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)

Telomerase, a ribonucleoprotein that adds telomeric repeats onto chromosome ends, is involved in telomere length maintenance and permits unlimited cell proliferation. We examined the possibility that higher telomerase activity is associated with the replicative phase of the cell cycle using gastric cancer cell lines treated with anticancer drugs. Telomerase activity increased at the time point of S-phase accumulation in NUGC-3 cells (5 x 10(5) cells/ml) incubated with CDDP (0.5 microgram/ml), paclitaxel (0.01 microM), or VP-16 (1 microM) and in MKN-28 cells incubated with CDDP. When these cell lines were incubated with 5-fluorouracil (10 microM) or CPT (0.1 microM), the increase of telomerase activity preceded the S-phase accumulation. Our results suggest that telomerase activity be regulated by the cell cycle.
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PMID:[Telomerase activity during the cell cycle in gastric cancer cell lines]. 961 22

Side effects due to administration of anti-cancer drugs often cause the treatment to be abandoned or a decrease in the amount of anti-cancer drugs. Recently, the anti-tumor effects of "low-dose CPT-11", which can be administered at the outpatient clinic, are reported. We performed "low-dose CPT-11 + CDDP" as a neoadjuvant chemotherapy to a patient with advanced gastric cancer. CPT-11 and CDDP combination chemotherapy caused very few side effects, so we could continue the treatment and achieve anti-tumor effects. Consequently, surgery could be performed, but disseminated metastasis was found so that the surgery ended as a non-curative operation. However, it was considered that this method of "low-dose CPT-11 + CDDP" was very effective as the neoadjuvant chemotherapy in a patient with advanced gastric cancer.
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PMID:[A case of advanced gastric cancer treated with neoadjuvant chemotherapy of low-dose CPT-11 + CDDP]. 1143 51

Randomized trials demonstrated the significantly improved survival benefit of 5-fluorouracil (5-FU) based chemotherapy in patients with unresectable advanced gastric cancer (AGC) in comparison with best supportive care (BSC). However there is no chemotherapy considered worldwide to be the standard treatment for AGC and there is no consensus as to whether combination or single agent therapy is preferable. Therefore, 2 large Phase III studies JCOG 9912 5-FU vs TS-1 vs CPT + CDDP and TS-1 vs TS-1 + CDDP are now ongoing to establish an acceptable frontline standard for patients with AGC. We need to develop new agents and combination chemotherapy regimens to achieve greater survival benefit in AGC.
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PMID:[Controversial issues in chemotherapy for inoperable gastric cancer]. 1451 2

The cross talk between cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and RhoA-mediated signal transductions and the effect of this cross talk on biologic features of human prostate and gastric cancer cells were investigated. In the human gastric cancer cell line, SGC-7901, lysophosphatidic acid (LPA) increased RhoA activity in a dose-dependent manner. The cellular permeable cAMP analog, 8-chlorophenylthio-cAMP (CPT-cAMP), inhibited the LPA-induced RhoA activation and caused phosphorylation of RhoA at serine(188). Immunofluorescence microscopy, Western blotting, and green fluorescent protein (GFP)-tagged RhoA location assay in live cells revealed that RhoA was distributed in both the cytoplasm and nucleus of SGC-7901 cells. Treatment with LPA and/or CPT-cAMP did not induce obvious translocation of RhoA in the cells. The LPA treatment caused formation of F-actin in SGC-7901 cells, and CPT-cAMP inhibited the formation. In a modified Boyden chamber assay, LPA stimulated the migration of SGC-7901 cells, and CPT-cAMP dose-dependently inhibited the stimulating effect of LPA. In soft agar assay, LPA stimulated early proliferation of SGC-7901 cells, and CPT-cAMP significantly inhibited the growth of LPA-stimulated cells. In the prostate cancer cell line, PC-3, LPA caused morphologic changes from polygonal to round, and transfection with plasmid DNA encoding constitutively active RhoA(63L) caused a similar change. Treatment with CPT-cAMP inhibited the changes in both cases. However, in PC-3 cells transfected with a plasmid encoding mutant RhoA188A, LPA induced rounding, but CPT-cAMP could not prevent the change. Results of this experiment indicated that cAMP/PKA inhibited RhoA activation, and serine188 phosphorylation on RhoA was necessary for PKA to exert its inhibitory effect on RhoA activation. The cross talk between cAMP/PKA and RhoA-mediated signal transductions had significant affect on biologic features of gastric and prostate cancer cells, such as morphologic and cytoskeletal change, migration, and anchorage-independent growth. The results may be helpful in implementing novel therapeutic strategies for invasive and metastatic prostate and gastric cancers.
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PMID:The cross talk between protein kinase A- and RhoA-mediated signaling in cancer cells. 1624

Degradable starch microspheres (DSMs) provide transient occlusion of small arteries and are thought to improve the therapeutic effect of anticancer drugs. Irinotecan (CPT-11) is one of the most effective anticancer agents. We herein report cases with liver metastases treated with transarterial chemoembolization with DSM, CPT-11, and mitomycin-C (DSM-CPT therapy). Five patients underwent DSM-CPT therapy for liver metastases that originated from colorectal cancer for four and gastric cancer for one. They all lack indication for surgery. They were all male with an age range of 42-78 years (mean, 55.2 years). Three of them had pretreatment histories with 5-fluorouracil or related agents, and four of them had combined systemic or local chemotherapy at the period. Required doses for stasis of whole blood flow of hepatic artery of DSMs were used with CPT-11 and mitomycin-C. After one to six injections, four patients had a partial response and the disease progressed in one patient with gastric cancer origin. Two of the partial response patients underwent surgery after 2 months of the partial response period. Carcinoembryonic antigen and CA19-9 levels in partial response patients decreased to 16.1% and 19.3% of the level before treatment, respectively. DSM-CPT therapy can be a potential therapy for liver metastases.
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PMID:Transarterial chemoembolization with degradable starch microspheres, irinotecan, and mitomycin-C in patients with liver metastases. 1645 58

The patient was a 42-year-old female diagnosed with unresectable highly advanced gastric cancer complicated by peritoneal dissemination. We performed systemic chemotherapy with MTX+5-FU as the first-line treatment, which stabilized the disease. Since the patient initially wished a radical resection, we tried chemotherapy with weekly PTX as a second-line treatment. Her therapeutic response remained between a partial response and a stable disease for about five months, followed, however, by progressive disease. The result of the third-line treatment with CPT-11+CDDP was again a progressive disease, so we switched her regimen to single-agent S-1 as a fourth-line treatment. The ascites disappeared three months after the change in regimen. As of March 2006, the patient had survived for 17 months since diagnosis (8 months since the ongoing S-1 therapy started) and the disease is currently stabilized, and preserving a favorable performance status. However, in June 2006, the patient died of pneumonia 20 months after the diagnosis.
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PMID:[A case of advanced gastric cancer with peritoneal dissemination effectively treated with fourth-line chemotherapy of S-1 alone]. 1756 56

We treated two patients in whom irinotecan (CPT-11)+cisplatin (CDDP) and irradiation showed efficacy against brain metastases of gastric cancer. CPT-11 and CDDP were administered on days 1 and 15 of a 28-day cycle at 60 mg/m(2) and 30 mg/m(2), respectively. The first patient was a 63-year-old man,who complained of headache and weakness. In March 2003, he was diagnosed as having Stage IV gastric cancer with peritoneal dissemination (T3, Nx, P1) and underwent total gastrectomy with D1 dissection. Chemotherapy with S-1 was continued after surgery. Two years and two months later, a metastatic tumor was found in the upper lobe of the right lung. The protocol was changed to S-1+CDDP, but progression of his disease occurred. The weekly paclitaxel (PTX) therapy was tried instead. Seven months later, he developed headache and weakness, and multiple brain metastases were diagnosed by CT scanning. We performed total brain irradiation (30 Gy) and started CPT-11+CDDP therapy, which was continued on a fortnightly basis at 60 mg/m(2) and 30 mg/m(2), respectively. The brain metastases regressed (PR), and this therapy led to a marked improvement in his quality of life. The second patient was a 78-year-old man, who complained of weakness of the lower extremities and dizziness. In November 2003, he was diagnosed as having stage IB gastric cancer (T2 (ss), N0, P0), and underwent total gastrectomy and splenectomy with D2 dissection. One year and four months later, local recurrence at the anastomosis was detected, as well as a metastatic tumor in the right lung. S-1, S-1+CDDP, and weekly PTX therapy were all tried. One year later, the patient was admitted with weakness and dizziness,and brain metastases were detected by CT scanning. We then performed Cyber Knife treatment and administered CPT-11+CDDP. As a result, his brain metastases partially regressed (PR).
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PMID:[Irinotecan+cisplatin and irradiation are effective for brain metastases of gastric cancer--two case reports]. 1763 47

The ACTS-GC trial suggested that adjuvant chemotherapy with S-1 should be adopted as the standard treatment for stage II/III gastric cancer after curative D2 gastric dissection. In the JCOG9912 trial (5-FU vs CPT-11+CDDP (CP), 5-FU and vs S-1), the MSTs were 9.0, 12.1, and 10.5 months for 5-FU, CP, and S-1, respectively, with S-1 demonstrating significant non-inferiority to 5-FU, while CP did not show statistically significant superiority to 5-FU. In the SPIRITS trial comparing S-1 alone with S-1+CDDP, the MSTs were 11.0 and 12.0 months for S-1 and S-1+CDDP, respectively, and S-1+CDDP showed statistically significant superiority to S-1 monotherapy. The GC0301/TOP-002 trial compared CPT-11+S-1(IRI-S)to S-1 alone in advanced gastric cancer patients. An analysis revealed an ORR of 26.9% for the S-1 monotherapy arm and 41.5% for the IRI-S arm (p=0.035). However, IRI-S did not show statistically significant superiority to S-1 alone in OS. On the basis of these results, S-1+CDDP was adopted as the standard cancer chemotherapy regimen for inoperable and recurrent gastric cancer in Japan. Thus, in the next revision, the contents of the description of the Japanese Guidelines for Treatment of Gastric Cancer (2nd Edition) will be changed. Now, the second-line treatment and the biological molecular targeting agents-based drug medicine treatment development are continued with an eye to the future.
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PMID:[Clinical development of chemotherapy for advanced gastric cancer]. 1879 98

A 69-year-old female patient with type 2 advanced gastric cancer (s-T4N0M0H0Cy0P0, f-Stage IIIA) located from lower corps to antrum underwent a distal gastrectomy with D2 lymphandectomy in May 2006. After surgical treatment, S-1+ docetaxel combined chemotherapy was started for pEM (+) due to direct invasion to pancreas head as the first-line chemotherapy. However, the local recurrence whose diameter was 24 mm at pancreas head was detected with enhanced CT in December 2006. Moreover, nevertheless CPT-11+CDDP combined chemotherapy or paclitaxel monotherapy as the second or the third-line chemotherapy, respectively, the diameter of the local recurrence enlarged to 38 mm in November 2007. Therefore, chemo-radiotherapy using with S-1 and CDDP was started in December 2007 and the diameter of local recurrence was reduced to 25 mm in January 2008. No adverse event of grade 3 or more occurred during chemo-radiotherapy except for grade 3 of neutropenia. Chemo-radiotherapy for this gastric-cancer patient with local recurrence of multiple anti-tumor drug resistance was effective and safe.
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PMID:[A case of advanced gastric cancer treated with chemo-radiotherapy as the fourth-line therapy]. 1910 21

We report a case of advanced gastric cancer that showed a complete histological response to neoadjuvant chemotherapy. The patient, a 56-year-old man, was diagnosed as having advanced gastric cancer with lymph node metastases( cT3 cN1 cH0 cP0 cM0, cStageIIIA). He was initially treated with combined neoadjuvant chemotherapy comprising CPT-11+S-1. S-1(120 mg/day)was administered orally for 21 days, followed by CPT-11(130 mg/body)divon days 1 and 15. The primary lesion and lymph node metastases were diminished by 2 courses of chemotherapy, and no serious toxicities were observed. Distal gastrectomy and lymph node dissection(D2)were performed. Only a small ulcer was observed on the resected stomach. Histological examination of the resected stomach and lymph nodes revealed no remaining viable cancer cells. The patient has been doing well without any recurrence for 1 year since the start of treatment.
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PMID:[Advanced gastric cancer showing complete response to neoadjuvant chemotherapy with CPT-11 and S-1-a case report]. 1915 74


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