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)

From a subtractive cDNA library, we isolated several cDNA clones which showed differential expression between highly and lowly metastatic human melanoma cell lines. One clone, designated nmb, showed preferential expression in the low-metastatic cell lines and was chosen for further characterization. Sequence analysis revealed that this clone represents a novel gene, encoding a putative transmembrane glycoprotein which showed the highest homology to the precursor of pMEL17, a melanocyte-specific protein. nmb RNA expression was absent in most tumor-cell lines tested and not restricted to the melanocytic lineage. Transfection of a partial nmb cDNA into a highly metastatic melanoma cell line (BLM) resulted, in 2 of 3 transfectants, in slower subcutaneous tumor growth and, in 1 of 3 transfectants, in reduction of the potential for spontaneous metastasis in nude mice.
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PMID:nmb, a novel gene, is expressed in low-metastatic human melanoma cell lines and xenografts. 781 55

We established two human thyroid tumor cell lines. One cell line (hPTC) was established from the tissue of a papillary thyroid carcinoma surgically excised from a 27-year-old female patient. The other cell line (hAG) was established from the tissue of an adenomatous goiter excised from a 59-year old female patient. Synthesis of cAMP by hPTC and hAG increased when they were stimulated by TSH. hPTC and hAG continued to divide as a monolayer in a tissue culture for three years and two years, respectively. We assessed the efficacy of anticancer drugs (doxorubicin:ADR, cisplatin:CDDP, nimustine:ACNU, bleomycin:BLM, cyclophosphamide:CPA, aclarubicin:ACR) with resard to hPTC. The hPTC cells were cultured in 24-well plates in the presence of the anticancer drugs for 48 hours, and the cellular DNA of the live cells was measured with diaminobenzoic acid. ADR had the lowest ED50 (0.029 mu g/ml) and the clinical blood concentration was 13.8 times that of the ED50. The clinical blood concentration divided by ED50 for the other anticancer drugs are, in order of higher values, 2.3 for CPA, 1.7 for BLM, 1.2 for CDDP, 0.5 for ACR, and less than 0.1 for ACNU. ADR showed time-independent effects since a 2-hour exposure of ADR to the hPTC cells resulted in the significant reduction of the cellular DNA content of the live cells even after 48 hours. The effects of the other anticancer drugs were time-dependent. We then studied the difference of the effects of ADR on hPTC and hAG. ED50 for hPTC was significantly low (0.035 mu g/ml) compared to that for hAG (0.460 mu g/ml). Since free radical formation is one of the major anticancer mechanisms of ADR the effects of free radicals on ED50's for hPTC and hAG were measured by adding glutathione (GSH), N-acetylcystein (NAC), buthionine sulfoximine (BSO), and alpha-tocopherol (alpha-toco) into the culture media. GSH catches up with free radicals in the extracellular fluid. NAC promotes production of GSH in the cytoplasm, but BSO interferes with the production of GSH in the cytoplasm. alpha-toco catches up with free radicals on the plasma membrane. GSH and alpha-toco did not effect ED50 for hPTC and hAG. However, NAC increased ED50 for hPTC and hAG, and BSO reduced ED50 for hPTC and hAG. The effects of NAC and BSO on ED50 for hPTC were greater than those for hAG.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Different effects of anticancer drugs on two human thyroid cell lines with different stages of differentiation]. 789 67

We recently isolated a cDNA clone that encodes the melanocyte lineage-specific antigen glycoprotein (gp)100. Antibodies directed against gp100 are an important tool in the diagnosis of human melanoma. Since the gp100 antigen is highly expressed in melanocytic cells, we investigated whether this antigen might serve as a target for antimelanoma cytotoxic T lymphocytes (CTL). Here, we demonstrate that cytotoxic tumor-infiltrating lymphocytes (TIL) derived from a melanoma patient (TIL 1200) are directed against gp100. HLA-A2.1+ melanoma cells are lysed by TIL from this patient. In addition, murine double transfectants, expressing both HLA-A2.1 and gp100, are lysed by TIL 1200, whereas transfectants expressing only HLA-A2.1 are not susceptible to lysis. Furthermore, the HLA-A2.1+ melanoma cell line BLM, which lacks gp100 expression and is resistant to lysis, becomes susceptible after transfection of gp100 cDNA. Finally, HLA-A2.1+ normal melanocytes are lysed by TIL 1200. These data demonstrate that the melanocyte differentiation antigen gp100 can be recognized in the context of HLA-A2.1 by CTL from a melanoma patient. Gp100 may therefore constitute a useful target for specific immunotherapy against melanoma, provided that no unacceptable cytotoxicity towards normal tissue is observed.
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PMID:Melanocyte lineage-specific antigen gp100 is recognized by melanoma-derived tumor-infiltrating lymphocytes. 811 68

Recent advances in adjuvant chemotherapy for malignant bone tumor have been improving the survival rate and making limb-salvage surgery a reliable technique. Ewing's sarcoma is treated by multiple agent chemotherapy. We treat Ewing's sarcoma by Rosen's T-11 protocol (CYT.ADM.MTX.VCR.ACT-D.BLM). This protocol is very effective, but results are poorer than for osteosarcoma. Newly developed protocols such as EICESS (European Intergroup Cooperative Ewing's Sarcoma Study)-92, including new drugs, should be investigated. The results with malignant fibrous histiocytoma are comparable to those for osteosarcoma. We have performed an original chemotherapy protocol, called "K-1 protocol." Patients were treated with three courses of intraarterial infusion of cisplatin (120 mg/m2) and caffeine (1.0-1.5 mg/m2/day for three days continuously) at two-week intervals. If the effect was insufficient, ADM (30 mg/m2/day for two days continuously) is added to this protocol. We treat malignant lymphoma in collaboration with a hematologist and radiologist. The 5-year survival rate of non-Hodgkin's lymphoma in our series was 56% in clinical stage III and 34% in clinical stage IV. We are trying third-generation chemotherapy to improve the survival rate.
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PMID:[Chemotherapy for Ewing's sarcoma, malignant fibrous histiocytoma and malignant lymphoma]. 821 63

Surgical tumor specimens obtained from twenty-five patients with renal cell carcinoma were subjected to the gel-supported culture developed by Hoffman for a clinical approach. Cell viability was determined by exposure to 3H-thymidine. The anti-cancer drugs examined in this set were 13 in total: ADM, AMR, BLM, MMC, VCR, VLB, etoposide, CDDP, 5-FU, MTX, IFN-alpha, IFN-gamma and TNF. The specimens were exposed to media containing 1x and 1/10x achievable human plasma peak concentrations of the agents. The overall susceptibility rate for growing tumors obtained from patients was 88% (22 of 25 patients). Susceptibility (less than 50% of control 3H-thymidine uptake) to ADM was observed to be highest (56%) in 12 of 22 patients, and to VLB and BLM (50%) in 11 patients each. On the other hand, that to MTX was observed in 1 patient at the lowest rate (5%), and that to the BRM group drugs was observed in 3 in IFN-alpha (14%), 1 in IFN-gamma (5%) and 2 in TNF (9%). However the number of effective drugs was not correlated to the grade, architecture and cell type. These results suggest that this assay system may be useful for a chemosensitivity test.
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PMID:[In vitro chemosensitivity test of human renal cell carcinoma using three-dimensional gel-supported culture system]. 821 67

The GPOH-MAHO trials designed in 3/82 and 7/88 for treatment of childhood testicular germ cell tumors registered 3/92 105 pts. In MAHO 82 study 57 pts. and in MAHO 88 study 48 pts. were treated. Histologically 60% of the tumors revealed yolk sac tumors (YST), 22% teratomas (TD) and 18% malignant teratomas (MTI, MTU, MTT). Beside unilateral orchiectomy, according to stage and histology a stratified chemotherapy was administered. Standard chemotherapy consisted of 4 courses VLB, BLM, DDP, after 2 courses standard chemotherapy if vital tumor was suspected: explorative laparatomy. According to laparatomy some patients received salvage chemotherapy of 3 courses VP 16, IFO and DDP. The following results were obtained: YST: 59 pts. with stage I. Of these 10 received adjuvant chemotherapy with VLB, BML, DDP. 49 pts. were followed according to wait and see policy and not treated by adjuvant chemotherapy; 8 pts. had a relapse. 5 were treated with standard chemotherapy and 1 pt. with salvage therapy. 1 pt. had stage II and another stage III. Both received standard chemotherapy. The survival of all 61 pts. is 100%. Median observation time is 4 years. TD: 25 pts. had stage I. No chemotherapy was given. The relapse free survival is 100%. Median observation time is 4 years. Malignant teratomas (MTI, MTU, MTT): 8 pts. had stage I. Of these 3 received adjuvant chemotherapy, 5 lymphadenectomy without chemotherapy. All patients survived without relapse. 8 pts. had stage II and received standard chemotherapy, of these 4 pts. had stage IIc and explorative laparotomy was done. According to the result 2 pts. received salvage therapy. All pts. survived relapse free.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Therapy of testicular germ cell tumors. Current status of the MAHO studies]. 839 20

A 24-year-old man admitted to our hospital because of hemoptysis and left precordial pain. Chest X-ray and chest CT scan showed a mass in the left anterosuperior mediastinum. Laboratory examination revealed elevated levels of AFP (550 ng/ml), which were highly indicative of malignant germ cell tumor. Imaging examination indicated that the mass was resectable, so surgery was performed prior to chemotherapy. Histological examination revealed an admixture of seminoma, immature teratoma, embryonal carcinoma and yolk sac tumor. Because the resection performed was incomplete, the patient received three courses of combination chemotherapy consisting of CDDP, VP-16 and BLM and 40 Gy irradiation. The serum level of AFP was normal after one course of combination chemotherapy. The patient has shown no sign of recurrence for 3 years since surgery.
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PMID:[A case of malignant mediastinal germ cell tumor benefited by multidisciplinary therapy]. 874 63

Before CDDP was clinically used, combination chemotherapy regimens like BLM + MMC, VCR + MTX-LV + BLM, VCR + MTX-LV + BLM + MMC had been used for recurrent tumors of the head and neck. In a phase II study with CDDP, we experienced two patients with long-term survival (12, 15+) who were treated with CDDP as a second-line chemotherapy for recurrent tumors. Cisplatin was evaluated as a potentially curative agent. After that, CDDP based regimens have been used as neo-adjuvant setting (first-line chemotherapy). So it became quite difficult to make up a second-line chemotherapy since CDDP based regimens have been used as the first-line chemotherapy. We conducted basic research on second-line chemotherapy for recurrent head and neck cancer: (1) cross-resistance studies on head and neck cancer cell lines resistant to CDDP, 5-FU, MTX and BLM; (2) second line chemotherapy for CDDP + PEP combination chemotherapy, which was developed by us, in human KB cell line; and (3) effects of etoposide plus mitomycin C on head and neck squamous cell carcinoma in monolayer and multicellular tumor spheroid. Based on our long-term experience with chemotherapy for head and neck cancer, and the results of the above-mentioned basic research, we established a policy to select second-line chemotherapy for recurrent head and neck cancer, especially in cases previously treated with chemotherapy.
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PMID:[Head and neck cancer]. 875

The highly metastatic human melanoma cell line BLM was transfected with the E1A or E1A + E1B regions of adenovirus 5 (Ad5). A series of progression markers, correlated with the malignant phenotype of parental BLM (including calcyclin, thymosin beta 10, plasminogen activator inhibitors types 1 and 2, urokinase type and tissue type plasminogen activators, vimentin, tissue type transglutaminase, and interleukin-6), was collectively repressed in the transfectants, whereas several control genes were not affected or even induced. The apparently coordinate repression of a set of markers by the same regulator gene, Ad5 E1A in this case, suggests the existence of one pathway under the control of a main switch and predicts that one or more as yet unidentified cellular master genes normally exert this function. A reduced oncogenicity was observed after subcutaneous inoculation of the E1A transfectants into nude mice and provides additional evidence in support of a tumor suppressor function of Ad5 E1A.
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PMID:Simultaneous suppression of progression marker genes in the highly malignant human melanoma cell line BLM after transfection with the adenovirus-5 E1A gene. 878 Jun 94

Recent evidence indicates that CD44, a multifunctional adhesion receptor involved in cell-cell as well as in cell-matrix interactions, plays an important role in local progression and metastasis of malignant tumors. We have studied a set of human melanoma cell lines differing in their metastatic potential in nude mice as well as in normal melanocytes for changes in CD44 expression and function. All melanocytes and melanoma cell lines tested highly expressed the CD44 standard form (CD44s, 85 kDa) but variants at low levels only. With respect to one of the CD44-associated functions primarily involved in tumor progression we found that two highly metastatic tumor cell lines, MV3 and BLM, showed fivefold higher migration rates towards hyaluronate than melanomas with low metastatic potential and normal melanocytes. Moreover, the highly metastatic cell lines expressed four- to sixfold higher levels of the CD44 epitope involved in hyaluronic acid-binding (monoclonal antibody Hermes-1) than less aggressive melanomas and melanocytes. Hermes-1 efficiently blocked haptotaxis to hyaluronate, supporting the functional relevance of this epitope. In contrast, expression levels of other CD44s epitopes recognized by seven different anti-CD44 monoclonal antibodies were unchanged, suggesting that the migratory behaviour of the cells depends on the formation of the hyaluronate-binding Hermes-1 epitope rather than on the overall CD44s surface expression, which was virtually identical in all melanoma and melanocyte cell lines tested. Differences in the accessibility of the hyaluronate-binding epitope defined by Hermes-1 correlated with the phosphorylation state of CD44s, probably reflecting different activation states of the receptor. Furthermore, immunoprecipitation and pulse/chase studies revealed a three- to fivefold increase in CD44 synthesis in the highly aggressive melanoma cells as compared to the other cell lines and the melanocytes, indicating a reduction of CD44 half-life and up-regulation of turnover. Moreover, highly aggressive melanoma cell lines were found to shed significant amounts of CD44 from the cell surface and to secrete its ligand hyaluronic acid, which may refer to an "autocrine' mechanism mediating melanoma cell motility.
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PMID:Migration of highly aggressive melanoma cells on hyaluronic acid is associated with functional changes, increased turnover and shedding of CD44 receptors. 883 18


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