Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The reduction in size of four experimental tumours (ISIS 130 and ISIS 208 immunocytomas, S 437 mammary adenocarcinoma, S 447 colon adenocarcinoma) was investigated in LOU rats under the influence of cytostatic agents belonging to different classes (5-fluorouracil, methotrexate, vinblastine, cisplatin, doxorubicin, cyclophosphamide). External tumour and rectal temperatures were measured at the same time, twice daily, during the whole experiment. With the rectal temperature of the rats kept constant, the reduction in tumour dimensions following chemotherapy correlated via a linear relationship with the duration and degree of tumour hypothermia for the three tumours S 437, ISIS 208, ISIS 130. However, for the same reduction in tumour volume following chemotherapy, the duration and degree of transient tumour hypothermia varied according to the type of tumour and cytostatic agent studied. There was not correlation between the decrease in size of S 447 and external tumour hypothermia. Even when the reduction in tumour size was statistically significant, the hypothermic tumour phase after drug administration was not sufficient to be significant, except for vinblastine. However, the temperature of this slowly growing tumour before chemotherapy was particularly low. The measurement of the degree and duration of external tumour hypothermia of tumours following chemotherapy would represent a new physiological technique for measuring the efficacy and duration of action of cytostatic agents.
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PMID:Correlation between size and external temperature in four rat tumours after treatment with cytostatic agents. 335 Aug 45

Aziridinylbenzoquinone (AZQ: NSC-182986), is a quinone derivative which has been shown to have activity in implanted murine tumor systems. Toxicity in small and large animals included hypothermia, diarrhea, anorexia, emesis, weight loss, and gastrointestinal bleeding. In addition, there was myelosuppression and elevated liver function tests. In a phase I study at the Mayo Clinic, dose-limiting toxicity was myelosuppression. Patients with prior radiation therapy or prior chemotherapy were more sensitive to this toxicity. A dose schedule of 27.5 mg/m2 q4 weeks was recommended for patients who had had no previous chemotherapy and 22.5 mg/m2 for previously treated patients or for patients who had had extensive prior radiation therapy. The objective of this study was to determine therapeutic activity for AZQ in patients with advanced colorectal adenocarcinoma.
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PMID:A phase II study of aziridinylbenzoquinone (AZQ) in advanced large bowel carcinoma. 718 Aug 32

Intraperitoneal chemo-hyperthermia with mitomycin C was used to treat 28 patients with far advanced digestive adenocarcinoma and histologically confirmed peritoneal carcinomatosis. Surgical resection of the primary tumor was possible in 17 cases. After closure of the abdominal wall, intraperitoneal chemo-hyperthermia was performed for 90 to 120 minutes under general anesthesia and 32 degrees C hypothermia, through 3 intraperitoneal drains forming a closed circuit, using 10 mg/l of mitomycin C in 6 liters of peritoneal dialysate heated to an inflow temperature of 46-49 degrees C. No mortality occurred, and there were 2 post-operative complications, with transitory biological side effects. In 9 out of 10 patients with preoperative malignant ascites, the ascites cleared after treatment. One-year survival rate was 54.2%. These encouraging preliminary results show that intraperitoneal chemohyperthermia with mitomycin C is a safe and reliable treatment for peritoneal carcinomatosis in far advanced digestive cancers.
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PMID:Regional chemotherapy (with mitomycin C) and intra-operative hyperthermia for digestive cancers with peritoneal carcinomatosis. 805 98

Surgical procedures in the juxtaheptic and intrapericardial inferior vena cava (IVC) are difficult because of the complexity of achieving vascular control in the area. We describe 10 patients with a variety of pathologies in this region who underwent venovenous bypass (VVB) or cardiopulmonary bypass with hypothermic circulatory arrest (CBCA). Renal cell carcinoma with IVC extension was present in three patients (with tumor extension into the right atrium in two), adrenal adenocarcinoma in one, septic IVC thrombus in one, and blunt IVC/hepatic trauma in five. Those patients without atrial involvement underwent VVB with a mean bypass time of 40 minutes (range 12-144). Those patients with tumor extension into the right atrium underwent CBCA with systemic hypothermia to 18(0)C, total body exsanguination for a bloodless field, and removal of the tumor by cavotomy and right atriotomy. The mean bypass, aortic cross-clamp, and circulatory arrest times were 152, 92, and 36 minutes, respectively. Eight of the 10 patients did well and went home within 4 weeks of surgery. Two patients died, one from metabolic sequelae of exsanguinating IVC injury (VVB) and one from sepsis 2 weeks postoperatively (CBCA).
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PMID:Extracorporeal methods of vascular control for difficult IVC procedures. 860 87

Weight loss in cancer cachexia is attributable to decreased food intake and/or enhanced energy expenditure. We investigated the roles of the uncoupling proteins (UCPs) UCPI, -2, and -3 in a murine model of cachexia, the MAC16 adenocarcinoma. Weight fell to 24% below that of non-tumor-bearing controls (P < 0.01) 18 days after MAC16 inoculation, with significant reductions in fat-pad mass (-67%; P < 0.01) and muscle mass (-20%; P < 0.01). Food intake was 26-60% lower (P < 0.01) than in controls on days 17-18. Non-tumor-bearing mice, pair-fed to match MAC16-induced hypophagia, showed less weight loss (10% below controls, P < 0.01; 16% above MAC-16, P < 0.01) and smaller decreases in fat-pad mass (21% below controls, P < 0.01). Core temperature in MAC16 mice was significantly lower (-2.4 degrees C, P < 0.01) than in controls, and pair-feeding had no effect. MAC16 mice showed significantly higher UCP1 mRNA levels in brown adipose tissue (BAT) than in controls (+63%, P < 0.01), and pair-feeding had no effect. UCP2 and -3 expression in BAT did not differ significantly between groups. By contrast, UCP2 mRNA levels in skeletal muscle were comparably increased in both MAC16 and pair-fed groups (respectively, 183 and 163% above controls; both, P < 0.05), with no significant difference between these two groups. Similarly, UCP3 mRNA was significantly higher than controls in both MAC16 (+163%, P < 0.05) and pair-fed (+253%, P < 0.01) groups, with no significant difference between the two experimental groups. Overexpression of UCP1 in BAT in MAC16-bearing mice may be an adaptive response to hypothermia, which is apparently induced by tumor products; increased thermogenesis in BAT could increase total energy expenditure and, thus, contribute to tissue wasting. Increased UCP2 and -3 expression in muscle are both attributable to reduced food intake and may be involved in lipid utilization during lipolysis in MAC16-induced cachexia.
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PMID:Increased gene expression of brown fat uncoupling protein (UCP)1 and skeletal muscle UCP2 and UCP3 in MAC16-induced cancer cachexia. 1081 Nov 17

Fibroblast growth factor 21 (FGF21) is a key regulator of metabolism under conditions of stress such as starvation, obesity, and hypothermia. Rapid induction of FGF21 is also observed in experimental models of pancreatitis, and FGF21 reduces tissue damage observed in these models, suggesting a nonmetabolic function. Pancreatitis is a debilitating disease with significant morbidity that greatly increases the risk of pancreatic ductal adenocarcinoma. The goals of this study were to examine the regulation and function of FGF21 in acinar cell injury, specifically in a mouse model of pancreatic injury (Mist1(-/-)). Mist1(-/-) mice exhibit acinar cell disorganization, decreased acinar cell communication and exocytosis, and increased sensitivity to cerulein-induced pancreatitis (CIP). Examination of Fgf21 expression in Mist1(-/-) mice by qRT-PCR, Northern blot, and Western blot analyses showed a marked decrease in pancreatic Fgf21 expression before and after induction of CIP compared with C57Bl/6 mice. To determine whether the loss of FGF21 accounted for the Mist1(-/-) phenotypes, we generated Mist1(-/-) mice overexpressing human FGF21 from the ApoE promoter (Mist1(-/-)ApoE-FGF21). Reexpression of FGF21 partially mitigated pancreatic damage in Mist1(-/-) tissue based on reduced intrapancreatic enzyme activation, reduced expression of genes involved in fibrosis, and restored cell-cell junctions. Interestingly, alteration of Fgf21 expression in Mist1(-/-) tissue was not simply due to a loss of direct transcriptional regulation by MIST1. Chromatin immunopreciptation indicated that the loss of Fgf21 in the Mist1(-/-) pancreas is due, in part, to epigenetic silencing. Thus, our studies identify a new role for FGF21 in reducing acinar cell injury and uncover a novel mechanism for regulating Fgf21 gene expression.
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PMID:Silencing of the Fibroblast growth factor 21 gene is an underlying cause of acinar cell injury in mice lacking MIST1. 2454 97