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)

Clinical application of etoposide (VP-16) for gynecologic malignancy has been investigated in trophoblastic disease, ovarian, endometrial and cervical cancer. Etoposide has proved to be one of the most effective agents for trophoblastic disease. It is widely used in single or multiple drug regimens in chemotherapy of the disease. Furthermore, this drug is observed to be active in the combination of BLM with CDDP for germ cell tumor of the ovary. It is now playing an important role in chemotherapy of this tumor.
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PMID:[Etoposide (VP-16) in gynecologic malignancy]. 897 99

Bloom syndrome (BS) is a rare autosomal recessive genetic disorder characterized by lupus-like erythematous telangiectasias of the face, sun sensitivity, stunted growth infertility and immunodeficiency. In addition, BS patients are highly predisposed to cancers. Although recently the causative gene of BS (BLM) was identified as a DNA helicase homologue, the function of BLM in DNA replication has not been elucidated. In this study, p53 mutation and microsatellite instability in B-cell lymphomas originating from 2 sibling BS patients were investigated. In the originally developed tumor of both patients, no p53 mutation was detected. In one patient, however, after treatment by ionizing radiation the B-cell lymphoma recurred, showing a 9-bp deletion in exon 7. In lymphoma cells and an EB-virus-transformed cell line from BS lymphocytes of this patient, microsatellite instability was also detected from the reduced length of microsatellite DNA markers, although in the other patient microsatellite instability was not detected. Thus, 2 B-cell lymphomas, despite having the same BLM mutation, showed different phenotypes in terms of p53 mutation and microsatellite instability.
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PMID:Microsatellite instability in B-cell lymphoma originating from Bloom syndrome. 898 Feb 51

Collagen IV, laminin and fibronectin are constituents of the cerebral extracellular matrix (ECM), which is critical in glioma cell invasion. The aim of the present study was to evaluate the integrin dependent cell-matrix interactions of two tumors with different invasive properties under matrixfree conditions. Two human glioma (GaMG, U373) and melanoma (MV3, BLM) cell lines were grown in serum free medium. Immunofluorescence microscopy of collagen IV, laminin, and fibronectin was performed. The adhesion of monolayer cells and their migration out of multicellular spheroids was quantified for these ECM components. Integrin chains known to act as laminin receptors were blocked by specific antibodies in additional migration assays. All cell lines expressed all the ECM components under serum free conditions. Tumor cell adhesion and migration in both glioma and melanoma cell lines was increased by all the ECM components, laminin being the strongest promotor of migration. However, migration was dose dependent in gliomas, whereas melanomas revealed a dose optimum of 10 micrograms/ml laminin. Antibodies against alpha 3 integrins significantly reduced migration on laminin in all cell lines, anti-beta 1 in all cell lines except U373. Anti-alpha 2 in BLM showed a strong effect, anti-alpha 6 was a stronger inhibitor in glioma than in melanoma cells. Integrins are functionally involved in tumor cell locomotion on laminin. The blocking of laminin related integrin chains markedly reduces cell motility in a varying manner between the cell lines. Moreover, different cell lines utilize different integrins as the laminin receptor.
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PMID:ECM dependent and integrin mediated tumor cell migration of human glioma and melanoma cell lines under serum-free conditions. 904 41

Treated with low dosage (5 ng.ml-1) of staurosporine for 18 h, human embryo lung 2BS cells were blocked at the G1/S boundary, but human gastric carcinoma BGC-823 cells still kept their cell cycle. In comparison with IC50 of 2BS and BGC-823 cells treated with cell cycle phase specific antitumor drugs adriamycin, Ara-C and BLM A5 alone or combined with staurosporine 5 ng.ml-1, the IC50 values increased from 0.325 microgram.ml-1, 5 micrograms.ml-1 and 6.5 micrograms.ml-1 to 0.45 microgram.ml-1, 10 micrograms.ml-1 and 6.5 micrograms.ml-1, respectively in 2BS cells; but decreased from 0.325 microgram.ml-1, 25 micrograms.ml-1 and 1.1 micrograms.ml-1 to 0.07 microgram.ml-1, 6.25 micrograms.ml-1 and 0.4 microgram.ml-1, respectively in BGC-823 cells. These results suggest that combination of staurosporine 5 ng.ml-1 with antitumor drugs showed different effects on tumor cells and normal cells. With the GSH fluorescent probe mBCL, we found that GSH contents increased in 2BS cells treated with staurosporine 5 ng.ml-1.
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PMID:[Protein kinase inhibitor staurosporine enhances cytotoxicity of antitumor drugs to cancer cells]. 927 19

Electrochemotherapy is a novel antitumor treatment involving the systemic administration of bleomycin followed by the delivery of electrical pulses to the tumor. The present study investigates the effects of electrochemotherapy on the growth of colon 26 cells inoculated subcutaneously into the backs of BALB/c mice. The mice were divided into the following four experimental groups: 20 that received no further treatment after the inoculation of colon 26 cells (control group); 20 that received 500 micrograms of bleomycin intraperitoneally 7 and 9 days after the inoculation (BLM group); 20 that received electric pulses to the tumor 7 and 9 days after the inoculation (EP group); and 30 that received electrochemotherapy 7 and 9 days after the inoculation (ECT group). During 28 days of observation, no deaths due to tumor progression occurred in the ECT group, but there were 18 in the control group, 11 in the BLM group, and 18 in the EP group. While weight loss was observed in all groups, it was most remarkable in the control group. Tumor growth was significantly inhibited in the ECT group, compared to the other experimental groups (P < 0.01). The results of this study demonstrated that electrochemotherapy significantly inhibited the growth of colon 26 tumors in mice, without causing any remarkable adverse effects.
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PMID:Electrochemotherapy significantly inhibits the growth of colon 26 tumors in mice. 930 43

The purpose of this study was to describe a new anti-cancer drug regimen for uterine cervical cancer. The cytotoxicities of some anti-cancer drugs regimens against the human uterine cervical cancer xenografted into nude mice have been studied. The activities of CDDP, CPT-11, TXL, CDDP + BLM, CDDP + MMC, CPT-11 + BLM, CPT-11 + CDDP, CDDP + 5-FU, CPT-11 + MMC, CPT-11 + TXL and CDDP + TXL for squamous cell carcinoma (TCR, TCK, TCG), and CDDP, MMC, TXL, CDDP + TXL, CDDP + MMC and MMC + TXL for adenocarcinoma (TCO, TCM, TCY), were evaluated comparing with a control group using saline. Five mice were used for each groups. When the xenografted tumor reached 6 mm in diameter, 1/5 LD50 of these drugs were administered into the peritoneal cavity of the mice once a week for three weeks. The effective regimens were CDDP + MMC, CDDP + BLM, CDDP + CPT-11 and CPT-11 + MMC for squamous cell carcinoma of the uterine cervix. CDDP + MMC, CDDP + TXL, MMC + TXL and CDDP were effective for endocervical adenocarcinoma. It was suggested that these new drug regimens should be used in clinical studies.
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PMID:[Evaluation of a new anti-cancer drug regimen against uterine cervical cancer in nude mice]. 935 Feb 46

DNA damage, mainly single strand breaks, was evaluated by single cell gel electrophoresis, in leukocytes of 36 healthy and 14 thyroid cancer-affected children prior to radio-therapy. The children come from the Gomel region, one of the areas most heavily radio-contaminated by the Chernobyl fallout. In addition, leukocytes were treated with a challenge dose of bleomycin (BLM, 1.5 micrograms/ml), to assess the presence of an adaptive response (AR) potentially resulting from chronic exposure to radionuclides. As controls, 13 children living in Pisa (Italy) were enrolled in the study. Children with thyroid cancer show higher (p < 0.001) DNA damage than healthy ones. No difference was found between healthy children from Gomel and from Pisa. A reduction in the response to BLM was significantly linked to low plasma levels of FT4 hormone (p < 0.0001), to the presence of the tumor (p < 0.002), to being female (p < 0.02), and to a higher 137Cs body burden (p < 0.03).
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PMID:Comet assay on children's leukocytes 8 years after the Chernobyl disaster. 971 Dec 71

Microsatellite instability (MSI) characterizes the hereditary nonpolyposis colorectal cancer syndrome but is also found in sporadic tumors. Frameshifts in microsatellites found in the coding regions (CDRs) of the TGFbeta1-RII, IGFIIR, hMSH3, hMSH6, and BAX genes indicate that MSI is involved in tumorigenesis by targeting genes that are directly implicated in the tumorigenic process. To identify additional genes targeted for MSI, we performed an analysis of the GenBank database that revealed 21 microsatellite repeats located in the CDR of 18 genes (12% of the analyzed sequences) whose function could be potentially associated with the tumorigenic process. Mutational studies of 57 sporadic gastrointestinal tumor DNAs revealed the presence of length variations in three of them: (a) BLM; (b) CBL; and (c) HOXA1. In the BLM gene, we found a frameshift mutation in a polyadenine repeat, whereas in the CBL proto-oncogene, an expansion of a trinucleotide repeat was detected with no translation shift. These alterations were present in 18 and 9%, respectively, of the genetically unstable sporadic gastrointestinal tumors analyzed, but in none of the cancers without the mutator phenotype. These changes were present in the DNA from the tumor but not in that from normal cells of the same patient. The HOXA1 retraction of a trinucleotide repeat was as frequent in both types of cancers and was also found in some normal paired tissues, therefore behaving as a neutral polymorphism. Our data extend the spectrum of unstable microsatellites located in gene CDRs and suggest that BLM and possibly CBL are involved in gastrointestinal tumorigenesis. Based on its proposed function, the BLM gene could represent a link between MSI and chromosomal instability pathways, because MSI targeting of the BLM gene could generate hypermutability and/or chromosomal instability.
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PMID:The coding region of the Bloom syndrome BLM gene and of the CBL proto-oncogene is mutated in genetically unstable sporadic gastrointestinal tumors. 973 83

The adoptive transfer of tumor-specific cytotoxic T cells (CTL) offers a promising perspective in cancer immunotherapy. However, the ex vivo-generated T lymphocytes are mostly IL-2-dependent. Here we explored the possibility of circumventing the requirement for IL-2, known for severe side effects in the patient, and of simultaneously targeting the CTL towards the tumor by the use of 2 bi-specific antibody fragments. As a model system, we used SCID mice bearing an s.c.-implanted human melanoma line (BLM-gp100) and in vitro-generated CTL specific for the gp100-derived immunogenic peptide YLEPGPVTA, which were injected i.v. with delay. To maintain the cytotoxic potential of the transferred CTL, 2 bi-specific antibody (biAb) fragments were generated which bound with one arm either CD3 or CD28, a combination known to support the activation of CTL. For targeting the CTL, both biAbs contained the F(ab') part of HD-Me13, an antibody recognizing p97, a non-immunogenic melanoma-associated surface molecule. In vitro and in vivo, the addition of the 2 biAbs increased the cytotoxic potential of the gp100-specific CTL and supported their clonal expansion in the absence of IL-2. Correspondingly, significantly higher numbers of CTL were recovered from melanoma-bearing SCID-mice that received the 2 biAb than from mice treated with the CTL only. In animals treated with CTL plus both biAbs, the primary tumor did not grow, and none of the mice developed metastases. Thus, this set of bi-specific antibody fragments was proved to target effector cells in the tumor-bearing host and to efficiently support in vivo clonal expansion and cytolytic activity of in vitro-generated CTL.
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PMID:Human melanoma therapy in the SCID mouse: in vivo targeting and reactivation of melanoma-specific cytotoxic T cells by bi-specific antibody fragments. 1020 66

Rothmund-Thomson syndrome (RTS; also known as poikiloderma congenitale) is a rare, autosomal recessive genetic disorder characterized by abnormalities in skin and skeleton, juvenile cataracts, premature ageing and a predisposition to neoplasia. Cytogenetic studies indicate that cells from affected patients show genomic instability often associated with chromosomal rearrangements causing an acquired somatic mosaicism. The gene(s) responsible for RTS remains unknown. The genes responsible for Werner and Bloom syndromes (WRN and BLM, respectively) have been identified as homologues of Escherichia coli RecQ, which encodes a DNA helicase that unwinds double-stranded DNA into single-stranded DNAs. Other eukaryotic homologues thus far identified are human RECQL, Saccharomyces cerevisiae SGS1 and Schizosaccharomyces pombe rqh1. We recently cloned two new human helicase genes, RECQL4 at 8q24.3 and RECQL5 at 17q25, which encode members of the RecQ helicase family. Here, we report that three RTS patients carried two types of compound heterozygous mutations in RECQL4. The fact that the mutated alleles were inherited from the parents in one affected family and were not found in ethnically matched controls suggests that mutation of RECQL4 at human chromosome 8q24.3 is responsible for at least some cases of RTS.
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PMID:Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome. 1031 67


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