Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the human prostate, a low affinity (p75) nerve growth factor (NGF) receptor (NGF-R) localizes to the epithelia while a NGF-like protein localizes to the stroma. This NGF-like ligand, derived from prostate stromal cell cultures, has been shown to participate in paracrine mediated growth of a human tumor epithelial cell line (TSU-prl) in vitro. In order to investigate the role of the NGF-R in neoplastic growth we have examined the expression of the NGF-R in normal prostate tissues, benign prostatic hyperplasia tissues, adenocarcinoma tissues, and four metastatic tumor cell lines of the human prostate. In primary epithelial cell cultures of normal human prostate the p75 NGF-R was localized by immunocytochemistry to cytoplasmic vesicles. Furthermore, Western blot analysis of the NGF-R in subcellular fractions of normal prostate tissue identified an M(r) 75,000 immunoreactive protein in the microsomal fraction under nonreducing conditions of sodium dodecyl sulfatepolyacrylamide gel electrophoresis. However, microsomal preparations of five prostatic adenocarcinoma and five benign prostatic hyperplasia specimens showed varying immunoreactivity among samples, all of which expressed less of the p75 NGF-R than the normal tissue. Interestingly, microsomal preparations of the human prostatic epithelial cell lines, TSU-prl, DU-145, PC-3, and LNCaP did not show NGF-R expression by immunoblot analysis. Hence, expression of the p75 NGF-R in normal prostate tissue, partial loss of NGF-R expression in benign and malignant prostate tissue, and complete loss of NGF-R expression in the four metastatic tumor cell lines, suggests an inverse association of p75 NGF-R expression with the neoplastic progression of the human prostate.
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PMID:Reduced expression of the low affinity nerve growth factor receptor in benign and malignant human prostate tissue and loss of expression in four human metastatic prostate tumor cell lines. 138 43

The purpose of this study was to establish an in vitro model for tumor progression in colorectal carcinogenesis, by transforming the premalignant human colonic PC/AA adenoma cell line to the malignant phenotype. A rare clonogenic variant AA/C1 [colony-forming efficiency (CFE) on plastic of 1.05%] was isolated from the diploid PC/AA adenoma cell line (C. Paraskeva, S. Finerty, and S. Powell, Int. J. Cancer, 41: 908-912, 1988). AA/C1 was aneuploid and when treated with 1 mM sodium butyrate for 14 days gave rise to the AA/C1/SB cell line which had an increased CFE on plastic (6.13%) although the cells remained anchorage dependent and nontumorigenic. After exposure of these AA/C1/SB cells to the carcinogen N-methyl-N'-nitro-N'-nitrosoguanidine an anchorage-independent cell line was isolated (AA/C1/SB10). On continuous in vitro passage, the CFE in agarose of AA/C1/SB10 has increased to 17.3% and the cells have become tumorigenic producing adenocarcinomas in athymic nude mice. AA/C1, AA/C1/SB, and AA/C1/SB10 cell lines have common chromosomal abnormalities including a pericentric inversion of chromosome 1 with deletion of part of the short arm and monosomy for chromosome 18. This in vitro progression provides the first reported experimental evidence for the adenoma to carcinoma sequence in the human colon, and the cytogenetic evidence suggests that it is relevant to in vivo carcinogenesis.
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PMID:Neoplastic transformation of a human colonic epithelial cell line: in vitro evidence for the adenoma to carcinoma sequence. 236 46

Laminin biosynthesis was compared in four pairs of human squamous cell carcinoma cultures derived from primary and recurrent or metastatic tumors in four patients with cancer of the larynx and hypopharynx to determine if changes in laminin production accompany tumor progression. Laminin profiles of the malignant cells were compared with laminin biosynthesized by nonmalignant human keratinocytes. Pulse-chase biosynthetic labeling of the cultures with [35S]methionine established that all of the squamous carcinoma cell lines synthesize immunoreactive A (Mr 400,000), B1 (Mr 205,000), and B2 (Mr 200,000) laminin subunits; assemble them to form the intact laminin molecule (Mr 950,000); and secrete a portion of the laminin they produce into the culture media. One aspect of laminin expression unique to keratinocytes, both malignant and nonmalignant, was the occurrence of three additional glycoprotein forms (Mr 195,000, 170,000, and 160,000) in the laminin immunoprecipitates. In contrast to the laminin subunits, these glycoproteins were not immunoreactive with the anti-laminin antiserum on Western blots. Two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis without and with reduction of disulfide bonds revealed that the laminin immunoprecipitates contained a family of oligomeric molecules. These ranged in apparent molecular weight from 370,000 to 950,000 and were composed of laminin subunits and the glycoprotein forms linked by interchain disulfide bonds. The malignant keratinocyte cell lines from different patients were distinguishable in terms of the array of laminin and glycoprotein forms displayed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the rate of [35S]methionine incorporation into laminin during the pulse-labeling, the fraction of [35S]methionine-labeled laminin secreted into the medium during the chase incubation, and the absolute amount of laminin secreted into the culture medium as determined by enzyme-linked immunosorbent assay. However, cell lines established from primary and metastatic or recurrent cancer in the same patient were indistinguishable in their profile of laminin biosynthesis and secretion. In comparison to primary cultures of nonmalignant foreskin basal keratinocytes, the malignant cells secreted into the culture medium a larger fraction of the laminin that they produce. This is an indication that the malignant keratinocytes in culture deposited a less stable basal lamina-like extracellular matrix than their malignant counterparts. The diminished integrity of the basal lamina matrix may be an important factor in the invasive growth of human epithelial cancer.
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PMID:Biosynthesis and secretion of laminin and laminin-associated glycoproteins by nonmalignant and malignant human keratinocytes: comparison of cell lines from primary and secondary tumors in the same patient. 245 36

Twenty-one patients with limited (12 cases) or extensive (9 cases) small cell lung cancer entered a pilot study with adriamycin (ADM) plus ifosfamide (IFX) as first line treatment for six planned cycles. ADM was administered at the dose of 60 mg/m2 iv push on day 1 and IFX at 3 g/m2/iv in 1-hour infusion on days 1 and 2. To prevent IFX-induced hemorrhagic cystitis, mercaptoethane sulfonate sodium (Mesna) was given after the administration of IFX at the dose of 500 mg/m2 by iv push four times (hour 0, 4, 8, 12) on days 1 and 2. In the absence of disease progression, chemotherapy was repeated every 3 weeks for 6 cycles. All patients were evaluable for analysis of response, toxicity and survival. The overall response rate clinically and radiologically assessed after four treatment cycles was 95.3% (CR 28.6%, PR 66.7%). However, by continuing the same drug treatment up to the sixth cycle, 7 of 14 partial responders showed tumor progression within the intrathoracic region. Therefore, at the end of the planned chemotherapy program the partial remission rate fell to 33.3%, for a total remission rate of 61.9% and a median total survival of 9 months (range 5 to 36+). The regimen was well tolerated with only one case presenting hemorrhagic cystitis. The results achieved with this drug combination appear comparable to those obtained with other conventional regimens. However, the high response rate achieved after four cycles and the low incidence of marrow toxicity suggest the use of this regimen for a short period with increased dose levels.
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PMID:Pilot study with adriamycin and ifosfamide in small cell lung cancer. 254 May 79

A patient with glioblastoma multiforme developed hyponatremia. This was accompanied by decreased mental awareness and seizures following cis-dichlorodiammine platinum II (DDP) chemotherapy. Treatment with hypertonic saline, furosemide diuresis, and fluid restriction promptly restored the serum sodium and neurologic status to normal. Hyponatremia did not recur despite subsequent tumor progression and increased intracranial pressure. The clinical picture suggested a drug-induced syndrome of inappropriate secretion of antidiuretic hormone. Hyponatremia should be considered when seizures or mental changes occur in patients treated with DDP.
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PMID:Cis-dichlorodiammineplatinum II-induced syndrome of inappropriate secretion of antidiuretic hormone. 282 77

Review of clinical data from 350 patients with small-cell lung cancer (SCLC) revealed hyponatremia (sodium less than 130 mEq/L) attributable to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in 40 patients (11%). Although hyponatremia was severe in most instances (median, sodium 117 mEq/L), symptoms attributable to water intoxication were identified in only 27% of hyponatremic episodes. Development of SIADH showed no correlation with clinical stage, distribution of metastatic sites, sex, or histologic subtype of small-cell carcinoma. SIADH occurred most often with initial presentation (33 of 40), and resolved promptly (less than 3 weeks) with initiation of combination chemotherapy in 80% of evaluable patients. The presence of SIADH did not influence response to chemotherapy or overall survival as an independent variable. However, in five patients profound hyponatremia developed immediately following primary cytotoxic therapy (range, one to five days). Despite initial control of SIADH, dilutional hyponatremia recurred in 70% of patients with tumor progression. Our findings suggest that development of clinically demonstrable SIADH in patients with SCLC is dependent on functional properties of the neoplastic cells, rather than tumor burden or metastatic site. The potential for development of clinically significant hyponatremia early in the course of cytotoxic therapy emphasizes the need to closely monitor patients, particularly those receiving chemotherapy regimens requiring substantial intravenous hydration.
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PMID:The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in small-cell lung cancer. 301 6

Oxidative stress has been suggested to play an integral role in the cancer process. It may be particularly significant during tumor progression, where there is likely to be a large amount of free radicals generated by infiltrating inflammatory cells and dying tumor cells. In order to test this hypothesis, a variety of free radical scavengers and antioxidants were assessed for their ability to inhibit tumor progression. The murine skin multistage carcinogenesis model was used to generate papillomas, which are a population of putative precancerous lesions. Various test agents were applied topically to papillomas in order to determine if they would decrease the incidence of the malignant lesion, squamous cell carcinoma. The agents tested included: reduced glutathione (GSH), butylated hydroxyanisole, vitamin E, copper(II) (3,5-diisopropylsalicylate)2, sodium benzoate, N-acetyl cysteine and disulfiram. Under the conditions of our experiments, only GSH and disulfiram inhibited tumor progression to a significant degree. Additional studies indicated that GSH prevented cancer development in a dose-dependent manner. Another experiment demonstrated that when papillomas received repeated topical applications of diethylmaleate, a GSH-depleting agent, tumor progression was enhanced. Collectively these data suggest that sufficient glutathione levels may be important in preventing cancer formation.
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PMID:Effect of exogenous glutathione on tumor progression in the murine skin multistage carcinogenesis model. 313 44

The effect of 4-methyl-4-aza-steroidal inhibitors of 5 alpha-reductase has been evaluated on tumor growth in the Noble rat model of prostatic adenocarcinoma. The growth characteristics of the tumor line 2Pr-121D(1) were consistent with heterogeneity of cell types, composed of androgen-sensitive and androgen-insensitive malignant cells. Both sodium 4-methyl-3-oxo-4-aza-5 alpha-pregnane-20 (s)-carboxylate and 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 and 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one significantly retarded tumor progression. Each agent increased tumor volume doubling time by approximately 62%. On the basis of their similarities to female rats and male castrate group, in terms of growth rate, tumor doubling time, and histologic characteristics, the treatments with the 4-methyl-4-aza-steroids appeared to produce effects common to both castration and estrogenization (chronic administration of pharmacologic doses of estrogen). The failure of 5 alpha-reductase inhibitors to be active as antiprostatic agents in vivo has hitherto detracted from their use of therapeutic agents. Present studies demonstrate that the 4-methyl-4-aza-steroidal inhibitors of 5 alpha-reductase may represent an alternative to orchiectomy and chronic estrogen therapy for the management of the hormone-dependent phase of prostate cancer.
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PMID:Retardation of prostate tumor progression in the Noble rat by 4-methyl-4-aza-steroidal inhibitors of 5 alpha-reductase. 385 54

Six patients with peritoneal carcinosis and ascites received 13 courses of ip cis-platinum (c-DDP). C-DDP (170-250 mg in 2L saline, dwell 4 h) was administered via Pig-Tail-Cordis catheter with concurrent infusion of sodium thiosulfate (bolus 7.5 g/m2 followed by 2.13 g/m2/h for 12 h). The patients received pre- and post-therapy hydration (250 ml/h) and mannitol-induced diuresis. Courses were given in 4 weekly intervals. With a dwell time of 4 h 27.0% +/- 14.6% (mean +/- SD) of platinum were recovered. Total serum platinum peaked at 3.1 +/- 1.0 microgram/ml. The peritoneal/serum ratio of platinum concentration was 49.5 +/- 12.6 after 1 h, 7.4 +/- 1.7 after 5 h and 4.2 +/- 1.7 after 12 h. Within 12 h 30.9% +/- 10.0% of the administered dose were excreted in urine. In 4 patients the ascites had disappeared lasting 14+, 15+, 5+, 3+ months. 2 patients died within 1 month caused by systemic tumor progression. Following toxicity was observed: 9/13 nausea and vomiting grade 1 (WHO), 2/13 hematological toxicity grade 2, 1/13 sterile peritonitis, no renal or neurological toxicity. This pilot study demonstrates a pharmacokinetic advantage of ip chemotherapy with c-DDP and an effectiveness against peritoneal carcinosis.
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PMID:[Therapy of peritoneal carcinosis with intraperitoneal administration of cis-diamminedichloroplatinum and systemic sodium thiosulfate protection. Clinical results of a pilot study and pharmacokinetics]. 391 89

Tumors obtained from the injection site of threshold subcutaneous inocula of L5178Y-F9 or SL2-5 lymphomas in syngeneic mice exhibited increased tumor frequencies and reduced sensitivities to other parameters of natural immune resistance in vivo and in vitro. An examination of the resistant phenotype of cells derived through this model of tumor progression revealed that the more aggressive in vivo grown cells were less able to inhibit natural killer (NK) cell cytolysis and to bind natural antibodies (NAb) measured through fluorescence analysis, although they could not be distinguished from the starting clones by absorption of NAb for complement-mediated lysis. The in vivo grown cells also exhibited a reduced sensitivity to hypotonic lysis, which was not detectable after preincubation at 4 degrees C or upon exposure to sodium azide, procedures that reduced the lysis of the starting clones. The differential susceptibility of the in vivo grown cells was increased to control levels by treatment with cycloheximide or colchicine. These studies suggest that a decreased sensitivity to lysis associated with a reduced autolytic process and an increased counterlytic mechanism, in addition to a reduced antigen expression for binding of NK cells and certain NAb contribute to this resistant phenotype, which may characterize tumors that arise under the selective pressure of natural resistance mechanisms in the natural course of neoplastic development.
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PMID:Phenotypic alterations in tumors that developed from threshold subcutaneous inocula. I. Reduced binding of natural antibodies and sensitivity to hypotonic lysis. 395 91


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