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 identified 68 patients with clonal T-large granular lymphocyte (T-LGL) proliferations who were seen at the Mayo Clinic between 1984 and 1992. Nineteen (28%) were asymptomatic at diagnosis, while the rest experienced fatigue (60%), B-symptoms (12%), and recurrent infections (15%). Associated comorbid conditions included rheumatoid arthritis (RA) in 26%. Severe anemia (hemoglobin [Hb] < 8g/dL) and neutopenia (absolute neutrophil count [ANC] < 500/microL) were seen in 19% and 40% of patients, respectively. Immunophenotypic studies showed CD3+, CD8+ phenotype in the majority (72%). Twenty-one patients (31%) have required no therapy, and remain relatively stable with a median follow-up period of 50 months. Treatment was required at either diagnosis (36 patients) or at subsequent follow-up (11 patients). Initial response rates were similar in patients treated with cyclophosphamide (CTX) with or without prednisone (69%), or prednisone alone (73%). Overall, 61 patients (90%) are alive with a median follow-up of 44 months. Actuarial median survival of this entire cohort is 161 months. The presence of anemia or symptoms does not appear to correlate with the tumor burden. In patients requiring therapy, a lower ANC and the presence of B-symptoms/infection were independently associated with a significantly lower probability of achieving a molecular or hematologic complete remission (H-CR). Intermittent immunosuppressive therapy is effective in achieving durable responses in a number of patients. T-LGL proliferations are associated with a favorable prognosis and response to therapy. However, significant heterogeneity exists in clinical presentation and associated comorbid conditions. These disorders should be included in the differential diagnosis of patients with unexplained cytopenias, particularly in the setting of RA and other autoimmune disorders. Analogous to the situation with monoclonal gammopathies, a term such as T-cell clonopathy of undetermined significance (TCUS) may be more appropriate to describe these patients.
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PMID:Clinical spectrum of clonal proliferations of T-large granular lymphocytes: a T-cell clonopathy of undetermined significance? 806 51

Anemia associated with advanced cancer is common. Contributing factors include the anemia of chronic disease, chemotherapy, radiation therapy, and bone marrow invasion with tumor. Based on the observation that endogenous erythropoietin (EPO) levels in anemic patients with cancer are inadequate for the degree of anemia, three randomized double-blind, placebo-controlled trials of recombinant human erythropoietin (rHuEPO) treatment in anemic patients with cancer were performed in patients (1) not receiving concomitant chemotherapy (NO CTX), (2) receiving myelosuppressive chemotherapy that did not include cisplatin (CTX-NO PLAT), and (3) receiving myelosuppressive cisplatin-containing chemotherapy (CTX-PLAT). In the NO CTX trial, patients were treated with rHuEPO 100 U/kg or placebo subcutaneously (SQ) three times per week for up to 8 weeks. In the CTX trials, patients were treated with rHuEPO 150 U/kg or placebo SQ three times per week for 12 weeks. Four hundred thirteen patients were enrolled (124, NO CTX; 157, CTX-NO PLAT; and 132, CTX-PLAT). In all three trials, patients receiving rHuEPO had a significantly (P < .004) greater increase in hematocrit (HCT) than placebo-treated patients. In the two CTX trials combined, rHuEPO-treated patients also had a significantly (P < or = .009) lower transfusion requirement than placebo-treated patients after the first month of therapy. Quality of life improved significantly (P < .05) in responding (> or = 6%-point HCT increase without transfusion) rHuEPO-treated patients compared with placebo-treated patients. Overall, no adverse events occurred more frequently in rHuEPO-treated patients compared with placebo-treated patients. Following completion of the double-blind phase, patients received rHuEPO on an open-label basis as needed for correction of anemia with the dose titrated to a maximum of 900 U/kg/wk. During total rHuEPO exposure (either started at the beginning of double-blind therapy for patients initially randomized to rHuEPO or at the beginning of open-label therapy for patients initially randomized to placebo; 363 treated/347 evaluable for efficacy), 40.0%, 56.1%, and 58.3% of the NO-CTX, CTX-NO PLAT, and CTX-PLAT patients, respectively, responded to rHuEPO therapy with an increase of HCT > or = 6% unrelated to transfusion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Recombinant human erythropoietin in the treatment of cancer and chemotherapy-induced anemia: results of double-blind and open-label follow-up studies. 820 22

The survival of bone-marrow granulocyte-macrophage colony-forming units (CFU-GM), an alkylating-agent-sensitive normal tissue, was assessed in mice bearing the EMT-6 parental tumor or the in vivo resistant EMT-6/CDDP, EMT-6/CTX, EMT-6/Thio, and EMT-6/Carbo tumors. The survival pattern of the bone-marrow CFU-GM recapitulated the survival of the tumor cells, mimicking the development of resistance and reversion to sensitivity upon removal of the selection pressure for each of the four alkylating agents. When the EMT-6 parental tumor was implanted in the opposite hind limb of animals bearing the EMT-6/CDDP or EMT-6/CTX tumor, the survival of the parental tumor cells after treatment of the animals with the appropriate antitumor alkylating agent was enhanced. The EMT-6/CDDP tumor was cross-resistant to CTX and high-dose L-PAM, whereas the EMT-6/CTX tumor was somewhat resistant to CDDP and markedly sensitive to VP-16. In each case, the survival pattern of the bone-marrow CFU-GM reflected the survival of the tumor cells. These results indicate that the presence of an alkylating-agent-resistant tumor in an animal can affect the drug response of tissues distal to that tumor.
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PMID:Protection of bone-marrow granulocyte-macrophage colony-forming units in mice bearing in vivo alkylating-agent-resistant EMT-6 tumors. 832 74

The ability of the antiangiogenic agents TNP-470 and minocycline, singly or in combination, to potentiate the antitumor effects of several cytotoxic therapies was assessed in the murine EMT-6 mammary carcinoma as well as in two drug resistant sublines of that tumor designated EMT-6/CTX and EMT-6/CDDP. The antiangiogenic agents alone or in combination did not alter the growth of the tumors. However, their administration along with cyclophosphamide, CDDP, or thiotepa substantially increased the tumor growth delay produced by these cytotoxic therapies in tumors responsive to the drugs--the increase was about 2-fold for TNP-470 and minocycline together. In drug resistant tumors, treatment with the antiangiogenic agents did not reverse drug resistance but did increase the effect of the cytotoxic drugs. Treatment with TNP-470/minocycline also increased the oxygenation of each of the three tumors. Thus, TNP-470/minocycline administration increased the efficacy of fractionated radiation therapy, especially when used along with a perflubron emulsion oxygen delivery agent/carbogen. These results indicate that treatment regimens including therapies directed toward the proliferating normal cells within a tumor mass as well as therapies directed toward the malignant cells can produce improved outcomes.
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PMID:Potentiation of cytotoxic therapies by TNP-470 and minocycline in mice bearing EMT-6 mammary carcinoma. 853 70

Previous reports of autologous bone marrow transplant (auto-BMT) have demonstrated that myeloablative therapy followed by cyclosporin A (CsA), with and without interferon (IFN), can generate autoreactive cytotoxic T lymphocytes (auto-CTL) with potential therapeutic benefit. This is the first report of an attempt to generate auto-CTL using CsA and IFN after a non-myeloablative regimen. Cyclophosphamide (CTX) 1,200 mg/m2 i.v. day 1 was followed by CsA and IFN-alpha days 2-28, administered in a sequential three-step Phase I dose-escalation scheme. Patients were evaluated twice weekly for clinical evidence of graft-versus-host (GVH) reaction. Peripheral blood mononuclear cells (PBMCs) were obtained before treatment, at time of clinical GVH reaction, and days 21 and 28, and analyzed for auto-CTL, natural killer (NK) cell, and lymphokine-activated killer (LAK) cell activity. Patients also underwent punch skin biopsy at the time of clinical GVH reaction or day 21 to identify histologic evidence of GVH. Fourteen patients completed therapy and were evaluable for immunologic studies and anti-tumor response. No increase in auto-CTL, NK cell, or LAK cell activity was seen. Clinical or histologic evidence of GVH reaction did not occur. We conclude that this myelosuppressive dose of CTX combined with CsA and IFN is unable to generate clinical or immunologic evidence of an auto-GVH reaction. Further efforts are warranted to evaluate other therapeutic attempts to generate auto-CTL with anti-tumor activity based on preliminary results of clinical benefit in auto-BMT.
J Immunother Emphasis Tumor Immunol 1995 Aug
PMID:Phase I trial of sequential cyclophosphamide, cyclosporin A, and interferon-alpha in patients with cancer: attempt to induce autologous graft-versus-host reaction to elicit an antitumor response. 857 66

The potential role of transforming growth factor-beta in in vivo resistance was examined by administration of transforming growth factor-beta-neutralizing antibodies to animals bearing the EMT-6/Parent tumor or the antitumor alkylating resistance tumors, EMT-6/CTX or EMT-6/CDDP. Treatment of tumor bearing animals with anti-TGF-beta antibodies by intraperitoneal injection daily on days 0-8 post-tumor cell implantation increased the sensitivity of the EMT-6/Parent tumor to cyclophosphamide (CTX) and cisplatin (CDDP) and markedly increased the sensitivity of the EMT-6/CTX tumor to CTX and the EMT6/CDDP tumor to CDDP, as determined by tumor cell survival assay. Bone marrow granulocyte-macrophage colony-forming units (CFU-GM) survival was determined from these same animals. The increase in the sensitivity in the tumors upon treatment with the anti-TGF-beta antibodies was also observed in increased sensitivity of the bone marrow CFU-GM to CTX and CDDP. Treatment of non-tumor-bearing animals with the anti-TGF-beta regimen did not alter blood ATP or serum glucose level but did decrease serum lactate levels. This treatment also decreased hepatic glutathione, glutathione S-transferase, glutathione reductase, and glutathione peroxidase in non-tumor bearing animals by 40-60% but increased hepatic cytochrome P450 reductase in these normal animals. Animals bearing the EMT-6/CTX and EMT-6/CDDP tumors had higher serum lactate levels than normal or EMT-6/Parent tumor-bearing animals; these were decreased by the anti-TGF-beta regimen. Treatment of animals bearing any of the three tumors with the anti-TGF-beta regimen decreased by 30-50% the activity of hepatic glutathione S-transferase and glutathione peroxidase, and increased by 35-80% the activity of hepatic cytochrome P450 reductase. In conclusion, treatment with transforming growth factor-beta-neutralizing antibodies restored drug sensitivity in the alkylating agent-resistant tumors, altering both the tumor and host metabolic states.
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PMID:Transforming growth factor-beta in in vivo resistance. 861 16

The efficacy of combination therapy including an oral gelatinase inhibitor (CT1746) and cytotoxic agent was analyzed using the murine Lewis lung carcinoma model. Primary tumors, pulmonary metastases, and sera from tumor-bearing animals had increased gelatinase B activity that was inhibited by CT1746 levels achievable in vivo. The combination of CT1746 and cyclophosphamide (CTX) was significantly more effective than either single agent in delaying local tumor growth (CT1746/CTX, 30.9 +/- 1.7 days; CT1746, 2.6 +/- 0.3 days; CTX, 19.5 +/- 1.1 days; P < .001) and reducing the number and size of pulmonary metastases [CT1746/CTX, 5 +/- 2 (15% metastases > 3 mm); CT1746, 15 +/- 4 (55% > 3 mm); CTX, 11 +/- 3 (63% > 3 mm); no treatment, 24 +/- 5 (62% > 3 mm); P < .001]. These data support the notion of combining matrix metalloproteinase inhibitors and cytotoxic agents to treat certain epithelial malignancies.
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PMID:Combination therapy including a gelatinase inhibitor and cytotoxic agent reduces local invasion and metastasis of murine Lewis lung carcinoma. 863 Oct 1

Among advanced ovarian cancer, OCCA has worse prognosis compared with serous cystadenocarcinoma because of its poor sensitivity to CDDP-based chemotherapy (CTX). Indeed, there has ever been no one patient with pure OCCA showing an appreciable response to CTX. OCCA has recently been increasing in prevalence and has occupied approximately 20-25% of all ovarian cancer. Thus, there is an urgent need to find effective regimens. Based on the results of chemosensitivity tests previously performed both in vitro and in vivo, we designed a combination of CPT (140 mg/m2, i.v.-infused over 4 hours on day 1, 15, and 29) and MMC (7 mg/m2, i.p. injection through a reservoir on day 1, 15, and 29). The course was repeated every 4 weeks. To date 10 pts were entered The median age was 53 (41-69). Among total 25 courses, grade 3 diarrhea was observed in 3 courses. Other toxic signs were acceptable. The responses by tumor size were 2 CR for disease < or = 2 cm in diameter, and 2 CR, 2 PR, 2 NC, and 2 PD for > 2 cm. Six responders showed a significantly longer survival compared with 4 non-responders (p < 0.0396 for Log-rank test). Thus, the present protocol is the first to demonstrate a significant activity for pure OCCA.
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PMID:[Successful treatment of clear cell adenocarcinoma of the ovary (OCCA) with a combination of CPT-11 and mitomycin C]. 867 17

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

Transforming growth factor-beta (TGF-beta) has been implicated in the in vivo resistance of the EMT-6/CTX and EMT-6/ CDDP murine mammary tumors. Both of these tumors have a higher number of intratumoral vessels than the EMT-6/ parent tumor. Animals bearing the resistant tumors have higher plasma levels of TGF-beta than animals bearing the parent tumors; however, upon treatment with cytotoxic therapies there is a greater rise in plasma TGF-beta levels in animals bearing the parent tumor than in animals bearing the resistant tumors. In situ hybridization for TGF-beta mRNA and immunohistochemical staining for TGF-beta protein showed that the resistant tumor levels of this growth factor are higher than those of the parent tumor prior to treatment; however, after cytotoxic therapy the increase in TGF-beta is greater in the parent tumor than in the resistant tumors. Treatment of tumor-bearing animals with the naturally occurring TGF-beta inhibitor decorin did not alter the sensitivity of the parent tumor to cyclophosphamide or to CDDP as determined by tumor cell survival assay. However, administration of decorin increased the sensitivity of the EMT-6/CTX tumor to cyclophosphamide and of the EMT-6/CDDP tumor to CDDP so that the drug resistance of these tumors was nearly ablated. A similar pattern was observed in the drug response of the bone marrow granulocyte-macrophage colony-stimulating factor of animals bearing each of the 3 tumors.
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PMID:Reversal of in vivo drug resistance by the transforming growth factor-beta inhibitor decorin. 909 65


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