Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eighty-seven patients with newly diagnosed Hodgkin's disease, pathologic stages IA, IIA, IIB and IIIA, were assigned at random to receive either extended field radiotherapy alone or that therapy followed by six cycles of MOPP (nitrogen mustard, Oncovin, procarbazine, prednisone) chemotherapy. Patients were entered into the study from January 1970 to January 1974. Patients were followed for a median of 69 + months from the end of all treatments. Patients whose disease was less than stage IIIA had a 31 per cent relapse rate with radiotherapy alone compared to a 6 per cent relapse rate with combined modality treatment (P = 0.04). No deaths from Hodgkin's disease have occurred in patients who received combined modality therapy, whereas 24 per cent of the patients who received radiotherapy alone have died with active disease. However, three patients with stage IIIA disease who were treated with both modalities have died from other causes (myocardial infarction, adenocarcinoma of lung, acute leukemia). Combined modality therapy of patients with early Hodgkin's disease may be superior to radiotherapy alone, especially for certain subgroups of patients discussed in detail.
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PMID:Combined modality treatment of Hodgkin's disease confined to lymph nodes. Results eight years later. 38 Mar 35

The N-nitrosoureas are the most active of a variety of N-nitroso compounds tested against L1210 leukemia in mice. Structure-activity studies show that the N-(2-chloro(or fluoro)ethyl)-N-nitrosoureido grouping is necessary for high-level activity in this test system, but a variety of carrier groups can be attached to the N'-nitrogen of the urea. For high-level activity against solid tumors in rodents, eg, the Lewis lung adenocarcinoma, the N'-substituent must be a cyclohexane ring, and the most active of these compounds are substituted at position 4 of the ring. The chemistry involved in the synthesis and reactions of the nitrosoureas is described. The possible relationship of the chemically reactive species generated by the decomposition of the nitrosoureas under in vivo conditions to biologic activity is discussed.
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PMID:Chemistry and structure-activity studies of the nitrosoureas. 95 7

The effect of selenite coadministration on the toxicity and antitumor activity of repeated treatment with high doses of cis-diamminedichloroplatinum (cis-DDP) was examined in mice. Sodium selenite was injected s.c. into separate abdominal sites of mice together with cis-DDP at a molar ratio of 1:3.5 (selenite to cis-DDP) on day 0. The same amount of selenite was given daily for 4 subsequent days (days 1-4). This fixed administration schedule was repeated weekly for a total of 7 weeks. Under the experimental conditions used, the lethal toxicity, renal toxicity [indicated by an increase in blood urea nitrogen (BUN) and plasma creatinine levels], hepatic toxicity (indicated by an increase in plasma GPT and GOT activity), and myelotoxicity (indicated by a decrease in the numbers of leukocytes and platelets) observed in mice given repeated doses of cis-DDP alone (15 or 25 mumol/kg, s.c.) were significantly depressed by the coadministration of sodium selenite. Treatment with cis-DDP alone (15, 20, or 25 mumol/kg, s.c.) resulted in some dose-dependent prolongation of the life span of mice transplanted either s.c. with colon adenocarcinoma 38 (colon 38) or i.p. with P388 leukemia (P388) but did not completely depress the tumor growth, and the animals died of either progressive disease or cis-DDP-induced toxicity. However, following the coadministration of 7.1 mumol/kg selenite with 25 mumol/kg cis-DDP, all of the mice transplanted either s.c. with colon 38 or i.p. with P388 survived for as long as 4 months after the end of the treatment and showed no evidence of malignancy. These results indicate that selenite coadministration enables the use of increasing doses of cis-DDP and, consequently, enhances the antitumor effect of cis-DDP by depressing its side effects.
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PMID:Effect of coadministration of selenite on the toxicity and antitumor activity of cis-diamminedichloroplatinum (II) given repeatedly to mice. 139

Three aniline derivatives melphalan (L-PAM), chlorambucil (CHL) and 4-[bis(2-chloroethyl)amino] benzoic acid (BAM) have been compared on the basis of their in vitro cytotoxicities, DNA interstrand crosslinking ability and DNA sequence selectivity. Cytotoxicity was assessed in the human colonic adenocarcinoma LS174T and leukaemic K562 cell lines using the sulpho-rhodamine B and tetrazolium dye reduction assays. The order of cytotoxicities was L-PAM greater than CHL greater than BAM in both cell lines with K562 being less sensitive than LS174T. This was different from the order CHL greater than L-PAM greater than BAM which would be predicted from simple chemical reactivity or rate of hydrolysis, parameters which have been used previously as indicators of biological potency for aromatic nitrogen mustards. DNA interstrand crosslinking in cells as determined by alkaline elution showed a correlation with IC50 values. The ranking order of activity was further predicted by the ability of the agents to produce interstrand crosslinks in isolated DNA. The extent of guanine N-7 alkylation, assessed using a modified DNA sequencing technique, mirrored cytotoxicity and crosslinking ability, but at equivalent levels of alkylation there was no significant difference in DNA sequence selectivity. These data demonstrates that simple chemical reactivity or hydrolysis rate is not a good indicator of DNA reactivity or cytotoxicity for a number of aniline mustards, whereas DNA interstrand crosslinking ability either measured directly in cells or in isolated DNA, gives a good indication of biological activity.
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PMID:The cytotoxicity, DNA crosslinking ability and DNA sequence selectivity of the aniline mustards melphalan, chlorambucil and 4-[bis(2-chloroethyl)amino] benzoic acid. 163 39

Administration of 4-methylthiobenzoic acid (MTBA) (100 mg/kg) strongly reduced cisplatin nephrotoxicity (7.5 mg/kg, 20 min after MTBA) in rats as determined by histopathology and blood urea nitrogen. Anti-tumour activity against a colonic adenocarcinoma, CC 531, that was implanted in rats, was unaffected by MTBA pretreatment. Studies with isolated renal proximal tubular cells (PTC) demonstrated that preincubation of the cells with MTBA diminished cisplatin nephrotoxicity in vitro as it did in vivo. Preincubation of the PTC with probenecid completely abolished the protective effect of MTBA against cisplatin toxicity. These data indicate that MTBA is actively transported into the PTC. The mechanism of action of MTBA was investigated by NMR studies which showed that cisplatin and cis-diamminediaquaplatinum(II), its hydrolysis product, reacted with the methylthio-sulphur. We suggest that MTBA after selective accumulation in the kidney inactivates cisplatin intracellularly by nucleophilic attack of the methylthio-sulphur to the Pt-moiety. Since MTBA shows no acute toxicity in the rat, even if administered at very high doses, it may be useful to suppress the nephrotoxic side effects of cisplatin anti-tumour therapy.
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PMID:4-Methylthiobenzoic acid reduces cisplatin nephrotoxicity in rats without compromising anti-tumour activity. 167 72

Conditioned medium (CM) from cultures of cytotoxic activated macrophages causes inhibition of mitochondrial respiration, DNA synthesis, and aconitase activity in murine EMT-6 mammary adenocarcinoma cells by an L-arginine dependent effector mechanism. CM induces cytotoxicity and nitrite synthesis in EMT-6 cells in a dose dependent manner. We have identified the soluble factors in CM that induce cytotoxicity and synthesis of inorganic nitrogen oxides from L-arginine by EMT-6 cells. Using functional inhibition experiments, the activity of lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF alpha), and interferon gamma (IFN gamma) in CM was investigated. The LPS inhibitor polymyxin B and TNF alpha antibody produced a modest decrease in nitrite production, while IFN gamma antibody markedly inhibited both nitrite production and cytostasis. Simultaneous treatment with polymyxin B, TNF alpha antibody, and IFN gamma antibody reduced EMT-6 cell nitrite production by 81%, and cytostasis by 74%. By Western blot, IFN gamma and TNF alpha were shown to be present in CM. When CM was subjected to hydrophobic interaction chromatography, a single peak of activity was eluted, and Western blot showed that the active fractions contained IFN gamma. Furthermore, IFN gamma antibody neutralized the activity in these chromatographic fractions. We conclude that induction of inorganic nitrogen oxide synthesis from L-arginine by the synergistic combination of IFN gamma, TNF alpha, and LPS accounts for most of the biologic activity of CM, and that IFN gamma is the major priming factor.
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PMID:Activated macrophage conditioned medium: identification of the soluble factors inducing cytotoxicity and the L-arginine dependent effector mechanism. 190 65

We have studied the effect of intraoperative body heat conservation and 24-h thermoneutrality on postoperative whole body protein turnover using stable isotope methodology in a group of elderly patients undergoing colorectal surgery for rectosigmoid adenocarcinoma. Two groups of eight patients were studied. One group (control, or cold) received routine intraoperative and postoperative care. All patients in the second group (warmed) were maintained at normothermia during anaesthesia and surgery; these patients were nursed after surgery in a warm room (ambient temperature 28-30 degrees C) for a period of 24 h. General anaesthesia, surgical care and nutritional support were similar in both groups. A constant nutritional intake, based on nitrogen 0.1 g kg-1 day-1 and energy 20 kcal kg-1 day-1, was provided orally for 7 days before surgery and i.v. after operation for 4 consecutive days. Whole body protein breakdown and synthesis, as assessed by stable isotope methodology, increased significantly 2 and 4 days after surgery in both groups (P less than 0.01), but the increase in protein breakdown in the warmed group on day 2 was significantly less than that in the cold group (P less than 0.05). The increase in leucine oxidation in the warmed group on the 2nd day after surgery was not significant, and was less than the increase observed in the cold group (P less than 0.05). However, by the 4th day, leucine oxidation was enhanced significantly in both groups (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Postoperative protein metabolism: effect of nursing elderly patients for 24 h after abdominal surgery in a thermoneutral environment. 201 44

Point mutations in codons 12, 13 or 61 of the oncogenes Ha-ras, Ki-ras or N-ras have been identified in human malignancies of many types. Using the PCR (polymerase chain reaction) technique for DNA amplification in vitro and stringent probing of the amplified DNA on dot blots with a library of specific oligonucleotides, we have screened for the presence of ras mutations in oral and para-oral malignancies and some associated lesions. The material, from UK patients, consisted of 22 oral squamous-cell carcinomas including 5 neck metastases, 1 oral mucosal dysplasia, 1 proliferative verrucous leukoplakia, 1 antral and 1 tonsillar carcinoma, 1 basal-cell carcinoma, 1 salivary adenocarcinoma, 1 salivary adenoid cystic carcinoma and 1 lung adenocarcinoma metastatic to the gingiva. Genomic DNA was extracted from tissues which were fresh or preserved in liquid nitrogen. Two DNA samples contained point mutations in codon 61 of Ki-ras. One of these mutations was in the lymphocytes infiltrating a retromolar SCC. The other mutation (CAA to CAU; substitution of glutamine by histidine) was in the lung adenocarcinoma metastasis. The absence of ras mutations in the epithelium of primary oral squamous-cell carcinomas is of considerable interest as other work in our Department on Indian cases of oral carcinomas associated with chewing tobacco (quid) revealed that 35% of these had a codon 12, 13 or 61 mutation in Ha-ras. While ras activations arising from point mutations may occur in a high proportion of oral malignancies associated with chewing tobacco (quid), this was not the case in UK oral malignancies, even where tobacco was smoked.
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PMID:Ras mutations in United Kingdom examples of oral malignancies are infrequent. 204 May 36

We collected clinical, laboratory and endoscopic data prospectively in patients presenting with acute non-variceal upper gastrointestinal bleeding admitted to the care of one surgical team. During a 30-month period 52 patients were subsequently proven to have gastric adenocarcinoma; 30 patients underwent elective operation, and emergency surgery for bleeding was performed on 14 occasions. There were 13 hospital deaths (25%), 13.5% at 30 days. Emergency surgery was associated with a higher mortality rate (42.9%) than elective procedures (13.3%) (P less than 0.03). Factors associated with a poor prognosis were active haemorrhage at initial endoscopy, an admission blood urea nitrogen greater than 16 mmol/l, preoperative transfusion greater than 4 units, total transfusion greater than or equal to 9 units and a lowest recorded haemoglobulin during hospitalization of less than 7.5 g/dl. The unacceptably high mortality rate associated with surgery for continued haemorrhage or rebleeding episodes suggest that earlier elective operative intervention be advocated in patients presenting with acute bleeding and in whom gastric cancer is visualized. This is recommended particularly if the initial bleeding episode is severe, or active haemorrhage is visualized during initial endoscopy.
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PMID:Risk factors for mortality in patients with gastric adenocarcinoma presenting with acute haemorrhage. 204 79

The authors related two cases of multiple myeloma BJX and GX combined with hypernephroid cancer. In both cases, the diagnosis of myeloma was supported by morphological examination of the bone marrow and immunochemical identification of monoclonal immunoglobulin. In female patient C, adenocarcinoma developed in the presence of polycystosis in the left kidney operated before. The diagnosis of hypernephroma was established simultaneously with the diagnosis of multiple myeloma BJX, stage III B. The patient was operated on 15 months after institution of polychemotherapy in the presence of myeloma reduction and recovery of nitrogen secretory renal function. The patient survived for 2.5 years after the operation, retaining work fitness for 2 years. She died from terminal exacerbation of myeloma. On autopsy no cancer metastases were detected. In male patient Ch. with myeloma GX, stage II A, hypernephroid cancer of the right kidney was diagnosed 7 months after the diagnosis of myeloma was established. Radical operation resulted in complete somatic and hematological compensation of the patient. The residual mass of myeloma does not manifest itself clinically after 9 courses of polychemotherapy carried out in the preoperative period. It is only detectable by the laboratory tests. The follow-up of the patient is continued.
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PMID:[The successful surgical treatment of hypernephroid cancer in 2 patients with multiple myeloma]. 228 96


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