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)

Glutathione (GSH) depletion in mitogen-stimulated T lymphocytes has been shown to markedly inhibit their proliferative response. This block in proliferation is associated with a significant reduction in total RNA and DNA synthesis; however, the specific mechanism involved in this inhibition of proliferation is unknown. Miller et al. have reported that lowering intracellular GSH levels by greater than 30%, in murine and human tumor cell lines of non-hematopoietic origin, leads to down-regulation of HA-, Ki- and N-ras oncogene expression [Miller. A.C., Gafner, J., Clark, E.P. and Samid, D. (1993) Mol. Cell Biol., 13, 4416-4422]. The reduction in ras transcript levels correlated with the extent of GSH depletion and was independent of the specific mode of oncogene activation. Since the activity of p21(ras) is thought to be involved in pathways of T cell activation, we set out to determine whether down-regulation of ras expression in T cells could be the mechanism by which T cell proliferation was inhibited in GSH-depleted T lymphocytes. Despite reducing the GSH level of concanavalin A-activated human peripheral blood mononuclear cells by 66%, no effect on ras mRNA expression was observed. Similarly, no reduction of ras transcript levels were detected in a human T cell line (Jurkat) or in a human monocytic cell line (THP-1) depleted of glutathione. Our results demonstrate that the mechanism by which GSH depletion inhibits T cell proliferation does not appear to involve a decrease in ras mRNA expression. In addition, our results suggest that differences in the regulation of ras mRNA expression may exist between lymphoid/monocytic cells of non-hematopoietic origin.
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PMID:N-ras mRNA expression is unaffected in glutathione-depleted cells of hematopoietic origin. 765 16

Twenty patients with unresectable hepatocellular carcinoma were treated by intra-arterial subsegmental injection of Cisplatin/4-0-Tetrahydro-Pyranyl-adriamycin Lipiodol suspension (CTLS). The mean single doses of Lipiodol, cisplatin and THP were 2.3 ml, 85 mg and 8.9 mg, respectively. The therapy was given once in 10 patients, twice in 8 and 3 times in two. Over 25% reduction in tumor size was recognized in 12 patients (60%). Fifty or more % decrease of alfa-feto-protein (AFP) was observed in all of 7 patients (100%) with the initial serum AFP level of more than 200 ng/ml. Although transitional and mild symptoms, such as fever, abdominal pain and vomiting were recognized in some cases, no severe complications were encountered. This method is promising as an excellent procedure for unresectable hepatocellular carcinoma.
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PMID:[Anticancer and side effect of arterial subsegmental chemoembolization using cisplatinum/pirarubicin lipiodol suspension (CTLS) for hepatocellular carcinoma]. 769 22

Thirteen tumor-derived cell lines of human and nonhuman origin and from various tissues were examined for the presence and density of sigma-1 and sigma-2 receptors. Sigma-1 receptors of a crude membrane fraction were labeled using [3H](+)-pentazocine, and sigma-2 receptors were labeled with [3H]1,3-di-o-tolylguanidine ([3H]DTG); in the presence or absence of dextrallorphan. [3H](+)-Pentazocine-binding sites were heterogeneous. In rodent cell lines (e.g., C6 glioma, N1E-115 neuroblastoma, and NG108-15 neuroblastoma x glioma hybrid), human T47D breast ductal carcinoma, human NCI-H727 lung carcinoid, and human A375 melanoma, [3H](+)-pentazocine bound to high- and low-affinity sites with Kd1 = 0.67-7.0 nM, Bmax1 = 25.5-108 fmol/mg protein, Kd2 = 127-600 nM, and Bmax2 = 942-5431 fmol/mg protein. However, [3H](+)-pentazocine bound to a single site in other cell lines. In human U-138MG glioblastoma, SK-N-SH neuroblastoma, and LNCaP.FGC prostate, Kd = 28-61 nM and Bmax = 975-1196 fmol/mg protein, whereas in ThP-1 leukemia Kd = 146 nM and Bmax = 1411 fmol/mg protein. The sigma-1-like nature of [3H](+)-pentazocine-binding sites was confirmed by competition studies which revealed high affinity for haloperidol and enantioselectivity for (+)-pentazocine over (-)-pentazocine. Interestingly, human MCF-7 breast adenocarcinoma showed little or no specific binding of [3H](+)-pentazocine, suggesting the absence of sigma-1 receptors in this cell line. All cell lines examined expressed a high density of sigma-2 receptors with Kd values for [3H]DTG ranging from 20 to 101 nM and Bmax values of 491 to 7324 fmol/mg protein. Competition studies indicated possible heterogeneity of sigma-2 receptors. While sites labeled by [3H]DTG in all cell lines tested exhibited affinity for haloperidol and preference for (-)-pentazocine over the (+)-enantiomer, human cell lines generally showed 4- to 7-fold lower affinity for haloperidol and approximately 10-fold lower affinity for (-)-pentazocine compared with the rodent cell lines. The high density of sigma-1 and sigma 2-binding sites in these cell lines suggests important cellular functions in cancer, as well as potential diagnostic utility for tumor-imaging agents which target sigma sites. These cell lines may be useful as model systems in which to study the functions of sigma sites in normal tissues, as well as their possible role in tumor biology.
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PMID:Sigma-1 and sigma-2 receptors are expressed in a wide variety of human and rodent tumor cell lines. 781 73

A 49 year-old man was admitted to our hospital in May 1989, with a cervical tumor and leukocytosis. He had been pointed out leukocytosis for last two years. Peripheral blood examinations demonstrated an increase of leukocytes (39,500/microliters) with low neutrophil alkaline phosphatase, eosinophilia and immature cells. Examination of bone marrow revealed normoplasia with 5.6% eosinophils, 1.4% myeloblasts, 2.6% promyelocytes and 250/microliters megakaryocytes. Cytogenetic analysis disclosed 46, XY, t (12;13) (p13;q12). Southern blot analysis showed no BCR rearrangement. The tumor cells had infiltrated the lymph nodes. Pathological finding agreed with the specimen of the lymph node as in the clot section of bone marrow. He was diagnosed as having a chronic myeloproliferative disorder with tumor formation and was treated with anti-leukemia drugs, including BH-AC, THP, VDS, MTX, VP-16, BUS, 6MP and uvenimex. He showed hematological remission, temporary, but he did not reach cytogenetical remission and died in April 1990. Further study in a large series is necessary to define whether the abnormality of the chromosome with t(12;13) (p13;q12) is characteristic in cases with tumor formation.
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PMID:[Atypical chronic myeloproliferative disorder with translocation (12;13) (p13;q12) and tumor formation]. 786 15

Primary malignant germ cell tumors of the mediastinum are rare neoplasm, almost always occurring in young adult males. This report described embryonal carcinoma in a 13-year-old girl. The patient was checked up at chest X-ray examination of middle-school pupils on June 1989, and was referred to us because of rapid enlargement of the shadow on October 1989. Chest rentogenograms on admission showed a large mass at the anterior mediastinum, and MRI also revealed a multicystic one extending to the right hemithorax and pressing the superior vena cava and the right atrium. Her serum AFP level was high at 211.1 ng/ml. At operation, on November 6, 1989, a large tumor (110 x 95 x 75 mm) was removed completely through median sternotomy. Histological study of the lesion revealed a wide spread of cystic mature teratoma containing some foci of embryonal carcinoma. Positive immunochemical reaction indicated the presence of AFP in these carcinoma cells. She was treated with 13 courses of anti-cancer chemotherapy by various combinations of CDDP, THP-ADR, VP-16, VCR, ACD, CPM, CBDCA, for one postoperative year. She showed clinical improvement and has continued to be free from recurrence now at 52 months after surgery.
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PMID:[A case of primary mediastinal teratocarcinoma in a young girl]. 788 48

We have tested the effect of several bile acids on the proliferation and differentiation of the HL60 human promyelocytic leukemia cell line in vitro. Deoxycholate, chenodeoxycholate and lithocholic acid caused dose-dependent inhibition of cell proliferation and induction of differentiation along the monocyte/macrophage pathway as determined by morphology, NBT test, non-specific esterase, and staining by monoclonal antibodies against specific cell-surface antigens. Optimal effects were obtained at 100, 75, and 60 microM of the 3 bile acids respectively. Cell-cycle flow-cytometric analysis showed that a substantial fraction of HL60 cells accumulated at the G0/G1 transition. Protein-kinase-C inhibitors such as sphinganine and H-7 inhibited the differentiation-inducing effect of bile acids, suggesting a possible role for PKC in this regulation. When bile acids were combined with non-effective concentrations of all-trans retinoic acid, enhancement of the monocytic differentiation of THP-1 human leukemia cells was observed. Our findings demonstrate induction of tumor-cell differentiation by bile acids, compounds that present minimal undesirable effects in humans.
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PMID:Inhibition of proliferation and induction of monocytic differentiation on HL60 human promyelocytic leukemia cells treated with bile acids in vitro. 792 7

A patient with navel metastasis from ovarian carcinoma was treated by immunotherapy and neo-adjuvant intraarterial infusion chemotherapy (OK-432 i.c., VP-16 25 mg/body x 10 days po, CDDP 100 mg/m2 iA, CPM 200 mg x 3 days/body i.v., THP 50 mg/m2 iA). Maximal blood concentration of THP was 1.081 micrograms/ml at 1 hour intraarterially and 0.091 microgram/ml at 2 hour intravenously. THP concentration of arteria is ten times higher than that of venous. And the area under the curve (AUC) of THP is 3.46 micrograms/ml/hr intraarterially and 0.43 microgram/ml/hr at intravenous. Two courses of the neo-adjuvant intraarterial chemotherapy were done. One month after, the first operation was performed. Each tissue platina concentration is 9.72 micrograms/ml is 9.72 micrograms/cm3 uterus cervix, 7.10 micrograms/cm3 uterus corporis, 5.72 micrograms/cm3 left ovarium, 2.64 micrograms/cm3 right ovarium, 0.52 microgram/cm3 paraaortic lymph node. After the immuno-chemotherapy, the metastatic tumor appeared remarkably smaller and the main tumor regained normal size and we achieved the optimal operation successfully. This patient was treated with double platina chemotherapy by intraperitoneal infusion using implantable reservoir access after the first operation (VP-16 200 mg/m2 i.p. D1, CDDP 100 mg/m2 ip D1, CBDCA 300 mg/m2 i.v. D3). This patient can keep the state of cytological complete remission for more than four months after the second look operation. Now she continues maintenance immuno-chemotherapy from a home doctor.
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PMID:[A case report: ovarian carcinoma IVth can become complete remission by immunochemotherapy]. 794 76

The patient was a 2-year-old who was admitted with the diagnosis of liver tumor. The diagnosis at admission was stage III A hepatoblastoma complicated with tumor thrombosis of portal vein. Soon after the admission, the patient's general condition became deteriorated with increased ascites and severer jaundice. As the patient was considered to be in oncogenic emergency, chemotherapy with systemic administration of ADR and CDDP was started. Despite decreases in tumor marker and tumor shrinkage on imaging examinations, tachycardia and arrythmia occurred from the end of the second course of chemotherapy, suggesting ADR-induced cardiomyopathy, when the systemic administration of ADR was switched to less cardiotoxic hepatic arterial infusion of THP-ADR. Following 13 courses of intra-arterial infusion with the total dose of THP-ADR of 200 mg/m2, the tumor was found to have reduced markably in size and thus surgical resection of the tumor was performed. Our experience of this case indicates that, considering the pharmacokinetics and side effects, THP-ADR should be a very effective anti-tumor agent for intra-arterial hepatic infusion. The patient died 10 months after surgery because of multiple metastases into the brain and lungs.
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PMID:[A case of hepatoblastoma using intraarterial hepatic chemotherapy with THP-ADR]. 794 96

The effect in combination therapy of high energy under water shock waves (HESW) and anticancer drugs for subcutaneous murine bladder cancer (MBT-2) in C3H/He mice was examined. HESW were generated by piezoceramics and directed to the subcutaneous tumor under ultrasonographic guidance. The subcutaneous tumor was exposed to HESW alone (100 MPa, 1000 shots, 3 shots/sec) or in combination with pirarubicin (THP, 5 mg/kg, i.p.) or carboplatin (CBDCA, 40 mg/kg, i.p.). Remarkable bleeding in the tumor was seen immediately after the exposure of HESW, destroyed cancer cells appeared after one day and wider and clearly bordered tumor necrosis was observed after three days. In the HESW alone therapy, tumor growth of smaller tumors (< 10 mm3, n = 8) were suppressed more than that of larger tumors (10-35 mm3, n = 11). Tumor growth ratio on the 14th day (TGR 14) (tumor volume on the 14th day/tumor volume on the 1st day) was examined in larger tumors. TGR 14 were 152.2 +/- 146.6 (mean +/- S.D.) in the control (n = 20), 116.3 +/- 98.9 in HESW alone (n = 11), 75.5 +/- 110.7 in THP alone (n = 8), 90.7 +/- 61.6 in CBDCA alone (n = 6), 75.8 +/- 72.2 in THP + HESW (n = 9), 3.2 +/- 4.5 in CBDCA + HESW (n = 8) and 0.8 +/- 1.3 in CBDCA + HESW 2 cycles (n = 9). Evident suppression on tumor growth was more often seen in CBDCA + HESW and CBDCA + HESW 2 cycles therapies than in the other therapies (p < 0.01). The cumulative survival rates were higher in CBDCA + HESW and CBDCA + HESW 2 cycles therapies than in the other therapies (p < 0.05). Tumor metastasis was seen only in the lungs of the dead mice after 19 days. Lung metastases were seen in 1/6 in the control, 0/5 in HESW alone, 1/5 in CBDCA alone, 0/6 in CBDCA + HESW and 1/5 in CBDCA + HESW 2 cycles therapy, respectively.
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PMID:[Combination therapy of high energy under water shock waves and anticancer drugs for subcutaneous murine bladder cancer (MBT-2)]. 799 Feb 95

The supernatant of a cell line of squamous cell carcinoma of the head and neck (SCCHN), PCI-50, was previously shown to induce activation, promote proliferation and increase antitumor cytotoxicity of freshly purified human natural killer (NK) cells and CD4+ T lymphocytes [Arch Otolaryngol Head Neck Surg (1994) in press]. This supernatant was found also to promote the growth of a variety of hematopoietic cell lines, including Jurkat, THP-1, K562, NK-92 or Epstein-Barr-virus-transformed B cell lines. The Jurkat cell line was selected as a reporter cell in an 18-h proliferation assay established to measure the growth-promoting activity of PCI-50 supernatant. The presence of soluble tumor-derived factors able to induce proliferation of Jurkat cells was demonstrated in the supernatant produced by several other SCCHN cell lines but not in that produced by a gastric cancer cell line (HR) or renal cell carcinoma line (5117G8). The growth-promoting PCI-50 supernatant was shown to contain 28 +/- 0.5 pg/ml interleukin-6 (IL-6) in vitro but was negative for interferon gamma, IL-1, IL-2, IL-4, tumor necrosis factor alpha, granulocyte/macrophage-colony-stimulating factor and IL-12. The addition of any of these recombinant cytokines to Jurkat cell cultures did not significantly promote growth, while PCI-50 supernatant was consistently growth-stimulatory. This supernatant neither enhanced intracellular Ca2+ concentration in Jurkat cells nor induced up-regulation of activation antigens on the cell surface, although it supported growth of Jurkat cells in the absence of IL-2. The growth-promoting activity in the PCI-50 supernatant was acid-labile at pH 2 for 4 h, heat-resistant at 96 degrees C for 1 h and sensitive to treatments with trypsin and pepsin. Preincubation of the PCI-50 producer cells with tunicamycin or cyclohexamide reduced the level of growth-promoting activity in the supernatant. A partial purification of this activity was achieved using Amicon filtration, chromatography on concanavalin-A-Sepharose and then a hydroxyapatite column and high-pressure liquid chromatography gel filtration. The partially purified glycoprotein had a molecular mass of 50-70 kDa, as determined by gel filtration.
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PMID:Proliferation of hematopoietic cell lines induced by a soluble factor derived from human squamous cell carcinomas of the head and neck. 800 Oct 29


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