Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocyte nuclear factor 1beta (HNF1beta, TCF2) is a tissue-specific transcription factor whose mutation in humans leads to renal cysts, genital malformations, pancreas atrophy and maturity onset diabetes of the young (MODY5). Furthermore, HNF1beta overexpression has been observed in clear cell cancer of the ovary. To identify potential HNF1beta target genes whose activity may be deregulated in human patients, we established a human embryonic kidney cell line (HEK293) expressing HNF1beta conditionally. Using Flp recombinase, we introduced wild type or mutated HNF1beta at a defined chromosomal position allowing a most reproducible induction of the HNF1beta derivatives upon tetracycline addition. By oligonucleotide microarrays we identified 25 HNF1beta-regulated genes. By an identical approach, we identified that the related transcription factor HNF1alpha (TCF1) affects only nine genes in HEK293 cells and thus is a less efficient factor in these kidney cells. The HNF1beta target genes dipeptidyl peptidase 4 (DPP4), angiotensin converting enzyme 2 (ACE2) and osteopontin (SPP1) are most likely direct target genes, as they contain functional HNF1 binding sites in their promoter region. Since nine of the potential HNF1beta target genes are deregulated in clear cell carcinoma of the ovary, we propose that HNF1beta overexpression in the ovarian cancer participates in the altered expression pattern.
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PMID:Identification of target genes of the transcription factor HNF1beta and HNF1alpha in a human embryonic kidney cell line. 1629 91

A growing body of evidence supports or rejects preventive interventions in asymptomatic adults. Thus, counseling for smoking cessation and some immunizations have been shown to be cost-effective. Evidence supports screening for body weight (obesity), hypertension, hyperlipidemia, cervical cancer, colorectal cancer and breast cancer. Screening for lung, pancreatic and ovarian cancer has no effect on outcome and should not be performed. Controversial preventive interventions include general screening for diabetes mellitus in the young adult, thyroid disorders and prostate cancer. Physicians should be aware of a possible hidden agenda in patients presenting for a check-up.
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PMID:[Check-up-examinations in internal medicine]. 1636 64

Patients with ovarian cancer with clear cell histology often have venous thromboembolism (VTE) even before surgery. In view of the possible association between clear cell histology and VTE in endometrial cancer, we measured the plasma levels of thrombin-antithrombin III complex (TAT) and D-dimer (DD) in the preoperative examinations of a patient with clear cell adenocarcinoma of the endometrium. Plasma TAT and DD were both highly elevated, though the patient had no symptoms of VTE or risk factors such as obesity or diabetes mellitus. Ultrasound Doppler examination and lung perfusion scintigraphy just before surgery revealed a thrombosis in the left popliteal vein and a pulmonary embolism. After implanting an inferior vena cava filter to prevent a fatal embolism of the lung, we performed abdominal total hysterectomy, bilateral salpingo-oophorectomy, and sampling of the pelvic lymph nodes. The VTE gradually disappeared and the plasma levels of TAT and DD returned to normal after surgery. Possibly, the VTE in this patient may have been associated with the clear cell histology.
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PMID:Successful diagnosis of thromboembolism before surgery in a woman with clear cell adenocarcinoma of the endometrium. 1636 52

Imprinting within domains occurs through epigenetic alterations to imprinting centers (ICs) that result in the establishment of parental-specific differences in gene expression. One candidate IC lies within the imprinted domain on human chromosome region 6q24. This domain contains two paternally expressed genes, the zinc finger protein gene PLAGL1 (ZAC/LOT1) and an untranslated mRNAcalled HYMAI. The putative IC overlaps exon 1 of HYMAI and is differentially methylated in somatic tissues. In humans, loss of methylation within this region is seen in some patients with transient neonatal diabetes mellitus, and hypermethylation of this region is found in ovarian cancer and is associated with changes in expression of PLAGL1, suggesting that it plays a key role in regulating gene expression. Differential methylation within this region is conserved in the homologous region on mouse chromosome 10A and is present on the maternal allele. In this paper, we report that DNA methylation is established during the growth phase of oogenesis and that this coincides with the establishment of monoallelic expression from this region lending further support to the hypothesis that this region functions as an IC.
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PMID:Establishment of the primary imprint of the HYMAI/PLAGL1 imprint control region during oogenesis. 1657 87

It is unclear whether hypertension and antihypertensive medication use are associated with breast cancer. In order to examine these associations, we conducted a case-control study among women aged 50-75 years. Breast cancer cases were ascertained via a population-based cancer registry (n=523) and controls were ascertained via random-digit-dialing (n=131). Participants completed a self-administered questionnaire which queried history of hypertension, antihypertensive medication use and risk factors. Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI), adjusted for age, body mass index (BMI), diabetes, smoking, alcohol use, menopausal status, family history of breast or ovarian cancer, age at first full-term pregnancy and education. History of treated hypertension was associated with significant increased risk of breast cancer (OR, 1.77; 95% CI, 1.04-3.03) and this association appeared only in women with BMI > or =25 kg/m(2) (OR, 2.30; 95% CI, 1.12-4.71). Diuretic use was also associated with elevated breast cancer risk (OR, 1.79; 95% CI, 1.07-3.01). The risk associated with diuretic use increased with duration of use (P for trend, <0.01). Use of other blood pressure medications was not found to be associated with breast cancer risk. These results support a positive association between treated hypertension, diuretic use and breast cancer risk among women aged 50-75 years.
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PMID:Hypertension, diuretics and breast cancer risk. 1688 97

The purpose of this study was to document the prevalence of diabetes among newly diagnosed cancer patients and to evaluate the influence of diabetes on stage at diagnosis, treatment and overall survival. We performed a population-based analyses of all 58,498 cancer patients newly diagnosed between 1995 and 2002 in the registration area of the Eindhoven Cancer Registry. Stage of cancer, cancer treatment and comorbidities were actively collected by hospital medical records review. Follow-up of all patients was completed until January 1, 2005. Nine percent of all cancer patients had diabetes at the time of cancer diagnosis. The prevalence of diabetes was highest among patients with cancer of the pancreas (19%), uterus (14%) and among young men with kidney cancer (8%). Colon, breast and ovarian cancer patients with diabetes were more often diagnosed with a higher tumour stage (p < 0.05). Patients with diabetes and cancer of the oesophagus, colon, breast and ovary were treated less aggressively compared to those without diabetes (p < 0.05). During the follow-up period 3,902 of 5,555 cancer patients with diabetes died and 29,909 of 52,943 cancer patients without diabetes died. For all cancers combined, in a multivariate cox-regression model, adjusting for age, gender, stage, treatment and cardiovascular disease, patients with diabetes experienced a significant increase in overall mortality (HR = 1.44, 95% CI 1.40-1.49), ranging however from 0 to 40% for different types of cancer, compared to those without diabetes. In conclusion, diabetic cancer patients frequently were treated less aggressively and had a worse prognosis compared to those without diabetes.
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PMID:Less aggressive treatment and worse overall survival in cancer patients with diabetes: a large population based analysis. 1723 May 9

HPV infection is by far the most frequent sexually transmitted disease. Our aim in this prospective nonrandomized study was to investigate the frequency with which different subtypes of the human papillomavirus (HPV) are found in gynaecological malignant and benign conditions and to compare the rate of infection between them. Detailed data of 195 women were selected and divided into three groups. The first group consisted of specimens from 68 women with cervical cancer. The second group consisted of specimens from 43 women with endometrial and ovarian cancer. The third group consisted of 84 specimens from women who were operated on for benign gynaecological diseases. Seven oncogenic types of HPV (6, 11 [low-risk subtypes] 16, 18, 31, 33, and 51 [high-risk subtypes]) were investigated by using the in situ hybridization technique. The HPV detection rate was higher in the cervical cancer group (74.8%), compared with the second (27.9%) and third (45.2%) groups. The most common HPV subtypes in the first group were 16 and 18. The most common subtypes in the second group were the 31, 33, and 51, and in the third group the 6 and 11 subtypes. Women developed cervical cancer at a younger age than endometrial or ovarian cancer. Smoking and exposure to multiple sexual partners appeared related to the development of cervical cancer. The use of contraceptive pill, dietary habits, and diabetes did not seem to increase the risk of HPV infection in this population. As it is common in other populations, in this selected population of Greek women we were able to confirm that in women with cervical cancer the most common HPV subtypes are 16 and 18. Education of adolescents on the epidemiological association of smoking and unprotected intercourse with cervical cancer will certainly help to reduce the rates of development of preinvasive and invasive cancer of the cervix in young women.
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PMID:Human papillomavirus infection in malignant and benign gynaecological conditions: a study in Greek women. 1736 79

Papillary thyroid carcinoma is a slow growing tumor with low metastatic potential. The most frequent sites of distant metastases are lung and bone; less frequent sites are brain, liver, kidney, and skin. Ovarian metastases from papillary thyroid carcinoma are exceptional. We describe a case of bilateral ovarian metastases from a papillary thyroid carcinoma associated with autoimmune thyroiditis in a 38-year-old woman who underwent thyroidectomy and cervical lymph-node dissection 7 years before, followed by 948 mCi of 131I. A primary ovarian cancer could be excluded by the typical pathological aspects of a papillary thyroid carcinoma in a context of an aggressive form of thyroid cancer. On the other hand, the clinical history and the absence of normal thyroid epithelium and teratomatous components could exclude a papillary thyroid carcinoma arising in struma ovarii. This is a singular case of papillary thyroid carcinoma metastasizing to the ovary, combined with an autoimmune thyroiditis.
Exp Clin Endocrinol Diabetes 2007 Jun
PMID:A special case of bilateral ovarian metastases in a woman with papillary carcinoma of the thyroid. 1770 87

The aim of this retrospective study was to clarify the clinopathologic profile of endometrial cancers in women aged 45 years or younger. All patients with histopathologically confirmed endometrial cancer treated at Songklanagarind Hospital from 1996-2005 were included. Of the 51 identified, 40 (78.4%) were in stage I, 7 (13.7%) in stage II, and 4 (7.8%) in stage III. The age range was 25-45 years (median 41) with a body mass index ranging from 17.6-44.2 (median 27.2). Eighty one percent reported abnormal vaginal bleeding, and twenty four percent polycystic ovaries. Prevalences of diabetes mellitus, hypertension and thyroid disease were 17.7%, 15.7%, and 3.9%, respectively. Seven cases (13.7%) had synchronous ovarian cancer with endometriod adenocarcinoma as the most common histopathological form. Forty patients had well differentiated, 8 moderately differentiated and 2 poorly differentiated tumors. The 5-year disease-free survival (and 95% CI) and 5-year overall survival rates were 88.0% (75.1-94.4%) and 87.5% (74.1-94.2%), respectively. Univariate analysis revealed that patients who had a history of hypertension or lymph node metastasis had a poor prognosis. We conclude that the majority of women aged 45 years or younger with endometrial cancer were obese and the tumors were most commonly in an early stage and were well differentiated.
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PMID:Endometrial cancer in Thai women aged 45 years or younger. 1843 75

Insulin-degrading enzyme (IDE, insulysin, insulinase; EC 3.4.22.11), a thiol metalloendopeptidase, is involved in intracellular degradation of insulin, thereby inhibiting its translocation and accumulation to the nucleus. Recently, protein expression of IDE has been demonstrated in the epithelial ducts of normal breast and breast cancer tissue. Utilizing four different antibodies generated against different epitopes of the IDE molecule, we performed Western blot analysis and immunohistochemical staining on several normal human tissues, on a plethora of tumor cell lines of different tissue origin, and on malignant breast and ovarian tissue. Applying the four IDE-directed antibodies, we demonstrated IDE expression at the protein level, by means of immunoblotting and immunocytochemistry, in each of the tumor cell lines analyzed. Insulin-degrading enzyme protein expression was found in normal tissues of the kidney, liver, lung, brain, breast and skeletal muscle, as well as in breast and ovarian cancer tissues. Immunohistochemical visualization of IDE indicated cytoplasmic localization of IDE in each of the cell lines and tissues assessed. In conclusion, we performed for the first time a wide-ranging survey on IDE protein expression in normal and malignant tissues and cells thus extending our knowledge on the cellular and tissue distribution of IDE, an enzyme which to date has mainly been studied in connection with Alzheimer's disease and diabetes but not in cancer.
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PMID:Expression of metalloprotease insulin-degrading enzyme insulysin in normal and malignant human tissues. 1881 47


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