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 assessed the response of various tumors, following each of three consecutive courses of CHOP or CHOP-Bleo therapy in 32 untreated patients with intermediate or high-grade non-Hodgkin's lymphoma (NHL), and also retrospectively compared these results to those for a group in whom complete remission (CR) had been obtained within five courses and a non-CR group. A low CR rate was observed in these patients who showed no or only temporary antitumor effects (persistent increase, no change, or increase after a transient decrease) after two courses of therapy. Furthermore, we measured total tumor volume and tumor regression rate after each course of therapy in 21 patients who had measurable tumors, and determined their cut off values for distinguishing between CR and non-CR. When the cut off values were applied to the effects observed in the 21 patients, positive predictive values after each course of therapy were high. False negative values after the second course of the therapy were low, and showed 0% when the cut off value determined from tumor regression rate was used. These results suggest that we can accurately predict the probability of CR after the second course of CHOP or CHOP-Bleo therapy, although this should be further confirmed by prospective study. In addition, such an analysis may prove useful in setting up individualized response-adapted therapy for NHL.
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PMID:[Assessment of the antitumor effect after remission induction therapy for non-Hodgkin's lymphoma--an approach to a response-adapted therapy]. 170 33

The preference of bleomycin, a DNA strand scission antitumor agent, to damage extrachromosomal (episomal) DNA was investigated. These episomes contain transcriptional promoters, replication origins, and oncogenes from MMTV, BPV, and v-Ha-ras and confer a neoplastic phenotype to a mouse fibroblast cell line. We found that bleomycin induces dose-dependent single- and double-stranded cleavage of intracellular episomes as measured by topological forms conversion. Bleomycin scission of episomes occurs within 1 min, and upon drug removal, damaged episomes are as rapidly repaired. By expressing the episomal and genomic damage as breaks per nucleotide, bleomycin has a 30-50-fold cleavage preference for episomal chromatin compared to genomic DNA. The episomes have preferred regions of the bleomycin-induced damage, particularly within the MMTV LTR and BPV origin of replication. Also, it is possible to assess bleomycin action on episomes in solid tumors in mice. Single intravenous injections of BLM into tumor-bearing mice result in single- and double-stranded cleavage of episomes that are dose related and occur within 1 min. Specific double-stranded breaks occur in the same regulatory regions of episomes in solid tumors and in cultured cells. Finally, we observe that damage to the episomal drug target occurs at therapeutic doses in mice.
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PMID:Extrachromosomal chromatin: novel target for bleomycin cleavage in cells and solid tumors. 170 27

The ability of cultured human fibroblasts to reorganize and contract three dimensional collagen I gels is regarded as an in vitro model for the reorganization of connective tissue during wound healing. We investigated whether adhesion receptors of the integrin family are involved. It was found that synthesis and transcription of the alpha 2 beta 1 integrin (but not of alpha 1 beta 1 or alpha 3 beta 1) is selectively upregulated when fibroblasts are seeded into type I collagen gels. Time course experiments revealed that high synthetic levels of alpha 2 beta 1 parallel the gel contraction process and return to "baseline" levels after the contraction has subsided. Furthermore, function-blocking mAbs directed to the alpha 2 and beta 1 chain of integrins inhibited gel contraction. Remodelling of connective tissue can be important for tumor cells during invasion and formation of metastases. Therefore, we tested human melanoma cell lines for this function. Five out of nine melanoma lines contracted collagen gels in vitro. Among these, two highly aggressive melanoma cell lines (MV3 and BLM) most efficiently contracted gels almost reaching the rate of normal adult fibroblasts. In these cells, synthesis of alpha 2 beta 1 was also significantly upregulated when seeded into collagen I gels. Moreover, function blocking anti-alpha 2 in conjunction with anti-beta 1 chain mAbs completely inhibited gel contraction for several days. Other melanoma cells (530) with lower metastatic potential which were not able to contract gels, showed no induction of alpha 2 beta 1 synthesis in gel culture. Our results suggest an important role of integrin alpha 2 beta 1 in the contraction of collagen I by normal diploid fibroblasts during wound healing and in the reorganization of collagen matrices by highly aggressive human melanoma cells.
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PMID:Integrin alpha 2 beta 1 is upregulated in fibroblasts and highly aggressive melanoma cells in three-dimensional collagen lattices and mediates the reorganization of collagen I fibrils. 195 83

Polyamines are essential for normal and neoplastic growth. Ornithine decarboxylase (ODC) is the first and rate-limiting enzyme in the polyamine biosynthetic pathway. alpha-Difluoromethylornithine (DFMO) is an enzyme-activated irreversible inhibitor of ODC, and a known anti-neoplastic agent. The purpose of this study was to examine the susceptibility of various human cancers to inhibition by DFMO in vivo. We have studied three human pancreatic adenocarcinomas, designated CAV, SKI, and PGER, two human colon adenocarcinomas (LS-180 and WIDR), and three metastatic cell lines of a human gastric adenocarcinoma (BHM, BMM, BLM) that were growing in congenitally athymic (nude) Balb/c mice. Mice bearing each tumor were divided into two groups; one group served as controls and the other group received DFMO 3% in drinking water. Tumor growth and weight, and content of DNA, RNA, protein and polyamines were determined and correlated. DFMO significantly inhibited the growth of three of the three gastric tumors, two of the three pancreatic tumors and neither of the two colon tumors. The tumor content of DNA, RNA and protein exhibited a pattern that was parallel to tumor growth. The tumor polyamine concentration did not correlate with sensitivity to DFMO. These findings provide clear evidence for important differences in the sensitivity of various human cancers to growth inhibition by DFMO and indicate that endogenous polyamine levels alone do not predict the sensitivity of the tumors to DFMO.
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PMID:Differential sensitivity of various human tumors to inhibition of polyamine biosynthesis in vivo. 198 77

Flow cytometry (FCM) permits instantaneous determination of the percentages of cells in various phases of cell cycle using BrdU-PI double staining method, and allowing rapid evaluation of the effects of irradiation and anti-cancer drugs (ACNU, ADR, BLM) on the cell kinetics. In this study, the growth inhibition and changes in the cell kinetics after irradiation and chemotherapy were examined according to the growth curve analysis and BrdU-PI method to evaluate the usefulness of BrdU-PI method for assessment of the effect of the treatments. By the conventional method based on the DNA histogram, accurate determination of S cell fraction was difficult due to overlapping of the DNA contents of G1 cells and early S cells and those of late S cells and G2 cells. BrdU-PI double staining allowed direct differentiation of G1, S, and G2 + M cells, especially between G1-S and S-G2 + M cells. The analysis of cell kinetics using BrdU is advantageous in comparison to the conventional autoradiographic methods because it allows more rapid assay with very high sensitivity. By the present BrdU method, rapid transition to the G1-S phase was observed within 4 hours after exposure to radiation and anti-cancer drugs. This initial G1 arrest induced by irradiation was confirmed for the first time by the present BrdU-PI double staining. The present method is considered to be indispensable for evaluation of the percentage of S cells in the tumor tissue and analysis of cell kinetics after irradiation and chemotherapy against cancer.
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PMID:[Analysis of cell kinetics using BrdU monoclonal antibody on cultured tumor cells after irradiation and treatment with anti-cancer drugs]. 208 23

Chemosensitivity assays including colony forming assay (CFA), MTT dye reduction assay (MTT assay) and thymidine incorporation assay (TIA) for cultured rat and human glioma cells were conducted to determine the correlation among them and the in vivo antitumor efficacy of anticancer drugs using rats implanted glioma cells. Cytotoxicity of various agents such as ACNU, ACR, CDDP, VCR or BLM, was estimated from the concentrations which caused 50% inhibition of the cell growth at the peak plasma concentration. The survival time of tumor bearing rats was assessed after ip treatment with these agents at their estimated clinical doses. This parameter was greater in the drugs that were shown to be highly sensitive in CFA and was consistent with the data for CFA. In the chemosensitivity assays, CFA closely correlated to MTT assay for all agents except VCR, but poorly so to TIA. The results in this study indicate that MTT assay seemed to be useful for determining the chemosensitivity of anticancer drugs and that chemosensitivity assay should be conducted depending on the nature of anticancer drug.
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PMID:[Chemosensitivity assays for malignant gliomas]. 224 Nov 89

The overall therapeutic strategy for the management of lymphomas at the M.D. Anderson Cancer Center consists of devising new drug combinations that are tested first in patients with relapsed lymphoma and, if successful, are then incorporated into first-line management. This article describes the preliminary results of the alternating triple therapy (ATT) first-line regimen for patients with M.D. Anderson stages B, C, and D of intermediate-grade lymphomas. This regimen is based on three non-cross-resistant combinations, two of which were originally developed as salvage therapy. Statistically significant improvement in the overall survival and failure-free survival at 1 year has already been seen for the stage D patients (high tumor burden and high lactate dehydrogenase levels). A new therapeutic strategy in current use for patients with Ann Arbor stages III and IV low-grade lymphoma is also described. This regimen consists of CHOP-Bleo (cyclophosphamide, doxorubicin, vincristine, prednisone-bleomycin) alternating with ESHAP (etoposide, Solu-medrol [methylprednisolone, Upjohn Company], Ara-C [cytarabine], platinum) and NOPP (Novantrone [mitoxantrone, American Cyanamid Company], Oncovin [vincristine Eli Lilly and Company], procarbazine, prednisone). Maintenance interferon (IFN) is also used for 1 year. Finally, the current salvage regimen in use at the M.D. Anderson Cancer Center is described. This MINE-ESHAP regimen consists of an induction with mesna, ifosfamide, Novantrone (mitoxantrone), and etoposide, which is administered until maximum response and followed by consolidation with 3 to 6 courses of ESHAP. The preliminary results of this regimen are encouraging, but more follow-up is required before any conclusions can be drawn.
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PMID:Recent trends in the management of lymphomas at M.D. Anderson Cancer Center. 225 21

Neo-adjuvant chemotherapy, followed by definitive surgery and/or radiotherapy was utilized in nine patients with carcinoma of the hypopharynx and cervical esophagus starting in December, 1983. They were treated with combination chemotherapies which included CDDP, PEP (BLM), and MTX. The patients' ages ranged from 52 to 70 years with an average of 57. The histologic types were all squamous cell carcinoma and performance status was 1 in all cases. There were 7 stage III and 2 stage IV. Of 9 patients, 3 showed complete response and 6 showed partial response of the primary tumor with an overall response rate of 100%. Of 8 patients, 3 showed complete response and 2 showed partial response of the metastatic node with an overall response rate of 62.5%. Toxic effects included alopecia in 9 patients, nausea/vomiting in 7, eczema in 4, RBC below 350 X 10(4)/mm3 in 5, WBC below 3000/mm3 in 1, peak serum creatinine above 2 mg/dl in 1. All patients except one with renal toxicity were able to start definitive treatment soon after chemotherapy, the primary and regional lesions being subsequently well controlled in all 9 patients. Neo-adjuvant chemotherapy appears to be very effective for the reduction of tumor bulk. This multidisciplinary therapy should be expected to increase survival rate.
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PMID:[A neo-adjuvant chemotherapy for carcinomas of the hypopharynx and cervical esophagus]. 240 26

The human tumor clonogenic assay (HTCA) and the human tumor xenograft system implanted in nude mice were performed simultaneously in an ovarian cancer patient as chemosensitivity testing. Eight anticancer drugs (5-FU, MMC, VCR, ACD, BLM, VLB, CDDP, and ADM) were applied to the HTCA and the human tumor xenograft system. In the HTCA, 5-FU and MMC were sensitive, VCR was moderately sensitive, and ACD, BLM, VLB, CDDP, and ADM were resistant. In the human tumor xenograft system, MMC, VCR, and ADM showed tumor regression (++), and CDDP, VLB, BLM, 5-FU, and ACD exhibited no response (-). Two of the three drugs, which were classified as sensitive or intermediately sensitive in the HTCA, showed tumor regression (++) in the human tumor xenograft system. And four of the five drugs, which were resistant in the HTCA, exhibited no response (-) in the human tumor xenograft system. Clinically, PVB therapy (CDDP, VLB, and BLM) was applied to the present patient, but after recurrence, 5-FU + MMC therapy was applied on the basis of the results of the HTCA. In addition, ADM was added with reference to the results of the human tumor xenograft system. As a result of this therapy, the tumor growth was inhibited. It is possible from the present data that simultaneous chemosensitivity testing of the HTCA and the human tumor xenograft system implanted in nude mice is very useful when choosing sensitive anticancer drugs.
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PMID:[Chemotherapy of ovarian cancer based on in vitro (HTCA) and in vivo (nude mice) chemosensitivity testing]. 241 31

Mice bearing transplanted glioma received 0.9% NaCl, 0.1 mg of BLM, or 200-250 microCi of 111In-BLM (0.1 mg BLM) daily for 5 days intraperitoneally. After therapy, tumor sizes were in the order NaCl greater than BLM greater than 111In-BLM. On the 11th day after the first injection, tumor size (mm3) in the 111In-BLM group was 1,220; in the BLM group, it was 2,310 (P less than .025). After intratumor injection of a total dose of 0.1 mg of BLM/gm tumor weight, or of 1 mCi/gm tumor weight of 111In-BLM (carried by 0.1 mg of BLM/gm tumor weight), the tumor size decreased in the 111In-BLM group more than in the BLM group. On the 5th day after the 2nd dose therapy, the tumor size in the 111In-BLM group was 2,020; in the BLM group it was 4,220 (P less than .05). Host weights for these two groups were similar. The necrotic area in the tumor was much greater in the 111In-BLM group than in the BLM group. These results suggest the use for radiotherapy and chemotherapy.
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PMID:Use of 111In-bleomycin for combining radiotherapy and chemotherapy on glioma-bearing mice. 241 54


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