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)

In order to clone candidate tumor suppressor genes whose loss contributes to the pathogenesis of neuroblastoma (NB), we performed polymerase chain reaction (PCR) screening using a high-density sequence tagged site-content map within a commonly deleted region (chromosome band 1p36) in 24 NB cell lines. We found a approximately 480 kb homozygously deleted region at chromosome band 1p36.2 in one of the 24 NB cell lines, NB-1, and cloned the human homologue (KIF1B-beta) of the mouseKif1B-beta gene in this region. The KIF1B-beta gene had at least 47 exons, all of which had a classic exon-intron boundary structure. Mouse Kif1B is a microtubule-based putative anterograde motor protein for the transport of mitochondria in neural cells. We performed mutational analysis of the KIF1B-beta gene in 23 cell lines using 46 sets of primers and also an allelic imbalance (AI) analysis of KIF1B-beta in 50 fresh NB samples. A missense mutation at codon 1554, GTG (Gly) to ATG (Met), silent mutations at codon 409 (ACG to ACA) and codon 1721 (ACC to ACT), and polymorphisms at codon 170, GAT (Asp) to GAA (Glu), and at codon 1087, TAT (Tyr), to TGT (Cys), were all identified, although their functional significances remain to be determined. The AI for KIF1B-beta was slightly higher (38%) than those for the other two markers (D1S244, D1S1350) (35 and 32%) within the commonly deleted region (1p36). Reverse transcriptase-PCR analysis of the KIF1B-beta gene revealed obvious expression in all NB cell lines except NB-1, although decreased expression of the KIF1B-beta gene was found in a subset of early- and advanced-stage NBs. These results suggest that the KIF1B-beta gene may not be a candidate for tumor suppressor gene of NB.
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PMID:Genomic structure and mutational analysis of the human KIF1B gene which is homozygously deleted in neuroblastoma at chromosome 1p36.2. 1152 94

The neonatal mouse model, in various forms, has been used experimentally since 1959 and a large number of chemicals have been tested. The neonatal model is known to be very sensitive for the detection of carcinogens that operate via a genotoxic mode of action. In contrast, it is known not to respond to chemicals that act via epigenetic mechanisms, commonly observed in the two-year carcinogenicity studies. As such, the model has a high sensitivity and specificity in its response. Dose selection for the neonatal model is based on the maximum tolerated or feasible dose. Traditionally, compounds have been tested via the IP route of administration in this model. In some cases, this has limited the amount of material that can be administered because of the low dosing volumes (10 to 20 microL) that can be administered IP. For the ILSI project, the neonatal model was adapted for oral administration, which has the advantages of being the same route for which most pharmaceuticals are administered. In addition, a 10-fold increase in the volume of administration (100 to 200 microL) and the ability to dose drugs in suspension, permits much higher doses to be used as compared to the IP route of administration. The spontaneous tumors in the neonatal model occurred mainly in the liver of male mice and lung of male and female mice with a few tumors observed in the Harderian gland. The positive control, DEN produced a robust, uniform, and reproducible tumor response with the target organs essentially limited to liver and lung. A total of 13 compounds out of the 21 ILSI ACT compounds were evaluated in the neonatal model involving 18 studies with duplicate studies for some compounds. The genotoxic carcinogens including those used as positive controls were clearly positive (cyclophosphamide, diethylnitrosamine, 6-nitrochrysene). The non-genotoxic rodent carcinogens were clearly negative (chlorpromazine, sulfisoxazole, sulfamethoxazole, clofibrate, DEHP, haloperidol, metaproteranol, and phenobarbital). The non-genotoxic human carcinogen (cyclosporin) was clearly negative. The two other human carcinogens phenacetin and DES were negative and interestingly estradiol was negative in one of the two oral studies, but was clearly positive in the other. Considering the mode of action for three of the human carcinogens (DES, cyclosporin and phenacetin), which were negative in this model, the mode of action in humans is likely to be epigenetic. Overall, for the 3 clearly genotoxic chemicals, all were positive. For the 9 clearly non-genotoxic chemicals, all 9 were negative. The two human carcinogens for which genotoxicity may or may not play a role (DES and phenacetin) were negative and estradiol was positive in I of the two oral studies. Overall, the extensive database for compounds tested in the neonatal mouse model would support its use as an alternative model for the assessment of the carcinogenic potential of a chemical. The model responds to chemicals that act via a genotoxic mode of action that represent a greater concern for human cancer risk.
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PMID:Neonatal mouse model: review of methods and results. 1169 48

We describe here the case of an 82-year-old woman presenting with a hemorrhagic tumor on the anterior vaginal wall. She was diagnosed with malignant fibrous histiocytoma (MFH) from the findings of cytological analysis of biopsied surface tissue, histopathologic analysis of biopsied tissue, immunohistochemical staining, and electron microscopy. Cytological analysis of the biopsy sample harvested from the tumor surface showed multinucleated giant cells and large atypical cells with rough, granular, chromatin, as well as notable nucleoli. A storiform pattern was observed histopathologically, and immunohistochemical staining confirmed positive reactions to alpha 1-antichymotripsin (alpha 1-ACT), vimentin, and lysosome, but negative reactions to epithelial membrane antigen (EMA), cytokeratin, and alpha-smooth muscle action (alpha-SMA). Electron microscopy showed histiocyte-derived cells with a segmented nucleus with a large groove, pseudopodic cytoplasmic projections, and lysosome-like structures. However, intercellular adhesion factors were not notable, and microvilli were absent. Based on the above findings, a diagnosis of MFH originating from the vaginal wall was made. Because of the patient's advanced age, and, in accordance with her wishes, three courses of cancer chemotherapy, consisting of doxorubicin hydrochloride, fluorouracil, and cisplatin were carried out, without surgery. No reduction in the size of the tumor was seen at follow up, and despite the absence of metastasis and no exacerbation of her general condition, she died suddenly at home 2 years after being discharged.
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PMID:Malignant fibrous histiocytoma of the vagina. 1170 86

Anaplastic thyroid carcinoma is one of the most aggressive human malignancies. Outcomes of intensive multimodal therapy have been far from satisfactory. Furthermore, p53 gene dysfunction, often found in this type of cancer, is known to impair the efficacy of the therapeutic agents. Specific ligands for peroxisome proliferator activated receptor gamma (PPAR-gamma) induce growth suppression in some tumor cells. In this study, we investigated the role of PPAR-gamma in anaplastic thyroid cancer cell lines (OCUT-1, ACT-1). PPAR-gamma was expressed and functional in both cell lines. Activation of PPAR-gamma with its specific ligands, troglitazone and 15-deoxy-delta 12,14-prostaglandin J2, inhibited cell growth in a dose-dependent manner through inducing G1 cell cycle arrest. P53 protein expression differed in OCUT-1 and in ACT-1, though the levels stayed constant irrespective of ligand exposure in both cell lines. In contrast, p21 and p27 proteins were induced in a dose-dependent manner in both situations. This study showed that PPAR-gamma ligands were able to induce growth suppression in anaplastic thyroid cancer cells via a p53-independent, but p21- and p27-dependent cytostatic pathway. These tumor-suppressive effects of PPAR-gamma may provide a novel approach to the treatment of anaplastic thyroid cancer.
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PMID:Peroxisome proliferator-activated receptor gamma activation induces cell cycle arrest via the p53-independent pathway in human anaplastic thyroid cancer cells. 1249 76

Prostate-specific antigen (PSA), the most important tumor marker for the detection of prostate cancer, exists in serum in a free, uncomplexed form (free PSA [fPSA]), and as bound to protease inhibitors (mainly alpha1-antichymotrypsin [ACT]). The measurement of complexed PSA (cPSA) concentration in serum has been shown to have better sensitivity and specificity than serum total PSA concentration. A new chemiluminescent immunoassay for cPSA for use on the Bayer ACS:180 fully automated system (Bayer Corp, Tarrytown, NY) has been developed and evaluated. The precision of the new assay was <3.9% (within-run coefficient of variation [CV]) and <5.0% (total CV). The analytical sensitivity (95% upper limit of noise at zero calibrator) was <0.03 ng/mL. A comparison of the ACS:180 cPSA results with the cPSA concentrations calculated from the ACCESS (Beckman-Coulter) PSA and fPSA assays yielded the following regression equation: ACS:180 cPSA=0.93* (calculated ACCESS cPSA)+0.43, R=0.993, n=95. The mean dilution and spike recovery for five samples were both 98%. No interference was observed from hemoglobin, triglyceride, or bilirubin (NCCLS protocol). These results indicate that the ACS:180 cPSA assay is precise, and compares well with the calculated cPSA from ACCESS total and free-PSA results.
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PMID:Evaluation of an automated chemiluminescent immunoassay for complexed PSA on the Bayer ACS:180 system. 1293 46

The 384-well microplate contains four times as many wells as the regular 96-well microplate. Establishing enzyme linked immunosorbent assay (ELISA) on 384-well microplate should lead to savings in reagents and specimens. To determine that ELISAs on 384-well microplate have acceptable assay precision, ELISAs for tumor markers, including AFP, PSA-ACT, CEA, CA 125, CA 15-3, and CA 19-9, were compared to the same ELISAs established on 96-well microplate. We found that ELISAs established on 384-well microplate had similar sensitivity and covered similar concentration ranges as ELISAs on 96-well microplate. All within-day and day-to-day precisions for the 384-ELISA had %CV less than 10%. Compared to ELISA on 96-well microplate, 384-ELISA used less reagents, less specimen, and exhibited approximately a two-fold increase in sensitivity. Overall cost of the 384-384-ELISA was also greatly reduced. Our results suggest that 384-ELISA is suitable for use in routine clinical laboratories.
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PMID:Establishment of ELISA on 384-well microplate for AFP, CEA, CA 19-9, CA 15-3, CA 125, and PSA-ACT: higher sensitivity and lower reagent cost. 1461 48

One of the mechanisms repressing apoptosis in tumor cells can involve the expression of anti-apoptotic NF-kappaB target genes. In this study, we demonstrated that a potent NF-kappaB inhibitor, Nalpha-tosyl-L-lysinyl chloromethyl ketone (TLCK), inhibits apoptosis of THP-1 cells triggered by etoposide (VP16), and actinomycin D (ACT D) or cycloheximide inhibits apoptosis. However, persistent activation of NF-kappaB by lipopolysaccharide (LPS) led to the survival of leukemic cells against VP16-induced apoptosis. Thus, the molecular events (Bax/X-chromosome-linked IAP (XIAP)) occurring downstream of NF-kappaB activation during VP16 and/or LPS stimulation may become important to understand the multiple effects of NF-kappaB.
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PMID:Dual role of NF-kappaB in apoptosis of THP-1 cells during treatment with etoposide and lipopolysaccharide. 1463 82

The number of patients with prostatic cancer is recently increasing in Japan and it is well known that serum PSA determination is routinely used as a tumor marker of prostatic cancer. However, the reference values of PSA are widely varied, because the reactivities of the antibody to free PSA and ACT-PSA are different in each kit. Thus, there is no compatibility among values determined by available kits. In this study, we sent a questionnaire on PSA determination to 180 hospitals with more than 200 beds. The recovery rate to the questionnaire was 80.5% (145/180) and the determination was performed in house at 47 hospitals out of 145. Stamey in Stanford University recommended to set the ratio of complex PSA to free PSA 9:1 in the reference material. It is expected that PSA ad hoc committee in Japan reported that the inter-kit variability is becoming small. It can be said that the standardization for PSA determination is progressing. To discriminate prostatic cancer from benign prostatic hypertrophy, free PSA ratio or complex ACT-PSA is recommended. Further accumulation of data on PSA will be necessary to confirm this matter.
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PMID:[The present status of convergence in PSA reference values--from the surveillance in the Tokai-Hokuriku district]. 1467 84

Retrospective analysis of 29 children with bilateral Wilms' Tumour, 14 boys and 15 girls, aged 4m-5 years, from regional centres of paediatric oncology in Poland, treated according to the O1-92 PPGL Protocol of Wilms' tumour, was performed. All patients were treated with two (ACT + VCR) or three (ACT, VCR, DOX) cytostatic drugs preoperatively, and 26 were operated upon after cytoreductive pretreatment. In 12 children nephrectomy was performed. In 28, kidney sparing surgery was possible and made with success. 2 patients who presented disseminated disease and 1 with nephroblastomatosis were given chemotherapy. 19 out of 29 (65.5%) are alive including 1 patient with nephroblastoma. EFS calculated according to Kaplan-Meier analysis for this group, was 58% at 67 months.
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PMID:[Bilateral Wilms' tumour. Results of treatment in 29 children]. 1496 44

Prostate-specific antigen (PSA) is a widely used serum marker for prostate cancer, but has limited specificity for distinguishing early prostate cancer(PCa) from benign disease since serum PSA can leak from both tumor and prostate tissues with benign disease. Molecular forms of free PSA have been identified that are associated with either benign or malignant prostate tissues. BPSA is a form of free PSA that is associated with benign prostatic hyperplasia(BPH), the predominant benign disease in men. The inactive precursor of PSA, proPSA, is associated with prostate tumors. We have developed research immunoassays with high sensitivity and specificity for BPSA and proPSA. Each of these PSA forms can range from 0-50% of the free PSA in individual serum samples in the total PSA range of 2-10 ng/ml. Typically, BPSA represents from 20-30% of the free PSA in serum, while proPSA ranges from 30-40% of the free PSA. ProPSA greatly improves the early detection of cancer in men with less than 4 ng/ml total PSA. More importantly, proPSA is more highly associated with aggressive cancers than other PSA forms such as PSA-ACT and free PSA. The BPH-associated BPSA and cancer-associated proPSA forms are complementary and provide improved detection of prostate cancer from benign disease.
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PMID:Tumor-associated forms of prostate specific antigen improve the discrimination of prostate cancer from benign disease. 1513 20


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