Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty-one dogs with a variety of histopathologically diagnosed, measurable tumors were treated with cisplatin (cis-diamminedichloroplatinum, Platinol, Bristol Laboratories, Syracuse, NY 13221-4755) as a single agent at a dosage of 60 mg/m2 given intravenously at 3-week intervals. In an attempt to avoid renal toxicity of cisplatin, saline diuresis was induced and maintained for 4 hours before and 2 hours following cisplatin administration. The dogs received one to ten doses of cisplatin. To determine response to therapy and to monitor toxicity of the drug, the dogs were evaluated with physical examinations including tumor measurements, radiography, complete blood counts, platelet counts, urinalyses, serum urea nitrogen concentrations, and serum creatinine concentrations. An overall response rate of 19% was observed. Complete remission occurred in one of 11 dogs with squamous cell carcinomas and one of one dog with a mediastinal undifferentiated carcinoma. Partial remissions were documented in one of 11 dogs with squamous cell carcinomas, two of three dogs with metastatic osteosarcomas, one of three dogs with nasal adenocarcinomas, and one of one dog with a thyroid adenocarcinoma. Toxic side effects were primarily gastrointestinal in nature, with vomiting occurring 1-6 hours after cisplatin administration in 27 of 41 dogs. Severe anorexia occurred in three dogs, and hemorrhagic diarrhea was observed in one dog. One dog developed grand mal seizures and died 3 hours following therapy. Granulocytopenia was documented in six dogs, and thrombocytopenia was observed in four dogs. One dog showed an increase in serum urea nitrogen and creatinine concentrations, but this patient had known pre-existing renal disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cisplatin therapy in 41 dogs with malignant tumors. 322 54

Ethacrynic acid and piriprost (6,9-deepoxy-6,9-(phenylimino)-delta 6,8-prostaglandin I1) have been shown to potentiate the cytotoxic activity of chlorambucil in rat and human tumor cell lines. Walker 256 rat breast carcinoma cells (WS), with acquired resistance to nitrogen mustards (WR), and two human colon carcinoma cell lines, HT 29 and BE, were sensitized to chlorambucil when either ethacrynic acid or piriprost was administered at the same time as the alkylating agent. Both as single agents and in combination with chlorambucil, there was inhibition of glutathione S-transferase activity as measured with 1-chloro-2,4-dinitrobenzene as a substrate. A depletion in intracellular glutathione was also evident following ethacrynic acid alone or in combination with chlorambucil. Thus, diuretic plant phenols or prostaglandin analogues may have potential therapeutic utility in combination with alkylating agents.
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PMID:Ethacrynic acid and piriprost as enhancers of cytotoxicity in drug resistant and sensitive cell lines. 328 31

Over two decades, experience with estramustine has provided limited data which support an estrogenic mechanism of action and no data which indicate the nitrogen mustard involvement in the cytotoxic properties of the drug. Consideration of the carbamate-ester portion of estramustine supports the pharmacokinetic evidence that estramustine has a long half life since enzymatic hydrolysis of the carbamate is an uncommon event. Using a variety of immunocytochemical and cellular morphology procedures, estramustine per se has been found to express anti-cytoskeletal properties through non-covalent binding to microtubule associated proteins (MAP's). In both fish erythrophores and in dividing human prostatic carcinoma cells, estramustine exerts an antimicrotubule effect at micromolar concentrations. Thus, estramustine possesses unique pharmacology and protein binding specificity. As such, it should not be classified as an alkylating agent. The estrogenic effects, while possibly of relevance to clinical administration, are not the primary mechanism by which the drug exerts cytotoxicity.
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PMID:Hormone-independent, non-alkylating mechanism of cytotoxicity for estramustine. 330 87

Immunofluorescent studies in human prostatic carcinoma cells (DU 145) and cultured squirrel fish epithelial cells (a non-cancer cell) revealed that estramustine, a conjugate of estradiol and nor-nitrogen mustard, possessed microtubule disassembly properties. Sixty microM estramustine produced disassembly at both the proximal and distal ends of microtubules, producing short pieces of less than 2 microM which were "wavy" and oriented in a random manner. With increased time of drug exposure these short microtubules disappeared, to be accompanied by a gradual disassembly of a small population of longer microtubules (greater than 7-8 microM). In dividing DU 145 cells it was possible to show a different degree of sensitivity of specific microtubule-containing cellular structures. In mitotic figures the asters were most sensitive and disappeared completely following exposure to estramustine. These were followed by the "pole-to-pole" and "chromosomal" fibers. In cytokinesis, the intercellular fibers between daughter cells were comparatively resistant to the drug. Estramustine did not induce disassembly of the vimentin filaments in non-dividing or dividing cells but did cause their collapse around the nucleus or the mitotic apparatus. These data suggest that specific microtubules have differing sensitivity to estramustine.
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PMID:Immunofluorescent studies of the anti-microtubule effects of the anti-cancer drug estramustine. 332 49

A 5-year-old intact male llama (Llama glama) with gastric squamous cell carcinoma and generalized metastasis is presented. Weight loss, anorexia and cachexia were the presenting clinical signs. Abnormal laboratory findings included neutrophilia, lymphopenia, increased serum activity of hepatic enzymes, mildly increased serum urea nitrogen concentration and elevated protein concentration and nucleated cell count in the peritoneal fluid. Fasciola hepatica ova were identified by fecal sedimentation examination. The presence of flukes, as well as carcinoma metastasis, probably contributed to the increased serum hepatic enzyme activity. Similarities to gastric squamous cell carcinoma in the equine and bovine species are discussed. This case suggests that neoplasia, although rarely reported in the llama, must be considered in the differential diagnostic list for anorexia and weight loss in the llama.
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PMID:Gastric squamous cell carcinoma and fascioliasis in a llama. 340 19

Although various complications such as electrolyte imbalance and urinary infection are known to be induced by ureterosigmoidostomy, it is still a surgical technique difficult to ignore since it allows patients to lead an almost normal life without the encumbrance of external urinary devices. At our hospital, we performed eighteen ureterosigmoidostomy operations between 1976 and 1985. Herein, we review the postoperative conditions of electrolyte, renal function and other complications. The patients (16 male, 2 female) were between 53 and 72 years old, the mean age being 61.5 years. The primary diseases were bladder tumor (14 patients), prostatic cancer (2), carcinoma of the female urethral diverticulum (1) and urethral stricture (1). As to the electrolytes, both serum Na and serum K values fluctuated within the normal range. Hyperchloremia was detected in 4 cases (22.2%), but it was only slightly above the normal range and the conditions were more or less stabilized a year after the operation. Although blood urea nitrogen had a tendency to elevate one or two years after the operation, serum creatinine fluctuated within the normal range. During the observation period, only 7 of the 18 cases (38.9%) showed complications, the major complication being pyelonephritis (3 cases). Postoperative excretory urogram revealed slight to medium hydronephrosis two months after the operation in 9 of the 18 cases (50%), but most of these conditions were normalized within a year. Four patients died after leaving hospital; 3 due to the recurrence of cancer and one due to pneumonia. The 14 other outpatients are enjoying a normal life without the use of any external urinary device.
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PMID:[Ureterosigmoidostomy--clinical review of 18 cases]. 344 31

Neoplastic tissue was obtained at operation from 10 renal cell carcinomas, from the adjacent 'normal' kidney in 6 cases and from 1 other normal kidney. The biopsies were snap frozen in liquid nitrogen and sections were subsequently stained with monoclonal antibodies against major histocompatibility complex (MHC) antigens, class I and II, and several types of mononuclear cell, by the indirect immunoperoxidase method. The degree of staining or the number of cells stained was estimated as heavy 4, through moderate 3, few 2, occasional 1, or nil 0. MHC Ag were consistently expressed, grade 2-4, by the glomeruli and proximal convoluted tubules of normal kidney, but were absent in 8 of 10 carcinomas. There was a grade 3-4 mononuclear cell infiltration in the stroma of normal kidney and between the carcinoma cells which was composed principally of macrophages. However in the two carcinomas expressing MHC Ag there was also a grade 2-3 infiltration with T lymphocytes. The absence of MHC Ag on carcinoma cells mitigates against attempts to potentiate the patient's immune response to his tumour, e.g. by renal artery embolisation.
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PMID:Expression of histocompatibility antigens and characterisation of mononuclear cell infiltrates in human renal cell carcinomas. 350 Jul 37

Previous studies carried out in the authors' Institute revealed that one of the active metabolites of Antineoplaston A10 is phenylacetylisoglutamine. The objective of this study is screening of N,N'-disubstituted L-isoglutamine derivatives for selection of novel anticancer agents. A series of seven derivatives of L-isoglutamine was synthesized as potential chemotherapeutic agents. Antitumor activity studies were performed in tissue culture of breast carcinoma cells HBL-100. The acute toxicity study was carried out on a group of 60 HA/ICR Swiss mice. Among the compounds tested N alpha-(phenylacetylamino)-gamma-(4-amino-N-benzyl-piperidinyl)-L-g lutamyl amide was found to have the best anticancer activity and no significant acute toxicity. The LD50 was calculated by the moving average method and determined as 4.5 g/kg i.p. in mice. It is concluded that the important structural features for good antineoplastic activity are lipophilic groups on both amine and amide nitrogen of isoglutamine. The activity is also increased when the phenyl group present at the side chain is at least two carbon atoms away from the amide nitrogen.
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PMID:N,N'-disubstituted L-isoglutamines as novel cancer chemotherapeutic agents. 356 17

A 53-year-old woman presented with an extensively metastatic and rapidly growing breast adenocarcinoma, markedly elevated lactate dehydrogenase, and mildly elevated blood urea nitrogen. She received 5-fluorouracil, doxorubicin, and cyclophosphamide. Eighteen hours after chemotherapy she was noted to have hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and acute renal failure. She experienced cardiac arrest and died 72 hours after receiving chemotherapy. A postmortem liver biopsy revealed adenocarcinoma undergoing necrosis. This case represented the acute tumor lysis syndrome that occurred after chemotherapy of breast carcinoma. Patients with metastatic breast carcinoma and similar presentations should be considered for prophylactic therapy with allopurinol and hydration before chemotherapy.
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PMID:Fatal acute tumor lysis syndrome with metastatic breast carcinoma. 359 99

Tumor cell resistance to alkylating agents was studied by examining Walker 256 rat mammary carcinoma cells differentially sensitive to nitrogen mustards. A resistant subpopulation (WR) was selected by exposure to chlorambucil. WR cells showed approximately a 15-fold resistance to the cytotoxic effects of nitrogen mustards and elevated glutathione S-transferase (GST) activity when compared to the sensitive parent cell line (WS). To extend these findings, the GSTs from WR and WS were purified by affinity chromatography on S-hexylglutathione coupled to epoxy-activated agarose. Substrate specificity experiments using purified GSTs demonstrated different profiles of enzyme activity for WR and WS and suggested differential isoenzyme expression in these two cell lines. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis revealed that the major GST present in both WR and WS was a 26,000-Da subunit that was immunologically distinct from the rat liver GSTs. This GST subunit cross-reacted with antibodies against anionic human placental GST. In addition, three GST forms common to rat liver (29,500, 28,500 and 27,500 molecular weight) were also identified. Overexpression of the 29,500-Da protein was observed in WR cells. These data suggest that differential expression of GST subunits may contribute to the nitrogen mustard-resistant phenotype.
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PMID:Glutathione S-transferases in nitrogen mustard-resistant and -sensitive cell lines. 360 Jun 2


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