Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although cisplatin has been shown to induce both apoptosis and necrosis in cancer cells, the potential interconnections between these modes of cell death induced by the drug remain unknown. We studied this phenomenon in gastric cancer cell lines and identified one cell line (SGC-7901) that underwent apoptosis, and another cell line (BGC-823) that primarily underwent nonapoptotic cell death, in response to cisplatin. Apoptosis in cisplatin-treated SGC-7901 cells seemed to be caspase dependent and was mediated, at least in part, by the BH3-only protein, Noxa. This was evidenced by the rapid upregulation of Noxa and inhibition of apoptosis by small interfering RNA knockdown of Noxa. Nonapoptotic cell death induced by cisplatin in BGC-823 cells was characterized by lack of DNA fragmentation, delayed externalization of phosphatidylserine, caspase independence, plasma membrane disruption, and intracellular vacuole formation, indicative of necrosis. Surprisingly, blockage of apoptosis induction by a general caspase inhibitor or by Noxa small interfering RNA in SGC-7901 failed to protect against cisplatin-induced cell death. Under such conditions, SGC-7901 cells displayed cellular features associated with necrosis. Cisplatin-induced apoptosis, thus, seems to precede necrosis when the apoptotic machinery is operative. When the apoptosis program is defective, necrotic cell death takes place as an alternative pathway leading to cell demise. Induction of different modes of cell death that are interrelated in the same cells by cisplatin has the potential to be exploited in formulating new adjuvant cancer therapies.
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PMID:Inhibition of apoptosis facilitates necrosis induced by cisplatin in gastric cancer cells. 1817 12

There are few reports on use of symptomatic benefits as an alternative or adjunctive for the assessment of objective response in chemotherapy of the advanced cancer. This study is performed to assess the symptomatic benefits (the clinical benefit response), in addition to the efficacy and toxicity of cisplatin plus infusional 5-fluorouracil (5-FU) combination as second-line therapy in patients with advanced gastric cancer. Fifty-eight advanced gastric cancer patients with previous chemotherapy were enrolled into the study. Cisplatin 20 mg/m(2) was given for 5 days, and 5-FU was given 1000 mg/m(2) as 20 h continuous infusion for 5 days, repeated every 28 days. The overall objective response rate was 11.3%, and overall tumour control rate was 33.9%. The clinical benefit response, in terms of weight gain, reduction in analgesic consumption and the improvement in performance status observed in 12 patients [six patients with partial response (PR) and six patients with stable disease (SD)] (22.6%), while the rates of the clinical benefit response in patients with PR and with SD were 100% and 50% respectively. Cisplatin plus infusional 5-FU combination seems to improve disease-related symptoms (clinical benefit response) of patients with advanced gastric cancer, even in patients without objective response.
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PMID:The symptomatic benefit (the clinical benefit response) from the second-line chemotherapy in patients with advanced gastric adenocarcinoma. 1818 88

This study investigated the expression of TRAIL and its receptors in human gastric cancer and normal gastric tissues, the effects of rh-TRAIL with or without chemotherapeutic drugs in apoptosis of the gastric cancer cell line SGC7901 and the expression changes of DR4 and DR5 in SGC7901 cells influenced by chemotherapeutic drugs. The expression of TRAIL, DR4 and DcR1 were studied in 34 cases of human gastric cancer tissues and 15 cases of adjacent normal mucosa tissues, as well as 21 cases of distant normal mucosa tissues by means of immunohistochemistry. In addition, the expression of FasL were studied in gastric cancer tissues by immunohistochemistry. The effects of treatment with rh-TRAIL alone and/or chemotherapeutic drugs on SGC7901 cell growth inhibition were measured by MTT assay and the mRNA changes of DR4 and DR5 were detected by RT-PCR technique. The expression of TRAIL, DR4 and DcR1 in gastric cancer were lower than those of normal tissues (P<0.05). There was significant relationship between the expression of TRAIL and Borrmann type of gastric cancer (P=0.039), and so was the expression of DcR1 and tumor location (P=0.01). The correlation coefficient between the expression of TRAIL and FasL was 0.354 (P=0.04). Rh-TRAIL protein had inhibiting effect on the growth of SGC7901 cells. DDP and 5-FU increased the growth-inhibiting ability of rh-TRAIL to SGC7901 cells. DDP facilitated the induction of expression of DR4 and DR5 significantly in cell line (P<0.05), but 5-FU influenced only the expression of DR5 significantly. From the results, we concluded that the expression of TRAIL and its receptors were lower in gastric cancer than those of normal tissue, and the apoptosis-inducing effect of rh-TRAIL was enhanced when concomitant with chemotherapeutic drugs.
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PMID:The expression of TRAIL and its receptors in gastric cancer and the apoptotic effect of rh-TRAIL on SGC7901 cells. 1921 26

A cisplatin (DDP) resistant cell line (SGC7901/DDP) from a Chinese gastric cancer cell line (SGC7901) was established by step-increasing DDP treatment, and the resultant cell line showed an over 21.9-fold increased resistance to DDP. To identify the mechanism of DDP resistance, the differential gene expression panel was examined by Affymetrix microarray. Among the identified differential genes, 681 genes expression were increased and 1139 genes were decreased. To confirm these gene changes furtherly, one of the upregulated gene, MRP4 was identified with increased mRNA and protein level of SGC7901/DDP by RT-PCR and Western-blot analysis compared with its parental cell line. By using the small interfering RNA (RNAi) to decrease the MRP4 expression, the DDP resistance phenotype of SGC7901/DDP was reversed. These data suggest that MRP4 is a DDP resistance candidate gene of SGC7901 gastric cancer cell line.
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PMID:Silencing MRP4 by small interfering RNA reverses acquired DDP resistance of gastric cancer cell. 1988 72

The patient was a 76-year-old Japanese woman suffering from a left cervical tumor. An endoscopic examination revealed type 3 gastric cancer in the middle body of the stomach. 18FDG-PET-CT demonstrated distant multiple lymph node metastases in cervical, supraclavicular and superior mediastinum. Histopathological study showed poorly-differentiated adenocarcinoma in both stomach and supraclavicular lymph node. Serum CA19-9 was 794 U/mL. Since a curative operation was deemed impossible, S-1(100 mg/body) was administered orally for 21 consecutive days with a 14-day interval as one course combined with intravenous Lentinan (2 mg/body) once a week. Cisplatin (CDDP 60 mg/m2) was infused on day 8. The serum CA19-9 level decreased to 176 U/mL after a course of the regimen, to 39 U/mL after the second course, and to the normal level after the 3rd course finally. However, gastric endoscopic biopsy still showed a remnant malignant lesion. After 5 courses of the chemotherapy, both the primary lesion and the distant lymph node swelling disappeared on gastroscopy and PET-CT, respectively, which was a so-called complete response(CR). After that, only S-1 was administered for 3 weeks followed by a drug-free week as a course. The patient has now been in good health without a recurrence for 4 months after recognition of CR.
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PMID:[A case of advanced gastric cancer with distant lymph node metastases in cervical, supraclavicular and superior mediastinum successfully treated with S-1/Cisplatin (CDDP)/Lentinan combination chemotherapy]. 2041 31

FTY720, a new immunosuppressant, derived from ISP-1, has been studied for its putative anti-cancer properties in the recent years. In this study, we have reported that FTY720 greatly inhibited gastric cancer cell proliferation for the first time, and found this effect was associated with G1 phase cell cycle arrest and apoptosis. Results from our Western blotting and Real-time PCR showed that FTY720 induced obvious PTEN expression in a p53-independent way, consistent with a substantial decrease in p-Akt and MDM2. FTY720 dramatically increased the expression of Cip1/p21, p27, and BH3-only proteins through the accumulation of p53 by PTEN-mediated inhibition of the PI3K/Akt/MDM2 signaling. Suppression of PTEN expression with siRNA significantly reduced the p53 and p21 levels and activated Akt, resulting in decreased apoptosis and increased cell survival. Furthermore, we have observed an additive effect of FTY720 in killing gastric cancer cells when in combination with Cisplatin, partly through PTEN-mediated Akt/MDM2 inhibition. In vivo study has also shown that tumor growth was significantly suppressed after FTY720 treatment. In conclusion, our results suggest that FTY720 induces a significant increase of PTEN, which inhibits p-Akt and MDM2, and then increases the level of p53, thereby inducing G1 phase arrest and apoptosis. We have characterized a novel immunosuppressant, for the first time, which shows potential anti-tumor effects on gastric cancer by PTEN activation through p53-independent mechanism, especially in combination with Cisplatin. This PTEN target-based therapy is worth further investigation and warrants clinical evaluation.
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PMID:PTEN- and p53-mediated apoptosis and cell cycle arrest by FTY720 in gastric cancer cells and nude mice. 2050 84

Background. Intraperitoneal (i.p.) chemotherapy is frequently utilized in patients with advanced gastric cancer or peritoneal dissemination. We investigated whether i.p. administration of cisplatin at high or low doses would impair host local immunity with respect to the induction of natural killer (NK) cell suppressive factor in the murine peritoneal cavity. Methods. Cisplatin was administered at a total dose of 10 mg/kg according to two schedules: high-dose bolus injection (HB; 10 mg/kg) and low-dose consecutive injections (LC; 2 mg/kg daily for 5 days). The supernatant obtained from the peritoneal lavage fluid was added during normal splenocyte-mediated NK cytotoxicity assay. The phenotypes of peritoneal exudate cells were analyzed using anti-F4/80 monoclonal antibody (MAb) and anti-I-A MAb. Results. NK cell activity was significantly inhibited by the supernatant obtained from the HB group 7 days after the administration of cisplatin (40.6% of NK cell activity in controls; P < 0.05). This inhibition was partly restored by prostaglandin E(2) (PGE(2)) antiserum (69.5% of NK cell activity in controls). NK cell activity was not inhibited at any point by exposure to the supernatant of the LC group. I-A(-) peritoneal macrophages were more abundant in the HB group than in the LC group (2.9 x 10(6) vs 4.6 x 10(5) on day 3; P < 0.05). Conclusion. These results suggest that intraperitoneal bolus administration of high-dose cisplatin induces NK suppressive factors, including PGE(2), in the peritoneal cavity, whereas low-dose consecutive administration does not.
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PMID:Induction of natural killer suppressive factor in murine peritoneal cavity by intraperitoneal bolus administration of high-dose cisplatin. 2056 97

The effect of trastuzumab on patients with HER-2/neu (HER2)-positive gastric cancer has been confirmed in a phase III clinical trial (ToGA study). However, the optimized sequence and synergic mechanism of trastuzumab and chemotherapy are not clear. Our study investigated the effects and mechanisms of trastuzumab in combination with 5-Fluorouracil (5-Fu) or cisplatin (DDP) on gastric cancer cell lines. Flow cytometry was used to determine HER2 expression and cell cycle. MTT assay was performed to evaluate cytotoxicity. Western blotting and RT-PCR were used to analyze signaling transduction and mRNA expression. Sequential 5-Fu followed by trastuzumab and trastuzumab plus DDP followed by trastuzumab produced the best inhibitory effects. Inhibition of HER2-PI3K-AKT signal transduction, downregulation of nucleotide excision repair cross-complementation 1 (ERCC1), and interference with cell cycle distribution may elucidate the synergism between trastuzumab and chemotherapy. These results provide some evidence for designing a rational regime when trastuzumab is being considered to be used in patients with gastric cancer.
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PMID:The sequence-dependent cytotoxic effect of trastuzumab in combination with 5-Fluorouracil or cisplatin on gastric cancer cell lines. 2059 Apr 42

This report presents a case of highly advanced gastric cancer that achieved a histologically complete response (CR) to preoperative chemoradiotherapy with S-1 plus low-dose Cisplatin. A 60-year-old male patient underwent FDG positron emission tomography (PET) during a routine health examination. The patient was found to have swollen paraaortic lymph nodes. Shortly thereafter, he was diagnosed with gastric carcinoma with a type 2 tumor in the antrum with paraaortic lymph node metastases based on FDG-PET, endoscopic examination and abdominal computed tomography. After the completion of chemoradiation therapy (CRT), the tumor and the paraaortic lymph node metastases disappeared. The patient underwent surgery 5 wk after the completion of CRT, including a subtotal gastrectomy with Roux-en-Y reconstruction, D3 lymph node dissection and a left adrenalectomy. No cancer cells were detected in the resected specimen either in the primary lesion or lymph nodes, thus confirming a pathologically CR to CRT (CR grade 3). The patient has been stable and well without any evidence of recurrence for 48 mo after surgery. Such a preoperative CRT regimen might therefore be very effective for treatment of some advanced gastric cancers.
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PMID:Complete response to preoperative chemoradiotherapy in highly advanced gastric adenocarcinoma. 2116 Jun 41

Gastric cancer-the second most common cause of cancer-related deaths worldwide-is a global health problem. Most cases present at advanced stages and are incurable due to locally advanced or metastatic disease. Although advanced gastric cancer is relatively chemosensitive, a gold standard chemotherapy regimen has yet to emerge, and response rates are of short duration. Cisplatin and 5-fluorouracil (CF) have emerged as the backbone agents in treating this disease. The pivotal V325 trial demonstrated the efficacy benefit of adding docetaxel to CF (DCF). DCF, however, is associated with significant toxicity, making it less tolerable to patients. As a result, docetaxel-containing regimens have been extensively studied and improved upon to mitigate toxicity while maintaining efficacy. Various dosing and scheduling permutations of the original DCF regimen have emerged, and substitutions with other 5-fluorouraci and platinum analogs have been studied. In this review we highlight some of these studies using docetaxel-based regimens as well as new approaches using targeted therapy, including monoclonal antibodies and tyrosine kinase inhibitors. Continuing efforts to improve the efficacy and tolerability of docetaxel-based chemotherapy, combining pharmacokinetic parameters and pharmacogenetic correlates, will further assist in developing optimized regimens. Emerging data using targeted therapy and biologics in combination with chemotherapy are promising, but results of ongoing studies are required to establish the safety and efficacy of these regimens.
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PMID:Refining docetaxel-containing therapy for gastric cancer. 2204 25


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