received systemic 5-fluorouraci-based adjuvant chemotherapy, and intratumoral expression of TS and TP in 51 gastric cancer tissue samples was tested by realtime quantitative PCR.RESULTS: The median disease-free survival (DFS) time was 10.2 mo in the patients. There were no significant differences in DFS between the groups with high and low levels of TP. However, the group with low level of TS had a longer DFS (14.4 mo vs 8.3 mo, P = 0.017). The median overall survival (OS) time was 18.5 mo, and there were significant differences in OS between the groups with high and low levels of TS or TP (for TS, 17.0 mo vs 21.3 mo, P = 0.010; for TP, 16.6 mo vs 22.5 too, P = 0.009). Moreover, the coupled low expression of these two genes was strongly associated with a longer survival time of patients as compared with that of a single gene.CONCLUSION: Expression of TS and TP mRNA is a useful predictive parameter for the survival of postoperative gastric cancer patients after 5-fluorouracilbased adjuvant chemotherapy.
文摘AIM: Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoforms of kit kinase or platelet-derived growth factor receptor alpha (PDGFRA), which are potential therapeutic targets for imatinib mesylate (Glivec). Partial response occurred in almost two thirds of GIST patients treated with Glivec. However, complete response (CR) after Glivec therapy was sporadically reported. Here we illustrated advanced GIST patients with CR after Glivec treatment. METHODS: Between January 2001 and June 2005, 42 advanced GIST patients were treated with Glivec. Patients were administered 400 mg of Glivec in 100-mg capsules, taken orally daily with food. The response of the tumor to Glivec was evaluated after one month, three months, and every three months thereafter or whenever medical need was indicated. Each tumor of patients was investigated for mutations of kit or PDGFRA. RESULTS: The median follow-up time of the 42 ad-vanced GIST patients treated with Glivec was 16.9 months (range, 1.0- 47.0 months). Overall, 3 patients had complete response CR (7.1%), 26 partial response (67.8%), 5 stationary disease (11.9%), and 3 progressive disease (11.9%). The median duration of Glivec administration for the three patients was 36 months (range, 23-36 months). The median time to CR after Glivec treatment was 20 months (range, 9-26 months). Deletion and insertion mutations of c-kit exon 11 and insertion mutation of c-kit exon 9 were found in two cases and one case, respectively. CONCLUSION: Complete response (CR) can be achieved in selected advanced GIST patients treated with Glivec. The median time to CR after Glivec treatment was 20 months. Deletion and insertion mutations of kit exon 11 and insertion mutation of kit exon 9 contribute to the genetic features in these selected cases.
文摘OBJECTIVE To examine the therapeutic effects and toxicity of high-dose-folinic acid plus a 5-fluorouracil(5-FU)bolus and continuous infusion with 5-FU combined with locally produced oxaliplatin(L-HOP)in treating advanced gastric carcinoma patients. METHODS Sixty-five patients with advanced gastric carcinoma were treated with high-dose-folinic acid plus a 5-FU bolus and a 48-h continuous infusion of 5-FU combined with oxaliplatin.The effects of treatment and toxicity were observed. RESULTS There were 4 complete responses,26 partial responses, 30 with no change and 5 with progressive disease.The overall effective response rate was 46.2%(30/65).The median duration was 7 months,with the main side effects including nausea and vomiting,peripheral phlebitis,alopecia,leukopenia,dental ulcers, peripheral neuritis and diarrhea.All the side effects were tolerated and minimal. CONCLUSION The results showed that high-dose folinic acid plus a 5-FU bolus and continuous infusion of 5-FU combined with oxaliplatin appears to be a safe and effective therapy for patients with advanced gastric carcinoma.This therapeutic regimen is of value for these patients.
文摘In this article, we have reviewed the main therapeutic measures for the treatment of Zollinger-Ellison syndrome (ZES). Review of the literature was based on computer searches (Pub-Med, Index Medicus) and personal experiences. We have evaluated all the measures now available for treating patients with sporadic gastrinomas or gastrinomas associated with Multiple Endocrine Neoplasia Type 1, (MEN 1) including medical therapy such as antisecretory drugs and somatostatin analogs (SST), chemotherapy and chemoembolization, and surgical procedures. In ZES patients, the best therapeutic procedure is surgery which, if radical, can be curative. Medical treatment can be the best palliative therapy and should be used, when possible, in association with surgery, in a multimodal therapeutic approach.
文摘Gastrointestinal stromal tumors (GIST) are rare mesenchymal smooth muscle sarcomas that can arise anywhere within the gastrointestinal tract. Sporadic mutations within the tyrosine kinase receptors of the interstitial cells of Cajal have been identified as the key molecular step in GIST carcinogenesis. Although many patients are asymptomatic, the most common associated symptoms include: abdominal pain, dyspepsia, gastric outlet obstruction, and anorexia. Rarely, GIST can perforate causing life-threatening hemoperitoneum. Most are ultimately diagnosed on cross-sectional imaging studies (i.e., computed tomography and/or magnetic resonance imaging in combination with upper endoscopy. Endoscopic ultrasonographic localization of these tumors within the smooth muscle layer and acquisition of neoplastic spindle cells harboring mutations in the c-KIT gene is pathognomonic. Curative treatment requires a complete gross resection of the tumor. Both open and minimally invasive operations have been shown to reduce recurrence rates and improve long-term survival. While there is considerable debate over whether GIST can be benign neoplasms, we believe that all GIST have malignant potential, but vary in their propensity to recur after resection and metastasize to distant organ sites. Prognostic factors include location, size (i.e., > 5 cm), grade (> 5-10 mitoses per 50 high power fields and specific mutational events that are still being defined. Adjuvant therapy with tyrosine kinase inhibitors, such as imatinib mesylate, has been shown to reduce the risk of recurrence after one year of therapy. Treatment of locally-advanced or borderline resectable gastric GIST with neoadjuvant imatinib has been shown to induce regression in a minority of patients and stabilization in the majority of cases. This treatment strategy potentially reduces the need for more extensive surgical resections and increases the number of patients eligible for curative therapy. The modern surgical treatment of gastric GIST combines the novel use of targeted therapy and aggressive minimally invasive surgical procedures to provide effective treatment for this lethal, but rare gastrointestinal malignancy.
文摘The Clinical Practice Guideline on Acupuncture and Moxibustion:Gastroesophageal Reflux Disease(GERD)(WFAS 007.9-2023),officially released by the World Federation of Acupuncture-Moxibustion Societies(WFAS)on October 9,2023,represents the inaugural acupuncture and moxibustion clinical practice guideline dedicated to GERD globally.This guideline outlines its purpose,scope,target audience,and relevant environments,along with detailing the acupuncture and moxibustion treatment methodology for GERD,as well as the guideline development process and recommendations.This article specifically emphasizes the recommendations of the guideline,highlighting the crucial importance of both the dissemination and adherence to this guideline to standardize acupuncture and moxibustion treatments for GERD.Such standardization plays a pivotal role in the advancement and widespread utilization of acupuncture and moxibustion in the management of GERD.
基金supported by the Science and Technology Commission of Shanghai Municipality (16ZR1410400, 14DZ2270100)the State Scholarship Council (201506145040)
文摘Gastric cancer imposes a considerable health burden worldwide, and its mortality ranks as the second highest for all types of cancers. The limited knowledge of the molecular mechanisms underlying gastric cancer tumorigenesis hinders the development of therapeutic strategies. However, ongoing collaborative sequencing efforts facilitate molecular classification and unveil the genomic landscape of gastric cancer. Several new drivers and tumorigenic pathways in gastric cancer, including chromatin remodeling genes, Rho A-related pathways, TP53 dysregulation, activation of receptor tyrosine kinases, stem cell pathways and abnormal DNA methylation, have been revealed. These newly identified genomic alterations await translation into clinical diagnosis and targeted therapies. Considering that loss-of-function mutations are intractable, synthetic lethality could be employed when discussing feasible therapeutic strategies. Although many challenges remain to be tackled, we are optimistic regarding improvements in the prognosis and treatment of gastric cancer in the near future.