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)

Etoposide delivery to 9L gliosarcoma model in Fischer 344 rats was evaluated. Etoposide 2 mg/body was given intravenously (IV) or intracarotidly with (IHIC) or without (IC) intravenously administrated angiotensin II. Mean etoposide concentration of tumors was 5.08 micrograms/g for IHIC group, 2.27 micrograms/g for IC group and 0.70 micrograms/g for IV group. The difference in etoposide concentration between IHIC group and IV group was statistically significant (p less than 0.05). In addition, etoposide concentrations of the normal brain tissues were lower than concurrent plasma concentrations in all groups. The etoposide concentration was increased in the tumor and very low in the normal brain tissues in Fischer 344 rats with 9L gliosarcoma by induced hypertension with angiotensin II. These studies might suggest that intraarterial chemotherapy by induced hypertension with angiotensin II was useful on treatment of malignant brain tumors.
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PMID:[Etoposide delivery to malignant brain tumors by induced hypertension with angiotensin II]. 233 69

Previously, we reported on the resistance to cis-diamminedichloroplatinum(II) (cis-DDP) of tumor cells in IgM immunocytoma tumors. In vitro cell lines were established, from tumors both sensitive and resistant to cis-DDP. The cultured cells obtained from the parent tumor were designated IgM-I, and those from a cis-DDP resistant tumor IgM/cDDP. In vitro dose response studies showed a difference in cis-DDP sensitivity with a resistance factor of approximately 20 at a relative survival of the tumor cells of 50 percent. The resistance factor was determined both in an assay with continuous cis-DDP exposure for 72 h, and in a clonogenic assay after an exposure for 1 h to various dosages of cis-DDP. The IgM/cDDP cells showed cross-resistance, in vitro and in vivo, to the currently used cis-DDP analogs carboplatin (CBDCA or JM8) and iproplatin (CHIP or JM9). Cross-resistance was also observed against the recently developed platinum(IV) compound tetraplatin. In addition, the cell line IgM/cDDP was resistant to other drugs interacting with DNA, such as doxorubicin (DXR), mitomycin C (MMC) and melphalan (L-PAM). For two non DNA-interacting drugs, vincristine (VCR), a mitosis inhibitor, and VP-16, a topoisomerase inhibitor, both cell lines were equally sensitive.
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PMID:Resistance of in vitro grown IgM immunocytoma cells to cis-diamminedichloroplatinum (II) (cis-DDP) and cross-resistance to other DNA interacting drugs. 234 18

The value of the 6-day subrenal capsule assay (SRCA) in predicting the effectiveness of chemotherapy was tested using three human choriocarcinomas. The SRCA method proved to be a valuable chemopredictive test for choriocarcinoma. The results of experimental chemotherapy in nude mice and the results of the SRCA in two types of choriocarcinoma correlated well. Two of three choriocarcinomas showed sensitivity to MAC combination chemotherapy [methotrexate, actinomycin D, cyclophosphamide), and all three showed greater sensitivity to VP-16. The administration of VP-16 for treatment of all three types of choriocarcinoma significantly reduced tumor size in a dose-dependent fashion. From these observations, we speculate that the SRCA may be applied to assess the effectiveness of chemotherapy against human choriocarcinoma.
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PMID:Subrenal capsule assay as a test to predict the effectiveness of chemotherapy in choriocarcinoma. 235 24

The epipodophyllotoxin glucopyranosides have previously been shown to interact with membrane lipids and to alter the activity of several lipid-embedded membrane proteins. To determine if these agents are acting as general membrane perturbants, we have further examined their effects on membrane processes in Ehrlich ascites tumor cells. [3H]VM-26 and [3H]VP-16 were taken up rapidly and concentrated within the cells in proportion to their lipophilicity. Neither agent was found to have any significant effect on the influx of L-[3H]leucine or alpha-[3H]aminoisobutyric acid. Likewise, these drugs had no significant effects on the hexose transporter. The nucleoside transporter, which is structurally and functionally similar to the hexose transporter, was dramatically affected, however. VM-26 was a non-competitive inhibitor of equilibrium-exchange influx of cytosine arabinoside in Ehrlich cells with a Ki of 15 microM. Equilibrium-exchange influx increased with temperature in control cells (Q10 = 2) but not in VM-26-treated cells; thus, VM-26 was a more potent inhibitor at higher temperatures. VM-26 also significantly reduced zero-trans influx in Ehrlich, P388, L5178Y, and ML-1 cells, and these effects were immediate in onset. VM-26 inhibited high-affinity binding of the nucleoside transport inhibitor nitrobenzylmercaptopurine riboside (NBMPR), but VM-26 enhanced non-specific NBMPR binding to Ehrlich cells. The apparent specificity of the epipodophyllotoxins for the nucleoside transporter is discussed.
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PMID:Effects of the lipophilic anticancer drug teniposide (VM-26) on membrane transport. 236 57

Between 1984 and 1986, 85 consecutive patients with Stage III-IV or multi-centric squamous cell carcinoma of the head and neck were given three courses of chemotherapy followed by curative external radiotherapy. Induction chemotherapy consisted of either DDP (100 mg/m2, d 1) + 5 FU (1 g/m2/d, d 1-5, continuous infusion) or DDP (100 mg/m2, d4) + Etoposide (60 mg/m2/d, d 1-5, intravenously). Radiotherapy was delivered 70 Gy over 7 weeks in gross tumor and palpable nodes and 50 Gy over 5 weeks in clinically negative nodal areas. Complete response (CR) rates of both the chemotherapies were 39% for the primary and 20% for the nodes whereas partial response (PR) rates were 22% and 40%, respectively. Six months after completion of radiotherapy, 70% of the primaries and 63% of the nodes achieved complete response. The analysis of responses to chemotherapy on one hand and to subsequent radiotherapy on the other shows that the response to chemotherapy can be regarded as predictive for subsequent radiotherapy (p less than 0.001) except in T1-T2 tumors. In these early stages radiotherapy can be efficacious despite a previous failure of chemotherapy (p less than 0.01).
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PMID:Relation between responses to induction chemotherapy and subsequent radiotherapy in advanced or multicentric squamous cell carcinomas of the head and neck. 237 Jan 82

BMY-40481-30 is a new, water-soluble derivative and probable prodrug of etoposide characterized by the presence of a phosphate group in position 4' of the E ring of the etoposide molecule. The compound was only weakly cytotoxic in vitro and, consequently, an investigation of its antitumor activity was conducted in several murine and human tumor (xenograft) models. Etoposide was administered ip or po whereas BMY-40481-30 was given ip, po or iv. The potency of the derivative, when administered parenterally, as defined on the basis of maximum tolerated dose (MTD), was less than the parent compound on a weight (mg/kg) basis in some experiments but comparable to etoposide in other instances. Comparison at the MTD of the two compounds showed that BMY-40481-30 administered ip was as active as etoposide against ip P388 leukemia. BMY-40481-30 given iv was more active than etoposide given ip in two of five experiments versus iv P388 leukemia, but the two compounds were comparably active in the other three studies. Of particular interest was the finding that the derivative was more active than the parent compound at many of the comparable (on a mg/kg basis) dose levels of both evaluated po versus iv P388 leukemia; MTD levels were not achieved, and hence not compared, for either compound using the po route of administration. Both etoposide and BMY-40481-30 yielded comparable maximum effects against ic P388 leukemia, ic L1210 leukemia, and sc B16 melanoma, but etoposide was more efficacious versus sc M5076 sarcoma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preclinical antitumor activity of a soluble etoposide analog, BMY-40481-30. 238 14

We studied the effects of two modulators of multidrug resistance (MDR), cyclosporine and verapamil, on the cytotoxicity of etoposide (VP-16) in normal bone marrow cells. VP-16 was toxic to normal bone marrow at concentrations greater than 50 microM, resulting in no granulocyte-macrophage colony-forming units (CFU-GM) in short-term methylcellulose cultures. However, in long-term marrow cultures (LTMC) treatment with VP-16 without the addition of MDR modulators resulted in only a twofold decrease in total cell number at a VP-16 concentration of 50 microM, compared to media alone in the adherent cell layer, and approximately 20% recovery of CFU-GM. The addition of MDR modulators did not result in excessive cytotoxicity, reducing the total CFU-GM by two- to threefold even at the higher VP-16 concentration. Therefore, these modulators in conjunction with VP-16 can be safely used on normal bone marrow cells and may provide an effective method to purge MDR-tumor cells.
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PMID:Assessment of purging with multidrug resistance (MDR) modulators and VP-16: results of long-term marrow culture. 238 45

In order to deliver a high concentration of anti-cancer drugs in tumor tissue, preoperative intra-arterial injection therapy using Etoposide (VP-16), Pirarubicin (THP-ADM) and Cisplatin (CDDP), was used for 22 patients with resectable advanced gastric cancer. The concentration of VP-16, Adriamycin (ADM) and platinum (Pt) were measured in cancer tissue, normal mucosa and lymphnodes without metastasis at the greater curvature, which were gathered operatively and in serum just before operation. Student's t test was performed with their data. The mean concentration of VP-16 was less than the detectable limit in all tissues and in serum. The mean concentration of ADM in cancer tissue was significantly higher than in normal gastric mucosa, in lymphnodes without metastasis, and in serum. The mean concentration of platinum in cancer tissue was higher than those in lymphnodes, normal mucosa, and serum, but no significant differences were noted among them. It was concluded that the intra-arterial injection of THP-ADM and CDDP was an effective method to maintain a high concentration of ADM and Pt in gastric cancer tissue. However, intra-arterial injection of VP-16 was not useful.
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PMID:[Clinical study of drug accumulation in gastric cancer after preoperative intra-arterial EA'P injection therapy]. 238 68

A consecutive series of 13 children (five girls) with advanced malignant germ cell tumors (MGCTs) were treated with between four and seven (median, six) courses of cisplatin, bleomycin, and either vinblastine (BVP) or VP-16 (BEP). There were seven gonadal primaries (four testis, three ovary) and six at extragonadal sites (three sacrococcyx, two thoracic, one extradural). Total or subtotal removal of primary tumor was carried out in nine patients at diagnosis and two others after some chemotherapy. Clinical complete remission (CR) was achieved in nine of ten patients with measurable disease and serum markers returned to normal in all 13 patients. Eleven remain disease-free 17 to 48 months (median, 28 months) after diagnosis. One patient (stage IV sacrococcygeal tumor) relapsed at the primary site 3 months after completing treatment, but is disease-free after further surgery, radiotherapy, and chemotherapy. Serial glomerular filtration rates were performed during treatment. Audiometry and pulmonary function tests were carried out where possible. Toxicity led to alteration of drug scheduling in two cases, but there were no permanent clinical renal, auditory, or pulmonary sequelae. These encouraging results confirm that MGCTs in children are as responsive as those in adults to cisplatin-containing chemotherapy and indicate that they may be as curable. The regimens are relatively well-tolerated and, with close monitoring, clinically significant toxicity should be avoidable.
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PMID:High complete response rate in children with advanced germ cell tumors using cisplatin-containing combination chemotherapy. 241 68

Between 1978 and 1982, 180 patients from Indiana University (Indianapolis) were entered on the Southeastern Cancer Study Group (SECSG) protocol 78 GU 240, a randomized comparison of cisplatin, vinblastine, and bleomycin (PVB) v PVB plus doxorubicin induction chemotherapy regimens, with a second randomization to maintenance vinblastine v no further therapy. One hundred forty-eight of these patients obtained a favorable response to chemotherapy, defined as a complete response (CR) or a surgical resection of teratoma. The prognostic significance of various patient characteristics was investigated using the logistic regression model. Two classifications for the extent of disease were considered: the Indiana staging system and the M.D. Anderson (MDA) staging system. The Indiana staging system had the greater prognostic significance. This staging system allowed the population to be split into three groups (minimal, moderate, advanced disease) in which the observed proportions of favorable responders were 99%, 90%, and 58%, respectively. Within the advanced group, the number of elevated tumor markers subdivided these patients into three groups, with the observed proportions of favorable responders being 73%, 65%, and 45%. The Indiana and MDA staging systems were subsequently prospectively used in SECSG protocol GU 81 332, a study randomizing patients to remission induction therapy with PVB v cisplatin, VP-16, and bleomycin. The prognostic value of the Indiana staging system was prospectively validated in this study.
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PMID:Prognostic factors for favorable outcome in disseminated germ cell tumors. 241 24


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