| 1. |
- Ahmad, Abrar, 1984-, et al.
(författare)
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Investigating the association between polymorphisms in connective tissue growth factor and susceptibility to colon carcinoma
- 2015
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 11:4, s. 2493-2503
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Tidskriftsartikel (refereegranskat)abstract
- There have been numerous studies on the gene expression of connective tissue growth factor (CTGF) in colorectal cancer, however very few have investigated polymorphisms in this gene. The present study aimed to determine whether single nucleotide polymorphisms (SNPs) in the CTGF gene are associated with a higher susceptibility to colon cancer and/or an invasive tumor growth pattern. The CTGF gene was genotyped for seven SNPs (rs6918698, rs1931002, rs9493150, rs12526196, rs12527705, rs9399005 and rs12527379) by pyrosequencing. Formalin-fixed paraffin-embedded tissue samples (n=112) from patients diagnosed with colon carcinoma, and an equal number of blood samples from healthy controls, were selected for genomic DNA extraction. The complexity index was measured using images of tumor samples (n=64) stained for cytokeratin-8. The images were analyzed and correlated with the identified CTGF SNPs and clinicopathological parameters of the patients, including age, gender, tumor penetration, lymph node metastasis, systemic metastasis, differentiation and localization of tumor. It was demonstrated that the frequency of the SNP rs6918698 GG genotype was significantly associated (P=0.05) with an increased risk of colon cancer, as compared with the GC and CC genotypes. The other six SNPs (rs1931002, rs9493150, rs12526196, rs12527705, rs9399005 and rs12527379) exhibited no significant difference in the genotype and allele frequencies between patients diagnosed with colon carcinoma and the normal healthy population. A trend was observed between genotype variation at rs6918698 and the complexity index (P=0.052). The complexity index and genotypes for any of the studied SNPs were not significantly correlated with clinical or pathological parameters of the patients. These results indicate that the rs6918698 GG genotype is associated with an increased risk of developing colon carcinoma, and genetic variations at the rs6918698 are associated with the growth pattern of the tumor. The present results may facilitate the identification of potential biomarkers of the disease in addition to drug targets.
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| 2. |
- Alehagen, Urban, 1951-, et al.
(författare)
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Genetic variance and plasma concentration of CD93 is associated with cardiovascular mortality : Results from a 6.7-year follow-up of a healthy community-living elderly population
- 2020
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 22:6, s. 4629-4636
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation is one of the fundamental processes in numerous diseases. Cluster of differentiation (CD) 93, a glycoprotein, has been reported to be associated with a number of these diseases. There are reports indicating that a high plasma level of CD93 is associated with adverse events in ischaemic heart disease. Additionally, there are reports indicating different cardiovascular risks between different single nucleotide polymorphisms (SNPs) of CD93. Therefore, the present study aimed to determine whether the plasma concentration of CD93 and polymorphism of rs2749812 in CD93 were associated with clinical conditions and mortality in an elderly population. In 470 healthy elderly community-living individuals a novel clinical examination involving echocardiography and blood sampling was performed. The population was followed for 6.7 years. Plasma levels of CD93 and SNP analyses of rs2749812 of CD93 using PCR methodology were used. During the follow-up period, 106 (22.6%) all-cause and 61 (13.0%) cardiovascular deaths were registered. Those with the highest plasma concentration had markedly higher all-cause mortality. Evaluating the A/A, A/G and G/G genotypes, the G/G group exhibited significantly higher cardiovascular mortality (P=0.026), and an almost two-fold increased risk in a multivariate Cox regression model compared with the A/G genotype. Evaluation of subgroups with respect to sex, diabetes and hypertension revealed markedly increased cardiovascular risk in the G/G genotype in all subgroups. All results persisted in the multiple models used. In the present study, the glycoprotein CD93 was demonstrated to have prognostic cardiovascular information, with increased risk for those with a high plasma concentration. Furthermore, the G/G genotype of rs2749812 of CD93 has a significantly higher cardiovascular risk, as demonstrated here, and could therefore be regarded as a possible cardiovascular risk biomarker that might in the future be used to offer optimised cardiovascular patient handling. However, this was a small study, and more research is required.
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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- Erlandson, Anna, et al.
(författare)
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Epigenetic mutations in CDKN2A in western Swedish families with hereditary malignant melanoma
- 2008
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Ingår i: Molecular Medicine Reports. - Athens, Greece : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 1:1, s. 89-91
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to identify the molecular genetic variations associated with an increased risk of hereditary malignant melanoma (HMM) in the western Swedish population. In 68 families with increased hereditary susceptibility to malignant melanoma, we previously reported a low frequency of alterations in the CDKN2A gene, which is regarded as the major melanoma predisposition gene. Among these alterations, we identified a novel mutation in 3 families (Asp108Tyr). In the present study, we focused on the possible role of heritable epimutations as a cause of the silencing of the CDKN2A gene. We used two different technical approaches to detect changes in CpG methylation in the promoter region of the CDKN2A gene; methylation-specific PCR (MSP) analysis of bisulfite-converted DNA and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). From families who tested negative for germ-line CDKN2A mutations, 64 unrelated patients with hereditary melanoma were included in the study. We showed a consistent lack of hypermethylation in the promoter region of CDKN2A in patients with HMM in our western Swedish population. A putative germ-line methylation of the CDKN2A, if any, is therefore likely to be a rare event in hereditary melanoma. This study demonstrates that there are probably additional and as yet unknown genetic factors present in western Swedish HMM families.
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| 7. |
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| 8. |
- Fragkiadaki, Persefoni, et al.
(författare)
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Telomerase inhibitors and activators in aging and cancer : A systematic review
- 2022
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 25:5
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Forskningsöversikt (refereegranskat)abstract
- The main aim of the present systematic review was to summarize the most frequently used telomerase regulators with an impact on aging and cancer that are referred to in in vitro and in vivo studies. For this purpose, a systematic review of the available literature on telomerase regulators referred to in articles from PubMed and Scopus libraries published from 2002 to 2021 and in accordance with PRISMA 2020 criteria, was conducted. Articles were included if they met the following criteria: They referred to telomerase modulators in aging and in cancer and were in vitro and/or in vivo studies, while studies that did not provide sufficient data or studies not written in English were excluded. In the present systematic review, 54 publications were included, of which 29 were full-text published studies, 11 were full-text reviews, 10 structure-based design studies and 4 abstracts are reported in this review. Telomerase regulators were then categorized as synthetic direct telomerase inhibitors, synthetic indirect telomerase inhibitors, synthetic telomerase activators, natural direct telomerase activators, natural telomerase inhibitors and natural indirect telomerase activators, according to their origin and their activity. On the whole, as demonstrated herein, telomerase regulators appear to be promising treatment agents in various age-related diseases. However, further in vivo and in vitro studies need to be performed in order to clarify the potentiality of telomerase as a therapeutic target.
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| 9. |
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| 10. |
- Jönsson, Anette, et al.
(författare)
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Long‑term follow‑up of buserelin‑induced enteric neuropathy in rats.
- 2016
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-3004 .- 1791-2997. ; 13:4, s. 3507-3513
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Tidskriftsartikel (refereegranskat)abstract
- A few patients have been shown to develop severe abdominal pain and gastrointestinal dysmotility during treatment with gonadotropin‑releasing hormone (GnRH) analogs. A rat model of enteric neuropathy has been developed by administration of the GnRH analog buserelin to rats. Loss of enteric neurons and ganglioneuritis throughout the gastrointestinal tract has been described, without other histopathological changes. The aim of the present study was to investigate the long‑term effects of this rat model on body weight, and on morphology and inflammatory changes in the gastrointestinal tract. Rats were administered subcutaneous injections of buserelin or saline once daily for 5 days and allowed to recover for 3 weeks. This regimen was repeated four times. The rats were weighed weekly and were sacrificed 16 weeks after the fourth treatment. The bowel wall was measured by morphometry, and the presence of enteric neurons, mast cells, eosinophils and T‑lymphocytes was evaluated. Buserelin‑treated rats were shown to have a lower body weight at sacrifice, as compared with the controls (P<0.05). Compared with controls, buserelin treatment caused loss of myenteric neurons in the ileum and colon (P<0.01), a thinner circular muscle layer in ileum (P<0.05) and longitudinal muscle layer in colon (P<0.05), increased number of eosinophils in the submucosa of the ileum (P<0.05), and an increased number of T‑lymphocytes in the submucosa and circular muscle layer of the fundus (P<0.01 and P<0.05, respectively) and circular muscle layer of the colon (P<0.05). Mast cells were equally distributed in the two groups. Thus, long‑term follow‑up of buserelin‑induced enteric neuropathy reveals reduced body weight, loss of myenteric neurons, thinning of muscle layers, and increased numbers of eosinophils and T‑lymphocytes in the gastrointestinal tract.
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