| 1. |
- Bu, Huajie, et al.
(författare)
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Genotype < 21CAs/>= 21CAs and allele < 21CAs of the MANBA gene in melanoma risk and progression in a Swedish population
- 2009
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Ingår i: Molecular medicine reports. - : Spandidos Publications Ltd.. - 1791-2997 .- 1791-3004. ; 2:2, s. 259-263
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Tidskriftsartikel (refereegranskat)abstract
- Cutaneous melanoma is characterized by poor patient outcome in its later stages. The search for genetic markers is therefore crucial for the identification of populations at risk for melanoma. Highly polymorphic CA repeats in 3 proximity in the MANBA gene were examined by PCR-capillary electrophoresis in 185 Swedish melanoma patients and 441 tumor-free age- and gender-matched individuals. The associations of the polymorphisms with melanoma risk, the pigment phenotypes of the patients and tumor characteristics were analyzed. A significant difference in allelic distribution between melanoma patients and tumor-free individuals was observed. The frequency of the MANBA genotype <21CAs/>= 21CAs was significantly higher in melanoma patients than in the controls. When comparing allele distribution in patients and their matched controls, the allele <21 CAs was found to be associated with the female gender (39.8 vs. 31.2%, P=0.041, OR=1.46, 95% Cl 1.02-2.10), but not with male gender (34.4 vs. 30.9%, P=0.39). Within the melanoma group, there were no differences in the distribution of the MANBA alleles associated with patient gender or age before or after 55 years at diagnosis, nor was there any association between the MANBA genotype and pigment phenotype or tumor sites. The MANBA allele <21CAs was, however, associated with thin melanomas at diagnosis (Breslow thickness <= 1.5 mm and Clark levels I and II). In conclusion, these data suggest that MANBA polymorphisms might be an indicator of tumor growth and progression and, together with other markers, could be used to identify individuals at increased risk of melanoma.
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| 2. |
- El-Salhy, Magdy, et al.
(författare)
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Low density of ghrelin cells in the oxyntic mucosa correlated to slow gastric emptying in patients with type 1 diabetes
- 2009
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 2:6, s. 893-896
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Tidskriftsartikel (refereegranskat)abstract
- Ghrelin is a peptide hormone that has been isolated from the stomach and localized to endocrine cells in the oxyntic mucosa. Ghrelin acts synergistically with GH-releasing hormone and increases appetite and feeding. It also accelerates gastric and small intestinal motility in rodents. Patients with diabetes suffer from slow gastric emptying, giving rise to nausea and vomiting. The present study was undertaken to establish the possible role of ghrelin in slow gastric emptying observed in patients with longstanding type 1 diabetes, and to correlate the results with the metabolic status of these patients. Eleven patients with type 1 diabetes along with 10 and 15 healthy volunteers as controls underwent gastrointestinal endoscopy/biopsy or gastric scintigraphy. Gastric emptying in patients and controls was measured by scintigraphy. Sections from biopsies of the oxyntic mucosa and duodenum were immunostained for ghrelin with the avidin-biotin complex method. The density of the cells was quantified with computerized image analysis. Both the lag phase and half-emptying time (T-50) were higher in patients with diabetes than in healthy volunteers. The T-50 was correlated with the blood glucose level. The density of ghrelin-immunoreactive cells in the oxyntic mucosa of patients with diabetes was significantly reduced compared to the healthy controls. Ghrelin cell density was correlated with both the lag phase and T-50, as well as with blood glucose level. The present finding of reduced density of ghrelin cells in patients with type 1 diabetes, which was well correlated with gastric emptying, indicates the possible role of ghrelin in the pathophysiology of gastroparesis observed in diabetes.
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| 3. |
- Eriksson, Staffan
(författare)
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Thymidine kinase 1 expression in atypical ductal hyperplasia significantly differs from usual ductal hyperplasia and ductal carcinoma in situ: A useful tool in tumor therapy management
- 2009
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 2, s. 923-929
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Tidskriftsartikel (refereegranskat)abstract
- Thymidine kinase 1 (TK1) is an enzyme involved in the synthesis of DNA precursors. In studies using immunohistochemistry, it was reported to be a more useful proliferation marker than Ki-67 and PCNA in breast, lung and colorectal carcinoma. In this study, we extend the work of prior breast carcinoma studies by investigating the expression of TK1 in 132 patients with usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). TK1 and Ki-67 expression were determined with monoclonal antibodies using the SP technique. The expression of TK1 was found to be significantly increased in the breast ductal carcinomas in the following manner: UDH
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| 4. |
- Mälarstig, Anders, et al.
(författare)
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Tumour-derived adhesion factor in colorectal cancer
- 2009
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 2:6, s. 971-976
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Tidskriftsartikel (refereegranskat)abstract
- Tumour-derived adhesion factor (TAF) has been shown to be associated with breast, prostate and colorectal cancer (CRC), acting as tumour suppressor or tumour promoter by mechanisms not as yet understood. Here, we comparatively analyzed the expression profile of TAF in plasma, tumour and paired normal tissue from patients with CRC. In addition, we investigated the relationship between TAF and systemic inflammation, mirrored by the elevation of interleukin-6 (IL-6) and TAF levels in plasma. Levels of TAF and IL-6 were determined by ELISA. Immunohistochemistry was performed to investigate the site of TAF expression. We also used a TaqMan system to investigate a TAF single nucleotide polymorphism (rs2041437) with a potential effect on CRC. TAF protein levels were significantly (Pless than0.001) higher in colorectal tumours than in normal tissue, and were increased in patients with Dukes stages B and C compared to A. Immunohistochemistry revealed heterogeneous TAF expression mainly in the epithelial cells of the cancer and normal tissue. The plasma TAF level was reduced in CRC patients compared with the controls (P=0.002), independent of the inflammatory marker IL-6. Regarding genotype and allelic distributions, significant differences between CRC patients and control subjects or associations between clinical characteristics and TAF levels in tissue and plasma were not observed. In conclusion, altered TAF protein expression in cancer tissue may be a potential biomarker in colorectal carcinogenesis. Further research exploring the regulation of TAF is required to evaluate whether TAF is linked to clinical outcome.
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| 5. |
- Sjölander, Annica, 1969, et al.
(författare)
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Alzheimer's disease: No effect of the CDK5 gene on CSF biomarkers, neuropathology or disease risk
- 2009
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-3004 .- 1791-2997. ; 2:6, s. 989-992
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Tidskriftsartikel (refereegranskat)abstract
- Cyclin-dependent kinase 5 (cdk5) has been identified as one of the kinases that phosphorylates tau at several Alzheimer's disease (AD)-associated sites. Cdk5 is predominantly expressed in neurons, and has higher activity in AD brains than in non-demented brains. To investigate the effect of the CDK5 gene on AD, we analyzed an SNP of the CDK5 gene (rs2069456) in 347 patients with AD and in 157 controls. CDK5 genetic data was investigated in subgroups in relation to biochemical and neuropathological markers for AD. We found no significant differences in genotype or allele distributions between AD patients and controls. None of the CDK5 gene variants influenced biomarkers for AD.
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| 6. |
- Ha, Chunfang, et al.
(författare)
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Adrenomedullin and its receptor, calcitonin receptor-like receptor, are aberrantly expressed in women with idiopathic menorrhagia
- 2009
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997. ; 2:1, s. 7-11
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Tidskriftsartikel (refereegranskat)abstract
- The human endometrium undergoes a unique process of benign angiogenesis under the control of ovarian steroids during reproductive life. Aberrant angiogenesis has been implicated in idiopathic menorrhagia, a common gynaecological complaint. One of the key factors involved in endometrial angiogenesis is adrenomedullin (AM), a multifunctional 52-amino acid peptide. AM mediates the activities of endometrial angiogenesis via calcitonin receptor-like receptor (CLR). The objective of the present study was to compare the endometrial expression of AM and CRL in women with and without idiopathic menorrhagia. Endometrial biopsies were obtained from 9 women with menorrhagia (>= 80 ml per menstruation) and 12 women with normal blood loss (<80 ml per menstruation). Protein and mRNA expression levels of AM and CLR were determined using immunohistochemistry and real-time PCR. Compared to the controls, patients with menorrhagia exhibited low immunostaining intensity of AM, while high CLR staining was observed in the epithelium (p<0.05). No difference in mRNA expression was observed between the groups. These data suggest that an imbalance in the AM/CLR system might alter endometrial angiogenesis in menorrhagia.
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| 7. |
- Isaksson-Mettävainio, Martin, et al.
(författare)
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c-Met expression in primary tumors and their corresponding distant metastases
- 2009
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Ingår i: Molecular Medicine Reports. - Umeå : Spandidos Publications. - 1791-2997. ; 1:6, s. 787-790
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Tidskriftsartikel (refereegranskat)abstract
- c-Met is a receptor tyrosine kinase that has beenimplicated in the pathogenesis and growth of a wide variety ofhuman malignancies, including CRC, but its role in metastasisis largely unknown. We compared c-Met expression in primaryhuman colorectal carcinomas and distant metastases from thesame patients. Formalin-fixed paraffin-embedded tissuesamples from 69 colorectal cancer patients were obtained. Theprotein expression of c-Met was evaluated immunohistochemicallyusing a commercial antibody. The difference inexpression between primary tumors and their correspondingdistant metastases was analyzed using the Wilcoxon signedranktest. c-Met expression was statistically significantlylower in the distant metastases compared to their correspondingprimary tumors (p<0.001), whereas no difference was foundbetween lymph node metastases and their correspondingprimary tumors (p=0.957). The degree of c-Met expressionwas not related to clinicopathological characteristics such astumor grade and Dukes' stage at the time of primary tumordiagnosis, or to the location of the distant metastases. Wedemonstrated that c-Met expression is often reduced in distantmetastases compared to their corresponding primary colorectaltumors. Additional studies of c-Met activation and signaltransduction will increase our knowledge about the role ofc-Met in colorectal cancer metastasis.
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| 8. |
- Ungerbäck, Jonas, et al.
(författare)
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Analysis of VEGF polymorphisms, tumor expression of VEGF mRNA and colorectal cancer susceptibility in a Swedish population
- 2009
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Ingår i: MOLECULAR MEDICINE REPORTS. - : Spandidos Publications. - 1791-2997. ; 2:3, s. 435-439
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor (VEGF) plays a significant role in tumor angiogenesis and is found to be overexpressed and involved in the development and progression of colorectal cancer (CRC). The VEGF gene contains several polymorphic sites known to influence VEGF expression. We examined the possible association between five polymorphisms, located in the promoter/5-untranslated region [-2578 (C/A), -2549 (del/ins 18 bp) -1154 (G/A), -634 (G/C)] or 3-untranslated region [+936 (C/T)] of the VEGF gene, and CRC Susceptibility and clinicopathological characteristics in 302 Swedish CRC patients and 336 healthy randomly selected controls. Both genotypes and combined haplotypes were analyzed. No significant differences were observed when VEGF genotype/haplotype frequencies in the CRC cases and controls were compared, nor were any associations found between the genotypes/haplotypes and clinicopathological characteristics. However, when the -2578 C and +936 T alleles were combined, a small but significant association with CRC susceptibility was detected (OR=1.6, 95% CI 1.3-1.9, p=0.01). In addition, VEGF mRNA expression was determined in a Subset of patients, revealing a 2-fold VEGF upregulation in CRC tissue compared to normal colonic mucosa, but no association between the genotypes or haplotypes and VEGF mRNA levels. Linkage analysis was performed, revealing that the polymorphisms in the promoter and 5-untranslated region were in tight linkage disequilibrium (LD) (vertical bar Dvertical bar=0.91-1.00), while the +936 C/T polymorphism was only weakly associated with the others (vertical bar Dvertical bar=0.05-0.19). In conclusion, VEGF is generally upregulated in colorectal tumors. However, the single nucleotide polymorphisms examined do not appear to influence the mRNA expression of VEGF in colorectal tumors, and most likely play a limited role in CRC development and progression.
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