Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Asparate and alanine aminotransferase activity is approximately the same in different lobes of cerebral hemispheres of people with an uninjured central nervous system. The maximal activity of lactate, malate and succinate dehydrogenase is in the temporal lobes and thalami, the minimal one is in the corpus callosum. The activity of aminotransferases in the brain tumour lowers: in the dedifferentiated tumour the asparate aminotransferase shows a 23-24% decrease; in the case of the meningeal sarcoma it is 2.5 times as low: the activity of alaine aminogransferase is almost 10 times as low. The activity of malate dehydrogenase decreases in the neuroectodermal tumours and sharply (almost twice) in multiform glioblastoma. In the dedifferentiated meningiomas the activity of all the dehydrogenases is increased.
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PMID:[Aminotransferase and dehydrogenase activity in human brain tumours]. 22 26

Among 2175 patients seen over the last three years in a non-specialized department of internal medicine with no intensive care unit, 100 had supranormal serum lactic dehydrogenase activities. These patients' case-reports have been analyzed. Nearly half the patients (47/100) had a malignant disease (cancer or hemopathy). Among the remaining patients, 19 had a hepatic disorder (alcohol hepatitis in 10, viral hepatitis in 8, and isoniazide hepatitis in 1), 7 had a heart disease (heart failure with hepatomegaly in 5, myocardial infarction in 2), and 27 had various other conditions (including hemolysis in 6 and polymyositis en 3). The value of serum LDH assay is obvious in situations other than acute conditions such as myocardial infarction of pulmonary embolism; these are better known and have not been studied here as their prevalence was low among the patients enlisted in our study. In comparison to other enzymes (alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGT), transaminases (GOT, GPT) that were also routinely assayed in our patients, abnormal serum LDH activities are much less common and their significance is quite different. An increase in serum and their significance is quite different. An increase in serum LDH activity indicates a serious condition, often with a fatal outcome. The "various other conditions" group includes patients with hemolysis, hepatitis and myositis; the other patients in this group either had severe infectious diseases or died suddenly in the first few days of their hospitalization before diagnosis had been established. Each etiologic group has been analyzed to asses the characteristics of patients with increased LDH activity according to each etiology. Analysis of coincident abnormalities of the other enzymes listed above shows marked differences between etiologic groups; diagnostic accuracy can thus be enhanced in certain conditions. Most patients with malignancies had poorly differentiated tumors, with metastases: 28 had an epithelial tumor, with hepatic and/or bone metastases in 23 cases, 5 had cancer of the liver, 10 had a malignant hemopathy (2 lymphomas, 5 myeloproliferative syndromes, 3 acute leukemias), and 4 had a sarcoma. Cancer of the lung is the most common malignancy (10 cases) and may be responsible for increased serum LDH activity even in patients without metastases. Serum LDH assay is of value for monitoring the course in patients with initially increased activities as it falls under effective therapy and rises during exacerbations.
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PMID:[Value and diagnostic significance of serum lactic dehydrogenase in internal medicine (author's transl)]. 628 24

The in vitro antiproliferative action of pineal indoles on several tumor cell lines including melanoma (B16), sarcoma (S180), macrophage-like cell line (PU5), fibroblasts (3T3), and choriocarcinoma (JAr) was examined by measuring the incorporation of 3H-thymidine by the tumor cells, and, in the case of melanoma cells, by also measuring the incorporation of 3H-leucine and 3H-uridine. Uptake of crystal violet was used to assess the viability of the tumor cells. The order of inhibitory potency of the indoles was found to be methoxytryptamine > melatonin, methoxytryptophol, hydroxytryptophol, and methoxyindoleacetic acid > serotonin and hydroxyindoleacetic acid. The possibility of an adverse effect of the indoles on the viability of normal cells was also investigated by employing a primary culture of rat hepatocytes. The release of glutamate-oxaloacetate transaminase by hepatocytes was not affected by the indoles, although the release of glutamate-pyruvate transaminase was increased to a small extent and the uptake of crystal violet was slightly inhibited.
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PMID:Antiproliferative effect of pineal indoles on cultured tumor cell lines. 848 4

We report on a 43-year-old man with a primary sarcoma of the liver. The patient was admitted to the hospital for evaluation of dyspnea, abdominal pain in the right upper quadrant, diarrhea, and fever. Physical examination revealed hepatomegaly. Increased laboratory values were found for gamma-GT, LDH, CA 125, and NSE, but not for aspartate and alanine aminotransferase. Computed tomography presented a tumor in the right lobe of the liver. Venous cavography revealed a caval tumor thrombus reaching up to the right atrium. Major liver resection combined with replacement of the vena cava inferior was proposed, but before operation the patient complained about shortness of breath. Spontaneous fragmentation of the tumor thrombus with consecutive embolization of the lungs was suspected. Despite lysis therapy the patient died because of right ventricular failure. Autopsy revealed a tumor measuring 8 cm in diameter, which was located in the right lobe of the liver and invaded the inferior vena cava. Because of multiple tumor aggregates seen in the left and right main pulmonary arteries acute tumor embolization of the lungs was regarded as cause of death. Histologically the tumor was composed of bizarre giant cells surrounded by irregular spindle cells. The positive immunoreactivity pattern of the tumor cells for vimentin, lysozym, and CD68 justified the diagnosis of a malignant fibrous histocytoma (MFH) of the liver.
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PMID:[Malignant fibrous histiocytoma of the liver]. 1076 47

Oxymetholone is a synthetic anabolic steroid used to treat a variety of conditions, including hypogonadism and delayed puberty. It is also used to correct hereditary angioneurotic edema, manage carcinoma of the breast, promote a positive nitrogen balance following injury or surgery, and stimulate erythropoiesis. Considerable amounts of androgens are consumed by athletes in attempts to improve athletic performance. The National Institute of Environmental Health Sciences and the National Cancer Institute nominated oxymetholone for study based on its extensive illicit pharmaceutical use and the limited evidence that it is a potential human carcinogen. Male and female F344/N rats received oxymetholone (greater than 99% pure) in 0.5% methylcellulose by gavage for 16 days, 14 weeks, or 2 years, and male and female B6C3F1 mice received oxymetholone in 0.5% methylcellulose by gavage for 16 days or 14 weeks. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse peripheral blood erythrocytes. 16-DAY STUDY IN RATS: Groups of five male and five female F344/N rats were administered 0, 160, 315, 625, 1,250, or 2,500 mg oxymetholone/kg body weight in 0.5% methylcellulose by gavage for 16 days. All male rats survived to the end of the study; one 2,500 mg/kg female died on day 14. The mean body weights of all dosed groups of males were significantly less than those of the vehicle controls, while those of 160 and 315 mg/kg females were significantly greater. 16-DAY STUDY IN MICE: Groups of five male and five female B6C3F1 mice were administered 0, 320, 630, 1,250, 2,500, or 5,000 mg/kg in 0.5% methylcellulose by gavage for 16 days. All mice survived to the end of the study. The final mean body weights of all dosed groups of females were greater than those of the vehicle controls. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were administered 0, 80, 160, 315, 625, or 1,250 mg/kg in 0.5% methylcellulose by gavage for 14 weeks. One male rat each in the 625 and 1,250 mg/kg groups died before the end of the study. The mean body weights of males administered 160 mg/kg or greater were significantly less than those of the vehicle controls; in contrast, the mean body weights of all dosed groups of females were significantly greater. A dose-related erythrocytosis, evidenced by increases in erythrocyte counts, total hemoglobin concentrations, and hematocrit values, occurred in dosed groups of rats at week 14. A dose-related hypocholesterolemia occurred at all time points in all dosed groups of rats. Dose- and time-related decreases in 5 -nucleotidase activity occurred in treated rats. There was a transient, treatment-related increase in the activity of alanine aminotransferase in males and females. For male rats administered oxymetholone, cauda epididymis, epididymis, and testis weights and spermatid counts and total spermatid heads per testis were significantly less than those of the vehicle controls, and total spermatid heads per gram testis were significantly greater. Female rats in the 80 mg/kg group spent more time in diestrus and less time in estrus than did the vehicle controls. Kidney weights of males and females and liver and uterus weights of females were increased compared to vehicle controls in rats that received 315 mg/kg or greater; thymus weights of males and females and sartorius muscle and testis weights of males were less. Compared to the vehicle controls, rats that received 160 mg/kg or greater had increased incidences of nonneoplastic lesions of the kidney and mammary gland, and the incidences of hydrometra of the uterus and dysgenesis of the ovary were increased in dosed groups of females. Female rats administered 315 mg/kg or greater had increased incidences of cytoplasmic vacuolization of the adrenal gland and myocardial degeneration of the heart. The severities of these lesions generally increased with increasing dose. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were administered 0, 160, 320, 630, 1,250, or 2,500 mg/kged 0, 160, 320, 630, 1,250, or 2,500 mg/kg in 0.5% methylcellulose by gavage for 14 weeks. All mice administered oxymetholone survived until the end of the study. The mean body weights of all dosed groups were similar to those of the vehicle controls. The percentages of motile sperm in 1,250 and 2,500 mg/kg males were significantly less than those of the vehicle controls. The estrous cycle lengths of 630, 1,250, and 2,500 mg/kg females were significantly longer, and females in the 1,250 and 2,500 mg/kg groups spent more time in diestrus and less time in estrus. Kidney and liver weights of males and females were greater and thymus weights of females were less than those of the vehicle controls. All dosed females had hyperplasia of the clitoral gland, metaplasia of the parietal layer epithelium of the Bowman's capsule in the kidney, and cytoplasmic alteration of the submandibular gland; these lesions were not observed in the vehicle control group. The incidences of hypoplasia of the ovary in 320 mg/kg or greater females and of parotid gland atrophy in 1,250 and 2,500 mg/kg females were increased. The results of the 14-week oral gavage studies were generally similar in rats and mice, but rats were much more sensitive to oxymetholone. Because it was not likely that a long-term mouse study would provide significant additional toxicity information, the NTP decided to conduct a 2-year study in rats only. 2-YEAR STUDY IN RATS: Groups of 90 male F344/N rats were administered 0, 3, 30, or 150 mg/kg in 0.5% methylcellulose by gavage, and 90 female F344/N rats were administered 0, 3, 30, or 100 mg/kg in 0.5% methylcellulose by gavage for up to 104 weeks, with 9 or 10 rats per group evaluated at 3, 6, 12, or 18 months. Survival and Body Weights: Survival of all dosed groups was similar to that of the vehicle controls. The mean body weights of the 30 mg/kg male group were generally within 10% of those of the vehicle controls, but those of the 150 mg/kg group were markedly decreased. Mean body weights of 3 and 30 mg/kg females were generally greater than those of the vehicle controls throughout the study. Determinations of Oxymetholone in Plasma: The concentrations of oxymetholone in plasma of male and female rats receiving 3 mg/kg for 6, 12, or 18 months were generally below the limits of quantification; therefore, all plasma concentrations in the 3 mg/kg group are considered to be estimates (Table 8). The plasma concentrations at 30 mg/kg were approximately one order of magnitude greater than those of the estimates for males and females receiving 3 mg/kg. There were no dose-related differences in plasma concentrations in female rats receiving 30 or 100 mg/kg, but plasma concentrations in males were significantly elevated in the 150 mg/kg group. It was concluded that oxymetholone kinetics was saturated at 30 mg/kg in female but not male rats. Pathology Findings: A wide spectrum of neoplasms and nonneoplastic lesions was seen in rats administered oxymetholone for 2 years. The incidences of hepatocellular adenoma and hepatocellular adenoma or carcinoma (combined) were significantly increased in 100 mg/kg females as were the incidences of basophilic and clear cell foci in 150 mg/kg males and 100 mg/kg females compared to vehicle controls. The incidences of alveolar/bronchiolar adenoma and adenoma or carcinoma (combined) were significantly increased in 30 mg/kg females. The incidences of mineralization in the lung of 150 mg/kg males and 30 and 100 mg/kg females were significantly increased. The incidence of keratoacanthoma was increased in 30 mg/kg females, and the combined incidence of squamous cell papilloma, keratoacanthoma, basal cell adenoma, squamous cell carcinoma, or carcinoma of the sweat gland was significantly increased in 100 mg/kg females. The incidences of subcutaneous tissue fibroma and fibroma or fibrosarcoma (combined) were significantly increased in 3 mg/kg males. At 2 years, the incidences of benign pheochromocytoma and benign or malignant pheochromocytoma (combined) of the adrenal gland in 150 mg/kg males and medullary hyperplasia in 100 mg/kg females were significantly increased. The incidences of cytoplasmic vacuolization of adrenal cortical cells were significantly increased in 30 and 150 mg/kg males at 18 months and 2 years and in 100 mg/kg females beginning at 12 months and in 30 mg/kg females at 2 years. The incidences of renal tubule adenoma in 3 and 150 mg/kg males were slightly increased. An extended evaluation of the kidney was conducted, and additional incidences of renal tubule adenoma were observed in step sections in vehicle control and dosed male rats. The combined single- and step-section incidence of renal tubule adenoma was significantly increased in 3 mg/kg males. The incidences of nephropathy were significantly increased in 30 and 150 mg/kg males at 2 years and in 100 mg/kg females beginning at 3 months. The severities of nephropathy were significantly increased in dosed groups of males at 2 years and in 100 mg/kg females at 18 months and 2 years. The incidences of mineralization of the kidney were significantly increased in 150 mg/kg males at all time points. The incidences of ovarian dysgenesis were significantly increased in 100 mg/kg females beginning at 3 months and in 30 mg/kg females beginning at 6 months, and severities increased with increasing dose. The incidences of chronic myocardial degeneration (cardiomyopathy) were significantly increased in 100 mg/kg females at 6 months and 2 years and the severity was increased at 2 years. The incidences of lobular hyperplasia were increased in 150 mg/kg males at 18 months and 2 years and in 30 and 100 mg/kg females at all time points. The incidences of seminiferous tubule degeneration were significantly increased in 30 and 150 mg/kg males at 2 years, and the incidences of mineralization of the testis were increased in 150 mg/kg males at 12 months and in 30 mg/kg males at 18 months and at 2 years. Decreased incidences of neoplasms occurred in male and female rats. The incidence of uterine stromal polyp or stromal sarcoma (combined) was significantly decreased in 100 mg/kg females at 2 years. The incidences of mammary gland fibroadenoma and fibroadenoma or carcinoma (combined) were significantly decreased in all dosed groups of females. The incidences of pituitary gland pars distalis adenoma were significantly decreased in 30 and 100 mg/kg females at 2 years. The incidences of testicular interstitial cell adenoma were significantly decreased in 30 and 150 mg/kg males at 18 months and in all dosed groups at 12 months and 2 years. The incidences of mononuclear cell leukemia were significantly decreased in 30 and 150 mg/kg males and 100 mg/kg females at 2 years. GENETIC TOXICOLOGY: Oxymetholone was not mutagenic in S. typhimurium strain TA97, TA98, TA100, or TA1535, with or without S9 metabolic activation. It did not induce chromosomal aberrations in cultured Chinese hamster ovary cells, with or without S9, and no increase in the frequency of micronucleated normochromatic erythrocytes was noted in peripheral blood samples from male or female mice treated for 14 weeks with oxymetholone. CONCLUSIONS: Under the conditions of this 2-year gavage study, there was equivocal evidence of carcinogenic activity of oxymetholone in male F344/N rats based on increased incidences of subcutaneous tissue fibromas and fibromas or fibrosarcomas (combined) of the skin, variably increased incidences of benign and benign or malignant pheochromocytomas (combined) of the adrenal gland, and increased incidences of renal tubule adenomas. There was clear evidence of carcinogenic activity of oxymetholone in female F344/N rats based on increased incidences of hepatocellular neoplasms. Increased incidences of alveolar/bronchiolar neoplasms and skin neoplasms in female rats were also related to oxymetholone administration. Decreased incidences of alveolar/bronchiolar neoplasms and testicular interstitial cell adenomas in males; uterine stromal polyps or stromal sarcomas (combined), mammary gland neoplasms, and pituitary gland pars distalis adenomas in females; and mononuclear cell leukemia in males and females were related to oxymetholone administration. In addition, gavage administration of oxymetholone to male and female F344/N rats resulted in a spectrum of nonneoplastic effects frequently reported with administration of synthetic anabolic androgens. Synonyms: Adroidin; anadroyd; anasteron; anasteronal; anasterone; androstan-3-one, androstano[2,3-c]1,2,5-oxadiazol-17-ol, 17-methyl-, (5-a,17-b)-; becorel; 4,5-dihydro-2-hydroxymethylene-17-a-methyltestosterone; dynasten; HMD; 17b-hydroxy-2- (hydroxymethyl)-17-methyl-5-a-androstan-3-one; 17-hydroxy-2-(hydroxymethylene)-17-methyl-(5-a,17-b)-; 17-hydroxy- 2-(hydroxymethylene)-17-methyl-5-a-17-b-androst-3-one; 17b-hydroxy-2-(hydroxymethylene)-17-a-methyl-5-a-androstan-3-one; 17b-hydroxy-2-(hydroxymethylene)-17-methyl-5a-androstan-3-one; 17-hydroxy-2-(hydroxymethylene)-17-methyl-5-a-17- b-androstan-3-one; 17b-hydroxy-2-hydroxymethylene-17a-methyl-3-androstanone; 2-hydroxymethylene-17-a-methyl-5- a-androstan-17-b-ol-3-one; 2-hydroxymethylene-17a-methyl dihydrotestosterone; 2-hydroxymethylene-17-a-methyl-17-b- hydroxy-3-androstanone; methabol; 17a-methyl-2-hydroxymethylene-17-hydroxy-5-a-androstan-3-one; oximetholonum; oximetolona; oxitosona-50; oxymethenolone; roboral; zenalosyn Trade names: Adroyd; Anadrol; Anapolon; Anapolon 50; Nastenon; Pardroyd; Pavisoid; Plenastril; Protanabol; Synasteron
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PMID:NTP Toxicology and Carcinogenesis Studies of Oxymetholone (CAS NO. 434-07-1) in F344/N Rats and Toxicology Studies of Oxymetholone in B6C3F1 Mice (Gavage Studies). 1257 78

TS-1 contains tegaful (FT), 5-chloro-2,4-dihydroxypyridine (CDHP; an inhibitor of 5-fluorouracil (5-FU) degradation) and potassium oxonate (Oxo; an inhibitor of 5-FU assimilation mainly in the digestive tract) in a molar ratio of 1:0.4:1. We evaluated the combination of TS-1 and low-dose cisplatin on mouse sarcoma. Male ddy strain mice at 6 weeks of age were s.c. transplanted with 5 x 106 sarcoma-180 (S-1800) cells and divided into groups of seven animals each: Group A, no treatment; Group B, 5-FU alone by continuous i.p. infusion of 10 mg/kg with a minipump (Alzet); Group C, TS-1 10 mg/kg p.o. alone; Group D, cisplatin 0.2 mg/kg i.p. alone; Group E, B+D; Group F, C+D. Treatment was given for 5 days. Antitumor activity was evaluated on the basis of the tumor weight on day 8, and white blood cell count, red blood cell count, platelet count, BUN, GOT and GPT were determined to detect adverse effects. Tumor weights (g, mean+/-SD) were 0.54+/-0.15 in Group A, 0.52+/-0.17 in Group B, 0.34+/-0.05 in Group C, 0.46+/-0.12 in Group D, 0.34+/-0.07 in Group E and 0.16+/-0.03 in Group F. There were no noticeable adverse effects. The combined TS-1+cisplatin regimen showed considerably enhanced antitumor activities since sarcomas were significantly (p<0.05) decreased as compared with tissue. Mean AUC(0-12) (ng/ml.h) estimated in the groups receiving 5-FU+cisplatin or TS-1 alone was measured to calculate AUC(0-12) by the trapezoidal rule. 5-FU concentrations in blood and tumor from blood concentration data were 435 in Group B, 2651 in Group C, 343 in Group E and 1538 in Group F, while mean AUC(0-12) (ng/g.h) estimated from tumor tissue concentration data were 345 in Group B, 3548 in Group C, 324 in Group E and 2020 in Group F. Cisplatin acted as a modulator of 5-FU, suggesting clinical benefits of the combination of TS-1 and low-dose daily cisplatin.
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PMID:Effect of combination of TS-1 and low-dose cisplatin on sarcoma-180 mouse sarcoma. 1285 91

The beta-carotene-yielding microalga, Dunaliella salina (Dunal) Teod. maintained in De Walne's medium was harvested and lyophilized. Fibrosarcoma was induced in rats by 20-methylcholanthrene. 0.5 g and 1.0 g of lyophilized D. salina powder was administered to the rats orally through carboxy methyl cellulose. Cisplatin was administered along with vitamin E to compare the protective effect of D. salina against fibrosarcoma. Administration of D. salina decreased the levels of cholesterol and lactate dehydrogenase as well as the activities of catalase, superoxide dismutase, serum aspartate aminotransaminase, serum alanine aminotransferase, when compared to control. A significant reduction in the levels of hepatic and renal RNA and DNA was observed in the sarcoma rats when treated with D. salina powder. Histopathological studies of tumor tissues showed regenerative and regressive changes. beta-carotene globules isolated from the powder of Dunaliella salina confirmed the presence of 9-cis-beta-carotene and all-trans-beta-carotene.
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PMID:Protective effect of Dunaliella salina (Volvocales, Chlorophyta) against experimentally induced fibrosarcoma on wistar rats. 1671 16

The spectrum of lipomatous tumors differs in the adult and pediatric populations, with liposarcoma being rare in children. Nearly 10% of individuals with Li-Fraumeni syndrome develop sarcomas in the first 2 decades of life; however, the frequency of sarcoma types and subtypes in this syndrome is unknown. Two atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDLS) were identified in the pathology files of our institution in young children from "classical" Li-Fraumeni and Li-Fraumeni variant kindreds with a known germline TP53 mutation (Y220C) in one of the families. The patients were 5 and 6 years of age and the ALT/WDLSs were the first expression of the syndrome. The tumors had a high degree of cellular atypia and differed from sporadic ALT/WDLS by strong nuclear immunoreactivity for p53 and absent mdm2 expression. This is the first report of 2 ALT/WDLSs presenting in children before 10 years of age, both in association with Li-Fraumeni syndrome/variant. ALT/WDLS in a young child should raise the possibility of a cancer predisposition syndrome and, in this setting, the p53(+)/mdm2(-) immunophenotype might be characteristic. Recognition of this lesion and its association is important for early diagnosis and subsequent tumor surveillance in the proband and affected family members.
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PMID:p53+/mdm2- atypical lipomatous tumor/well-differentiated liposarcoma in young children: an early expression of Li-Fraumeni syndrome. 2002 12

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of trabectedin for the treatment of advanced metastatic soft tissue sarcoma, in accordance with the licensed indication, based on the evidence submission from the manufacturer to NICE as part of the single technology appraisal (STA) process. The outcomes stated in the manufacturer's definition of the decision problem were overall survival (OS), progression-free survival (PFS), response rates, adverse effects of treatment, health-related quality of life, and cost per quality-adjusted life-year (QALY) gained. The clinical evidence was derived from one randomised controlled trial (RCT), in which the licensed dose of trabectedin was compared with a different dose of trabectedin, and three phase II studies. In the RCT, the median OS was 13.9 months for the licensed dose of trabectedin, which was not significantly different from that for the comparator dose of trabectedin, which was 11.8 months. From the phase II uncontrolled trials, median OS was reported as 9.2 or 12.8 months. The RCT reported significantly superior PFS for the licensed dose of trabectedin (median 3.3 months) over the comparator trabectedin dose (median 2.3 months). One phase II uncontrolled trial reported median PFS as 1.9 months in the licensed dose of trabectedin. The RCT reported PFS rates at 6 months were 35.5% for the licensed dose of trabectedin, and 27.5% for the comparator dose of trabectedin. From the phase II uncontrolled trials, PFS rates at 6 months were 24.4% or 29%. For the RCT, deaths attributed to trabectedin occurred in 3.1% of the licensed dose, and 2.3% of the comparator group. The most common severe adverse events were neutropenia, although with a low rate of febrile neutropenia, thrombocytopenia, and aspartate aminotransferase and alanine aminotransferase elevation, although these were reported to be non-cumulative and reversible. Following dialogue iterations with the ERG team, the manufacturer revised the model twice. However, despite revisions, errors/inconsistencies were found in the latest version of the model and were corrected by the ERG (only for the base case). In the latest manufacturer's submission, the cost per QALY gained of trabectedin compared with best supportive care (BSC) was estimated to be 56,985 pounds for the base case using effectiveness from the STS (Soft Tissue Sarcomas)-201 trial for trabectedin and a pool analysis of the European Organisation for Research and Treatment of Cancer data set for BSC. This analysis was constrained to patients with L-sarcomas only. When the joint uncertainty between parameters was considered, the cost-effectiveness acceptability curve showed that trabectedin has a very low probability of being cost-effective at a threshold of 30,000 pounds per QALY gained compared with BSC for any scenario. The guidance has yet to be issued by NICE.
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PMID:Trabectedin for the treatment of advanced metastatic soft tissue sarcoma. 2050 5

Latex of Calotropis procera has been described as a relevant source of pharmacologically active proteins, including proteins with anticancer activity. A previous in vitro study of laticifer proteins (LP) from C. procera reported that they had selective cytotoxic effects on human cancer cell lines. The aim of this study was to determine the effects of LP in vivo using mice transplanted with sarcoma 180. Biochemical, hematological, histopathological, and morphological analyses were performed in animals given LP by oral or intraperitoneal routes. LP significantly reduced tumor growth (51.83%) and augmented the survival time of animals for up to 4 days. Tumor growth inhibitory activity was lost when LP fraction was submitted to proteolysis, acidic treatment, or pretreated with iodoacetamide. However, LP retained its inhibitory activities on sarcoma 180 growth after heat treatment. Thus, it seems that heat-stable proteins are involved in tumor suppression. Biochemical parameters, such as the enzymatic activity of aspartate aminotransferase and alanine aminotransferase and urea content in serum were not affected in treated mice. It is worth noting that LP completely eliminated the 5-FU-induced depletion of leukocytes in mice even when given orally. The active proteins were recovered in a single fraction by ion exchange chromatography and still exhibited anticancer activity. This study confirms the pharmacological potential of proteins from the latex of C. procera to control sarcoma cell proliferation.
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PMID:In vivo growth inhibition of sarcoma 180 by latex proteins from Calotropis procera. 2051 95


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