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)

Critical assessment of head and neck cancer with respect to staging has, on occasion, been disappointingly ineffective. We have attempted to correlate the incidence of measureable uptake of cobalt 57 tagged bleomycin by primary squamous cell carcinoma and metastatic cervical lymph nodes. Forty-six cases have been evaluated with respect to histopathological confirmation of the suspected metastatic disease. We have found that this diagnostic measure increases our acumen in staging of head and neck cancer. The relevance of the Co-Bleo scans as a diagnostic aid is reported in 46 cases. Malignant tumors greater than 2 cm in size appear to demonstrate active uptake of the imaging agent. Small tumor size and excess background radioactivity contribute to the false-negatives (17%). Inflammatory conditions or benign tumors of the salivary apparatus may result in minimal uptake, thus, a false-positive result (10%). An increase in the radioactivity of the Co-Bleo may enhance the benefits of this procedure in the search for an undiagnosed primary, as well as undiagnosed local or distant metastases.
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PMID:Assessment of cobalt 57 tagged bleomycin as a clinical aid in staging of head and neck carcinoma. 616 36

Either intra-arterial infusions of MTX (500 mg over 10 days) or intra-arterial infusions of BLM (95 mg over 13 days) were administered as initial treatment to 85 patients with untreated squamous cell carcinomas of the oral cavity. Tumour regression was assessed 10-15 days after the end of chemotherapy. A sequential analysis was used, and BLM demonstrated a significantly greater local efficacy after the 32nd matched pair was assessed. The same results were observed when tumour response rates were compared, ignoring the matching, on the 85 patients, (P less than 0.001). The response rate for patients with neck nodes was low (10/38). Catheter management problems, toxic effects and lethal reactions were 2.5 times more frequent in the MTX group.
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PMID:A randomized EORTC trial comparing intra-arterial infusion with methotrexate vs bleomycin as initial therapy in carcinoma of the oral cavity. 618 43

Several types of human cultured tumor cells were tested for the sensitivity to BLM, an effective antitumor antibiotic for epidermoid (squamous cell) carcinomas. Three cell lines (HeLa, KB, Hepd) derived from epidermoid carcinomas were very sensitive to BLM under concentrations tested, whereas BLM-resistant HeLa cells (HeLa-BLMr), neoplastic cells derived from salivary glands (HPA, HSG), malignant fibrous histiocytoma (MFH) and melanoma (MEC) were much less sensitive to BLM than epidermoid carcinoma cell lines under the same conditions. To investigate the possible mechanism of BLM resistance, these cell lines, namely HeLa, HeLa-BLMr, HSG and MEC, were examined for i) BLM permeability into cells by using 3H-PEP which was a new derivative of BLM, ii) BLM-inactivating activity in cell extracts by bioassay for antibacterial activity with B. subtilis PCI 219 strain, and iii) DNA repair activity after UV irradiation. Consequently, as compared with BLM-sensitive HeLa cells, BLM less sensitive HeLa-BLMr, HSG and MEC cells showed 34%, 50% and 39% reduction per 10(6) cells in BLM permeability, 1.6-, 5.6- and 4.7-fold increase per mg protein in BLM inactivating activity, and 24.5-, one and 8-fold enhancement in DNA repair activity, respectively. Therefore, it was indicated that above three factors at least were involved in the BLM sensitivity of human tumor cells.
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PMID:[Sensitivity to bleomycin of human cultured tumor cells and analysis of related factors]. 619 72

111Indium-bleomycin (111In-BLM) and 57Co-bleomycin (57Co-BLM) were prepared and their distributions were compared in the tissues, blood, and urine in tumor-bearing and in untreated mice and rats. Autoradiographs of electrophoresis gels showed that patterns for urine from untreated and tumor-bearing animals, collected 1-3 h or 48 h after injection of 111In-BLM were similar to those for in vitro mixtures of urine and 111In-BLM, but differed from the patterns obtained with 111InCl3 under in vivo or in vitro conditions. In rats bearing mammary adenocarcinoma, 48 h after administration of the radiopharmaceutical, the activity ratio of tumor to eleven different tissues was 1.2-4.6 times higher for injected 111In-BLM than for 111InCl3 (P less than or equal to 0.001 or P less than or equal to 0.05). Imaging with a gamma camera depicted tumors in mice more distinctly with 111In-BLM than with 111InCl3. These findings were interpreted as reflecting the stability of 111In-BLM in vivo. The tumor concentration (%dose/g) was higher for the viable area than for the necrotic area for 111In-BLM, but the reverse was true for 57Co-BLM.
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PMID:Stability of 111In-bleomycin in vivo--properties compared with 57Co-bleomycin. 619 7

A new 111In-bleomycin complex (111In-BLMC) is here reported. Its radiochemical purity was 99% by thin-layer chromatography (TLC) (Rf 0.65) and in 5% agarose gel electrophoresis in 0.02 M NaHCO3 it migrated toward the anode. Autoradiographs of TLC and gel electrophoresis plates showed no change on storage for 3 weeks. Urine and plasma from untreated or glioma-bearing mice after injection of 111In-BLMC were analyzed by TLC and gel electrophoresis. Results indicated stability in vivo, nonbinding to transferrin, affinity to viable tumor, and excretion faster than 111In-BLM-B2, 111In-BLM, or 57Co-BLM. Tissue distributions 24 hr after injection of radiopharmaceutical showed activity ratios of tumor to blood, muscle, and brain of 13.1, 12.4, and 81.6, respectively, which were significantly higher than those for previously prepared 111In-BLM-B2 or 111In-BLM (except for brain, 0.05 less than P less than 0.1). The new 111In-BLM complex may be useful in clinical imaging and for combining radionuclide radiotherapy and chemotherapy.
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PMID:A new 111In-bleomycin complex for tumor imaging: preparation, stability, and distribution in glioma-bearing mice. 619 22

Sensitivities to anticancer drugs were tested with cultured cells from six osteosarcomas transplanted onto nude mice and those of six human osteosarcomas cultured in vitro directly from the original tumor. The suppression by the anticancer drugs of 3H-TdR incorporation into the cultured cells was examined. The cells that had been grafted onto nude mice were highly sensitive to ADM and MMC and less sensitive to BLM and MTX in all of the tumors tested. Similar results were obtained with cells cultured directly in vitro from the original tumor. These results were somewhat comparable with those achieved by measuring cell survival and the success of back transplants onto nude mice after treatment with drugs. If further information on appropriate labeled precursors can be developed, testing the sensitivity of tumors to drugs by measuring the suppression of nucleic acid synthesis should prove useful in clinical applications.
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PMID:An in vitro method for testing the sensitivities to drugs of human osteosarcomas grafted onto nude mice. 640 9

The glycoproteins recognized by monoclonal antibody (MAb) NKI-beteb are among the best diagnostic markers for human melanoma. MAb NKI-beteb reacts with melanoma cells throughout tumor development and does not cross-react with other tumor or normal cells, except for cells of the melanocytic lineage. Two other melanocyte lineage-specific MAbs, HMB-50 and HMB-45, show a specificity and staining pattern strikingly similar to the ones observed for NKI-beteb. Herein, we demonstrate that all three MAbs recognize protein products encoded by a single cDNA. Expression of this cDNA in BLM cells results in immunoreactivity with all three MAbs. In addition, we demonstrate co-distribution of the RNA species detected by the cDNA with the proteins recognized by the MAbs in tissue sections.
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PMID:Melanocyte lineage-specific antigens recognized by monoclonal antibodies NKI-beteb, HMB-50, and HMB-45 are encoded by a single cDNA. 750 84

Many single-agent phase II studies for patients with esophageal cancer had been performed, and at least five agents with modest activity have been indentified, BLM, MMC, CDDP, VDS and MTX, that revealed no CR. Even in the phase II study of 254-S, a new anticancer platinum complex, with a response rate of 43%, CR could not be recognized. Only two regimens of combination chemotherapy have been studied extensively, CDDP/BLM/VDS and CDDP/5-FU. The combination of CDDP/5-FU has gained popularity and JEOG phase II study revealed a response rate of 36%. As surgical adjuvant therapy, postoperative adjuvant therapy has been common in Japan. The 4th JEOG phase III clinical trial, comparing surgery alone and postoperative chemotherapy of CDDP/VDS, showed no additive effect to surgery by postoperative chemotherapy with such a regimen. In western countries, neoadjuvant chemotherapy is frequent and most of the regimens include CDDP/5-FU. Pathological CR rates were less than 10%, and median survival terms were from eight to 28 months. The rationale for the concurrent use of chemotherapy and radiotherapy is to combine an agent that has an effect upon systemic micrometastases with a modality that enhances local tumor control. In addition, a number of chemotherapeutic agents have radiosensitizing effects. In western countries, more than 35 trials studying over 1400 patients have been reported. The majority of trials have employed CDDP/5-FU combined with RT to a total dose of 30Gy. Pathological CR rates were from 20 to 40% and median survival terms were from 12 to 29 months. Both neoadjuvant chemotherapy and chemoradiotherapy did not change operative morbidity or mortality, and there was a statistically significant increase in survival in complete responders. However, early and median survival seems improved but cure rates are not. Both therapies require further investigation.
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PMID:[Chemotherapy and multimodality therapy in the treatment of esophageal cancer]. 754 Aug 23

By comparing two subsequent human tumor stages we previously described calcyclin as a new potential melanoma associated neoplastic progression marker positively linked with metastasis. In this study the calcyclin expression levels in a representative panel of human melanoma cell lines were correlated with the occurrence of DNase I hypersensitive (DH) regions and potential enhancer elements in a 6 kb genomic fragment spanning the human calcyclin gene. Examination of the chromatin structure of the transcription unit revealed no qualitative differences in DH sites within the panel of tested human melanoma cells, but especially the sequences around the transcription start site and a 1.5 kb upstream region appeared more accessible to the nuclease in frequently (BLM, MV3) as compared to poorly (530, 1F6) metastasizing cells. The genomic fragments that harbor one or more DH sites were subjected to functional analysis by luciferase reporter gene assays. Thus, an enhancer element was detected between 361 and 167 bp upstream of the transcription start site. This enhancer displayed equal activating potential (2-3 fold) both in weakly and in frequently metastasizing cells and was apparently recognized by transcription factors present in both types of human melanoma cells lines. We conclude that, in addition to a slight amplification of the encoding gene, the elevated calcyclin mRNA levels are only reflected in a selectively increased accessibility of the chromatin structure to DNaseI in metastasizing melanoma cells.
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PMID:Functional analysis of the human calcyclin gene promoter in a panel of human melanoma cell lines. 765 29

Diffuse large-cell lymphoma (DLCL) is a neoplasm that is curable with chemotherapy in an appreciable percentage of patients. However, not all patients are cured and the best drug combination and optimal dose intensity have not yet been established. In an attempt to improve complete response rate and survival with minimal toxicity, we devised an alternating combination chemotherapy consisting of CHOP-Bleo (cyclophosphamide, doxorubicin, vincristine, prednisolone, and bleomycin) and POEM-Bleo (prednisolone, vincristine, etoposide, mitoxantrone, and bleomycin). Between March 1986 and October 1990, 30 newly-diagnosed patients with advanced DLCL were treated with the regimen. Of these 30 patients, 14 (47%) were 61 years of age or more, 15 (50%) had stage IV disease, 14 (47%) presented with constitutional symptoms, and 7 (23%) had T-cell lymphoma. After the completion of therapy, 23 (77%) achieved a complete response and 6 (20%) had a partial response. The actuarial relapse-free survival at 5 years is 52% and the overall survival projected to 5 years is 47%. Toxicity was generally mild and well tolerated. Although this alternating regimen had substantial activity as front-line chemotherapy for advanced DLCL, we conclude that the observed response rate and survival do not essentially differ from those achieved with conventional regimens and further clinical trials are thus not warranted.
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PMID:Alternating chemotherapy of CHOP-Bleo and POEM-Bleo for diffuse large-cell lymphoma: a single-institutional study with a long-term follow-up. 769 30


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