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)

Mice were challenged with high (10(8)) or low (10(4)) numbers of allogenic tumor cells and assessed for cellular immunity. The responses obtained indicated that high dose challenge produced both delayed-type hypersensitivity (DTH) and cell-mediated cytotoxic reactivity (DCMC), while low dose challenge produced DTH, an apparent suppressive effect, and little or no DCMC. Pretreatment with 100 mg/kg of cyclophosphamide (CTX) 3 d before antigen failed to alter this pattern, but treatment 3 d after antigen administration abrogated both DTH and DCMC. Animals given a combined modulating protocol consisting of an initial low dose challenge followed on day 3 by CTX treatment and day 6 by a high dose challenge developed DCMC in the presence of a greatly reduced or absent DTH response. These results demonstrate the differential effects of allogeneic challenge dose on the development of cellular immunity; the differential effects of CTX treatment given prior to or following alloimmunization, and demonstrate how these effects can be combined to modulate the immune response by selectively activating subpopulations of T-lymphocytes.
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PMID:Effect of allogeneic challenge dose and cyclophosphamide treatment on the development of delayed-type hypersensitivity and cell-mediated cytotoxicity. 677 30

The effect of two anticancer agents, vincristine (VCR) and cyclophosphamide (CTX), on an established cell line (EXP-5) derived from human adenovirus serotype 12 (Ad 12)--induced retinal tumor was studied in vitro and in vivo. VCR at a concentration of 5 and 10 micrograms/ml of culture medium and CTX at 50 and 100 micrograms/ml suppressed growth in vitro. EXP-5 cells were transplanted into the vitreous of 56 inbred CDF (F 344 strain) rats. The implants grew almost exclusively as intravitreous tumors within one month. When the tumor was full grown in the vitreous, VCR and CTX were administered intravenously, singly or in combination, on a schedule based on the protocol CCG-961 for localized unilateral retinoblastoma, Reese-Ellsworth group 5. At a dosage of 0.05 mg/kg, VCR was effective in reducing tumor size; at a dosage of 5 mg/kg, CTX did not reduce tumor size. Combined VCR/CTX therapy induced reduction of about two thirds in tumor size in 2 of 10 treated animals; in all 10 animals, the tumor became morphologically less distinct during the course of treatment although some characteristic features remained. Cytotoxic tumor changes (necrosis, fibrous proliferation, cell transformation, and bizarre giant cells) were observed in all treated animals. This model used the EXP-5 cell line grown in the vitreous, thereby providing a potential tool for evaluating growth and chemotherapeutic responsiveness of retinoblastoma.
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PMID:Chemotherapeutic response of tumor derived from human adenovirus 12--induced retinal tumor cell line in syngeneic CDF (F 344) rats. 684 28

Sixty-five patients with Stages III and IV diffuse histiocytic lymphoma (DHL) were treated with two different and successive combination chemotherapy protocols. Twenty-seven patients were treated with the cyclophosphamide (CTX) L2 protocol, which included maintenance chemotherapy for three years. Thirty-eight patients received the NHL-3 program. Both protocols included radiotherapy (1350--4000 rad) to areas of initial bulky disease or persistent tumor, as well as central nervous system prophylaxis with intrathecal methotrexate or cytosine arabinoside in patients with bone marrow involvement. Two-year survival rates were 44 and 56%, respectively, for the CTX-L2 and NHL-3 protocols. Of the 65 patients, 59 were evaluable for response to therapy. The CTX-L2 produced a 58% total response (TR) rate, 39% complete (CR), and 19% partial (PR). The patients on NHL-3 achieved a TR rate of 82%, 33% CR, and 48% PR. The difference in TR was significant (P = 0.05), but in CR was not. Prior chemotherapy (P = 0.077) and serum lactic dehydrogenase (LDH) level above 500 U/liter (P = 0.01) significantly lessened the chances for achievement of a CR. However, sex, age, the presence of systemic symptoms, stage (III vs. IV), and prior RT were not found to be significantly related to CR rate. This analysis suggests that a high level of serum LDH characterizes a subgroup of patients with particularly aggressive DHL that requires a more intensive modality of treatment.
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PMID:Treatment of advanced diffuse histiocytic lymphoma: an analysis of prognostic variables. 706 63

Prostatic Carcinoma is known to be a hormonally responsive neoplasm which contains both estrogen and androgen receptors. Sixty-three heavily pretreated patients with Stage D prostatic adenocarcinoma received tamoxifen (Nolvadex) at a dose of 20 mg twice a day. Patients were examined every 4 weeks at which time they also had a white count, hemoglobin and platelet count, acid phosphatase, SMA-12, and recording of the status of their measurable or evaluable disease. If the evaluable disease was metastatic to bone, the relevant x-rays were repeated every 8 weeks. The median age of the patients was 66. The Karnofsky status of the patients for whom this information was known was 40% (6), 45% (1), 50% (1), 60% (8), 70% (11), 80% (6), 90% (5), and 100% (2). Forty-one patients were eligible for response evaluation; the majority had evaluable bone disease. No serious toxicity was encountered; two patients withdrew from the protocol because of nausea and vomiting and one patient had hot flashes. One complete response was seen in measurable nodal disease which is continuing after 13+ months, 1 minor response was seen in evaluable bone disease, and 4 patients had long (more than 10 months) stability of bone disease with subjective improvement. We conclude that although the response rate was low, patient acceptability was excellent and that tamoxifen may warrant further trial in a less heavily pretreated patient population.
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PMID:A phase II study Nolvadex: tamoxifen citrate in the treatment of advanced prostatic adenocarcinoma. 709 Oct 40

Fluoxymesterone (Halotestin), 10 mg p.o. BID, was given to 33 women with Stage IV breast cancer who had previously been treated wih the antiestrogen tamoxifen (Nolvadex) and of whom 17 had also undergone hypophysectomy. Objective remissions were obtained in 13 patients (39%) with an average duration of 11+ months. Response rate to fluoxymesterone was similar in patients who had previously responded to tamoxifen and in those who had failed. Duration of response was longer in the former group (12+ vs. 8 months), but this difference was not statistically significant. Of 17 patients who had been previously treated with tamoxifen and hypophysectomy, seven obtained further remission from fluoxymesterone for an average duration of ten months. Two patients with remissions from fluoxymesterone had previously failed to respond both to antiestrogen therapy and to the removal of the pituitary gland. Androgens appear to be an effective sequential endocrine treatment of Stage IV breast cancer after tamoxifen and hypophysectomy. The mechanism by which androgens induce tumor regression in some patients is probably not an antiestrogenic effect or an indirect effect mediated through the pituitary gland, but perhaps a direct action at the tumor level.
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PMID:Androgen-induced remissions after antiestrogen and hypophysectomy in stage IV breast cancer. 729 99

Rat brain cannabinoid receptor (CB-1) was stably transfected into the murine tumor line AtT-20 to study its coupling to inwardly rectifying potassium currents (Kir) and high voltage-activated calcium currents (ICa). In cells expressing CB-1 ("A-2" cells), cannabinoid agonist potently and stereospecifically activated Kir via a pertussis toxin-sensitive G protein. ICa in A-2 cells was sensitive to dihydropyridines and omega CTX MVIIC, less so to omega CgTX GVIA and insensitive to omega Aga IVa. In CB-1 expressing cells, cannabinoid agonist inhibited only the omega CTX MVIIC-sensitive component of ICa. Inhibition of Q-type ICa was voltage dependent and PTX sensitive, thus similar in character to the well-studied modulation of N-type ICa. An endogenous cannabinoid, anandamide, activated Kir and inhibited ICa as efficaciously as potent cannabinoid agonist. Immunocytochemical studies with antibodies specific for class A, B, C, D, and E voltage-dependent calcium channel alpha 1 subunits revealed that AtT-20 cells express each of these major classes of alpha 1 subunit.
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PMID:Cannabinoids activate an inwardly rectifying potassium conductance and inhibit Q-type calcium currents in AtT20 cells transfected with rat brain cannabinoid receptor. 747 17

We have studied the anti-tumor response to cyclophosphamide (CTX) in DBA/2 mice transplanted s.c. with 4 tumors exhibiting different responses to IL-2: ESb lymphoma and Friend leukemia cells (non-responsive or poorly responsive, respectively), p11-R-Eb and Eb lymphoma cells (both highly responsive to IL-2). CTX injections on days 7, 14 and 21 resulted in a significant anti-tumor response in mice transplanted s.c. with Friend leukemia cells or ESb cells, whereas no anti-tumor effect was observed in mice injected with Eb or p11-R-Eb cells. All 4 tumor cell lines were equally sensitive to the cytotoxic effects of mafosfamide, an in vitro active analogue of CTX. To define the host mechanisms responsible for the lack of an anti-tumor effect of CTX in mice transplanted with IL-2-responsive tumors, we studied several aspects of the spontaneous or IL-2-induced anti-tumor response in mice transplanted with p11-R-Eb cells. Injection of monoclonal antibodies (MAbs) to IFN-gamma completely abolished the anti-tumor effects of IL-2. Using a Winn assay, clear-cut anti-tumor activity was found in spleen cells from mice transplanted with the IL-2-responsive tumors. This activity was abolished by CTX, which also abrogated the anti-tumor response to IL-2 in mice injected with p11-R-Eb cells. Our results indicate an inverse correlation between sensitivity to IL-2 and response to CTX and emphasize the importance of initial host-tumor interaction in determining the type of response to IL-2 or CTX.
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PMID:Correlation between the sensitivity or resistance to IL-2 and the response to cyclophosphamide of 4 tumors transplantable in the same murine host. 762 94

We examined the cytotoxic activities of recombinant human tumor necrosis factor (rHTNF-alpha) and five chemotherapeutic agents, CTX, 5-Fu, VCR, DDP, KSM, against two human ovarian cancer cell lines, OVCAR3 and CAOV3, using the MTT assay. The results showed that cytotoxicities of rHTNF-alpha at 5 x 10-5 x 10(4) u/ml against OVCAR3 cell line for 24 h exposure were from 14.2 +/- 6.8% to 67.2 +/- 3.0%, and those against CAOV3 cell line were from 8.2 +/- 4.3% to 60.9 +/- 1.3%. The cytotoxic effects of all five chemotherapeutic agents against the two cell lines were much lower than that of rHTNF-alpha. Further, we studied the combined anticancer potential of rHTNF-alpha with chemotherapeutic agents against the two cell lines. Various degrees of synergism in cytotoxicities of DDP or KSM in combination with rHTNF-alpha were observed. The cytotoxic effect of rHTNF-alpha on CAOV3 cell were also morphologically observed under phase contrast and electron microscope. Based on experiment in vitro, the in vivo anticancer activity of rHTNF-alpha alone or in combination with KSM was examined against human ovarian cancer OVCAR3 subcutaneously transplanted in nude mice. After 8 weeks of treatment, a statistically significant difference of mean tumor volume was found between the control group and groups that received rHTNF-alpha or rHTNF-alpha plus KSM (P < 0.01).
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PMID:[An in vitro and in vivo study of antitumor effects of rHTNF-alpha on human ovarian cancer]. 780 56

The expression of several early-response genes and genes associated with malignant disease was assessed in the EMT-6/parent tumor and the EMT-6/CTX and EMT-6/CDDP in vivo resistant tumor lines growing as tumors or as monolayers in culture. In the absence of treatment the levels of mRNA for the genes c-jun, c-fos, c-myc, Ha-ras and p53 were increased in the EMT-6/CTX and EMT-6/CDDP as compared with the EMT-6/parent tumor, whereas the expression of erb-2 was similar in all three tumors. Although the cells from each of the three tumors show increased expression of early response genes after exposure to cisplatin (CDDP; 100 microM, 2 h) or 4-Hydroxyperoxycyclophosphamide (4-HC; 100 microM, 2 h) in culture, in mRNA extracted from tumor tissue these changes are absent or very small. Both C-jun and erb-2 were detectable in liver. There was increased expression of both of these genes in the livers of tumor-bearing animals as compared with non-tumor-bearing animals. The highest expression of both c-jun and erb-2 occurred in the livers of animals bearing the EMT-6/CDDP tumor. Treatment of the animals with CDDP or cyclophosphamide, in general, resulted in increased expression of both genes at 6 h post treatment. The increased expression of these genes may impart metabolic changes in the tumors and/or hosts that contribute to the resistance of these tumors to specific antitumor alkylating agents.
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PMID:Molecular characterization of the in vivo alkylating agent resistant murine EMT-6 mammary carcinoma tumors. 785 Sep 25

Eight-five consecutive patients with relapsed or refractory Hodgkin's disease (HD) underwent high-dose chemotherapy or chemo/radiotherapy followed by autologous bone marrow (ABMT) and/or peripheral blood stem cell (PBSC) transplantation. Two preparative regimens were used. Twenty-two patients (26%) without prior radiation received fractionated total body irradiation (FTBI) 1,200 Gy in combination with high-dose etoposide (VP-16) 60 mg/kg and cyclophosphamide (CTX) 100 mg/kg. Sixty-three patients (74%) with prior radiotherapy received carmustine (BCNU) 450 mg/m2 instead of FTBI. The median age was 32 years (range, 16 to 56). The median number of prior chemotherapy regimens was three (range, 1 to 7). Forty-three patients (51%) received transplants in first relapse or second complete remission (CR), whereas 33 (39%) received transplants after second or subsequent relapse. All relapsed patients, except one, received conventional salvage chemotherapy and/or radiotherapy in an attempt to reduce tumor bulk before transplant. At the time of analysis in April 1994, fifty-seven patients (67%) are alive, including 44 (52%) in continuous CR, with a median follow-up for the surviving patients of 28 months (range, 7 to 66). Thirty patients (35%) relapsed at a median of 9 months (range, 1 to 43). Eleven patients (13%) died of transplant-related complications including veno-occlusive disease of the liver (VOD) in five, acute and late interstitial pneumonitis in three, graft failure in one, cerebral hemorrhage in one, and therapy-induced myelodysplasia (MDS)/acute leukemia in one patient. At a median follow-up of 25 months (range, 0.6 to 66), the cumulative probability of 2-year overall and disease-free survival (DFS) of all 85 patients is 75% (95% confidence interval [CI] 64% to 84%) and 58% (95% CI 47% to 69%), respectively. Three independent prognostic variables were identified by univariate analysis: number of prior chemotherapy regimens, prior radiotherapy, and extranodal disease at ABMT. Multivariate stepwise Cox regression identified the number of prior chemotherapy regimens as the only significant prognostic factor predicting for both relapse and DFS. There were no significant differences in the outcome of the treatment between the two preparative regimens. Our results confirm that high-dose therapy and ABMT is an effective therapy for patients with relapsed or refractory HD. Earlier transplantation is recommended before the development of drug resistance and end organ damage that results from repeated attempts of salvage therapy.
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PMID:High-dose chemotherapy with or without total body irradiation followed by autologous bone marrow and/or peripheral blood stem cell transplantation for patients with relapsed and refractory Hodgkin's disease: results in 85 patients with analysis of prognostic factors. 785 68


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