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)

In multidrug-resistant (MDR) derivatives of the mouse lymphoid tumor P388, the emergence of MDR is associated with overexpression and transcriptional activation of the mdr3 gene, either in the absence of (P388/VCR-10) or concomitant with (P388/ADM-2) gene amplification. In both instances, Northern (RNA) blotting analyses have suggested the presence of altered mdr3 transcripts in these cells, possibly originating from novel transcription initiation sites. The mechanisms underlying mdr3 overexpression in these cells have been investigated. In P388/VCR-10 cells, Southern blotting analyses together with genomic DNA cloning and nucleotide sequencing have demonstrated the presence of an intact mouse mammary tumor virus (MMTV) within the boundaries of intron 1 of mdr3. cDNA cloning and nucleotide sequencing indicated that this integration event results in the synthesis and overexpression of a hybrid MMTV-mdr3 mRNA which initiates within the U3 region of the 5' long terminal repeat (LTR) of the provirus. Consequently, this mRNA lacks the normal exon 1 of mdr3 but contains (i) MMTV LTR-derived sequences at its 5' end, (ii) a novel mdr3 exon, mapping within the boundaries of intron 1 downstream of the MMTV integration site and generated by alternative splicing, and (iii) an otherwise intact 3' portion of mdr3 starting at exon 2. A similar type of analysis of P388/ADM-2 cells revealed that mdr3 overexpression in these cells is associated with the integration of an intracisternal A particle (IAP) within an L1Md repetitive element, immediately upstream of mdr3. The IAP insertion results in the overexpression of hybrid IAP-mdr3 mRNA transcripts that initiate within the 3' LTR of the IAP and which contain IAP LTR-derived sequences at the 5' end spliced 14 nucleotides upstream of the normal exon 1 of mdr3. Taken together, these results indicate that independent retroviral insertions were the initial mutagenic event responsible for mdr3 overexpression and survival during drug selection of these cell lines. Amplification of the rearranged and activated mdr3 gene copy occurred during further selection for high-level drug resistance in P388/ADM-2 cells.
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PMID:Activation of the mouse mdr3 gene by insertion of retroviruses in multidrug-resistant P388 tumor cells. 824 58

Alveolar soft part sarcoma (ASPS) is one of the soft tissue sarcomas characterized by metastasis early in the course of the disease, regardless of slow tumor growth. The ultimate clinical outcome is, therefore, very poor. To date, the efficacy of combination chemotherapy for this tumor has not been confirmed. We present a case of ASPS in an 8-year-old boy with bilateral pulmonary metastasis who received systemic combination chemotherapy (CPM/IFO/ACD/ADR/CD DP/VP-16 as induction, and VCR/ACD as maintenance therapy) for eleven months. The result showed that despite the prevention of tumor progression, such intensive chemotherapy could not cure the disease. Besides refinement of chemotherapy regimens, immunotherapy might be considered for ASPS.
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PMID:[Intensive chemotherapy for alveolar soft part sarcoma with lung metastasis in a child]. 833 54

In the last 20 years, eleven children with adrenocortical functional tumors were treated in the National Children Hospital of Costa Rica. There were nine females and two males and their ages ranged from nine months to 14 years. Eleven patients had features of virilism, five had stigmas of Cushing's syndrome and three hyperaldosteronism. The clinical diagnosis was established given the symptoms, hormonal tests and radiological and imagenological studies. The histologic diagnosis was carcinoma in six by clinical picture in one, and were adenoma in four. Three patients had regional and distant metastases. Four patients with carcinoma were treated by surgery and five received chemotherapy, two of them in presurgical stage, and four received radiotherapy. Two patients with carcinoma are alive and had no evidence of tumor recurrence ten and six years after diagnosis. Five are dead, two of them after partial response to chemotherapy. The four patients with adenoma were cured by complete surgical tumor resection, furthermore one of them received chemotherapy because there was not sure of his histologic benign condition. It is necessary more studies in use of chemotherapy in treatment of this tumors but in our experience CFM, VCR, Epi and Actin is a regimen that appears to be an active combination for the treatment in presurgical stage of adrenal cortical carcinoma.
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PMID:[Functioning tumors of the adrenal cortex in children. Clinical and therapeutic considerations on 11 cases]. 837 47

This laboratory has previously used a window chamber model to measure red blood cell velocity in mammary tumors and normal granulation tissues of the F-344 rat. Because red cell flux and hematocrit more accurately reflect the oxygen carrying potential of blood, we used this model to measure these parameters. Red blood cells were labelled with fluorescein isothiocyanate, and 0.2 ml. packed cells were injected intravenously into rats bearing an 8 to 10 day old R-3230 mammary carcinoma. beta-phycoerythrin (0.15 mg.) was also injected and served as a plasma dye to outline the blood vessels. A sample of peripheral blood was then taken and analyzed by flow cytometry to determine the labeled fraction of red blood cells. Flowing tumor and normal tissue vessels were recorded onto a VCR, and these video images were used to determine vascular length and diameter, RBC flux and velocity, and hematocrit. Median vessel diameter and loge (red blood cell flux) were significantly greater in tumors than in normal tissues (p = 0.007 and p < 0.025, respectively). After controlling for these variables, the median tumor hematocrit of 19% was not significantly greater than the median normal tissue hematocrit of 15%. This technique provides a nontoxic and reproducible method that is now being used to assist in the in vivo definition of tumor oxygenation.
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PMID:A comparison of tumor and normal tissue microvascular hematocrits and red cell fluxes in a rat window chamber model. 842 Aug 74

Seven binary vinca alkaloid congeners were newly synthesized as the C14' or C16'(20') or C14'16'(20') stereoisomers of C20'-modified VBL. These congeners lacked detectable antimicrotubule activity in assays of polymerization of purified microtubule protein and of mitotic arrest induction. The compounds modulated the cytotoxicity of VBL, VCR, and DOX in sarcoma and colon-tumor cell lines. In wild-type cell lines, each congener elicited a concentration-dependent enhancement of cytotoxicity that was drug- and cell-type-selective. For example, C20'-deoxy C14'16'20'-epi VBL sensitized sarcoma S180 cells 19-fold to DOX and 11-fold to VCR but had no effect on VBL cytotoxicity. In the rat colon-cancer cell lines there was preferential enhancement of VCR cytotoxicity by most congeners. In two MDR cell strains of S180, the modulation potency of each congener was independent of specific drug or of resistance level. As a result, the amount of modulator (concentration) required for reversal was proportional to the drug-resistance level. Such properties were not displayed by the monomeric vinca alkaloid modulator vindoline. The potency of drug modulation in both wild-type and MDR cells strains was dependent on the stereoisomeric form of the congener and its C20'-substituents.
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PMID:Modulation of drug cytotoxicity in wild-type and multidrug-resistant tumor cells by stereoisomeric series of C-20'-vinblastine congeners that lack antimicrotubule activity. 843 67

In independently derived drug-resistant sublines of the mouse lymphoid tumor P388, multidrug resistance is associated with the exclusive overexpression of the mdr3 gene. In P388/VCR cells, mdr3 overexpression occurs in the absence of gene amplification, while in P388/ADM-2 cells overexpression is associated with mdr3 gene amplification. The mechanism underlying mdr3 overexpression in these cells was investigated. Measurement of the rate of transcription by nuclear "run-on" assays showed that increased mdr3 expression in P388/VCR cells was caused by transcriptional activation of the gene. Analysis of the 5' end of mdr3 mRNA transcripts by primer extension indicated that in P388/VCR cells, these mRNAs extended approximately 200 nucleotides upstream exon 2, about 60 nucleotides longer than their counterparts expressed in normal tissues from the known transcription start site of the gene (TS1). Northern blotting experiments using discrete exon and intron probes derived from the 5' end of the gene near TS1, together with ribonuclease protection using a complementary RNA probe from the same region, demonstrated that transcriptional activation in P388/VCR cells occurred from a novel transcription start site named TS3, located either upstream of TS1 or within intron 1 at a site immediately upstream a novel exon. In P388/ADM-2 cells, Northern blotting and ribonuclease protection identified overexpressed mdr3 mRNAs initiating near TS1 and a large partially spliced mdr3 mRNA species initiating upstream of TS1 at a novel initiation site designated TS2. Therefore, mdr3 overexpression in independently derived multidrug-resistant isolates of P388 cells is associated with the appearance of novel transcription start sites in the gene and novel sequences at the 5' end of the overexpressed mRNAs.
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PMID:Transcriptional activation of the mouse mdr3 gene coincides with the appearance of novel transcription initiation sites in multidrug-resistant P388 tumor cells. 845 38

Cyclosporin A (CyA) overcomes P-glycoprotein (P-gp) associated multidrug resistance (MDR). P-gp expression is frequently observed among, not only various cancer cells, but also several normal tissues including bone marrow progenitor cells. These findings lead us to examine whether CyA enhances the myelotoxicity of anti-cancer agents. Bone marrow mononuclear cells were incubated with anti-cancer agents (vincristine, VCR; doxorubicin, ADM; etoposide, VP-16; cytarabine, Ara-C; methotrexate, MTX) and a concentration of CyA (0.5, 5.0 micrograms/mL). The methylcellulose assay for granulocyte-macrophage progenitors (CFU-GM) was conducted using the post-treated cells. There was no significant toxicity for marrow CFU-GM formation after 72 h incubation with CyA (84-108% of control). The inhibitory concentration that reduced colonies by 50% (IC50) was 12 nmol/L for VCR, 6 nmol/L for ADM, 220 nmol/L for VP-16, 15 nmol/L for Ara-C and 35 nmol/L for MTX, respectively. For VCR, ADM and VP-16, the number of CFU-GM was unchanged with the addition of CyA at 0.5 microgram/mL concentration. In contrast at 5 micrograms/mL CyA, the number of CFU-GM (% of control) was reduced significantly (P < 0.05 or P < 0.01). With MTX and Ara-C, the number of CFU-GM was unchanged after addition of CyA, even at 5 micrograms/mL concentration. We conclude CyA may therefore enhance cytotoxic drug sensitivity in MDR tumor cells at a clinically achievable concentration (0.5 microgram/mL) without marrow toxicity.
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PMID:Effect of cyclosporin A on human bone marrow granulocyte-macrophage progenitors with anti-cancer agents. 853 88

A reasonably facile and effective procedure is described for the preparation of inside-out plasma membrane vesicles from tumor cells. The method incorporates nitrogen cavitation, optimized with respect to the applied N2 pressure, in the absence of added divalent cations followed by differential centrifugation and discontinuous, sucrose gradient centrifugation. With the three tumor cell types utilized, multidrug-resistant (MEL/VCR-6) and parental (MEL/O) murine erythroleukemia cells and methotrexate-resistant (L1210/R24) L1210 leukemia cells, yields were in the range of 8-12 mg of plasma membrane vesicles/10(10) cells at a purity of 87-94% with average inside-out sidedness among preparations varying from 65 to 93% depending upon the cell type. Inside-out plasma membrane vesicles so derived were capable of sustaining ATP-dependent transport inward of two common antitumor cytotoxic agents, vinblastine and methotrexate. The former was demonstrated with inside-out vesicles from only P-glycoprotein-overexpressing, multidrug-resistant MEL/VCR-6 cells, while the latter was readily demonstrated in inside-out vesicles from all three cell types.
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PMID:Facile preparation of inside-out plasma membrane vesicles from tumor cells for functional studies of pharmacologically relevant translocating ATPases. 857 99

In the current study, we ran a chemosensity test on 7 human undifferentiated carcinoma cell lines against 10 anticancer compounds using MTT assay. Efficacy was estimated by comparing fifty percent inhibitory concentration (IC50) with the peak plasma concentration. The results showed that the 7 cell lines could be divided into two groups which had different (high or low) chemosensitivity, and that in the high sensitivity group, ACD, VCR, and etoposide were indicated as useful drugs. Our results suggest that it may be impossible to rescue all undifferentiated carcinoma patients by chemotherapy alone because the tumor may consist of 2 clones which have a different chemosensitivity.
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PMID:[In vitro chemosensitivity test for seven undifferentiated thyroid carcinoma cell lines using MTT assay]. 867

From January 1988 to October 1991, one hundred and twelve patients with non metastatic Ewing's sarcoma of bone were treated with a 6 drugs neoadjuvant chemotherapy protocol (IOR/Ew2) in which, to the four drugs usually used in the treatment of this tumor (vincristine, adriamycin, cyclophosphamide and dactinomycin), Ifosfamide and VP-16 were added. The local treatment consisted of radiation therapy in 52 cases, a surgical treatment was performed in 27 cases and in the remaining 33 cases both the previous treatments were used. At a mean follow-up of 4.5 years (3-6.5), 62 patients (55.3%) remained continuously free of disease and 50 relapsed: 41 with metastases, 8 with mestastases and local recurrence and 1 with local recurrence alone. These results do not differ from the ones obtained in our Institution in 98 patients treated between 1983 and 1988 with a neoadjuvant protocol (IOR/Ew1) in which only VCR, ADM, CTX and actD were used (3 year CDFS: IOR/Ew2 = 60.7%-IOR/Ew1 = 55.1%). In IOR/Ew2 a higher DFS rate was observed in the patients with tumor located in the axile bones in comparison with that obtained in the previous study (IOR/Ew2 = 48.6%, IOR Ew1 = 25.6%). Despite the fact that these results came from a not-randomized study, the authors conclude that the addition of Ifosfamide and VP-16 to the four drugs standard regimen do not improve the outcome of patients with Ewing's sarcoma of bone, with the possible exception of the patients with tumor located in the axile bones. This data should be confirmed in further and larger studies.
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PMID:[Neoadjuvant treatment of Ewing's sarcoma: results obtained in 122 patients treated with a 6-drug chemotherapeutic protocol (vincristine, adriamycin, cyclophosphamide, dactinomycin, ifosfamide and etoposide)]. 868 41


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