Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metastases of breast cancer are a major cause of treatment failure. To evaluate the therapeutic efficacy of suicide gene therapy in metastatic breast cancer, we used the herpes simplex virus thymidine kinase (HSV-tk) gene followed by ganciclovir (GCV) administration to treat breast cancer, generated by an adenocarcinoma cell line MOD in syngeneic mice. The bystander effect of HSV-tk + GCV on tumor cell killing was illustrated by demonstrating complete regression of subcutaneous tumors consisting of 90% parental tumor cells and 10% HSV-tk transformed tumor cells. To establish a model of breast cancer metastases in the liver, tumors were generated by intra-hepatic implantation of MOD cells in syngeneic animals. Two weeks after tumor cell implantation, replication defective adenoviral vectors expressing HSV-tk (ADV.tk), or beta-galactosidease (ADV. beta-Gal) were injected intratumorally, followed by buffer or GCV administration. Treatment with ADV.tk + GCV resulted in significant regression of tumor (P < .001), as assessed by computerized morphometric analysis of residual tumor. This was reflected as a significant prolongation of survival in treated animals (P < .001). These results demonstrate that ADV-mediated suicide gene therapy in vivo can be incorporated in a comprehensive treatment strategy for liver metastases of breast cancer.
Cancer Gene Ther
PMID:Adenoviral-mediated suicide gene therapy for hepatic metastases of breast cancer. 889 53

We investigated the association of non-insulin-dependent (Type 2) diabetes mellitus and depression symptoms in a representative community-dwelling elderly population independently of other conditions such as gender, age, status, disability, cognitive impairment and a number of chronic medical conditions such as chronic obstructive lung disease, degenerative joint disease, heart disease, cirrhosis of the liver, cholelithiasis, peptic ulcer and kidney stones. A total of 1339 elderly subjects living in southern Italy were randomly selected from electoral rolls and evaluated. All subjects were tested by the Geriatric Depression Scale to detect depression, the Mini-Mental State Examination to study cognitive function and the Activity Daily Living Index to evaluate disability. Non-insulin-dependent diabetes mellitus affected 14.7% of our sample. Depression was more prevalent in women over 75 years of age than in younger women (15.9 vs 8.1%, p < 0.001). In multiple linear regression analysis, diabetes mellitus was found to be significantly associated with depression independently of age, gender, loneliness, cognitive impairment, chronic obstructive lung disease, degenerative joint disease, heart diseases, cancer, kidney disease, cirrhosis of the liver and cholelithiasis. It is concluded that non-insulin-dependent diabetes mellitus is significantly associated with depression in the elderly, which may have clinical implications for the achievement of sufficient blood glucose control.
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PMID:Non-insulin-dependent diabetes mellitus is associated with a greater prevalence of depression in the elderly. The Osservatorio Geriatrico of Campania Region Group. 889 92

A retrospective analysis of presenting clinical symptoms was performed in 584 patients who were operated on at a surgical university hospital during the last two decades because of carcinoma of the exocrine pancreas or the periampullary region. Patients with carcinoma of the pancreatic head primarily presented with jaundice, those with localisation of the tumour in the pancreatic body and tail with pain. In contrast to the common opinion ampullary carcinomas produced jaundice only in 70% of patients. In our series ampullary carcinomas did not present clinical symptoms at an earlier stage than pancreatic head tumours as it is commonly speculated. At the time of surgery carcinomas of the ampulla and the pancreatic head were found to be in equivalent stages. A NIDDM was significantly associated with carcinomas of the pancreatic body. Diabetes mellitus is more likely a result of carcinomatous destruction of the pancreas rather than a precancerosis. Almost all periampullary tumours could be resected while the resection rate was only 41% in case of exocrine pancreatic tumours. Pancreatic carcinomas which presented with upper abdominal pain, back pain, weight loss, inappentence, and diarrhoea were significantly more often irresectable. Jaundice, however, was more frequent in patients with resectable tumours. Back pain is probably caused by infiltration of the retroperitoneum and the aortic plexus and thus represents the clinical sign of an often occult retroperitoneal tumour spread. The precise knowledge of the presenting symptoms in cancer of the pancreas and ampulla is of primary importance because diagnostic procedures only commences after onset of symptoms and no possibilities of an effective screening can be envisaged.
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PMID:[Clinical symptoms in cancer of the exocrine pancreas in peri-ampullary region. Old and new knowledge from the analysis of a surgical patient sample]. 896 95

A 15 year follow-up study of diabetic patients was performed in Osaka, Japan. The subjects studied were 1939 patients with non-insulin dependent diabetes mellitus (NIDDM), of whom 1000 (51.5%) were alive, 880 (45.4%) had died and 59 (3.0%) were untraceable at the end of 1993. The mortality rate per 1000 person-years of the subjects increased from 28.94 in 1960-1984 to 35.74 in 1985-1993, but the ratio of numbers of observed to expected deaths (O/E ratio) declined from 1.77 to 1.52 for the corresponding periods, suggesting an improvement in the prognosis for diabetic patients, with the exception of patients 65 years or over at the time of entry. Cerebro-cardiovascular and renal diseases were major causes of death, accounting for 48.4% of all deaths. In particular, disease of the heart was the cause of death in 20.5% of all deaths, cerebrovascular disease in 14.5% and renal disease in 12.0%. The O/E ratio was 11.30 for renal disease, which was remarkably high. The O/E ratios were 1.48 for malignant neoplasms, 3.02 for cancer of the liver and 2.15 for cancer of the pancreas. In the subjects less than 65 years of age at entry, a significant decrease in the O/E ratio for overall deaths, malignant neoplasms, disease of the heart, cerebrovascular disease and renal disease was observed, but no notable difference in the O/E ratio for ischemic heart disease was found between the periods 1960-1984 and 1985-1993. By contrast, in the case of subjects 65 years or more at entry, the O/E ratios for overall deaths, malignant neoplasms, disease of the heart, ischemic heart disease and cerebrovascular disease increased markedly in the later period, while there was a considerable decline in renal disease indicated during this period. The analysis suggested a structural change in causes of death of Japanese diabetic patients in recent years, with a relative increase in ischemic heart disease and a relative decrease in renal disease.
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PMID:A 15 year follow-up study of patients with non-insulin dependent diabetes mellitus (NIDDM) in Osaka, Japan. Long-term prognosis and causes of death. 896 90

Insulin resistance is a precursor to and primary cause of Type 2 diabetes mellitus. In addition, insulin resistance is associated with other chronic diseases, including gestational diabetes, cardiovascular disease, and cancer. Resistance to insulin's effects on carbohydrate metabolism include diminished actions of insulin to enhance glucose uptake and suppress endogenous glucose production. This chapter introduces new concepts related to the mechanism by which insulin stimulates glucose utilization in vivo and demonstrates that these processes are mechanistically linked to glucose production. Insulin acts rapidly in vitro to stimulate glucose uptake; in contrast, its effects in vivo are relatively slow in the conscious animal or human subject. The explanation for this difference between in vitro and in vivo dynamics is the delay associated with insulin transport across capillary endothelium of insulin-sensitive tissues (primarily muscle). Also, interstitial insulin is attenuated in concentration compared to plasma insulin at basal as well as under hyperinsulinemic conditions (plasma:interstitial ratio, 3:2). The sluggishness of insulin action and the attenuation in insulin concentration can be explained by a model in which transendothelial insulin transport is restricted and interstitial insulin binds to insulin-sensitive cells, where the hormone is internalized and degraded. Whether insulin transport occurs by a hormone-specific mechanism (i.e., via receptors on endothelial cells) was tested by comparing transport at physiological with pharmacological insulin concentrations-evidence supports a nonspecific mechanism of transport across endothelium (i.e., diffusion or transcytosis). Transendothelial transport alters the in vivo patterns of insulin signaling-biphasic plasma insulin after glucose injection is reflected in a simple, rapid increase in interstitial insulin to an elevated concentration. The time course of insulin's effect to suppress endogenous glucose output is a mirror image of its effect to enhance glucose uptake; however, there is no transendothelial barrier to insulin action at the liver. The similarity in action dynamics at periphery and liver was explained by a mechanism in which insulin crosses into peripheral tissue and alters a "second (blood-borne) signal" that, in turn, suppresses liver glucose production. Of various possible alternative candidates for the second signal, declining plasma free fatty acids appear to signal suppression of glucose production. We have proposed the "single gateway hypothesis" to explain insulin's action on carbohydrate metabolism in vivo: insulin crosses the endothelial boundary in skeletal muscle (to stimulate glucose disposal) and traverses the endothelial barrier in adipose tissue to suppress lipolysis. The declining free fatty acids are proposed to be a major factor in the insulin-mediated decline in glucose output. This mechanism can be contrasted with the classical concept that portal insulin controls the liver directly. Recent evidence supports the concept that, under normal levels of glucagonemia, less than 25% of the suppression of hepatic glucose output by insulin is due to a direct effect of insulin via the portal vein and that most of the effect (approximately 75%) is explained by the indirect single gateway mechanism. These results raise the question of whether hepatic insulin resistance in Type 2 diabetes can be explained by insulin resistance at the adipocyte, which causes a failure of reduction of FFA by insulin, leading to overproduction of glucose by the liver. The possible role of the single gateway mechanism in diabetes is under investigation.
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PMID:New concepts in extracellular signaling for insulin action: the single gateway hypothesis. 923 59

Recent sibling-pair linkage analyses have indicated possible linkage of noninsulin dependent diabetes mellitus (NIDDM) with a number of markers on the long arm of chromosome 7. A coincidental and recent discovery is that specific genetic anomalies identified on chromosome 7 in uterine leiomyoma tumor cells in many cases correspond, cytogenetically, to the same region where genetic linkage to insulin resistance has been identified. In the present study, 15 closely spaced microsatellite markers were used to finely map deletion breakpoints and to test for allelic loss of 7q markers in 12 uterine leiomyoma tumor samples with cytogenetically defined deletions. Of the 9 informative tumor samples, three exhibited breakpoints in the same region where genetic linkage to insulin resistance has been identified (between PON and UT901). Because breakpoints in neoplasias often occur within or adjacent to expressed sequences, these breakpoints may provide a molecular tool to aid in the identification of candidate genes for insulin resistance.
Cancer Genet Cytogenet 1998 Jan 15
PMID:Molecular analysis of chromosome 7q21.3 in uterine leiomyoma: analysis using markers with linkage to insulin resistance. 942 63

Turner syndrome afflicts approximately 50 per 100,000 females and is characterized by retarded growth, gonadal dysgenesis, and infertility. Much attention has been focused on growth and growth promoting therapies, while less is known about the natural course of the syndrome, especially in adulthood. We undertook this study to assess the incidence of diseases relevant in the study of Turner syndrome. The study period was from January 1, 1984 to December 31, 1993, and the study base was all women living in Denmark during the study period. We used data from the Danish Cytogenetic Central Register and the Danish National Registry of Patients to assess morbidity. This study supports several earlier studies reporting increased morbidity and confirms results of a recent study on cancer in Turner syndrome. Women with Turner syndrome seem to have an increased incidence of fractures, osteoporotic fractures in adulthood, and non-osteoporotic fractures in childhood. Furthermore, diabetes mellitus, both NIDDM and IDDM, was found with a markedly increased incidence in Turner syndrome, as well as ischemic heart disease, hypertension, and stroke. The risk of cancer, except cancer of the large bowel, does not seem to be elevated in Turner syndrome. Our data suggest that patients with Turner syndrome are extraordinarily prone to abnormalities constituting the metabolic syndrome (e.g., hypertension, dyslipidaemia, NIDDM, obesity, hyperinsulinemia and hyperuricemia). The present data may help to explain the decreased life span found in patients with Turner syndrome.
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PMID:Morbidity in Turner syndrome. 947 75

Both epidemiological and experimental studies have shown that physical exercise deserves particular attention in any consideration of approaches to the prevention of neoplasia, especially since it also exerts consistent beneficial effects on the other major chronic diseases prevalent in the Western world, atherosclerosis and non-insulin dependent diabetes mellitus (NIDDM). The organ sites for which strong evidence has been gained for a protective influence of exercise or an elevated risk with a sedentary existence include the colon, prostate, breast and endometrium. The underlying mechanisms appear to centre on the hormones insulin and oestrogen, serum elevation of both of these endocrine factors being associated with increased risk of neoplastic development. The immense potential benefit of an increased level of exercise in the general population suggests that commensurate measures should be taken in the field of cancer education.
Eur J Cancer Prev 1998 Jun
PMID:Physical exercise: a pillar for cancer prevention? 969 26

Recent epidemiological evidence points to a link between non-insulin dependent diabetes mellitus type II (NIDDM) and cancer of the colon, liver, pancreas, breast and endometrium. This appears to be due to the long period of hyperinsulinaemia which precedes the clinical phase of NIDDM, insulin promoting colon tumour development as well as acting as a hepatocarcinogen. Indeed, the hormone could play a central role in neoplasia, and its influence could explain the observed enhancing effects of obesity and a high fat diet, as well as the inhibition associated with physical exercise, dehydroepiandrosterone administration and high soluble fibre intake. Measures to decrease insulin levels, including lifestyle improvement and supplementation with agents known to decrease insulin resistance may therefore offer a general approach to prevention of cancer in a wide variety of organ sites of major clinical importance.
Eur J Cancer Prev 1998 Apr
PMID:Implications of the hyperinsulinaemia-diabetes-cancer link for preventive efforts. 981 71

A 70-year-old man is referred to a urologist for recommendations on the management of metastatic prostate cancer. His cancer was diagnosed 5 years ago, and he underwent radical prostatectomy at that time. The tumour was confined to the prostate gland (Gleason score 7), and during surgery the lymph nodes were assessed as being clear of cancer. Before the surgery, the patient's prostate-specific antigen (PSA) level had been 8 ng/mL. After the prostatectomy, PSA was at first undetectable, but recently the PSA level rose to 2 ng/mL and then, at the most recent test, to 16 ng/mL. A bone scan was ordered to investigate back discomfort, which has been persistent but easily controlled with acetaminophen. Unfortunately, the bone scan shows several sites of metastatic disease. The man's medical history includes type 2 diabetes, which has developed during the past 3 years and which is controlled by diet, as well as asymptomatic hypertension, which is managed by means of a thiazide diuretic. The patient asks what treatments are available, what impact they are likely to have on his disease and what risks are associated with the therapies.
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PMID:Prostate cancer: 9. Treatment of advanced disease. 995 46


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