Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of different concentrations of a transforming growth factor of type beta (TGF-beta) and of its combinations with the epidermal growth factor (EGF) and insulin exerted on proliferation of different types of cells in the culture medium with semisolid agar was determined. The following cell lines were tested: mouse fibroblasts of NIH-3T3 and Swiss-3T3 lines, fibroblastic line NRK-49F from rat kidney, cells of A-549 line from human lung carcinoma, HT-1080 line from human fibrosarcoma, and PS-103 line (clone 384/5) from sarcoma stimulated by polychlorvinyl plate implantation to mouse. It is detected that TGF-beta alone does not affect the substrate-independent proliferation of pseudonormal lines of fibroblastic cells, but stimulates it significantly in sarcoma and inhibits in carcinoma cells. If EGF and/or insulin are added to the culture medium besides TGF-beta, certain proliferative effect specific of either type of pseudonormal and malignant cells is detected. The results of the action of TGF-beta, and of its combinations with the most important polypeptide growth factors on several types of cells of different origin may be useful for determination of regulatory functions of TGF-beta in cell proliferation in vivo to promote better grounding of its utilization in the practice of medicine.
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PMID:[The effect of the beta-type transforming growth factor and its combination with epidermal growth factor and insulin on substrate-dependent proliferation of normal and tumor cells]. 268 71

Penclomedine, a synthetic alpha-picoline derivative, was identified as a potential antitumor agent in the P388 leukemia prescreen of the National Cancer Institute. Upon further evaluation in the National Cancer Institute in vivo tumor panel, the compound demonstrated good activity against two breast tumors. A single i.p. dose or five daily doses caused partial regressions of advanced-stage s.c. implanted mouse CD8F1 mammary adenocarcinomas. Also, penclomedine administered i.p. on Days 1,5, and 9 caused regression of the human MX-1 mammary carcinoma implanted under the renal capsule of athymic mice. In contrast, penclomedine demonstrated only marginal to moderate activity against the i.p. implanted L1210 leukemia and M5076 sarcoma and was inactive in three additional non-breast tumor models (i.p. B16 melanoma, i.v. Lewis lung carcinoma, and s.c. colon adenocarcinoma 38). Penclomedine administered p.o. and i.p. was equally effective against the subrenal capsule MX-1. Doses given p.o. every fourth day caused complete regression of 39 of 40 advanced-stage s.c. implanted MX-1 tumors but were much less effective against human H82 small cell lung carcinomas (13 of 80 complete regressions). Penclomedine p.o. also inhibited growth of the human MCF-7 and mouse 16/C breast adenocarcinomas. Further studies to support the development of penclomedine to clinical trial are in progress.
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PMID:Preclinical antitumor activity of an alpha-picoline derivative, penclomedine (NSC 338720), on human and murine tumors. 270 34

The pharmacokinetics of Ro 03-8799 has been studied in melanic and non-melanic tumor bearing mice after iv administration of 150 mg/kg. The peak concentration in B16 melanosarcoma tumor reached 152 micrograms/g, that is 7.6-fold higher than the plasma concentration at the same time. This concentration is 3-times greater than that obtained in the tumor of mice bearing non melanic sarcoma (DB16) or Lewis lung carcinoma (3LL). The exposure of B16 tumor (AUC) is respectively 15-times and 11-times higher than the 3LL and the DB16 ones. These experimental data confirm that this 2-nitro-imidazol compound has an important affinity for melanin and suggest that it might be used as a radiosensitizer for the treatment of malignant melanoma.
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PMID:Pharmacokinetics of Ro 03-8799 in mice bearing melanosarcoma: comparison with tumors without melanin. 270 90

New reactions of methyl 2,2-difluoro glycosides are described that were utilized for synthesis of some novel nucleoside derivatives. Thus, treatment of methyl 2-deoxy-2,2-difluoro-3,4-O-isopropylidene-alpha (beta)-D-erythro-pyranoside (2) with anhydrous HCl resulted in selective displacement of one fluorine atom with chlorine to give a 2-deoxy-2-chloro-2-fluoro glycoside 3. Reaction of 3 with silylated uracil in the presence of SnCl4 provided a 2-deoxy-2-fluoro-2-uracil-substituted glycoside 4. 2-Fluoro-2-deoxy glycosides substituted with other pyrimidines at C-2 were prepared similarly by the reaction of acylated 2,2-difluoro or 2-fluoro-2-bromo derivatives (5 and 6, respectively) with silylated pyrimidines. The resulting 2'-fluorinated isonucleosides were evaluated for their antitumor and antiviral activities. Compounds 7a,b, 8a,b, and 10a,b demonstrated 50% tumor cell growth inhibition in vitro (IC50) at 10(-4)-10(-5) M. At similar concentrations no antiviral activity was observed in vitro. Therapeutic activity was obtained with 7a,b and 8a,b in DBA/2 mice with L1210 leukemia. Administration of 7a,b at 500 mg/kg, ip daily, for 5 consecutive days, resulted in a 55% increase in life span (% ILS) while administration of 8a,b in the same manner at 200 mg/kg caused a 29% ILS. Treatment with 7a,b to mice with drug-resistant L1210 sublines (5-FU and araC) resulted in 22 and 57% increases in life span, respectively. Lewis lung carcinoma and M5076 sarcoma in mice also responded to the administration of 7a,b with reductions in tumor growth for both tumors and significant increases in life span in mice with Lewis lung carcinoma. Although the mechanism of action of 7a,b is not known, it has been found to be a relatively fast-acting, cell-cycle nonspecific cytotoxic agent that decreases [3H]deoxyuridine incorporation, blocks L1210 cells at the G2 phase of the cell cycle, and is not reversed by exogenous thymidine. These 2'-fluorinated isonucleosides have demonstrated biological activity and may have potential as antitumor drugs.
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PMID:2'-Fluorinated isonucleosides. 1. Synthesis and biological activity of some methyl 2'-deoxy-2'-fluoro-2'-pyrimidinyl-D-arabinopyranosides. 270 26

Two hundred patients treated with curative intent for Hodgkin's disease between October 1964 and April 1984 at a single institution were studied retrospectively for development of second malignancies. The minimum follow-up was 2 years (median, 11 years). The staging distribution was IA-B, 61; IIA, 54; IIB, 20; IIIA, 46; and IIIB, 19. Sixty-one percent of the patients had laparotomy. Initial management was irradiation alone (RA) in 143 patients and a combination of chemotherapy and irradiation (CB) in 57 patients. Actuarial 10-year survival rates were 82%, IA-B; 78%, IIA; 66%, IIB; 66%, IIIA; and 24%, IIIB. Cause-specific deaths due to Hodgkin's disease or complications of initial or salvage therapy occurred in 3% of IA-B patients, 18% of IIA-B patients, and 35% of IIIA-B patients. One patient had a prior T3N1 squamous cell carcinoma of the retromolar trigone, and a second was diagnosed with concurrent Hodgkin's disease and granulocytic sarcoma. Subsequent solid tumors have occurred in six patients from 5 to 21 years after treatment, including papillary carcinoma of the thyroid, renal cell carcinoma, unilateral breast carcinoma, cervix carcinoma in situ, and lung carcinoma after RA, and bilateral breast carcinoma after CB. Seven fatal hematopoietic disorders (HPDs) were observed, including four acute leukemias, one dysmyeloproliferative syndrome (DMPS), one autoimmune hemolytic anemia, and one aplastic anemia. Two occurred in patients initially managed with RA who subsequently required chemotherapy for relapse. Five HPDs occurred in patients initially managed with CB who never relapsed. All HPDs were observed between 2 and 7.5 years after administration of chemotherapy. Statistical analysis of the data using a rerandomization test on Gehan ranks of treatment and clinical variables showed significant correlations between development of a secondary HPD and (1) initial management with CB; (2) higher doses of chemotherapy; and (3) more advanced disease, particularly IIIB. When only the five events generally associated with treatment (i.e. the four leukemias and one DMPS) were considered, there was a significant correlation with exposure to chemotherapy and presentation with advanced disease. The patient population was small so that interdependence between treatment factors and initial extent of disease in affecting the risk of a secondary HPD cannot be discounted but should be further investigated with larger patient populations.
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PMID:The impact of stage and treatment modality on the likelihood of second malignancies and hematopoietic disorders in Hodgkin's disease. 271 Sep 53

Anterior stabilization during thoracotomy, using the patient's own ribs, was carried out seven times in six subjects with malignant lesions of the thoracic vertebrae. The primary malignancy was lung carcinoma in four cases, thyroid carcinoma in one case, and alveolar soft tissue sarcoma in one. Resection of the lung tumor and spinal surgery were carried out simultaneously. Four of the six patients had complete paraplegia and two had partial paraplegia prior to the operation. After the decompression and anterior stabilization, three subjects responded well and three responded poorly because of respiratory insufficiency.
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PMID:Anterior rib strut grafting for the treatment of malignant lesions in the thoracic spine. 278 17

A new fluorine-containing anthracycline derivative, ME2303, showed excellent antitumor activity against various experimental tumor models. The i.p. or i.v. administrations of ME2303 on Day 1 or on Days 1, 5, and 9 against i.p.-implanted L1210 leukemia cells rendered more than 50% of mice tumor free at wide ranges of nontoxic doses, whereas the incidence of cure obtained with Adriamycin (ADM) was less than that obtained with ME2303. ME2303 given i.p. or i.v. on Day 1 or Days 1, 5, and 9 was also effective against i.p.-implanted P388 leukemia cells, and higher incidences of cure were obtained than with ADM. ME2303 administered i.v. on Days 1, 8, 15, and 22 showed prominent antitumor activity against s.c.-implanted colon adenocarcinomas 26 and 38, Lewis lung carcinoma, B16 melanoma, and M5076 sarcoma. Against colon adenocarcinoma 26, ME2303 induced cure in 16 of 20 mice at doses of 35 to 71 mumol/kg, whereas no cure was observed with ADM. Significant growth inhibition of colon adenocarcinoma 38, Lewis lung carcinoma, B16 melanoma, and M5076 sarcoma cell lines was also observed at a dose of 18 to 106 mumol/kg. ME2303 was effective against human and murine multidrug-resistant cells in vitro. For example, human myelogenous leukemia K562 resistant to ADM (K562/ADM) was only 2.8-fold more resistant to ME2303, while the cells were 200-fold more resistant to ADM when the values for the concentration of drug required for 50% inhibition of cell growth were compared. ME2303 was also more effective than ADM against human leukemia CCRF-CEM resistant to vinblastine, human ovarian carcinoma A2780 resistant to ADM, human epidermoid carcinoma KB cells resistant to colchicine, and mouse leukemia P388 resistant to ADM and vincristine. Therapeutic effects were obtained in vivo against ADM- and, especially, vincristine-resistant P388 leukemia. ME2303 is one of the most interesting potential antitumor agents to be studied further.
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PMID:A fluorine-containing anthracycline (ME2303) as a new antitumor agent against murine and human tumors and their multidrug-resistant sublines. 279 Jul 78

Treatment of C57BL/6 mice bearing Lewis lung carcinoma or of BALB/c mice bearing EMT6 sarcoma with tumor necrosis factor (TNF), lipopolysaccharides (LPS) or interferon caused necrosis of the solid tumors and regression. Toxicity was observed in tumor-bearing animals when TNF or LPS were used at effective antitumoral doses. Similar antitumoral effects could be achieved using less than 1 million macrophages from C57BL/6, lung of from BALB/c peritoneal cavity expanded in vitro, and spontaneously fully activated to cytotoxicity during culture. This effect, observed after transfer twice a week by intravenous or peritumoral route, was not dependent on histocompatibility. Additive effects were observed after combined treatment with activated macrophages and a low dose of LPS or TNF. The biodistribution of labelled LPS and of labelled cytotoxic macrophages was studied in tumor-bearing mice. Although, as expected, LPS was concentrated essentially in the liver, a slow accumulation in the center of the tumor was observed. Macrophages injected intravenously accumulated in the lung and were then redistributed towards liver, kidney and the tumor periphery. Macrophages injected locally remained essentially in the tumor periphery with a slow redistribution in the body. The complementary localization of LPS and of cytotoxic macrophages respectively in the center and periphery of solid tumors might explain their synergism.
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PMID:Antitumoral effects of lipopolysaccharides, tumor necrosis factor, interferon and activated macrophages: synergism and tissue distribution. 281

Clinically significant adrenal hemorrhage due to adrenal metastases has rarely been reported. We describe three cases of this unusual entity, two from lung carcinoma and one from sarcoma. Adrenal hemorrhage was bilateral in two patients, and was the presenting manifestation of malignancy in two. A computed tomography diagnosis of hemorrhage within bilateral adrenal metastases was made when adrenal masses rapidly enlarged in one case, and when previously resolving hematomas showed enlargement in a second case. The third case was believed to represent a pheochromocytoma preoperatively. We conclude that significant adrenal hemorrhage can result from adrenal metastases and can be the presenting manifestation of metastatic tumor. In the patient without discernible risk factors for adrenal hemorrhage, underlying malignancy should be considered as a possible cause, even if the hemorrhage is bilateral.
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PMID:Clinically significant adrenal hemorrhage secondary to metastases. Computed tomography observations. 281 83

A hypothalamic hormone--melanostatin H-L-Pro-L-Leu-NH2- and its 9 analogs were synthesized and their antitumor properties studied. Melanostatin caused a 52-72% inhibition of tumor growth (p less than 0.05) in mice bearing adenocarcinoma of the mammary gland Ca-755, cervical carcinoma CC-5 and melanoma B-16. Non-cytotoxic analogs containing D-leucine or L-lysine showed low activity. Among analogs containing sarcolysine stereomers, chlorphenacyl or chlorambucil, derivatives with L-sarcolysin exerted a high antitumor effect on Ca-755, CC-5, Lewis lung carcinoma, lymphoid leukemia L-1210, sarcoma-37, melanoma B-16 and S-91 (80-99% inhibition of tumor growth, p less than 0.05). L-sarcolysin alone had a higher effect on S-91 only (p less than 0.05). Antitumor effect of melanostatin is due to its amino acid sequences. Melanostatin analogs modified by L-phenylalanine retain their antitumor properties.
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PMID:[Use of the peptide hormone melanostatin and its analogs for the synthesis of new antitumor compounds]. 289 89


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