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)

An early phase II study was conducted to evaluate the anti-tumor effects and toxicity of etoposide in patients with unresectable or relapsed advanced gastric cancer. From April 1991 to December 1992, 13 patients were enrolled into this study; one was subsequently considered ineligible. Before enrollment, all the patients had been treated with chemotherapy which did not include etoposide. Etoposide (100 mg/m2/day) was administered as an intravenous infusion over 120 min for five consecutive days and was repeated every four weeks. Seven patients received one course of this therapy and the remaining five received two. No patient showed a complete or a partial response. No change and progressive disease were observed in three and nine patients, respectively. The clinical toxicities (grade 3-4; WHO) of leukocytopenia, anemia and alopecia occurred in 50, 42, and 42% of the patients, respectively. We conclude that this dose of etoposide administered according to the present schedule is ineffective in previously treated patients with advanced gastric cancer.
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PMID:An early phase II study of etoposide (VP-16) in advanced gastric cancer. 855 65

IMC-HM cells were isolated from spontaneously induced ascitic IMC carcinoma cells that had been maintained intraperitoneally in CDF1 mice. Metastasis to the liver of subcutaneously implanted IMC-HM cells was detected 10 days after implantation into the flanks of mice (day 10), but metastasis to other organs was limited. Thereafter, however, tumor cells spread rapidly to lymph nodes, lung, spleen, ovary and other organs, and the mice died on day 13 to 18. We report here, together with the properties of IMC-HM cells, the effects of adriamycin, cisplatin, etoposide and a new indolocarbazole antitumor compound (NB-506) on this model of metastasis. Although these anticancer agents all inhibited the growth of the subcutaneous tumors, their effects on the life span of the tumor-bearing mice varied. Treatment with NB-506, started on day 1, more than doubled the survival period at doses 30 mg/m2 to 900 mg/m2. Further, treatment with NB-506, started on day 4 after resection of the primary tumor, inhibited growth of the metastasized tumor in the liver and other organs. Etoposide also increased the life span at a limited range of doses. However, the life-prolonging effects of adriamycin and cisplatin were marginal. These results demonstrate that IMC-HM carcinoma is a good model for spontaneous metastasis to the liver followed by lethal spread to many organs. Moreover, NB-506 was found to be highly effective against the growth not only of subcutaneous tumors, but also of tumors metastasized to the liver.
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PMID:Antimetastatic effect of a novel indolocarbazole (NB-506) on IMC-HM murine tumor cells metastasized to the liver. 864 90

Tumor endothelium is critical for solid tumor growth and is a potential site for anticancer drug action. Within 2 h, etoposide caused marked DNA strand breakage in xenograft tumor-derived endothelial cells (TDECs). Etoposide-induced DNA breakage was inhibited by culturing TDECs on gelatin, type IV collagen, laminin, fibronectin, and the integrin ligand hexapeptide, GRGDSP, but not the inactive peptide, GRADSP. It was also inhibited when TDECs were on surfaces coated with antibodies to alpha 5, beta 1, or beta 3 integrin subunits and by clustering integrins with soluble antibodies. After 8 h with etoposide, TDECs detached from the monolayer, and 50-kb DNA fragments were seen. Fibronectin inhibited both processes. Thus, integrins are survival factors for TDEC that inhibit the genotoxicity of etoposide and may influence the sensitivity of tumors to drugs.
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PMID:Integrin activation suppresses etoposide-induced DNA strand breakage in cultured murine tumor-derived endothelial cells. 879 83

Etoposide is one of the most widely used antineoplastics. Unfortunately, the same treatment schedules associated with impressive efficacy are associated with an increased risk of secondary acute myeloid leukemia (AML), which has prompted its withdrawal from some treatment regimens, thereby potentially compromising efficacy against the original tumor. Because etoposide-associated AML is characterized by site-specific illegitimate DNA recombination, we studied whether etoposide could directly cause site-specific deletions of exons 2 and 3 in the hprt gene. Human lymphoid CCRF-CEM cells were treated with etoposide for 4 hours, and DNA was isolated after subculturing. The deletion of exons 2 and 3 from hprt was assayed by a quantitative polymerase chain reaction (PCR) method. In the absence of etoposide treatment, the frequency of deletions of exons 2 and 3 was very low (5.05 x 10(-8)). After exposure to 10 mumol/ L etoposide, the frequency of the exon 2 + 3 deletion was increased immediately after and at 24 hours after etoposide treatment (65 to 89 x 10(-8)) and increased to higher levels (128 to 173 x 10(-8)) after 2 and 6 days of subculture (P < .001 overall). The frequency of the exon 2 + 3 deletion assessed at 6 days of subculture after 4 hours of 0, 0.25, 1, 2.5, 5, and 10 mumol/L etoposide treatment increased with etoposide concentration, ie, 5.05 x 10(-8), 89.2 x 10(-8), 108 x 10(-8), 142 x 10(-8), 163 x 10(-8), and 173 x 10(-8), respectively (P < .0001). Sequencing of a subset of amplified products confirmed the presence of DNA sequences at the breakpoints consistent with V(D)J recombination. By contrast, exon 2 + 3 deletions after etoposide treatment in the myeloid cell lines KG-1A and K562 showed no evidence of V(D)J recombinase in their genesis. We conclude that etoposide can induce the illegitimate site-specific action of V(D)J recombinase on an unnatural DNA substrate after a single treatment in human lymphoid cells.
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PMID:Etoposide causes illegitimate V(D)J recombination in human lymphoid leukemic cells. 882 41

A rare case of CA19-9 producing tumor in undescended testis was presented. A forty-three year old man visited to our hospital with a chief complaint of left flank pain. Serum tumor markers (AFP, beta-HCG, and CA19-9) were elevated. Abdominal CT scan demonstrated large solid mass with multilocular cysts were capsulated. The tumor resection was performed after 3 courses of CEB (Carboplatin, Etoposide, and Bieomycin) chemotherapy. Macroscopically, the tumor was consisted of necrotic mass and multilocular cysts. The tumor size was 25 x 8 x 5 cm and weight was 1000 g. Microscopically, the large part of tumor was necrotic due to chemotherapy, and the teratoma component which was consist of neural, muscular, and digestive tissue was seen in some area. In conclusion, this is a rare case of mixed germ-cell tumor in undescended testis located in abdomen.
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PMID:[CA19-9 producing mixed gonadal germ-cell tumor in undescended testis located in abdomen. A case report]. 883 Dec 15

Overexpression of the multidrug resistance-associated protein (MRP) gene has been implicated in the resistance of tumor cell lines to a wide array of chemotherapeutic agents, but its normal physiological function(s) remains unknown. We have compared the sensitivity to chemotherapeutic drugs and toxins of wild-type W9.5 embryonic stem cells (ES) and of single and double MRP gene knockout cells derived therefrom. MRP expression was totally abrogated in the double knockout cell line and partially abrogated in the single knockout cell line. Reverse transcription-PCR analyses demonstrated that the MDR1, MDR2, and MDR3 genes were not expressed in either wild-type or MRP knock-out cells. The cytotoxic activities of etoposide, teniposide, vincristine, doxorubicin, daunorubicin, and sodium arsenite were significantly greater in double knockout cells than in parental wild-type ES cells; single knockout ES cells displayed an intermediate level of sensitivity. In contrast, no difference in sensitivity to colchicine and 1-beta-D-arabinofuranosylcytosine existed between the cell lines. Etoposide accumulation in double knockout ES cells was 2-fold higher than in wild-type ES cells. These findings indicate that baseline MRP expression has the capacity to exert a protective role against the toxicity of multiple chemotherapeutic agents and natural toxins.
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PMID:Double knockout of the MRP gene leads to increased drug sensitivity in vitro. 896 83

Clinical application of etoposide (VP-16) for gynecologic malignancy has been investigated in trophoblastic disease, ovarian, endometrial and cervical cancer. Etoposide has proved to be one of the most effective agents for trophoblastic disease. It is widely used in single or multiple drug regimens in chemotherapy of the disease. Furthermore, this drug is observed to be active in the combination of BLM with CDDP for germ cell tumor of the ovary. It is now playing an important role in chemotherapy of this tumor.
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PMID:[Etoposide (VP-16) in gynecologic malignancy]. 897 99

Despite improvements in neurosurgical and neuroradiotherapeutic techniques, children with malignant brain tumors have a dismal prognosis. In an attempt to improve the efficacy of cytotoxic therapy, dose intensification of effective chemotherapeutic agents followed by autologous bone marrow transplantation (BMT) has been tried. Between May 1991 and August 1996, high-dose chemotherapy and autologous BMT were administered to 11 children with malignant brain tumors: 10 had recurrent (n = 8) or progressive (n = 2) disease, and 1 was treated before progression. The histological diagnoses were medulloblastoma (3), glioblastoma multiforme (2), supratentorial PNET (2), ependymoma (2), anaplastic astrocytoma (1), and anaplastic oligodendroglioma (1). In 6 of the 11 patients measurable disease was present at the time of BMT. The preparative regimen included BCNU 600 mg/m2 and VP16 1500 mg/m2 in 5 cases, and thiotepa 900 mg/m2 and VP16 1500 mg/m2 in 6 cases. The median times to achieve a neutrophil count over 0.5 x 10(9)/l and a platelet count over 50 x 10(9)/l were 14 and 28 days, respectively. The overall incidence of severe toxicity (grade III-IV) was 18% and consisted of oropharyngeal mucositis and diarrhea. Among the 6 patients with measurable disease at the time of BMT there were 2 with stable disease, whereas 4 patients had tumor progression: all these patients died of tumor recurrence 2-10 months after BMT. Five patients in whom there was no evidence of disease at the time of BMT are alive and free of progression with a median follow-up of 20 months (range 3-67). These preliminary results show that high-dose chemotherapy and BMT may be effective in children with malignant brain tumors. Etoposide-containing regimens seem to have significant activity in this setting, and the toxicity was manageable. The most important variable prognostic for progression-free survival is the disease status at the time of transplantation.
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PMID:Etoposide-containing regimens with autologous bone marrow transplantation in children with malignant brain tumors. 945 71

The clinicopathologic features of a patient with uterine leiomyosarcoma arising in the cervix are presented. A 47-year-old Japanese woman was admitted with complaints of hypermenorrhea and abdominal distention. A hysterectomy with bilateral salpingo-oophorectomy revealed a tumor weighing 10.5 kg, which was the largest cervical leiomyosarcoma reported in the literature. She was given eight courses of combination chemotherapy (VADIC and Hydroxyurea, DTIC, Etoposide) and is alive without evidence of recurrence 35 months after the initial therapy.
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PMID:Leiomyosarcoma of the uterine cervix. 960 Aug 26

The mechanism of action of anticancer chemotherapeutic agents is mainly thought to be due to a direct inhibition of tumor cell proliferation. The enhanced endothelial cell proliferation rate in tumor specimens raised the question of whether therapeutic effects of chemotherapeutic agents might be at least partially attributed to inhibition of tumor angiogenesis. In the present study, we investigated the potential effects of chemotherapeutic agents on human renal carcinoma angiogenesis with the alginate implantation model in mice. For the first time, we also compared results from the angiogenesis model with the inhibitory effects on growth of s.c. xenografts in nude mice. Vincristine and bleomycin exerted strong inhibition of tumor angiogenesis in both carcinoma lines close to the level of the standard antiangiogenic agent O-chloroacetyl-carbamyl-fumagillol (AGM-1470; T/C 22%). Adriamycin reduced angiogenesis of Caki-2 cells (T/C 33%) but had no effect on Caki-1 angiogenesis (T/C 137%). Etoposide and 5-fluorouracil reduced Caki-1 tumor angiogenesis but had no effect on Caki-2. Despite antiangiogenic effects in both carcinoma lines, vincristine, bleomycin, and AGM-1470 significantly reduced only the growth of fast-growing Caki-1 s.c. xenografts but not the slow-growing Caki-2. Antivascular effects by bleomycin and AGM-1470 were also shown by a decrease of microvessel density in nude mouse xenografts. Our findings suggest that chemotherapeutic agents may exert inhibition of tumor angiogenesis, which could be exploitable by combination therapy of fast-growing tumors. The resistance of the slow-growing Caki-2 carcinoma against acute angiogenesis inhibition indicates a need for well-tolerated angiogenesis inhibitors. Our results also suggest the use of fast-growing s.c. xenografts for demonstrating growth inhibition by antiangiogenic compounds. Further characterization of antiangiogenic compounds considered for clinical application should, however, have its focus on slow-growing tumors, which are not accessible for most therapeutic strategies.
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PMID:Antiangiogenic chemotherapeutic agents: characterization in comparison to their tumor growth inhibition in human renal cell carcinoma models. 960 94


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