Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report 27 cases of liver metastases treated with transarterial chemoembolization (TACE) with CPT-11, DSM, and mitomycin C (CPT-DSM therapy). In the 27 patients with liver metastases from colorectal cancer, CPT-DSM therapy was performed 47 times. All of these patients were a contra indication of hepatectomy. We compared a tumor marker before and after the treatment, and measured a serum level of SN-38, which is an active substance of CPT-11 and resolved from CPT-11. Although the level of CPT-11 was wearing off after CPT-DSM therapy, the peak of SN-38 level delayed 1 hour after the infusion. The CEA and CA19-9 levels were decreased to 54.2% and to 45.1% of the level before the treatment, respectively. Nine of the partial response and stable disease patients underwent surgery. The response rate was 59%. A 3-year survival rate was 20%. These results suggest that CPT-DSM therapy is one of the most effective anticancer agents. This TACE can be a feasible therapy for colorectal liver metastases as the first-line therapy.
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PMID:[Transarterial chemoembolization with irinotecan (CPT-11) and degradable starch microspheres (DSM) in patients with liver metastases from colorectal cancer]. 1821 91

Tumor cells are known to exhibit highly varied sensitivity to camptothecins (CPT; e.g., irinotecan and topotecan). However, the factors that determine CPT sensitivity/resistance are largely unknown. Recent studies have shown that the ubiquitin-like protein, IFN-stimulated gene 15 (ISG15), which is highly elevated in many human cancers and tumor cell lines, antagonizes the ubiquitin/proteasome pathway. In the present study, we show that ISG15 is a determinant for CPT sensitivity/resistance possibly through its effect on proteasome-mediated repair of topoisomerase I (TOP1)-DNA covalent complexes. First, short hairpin RNA-mediated knockdown of either ISG15 or UbcH8 (major E2 for ISG15) in breast cancer ZR-75-1 cells decreased CPT sensitivity, suggesting that ISG15 overexpression in tumors could be a factor affecting intrinsic CPT sensitivity in tumor cells. Second, the level of ISG15 was found to be significantly reduced in several tumor cells selected for resistance to CPT, suggesting that altered ISG15 regulation could be a significant determinant for acquired CPT resistance. Parallel to reduced CPT sensitivity, short hairpin RNA-mediated knockdown of either ISG15 or UbcH8 in ZR-75-1 cells resulted in increased proteasomal degradation of CPT-induced TOP1-DNA covalent complexes. Taken together, these results suggest that ISG15, which interferes with proteasome-mediated repair of TOP1-DNA covalent complexes, is a potential tumor biomarker for CPT sensitivity.
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PMID:ISG15 as a novel tumor biomarker for drug sensitivity. 1856 15

We evaluated the efficacy of anti-human VEGF antibody (bevacizumab) with or without irinotecan (CPT-11) against lung metastases in which neovascularization was already induced, as a postoperative adjuvant therapy using orthotopically implanted colon cancer in rat. The high VEGF productive KM12SM human colon cancer cells were injected into the cecal wall. At 5 weeks after the injection, the cecum was removed including the tumor. Then, 5 mg/kg of bevacizumab and 40 mg/kg of CPT-11 were administered, alone or in combination, intravenously once a week for 3 weeks, from day 15 after the cecal removal. The results show that the incidences of macroscopic and/or microscopic lung metastases in the bevacizumab-alone group (B) and in the combination group (C) were significantly lower (B, p=0.001 and C, p=0.037) than that in the control group at day 35 after the cecal removal. The number of lung metastases in B was 0.8+/-0.8 (p=0.024) and in C 2.4+/-1.8 (p=0.060), each value lower than the 12.4+/-4.2 of the control group. The growth of a subcutaneously implanted tumor was significantly inhibited in the combination group compared to either the CPT-alone (p=0.003) or the bevacizumab-alone groups (p=0.027). Apoptosis was significantly (p<0.001) induced in the combination group. In conclusion, a beneficial effect of bevacizumab against postoperative lung metastases may be expected even after the establishment of neovascularization in metastatic foci in nude rat. The results from the present subcutaneously implanted tumor model suggested that a higher efficacy may be expected when bevacizumab is combined with the cytotoxic agent CPT-11, compared to bevacizumab alone, against tumors with a variety of VEGF production levels in clinical situations.
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PMID:Efficacy of the combined use of bevacizumab and irinotecan as a postoperative adjuvant chemotherapy in colon carcinoma. 1869

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

From July, 2007 to June, 2008, we prospectively investigated the influence of Hange-shashin-to on the therapeutic and adverse effects of chemotherapy and the changes in quality of life(QOL)scores of the patients with metastatic gastric and colorectal cancer. Twenty patients receiving S-1/Irinotecan (CPT-11) therapy were randomly allocated into group A (with Hange-shashin-to) and B (without Hange-shashin-to). While the anti-tumor effects did not differ significantly between these two groups, severe side effects of more than grade 3 occurred less frequently in group A. Our results suggested that the decrease in QOL scores on day 15 might be alleviated in group A, compared to group B. Therefore, Hange-shashin-to can be one of the useful supportive medicines in the combination therapy of S-1/CPT- 11.
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PMID:[Clinical effects of Hange-shashin-to on combination therapy of S-1/irinotecan against the for patients with metastatic gastric and colorectal cancer]. 1975 17

A 78-year-old woman was admitted to our hospital complaining of persistent abdominal pain and diarrhea. Computed tomography (CT) and colonoscopy (CF)revealed a huge ascending colon tumor, invading the descending part of the duodenum. The patient was treated preoperatively with a combination of S-1 plus CPT-11 (S-1 80 mg/body day 1-29, CPT- 11 100 mg/body day 1, 8, 15 and 22). No serious side effect was observed except low-grade fever and grade 2 appetite loss and diarrhea. Tumor reduction was significant on the preoperative CT and CF, with the invasion to the duodenum obscured. Right hemicolectomy with wedge resection of the duodenum was performed. Resected specimen revealed residual tumor in a small area of the submucosal to proper muscular layer of the contracted ascending colon, without pathological invasion to the duodenum. No nodal metastasis was observed. The patient was administered UFT (300 mg daily)postoperatively for two years and is still alive and free of disease after three years and ten months since the operation.
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PMID:[Huge ascending colon carcinoma, treated successfully with S-1 plus CPT-11, followed by significant tumor reduction and curative resection--a case report]. 1992 Mar 99

Tuberous sclerosis complex 1 (TSC1) inhibits mammalian target of rapamycin (mTOR), a central promotor of cell growth and proliferation. The protein product of the TSC1 gene, hamartin (referred to as TSC1) is known to interact with Polo-like kinase 1 (Plk1) in a cell cycle regulated, phosphorylation-dependent manner. We hypothesized that the p53 target gene, Plk2, is a tumor suppressor, mediating its tumor suppressor function through interactions with TSC1 that facilitate TSC1/2 restraint of mTOR under hypoxic stress. We found that human lung tumor cells deficient in Plk2 grew larger than control tumors, and that Plk2 interacts with endogenous TSC1 protein. Additionally, C-terminal Plk2-GST fusion protein bound both TSC1 and TSC2 proteins. TSC1 levels were elevated in response to Adriamycin and cells transiently overexpressing Plk2 demonstrated decreased phosphorylation of the downstream target of mTOR, ribosomal protein p70S6 kinase during hypoxia. Plk2 levels were inversely correlated with cytoplasmic p70S6K phosphorylation. Plk2 levels did not increase in response to DNA damage (Adriamycin, CPT -11) when HCT 116 and H460 cells were exposed to hypoxia. TSC1-deficient mouse embryonic fibroblasts with TSC1 added back demonstrated decreased S6K phosphorylation, which was further decreased when Plk2 was transiently overexpressed. Interestingly, under normoxia, Plk2 deficient tumor cells demonstrated increased apoptosis in response to various chemotherapeutic agents including CPT -11 but increased resistance to apoptotic death after CPT-11 treatment under hypoxia, and tumor xenografts comprised of these Plk2-deficient cells were resistant to CPT -11. Our results point to a novel Plk2-TSC1 interaction with effects on mTOR signaling during hypoxia, and tumor growth that may enable targeting Plk2 signaling in cancer therapy.
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PMID:The p53 target Plk2 interacts with TSC proteins impacting mTOR signaling, tumor growth and chemosensitivity under hypoxic conditions. 2005 36

The polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) reduces proliferation of several cell types, including colon tumor cells, and regulates gene expression in a cell- and gene-selective manner. In hepatocytes, the fatty acid synthase (FAS) gene is down-regulated by DHA whereas the carnitine palmitoyltransferase-1 (CPT-1) gene is up-regulated. In adipocytes but not in hepatocytes, the expression of the cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) gene is stimulated by unsaturated FA, including DHA. We monitored the expression of the FAS, CPT-1 and PEPCK-C genes in rat and human colon and in colonic tumors from humans. The ratio of PEPCK-C to FAS transcripts was in favor of PEPCK-C in human and rat colon, whereas the opposite occurred in Caco2 tumoral cells. FAS gene expression declined from proliferative to differentiated Caco2 cells, while in contrast the expression of PEPCK-C and CPT-1 genes increased. DHA strongly induced expression of the PEPCK-C and CPT-1 genes, in correlation with decreased cell growth, while, as expected, it reduced FAS mRNA. We assessed the relative expression of PEPCK-C, CPT-1 and FAS genes in fragments of colonic tumors and adjacent non-tumoral tissue from a series of 10 patients. PEPCK-C and CPT-1 mRNAs are more abundant in non-tumoral tissues than in the tumoral counterpart, whereas the opposite occurred for the FAS gene. Therefore, the PEPCK-C gene can be defined as a new negative marker for colonic tumors and a target for the anti-tumorigenic action of omega-3 PUFAs.
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PMID:Down-regulation of the phosphoenolpyruvate carboxykinase gene in human colon tumors and induction by omega-3 fatty acids. 2069 Dec 46

Lymphatic metastasis plays a critical role in ovarian cancer, indicates poor prognoses and correlates to the majority of cancer deaths. Camptothecin derivatives exhibit promising activity for the treatment of solid tumors because of its specific inhibition of eukaryotic DNA topoisomerase I. Yet, its application is hindered due to extreme water insolubility and severe side effects. It is essential to establish an efficient and safe protocol for the administration of camptothecin versus tumor metastasis and growth. In the current research, we encapsulated camptothecin with N-trimethyl chitosan (CPT-TMC) to increase its water-solubility and lower its side effects, and tested it on a high potential lymphogenous metastatic model of human ovarian cancer. In the prophase study, we successfully transfected SKOV3 cells with VEGF-D recombinant plasmid DNA (pcDNA3.1(+)/VEGF-D) to construct a cell line named SKOV3/VEGF-D and establish a feasible lymphogenous metastatic model. The antitumor and antimetastatic activities of CPT-TMC were evaluated in nude mice subcutaneously inoculated with SKOV3/VEGF-D cells at the left hindlimb claw pad. The tumor-bearing mice were divided randomly into four groups and treated twice per week for three weeks. Evan's Blue Dye was used to delineate functional lymphatic vessels. Lymphatic metastasis rates were detected by hematoxylin and eosin (HE) staining. Expression of VEGF-D and MMP-9 were investigated by immunohistochemistry. In contrast to controls, administration of CPT-TMC achieved effective inhibition in primary tumor volume and lymphogenous metastasis, yet without apparent systemic toxic effects. These effects were associated with simultaneously down-regulated VEGF-D and MMP-9 expression, significantly decreased tumor-associated lymphatic and blood sprouts, tremendously reduced systemic toxic effects, dramatically increased tumor apoptotic index. Our data indicate that CPT-TMC is superior to CPT by maximizing its anticancer and antimetastatic activities with minimal toxicity on hosts. CPT-TMC may become a potentially therapeutic strategy against human advanced ovarian cancer.
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PMID:The antitumor and antimetastatic effects of N-trimethyl chitosan-encapsulated camptothecin on ovarian cancer with minimal side effects. 2081 74

A 62-year-old woman was admitted for epigastralgia, nausea and tarry stool.Abdominal CT showed a tumor to the jejunum from the duodenum, and peritoneal dissemination.Gastroduodenoscopy showed a type 2 tumor, and the histopathological examination revealed a well-to moderately-differentiated adenocarcinoma.Accordingly, she was diagnosed with primary adenocarcinoma of the small intestines and underwent surgery.The first-line chemotherapy with S-1/CPT-11 was started after surgery, and the tumor marker returned to normal.The treatment of 14 courses was continued until PD due to the enlargement of the peritoneal dissemination.Second - and third-line chemotherapy were performed; however, she died 20 months after the initial treatment.Although the incidence of primary adenocarinoma of the small intestines is relative- ly low, and there is no established chemotherapy at present, this case suggested that S-1/CPT-11may be an effective regimen for advanced primary adenocarcinoma of the small intestines.
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PMID:[Primary adenocarcinoma of small intestine with peritoneal dissemination treated with S-1 and CPT-11 combination chemotherapy]. 2167 97


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