296 research outputs found
E-cadherin adhesion molecule and syndecan-1 expression in various thyroid pathologies
Cadherins and syndecans are transmembrane glycoproteins implicated in cell-cell and cell-matrix adhesion. Impairment of cadherin and syndecan mediated adhesion is likely to constitute one of the main factors leading to the reduced cell-cell and cell-matrix adhesion characteristics of tumor cells and play a pivotal role in the acquisition of invasive and metastatic proprieties by neoplastic epithelial cells. Aim: To elucidate the role and alterations of syndecan-1 expression in comparison with those of E-cadherin in normal and pathological thyroid glands (TG). Methods: A total of 55 TG carcinomas, 40 TG adenomas, 40 cases of hyperplastic TG disorders and 20 cases of normal TG autopsy samples, were evaluated by immunohistochemistry. The staining intensity, and localization of syndecan-1 and E-cadherin in sequential sections were examined, and semi-quantified. Results: Immunostaining of syndecan-1 and E-cadherin was strong in normal follicular TG epithelial cells, and located mainly in basolateral membrane. No significant change was seen in either molecule in hyperplastic TG disorders compared with TG adenomas. A significant reduction in expression of both syndecan-1 and E-cadherin was seen in well-differentiated TG carcinomas as compared with normal TG epithelium (p = 0.0001 and p = 0.032, respectively). Similarly, there was a significant reduction of both molecules expression in poorly differentiated and anaplastic TG carcinomas compared to well differentiated tumors (syndecan-1: p = 0.0037; and E-cadherin: p = 0.075). Conclusion: Decreased E-cadherin and syndecan-1 expression along with decreasing cellular differentiation may be involved in the complex mechanism of progression of TG pathology.ΠΠ°Π΄Π³Π΅ΡΠΈΠ½Ρ ΠΈ ΡΠΈΠ½Π΄Π΅ΠΊΠ°Π½Ρ β ΡΡΠΎ ΡΡΠ°Π½ΡΠΌΠ΅ΠΌΠ±ΡΠ°Π½Π½ΡΠ΅ Π³Π»ΠΈΠΊΠΎΠΏΡΠΎΡΠ΅ΠΈΠ½Ρ, ΡΡΠ°ΡΡΠ²ΡΡΡΠΈΠ΅ Π² ΠΌΠ΅ΠΆΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ Π°Π΄Π³Π΅Π·ΠΈΠΈ ΠΈ Π°Π΄Π³Π΅Π·ΠΈΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ
ΠΊ ΠΌΠ°ΡΡΠΈΠΊΡΡ. ΠΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΡΡΠΈΡ
ΠΌΠΎΠ»Π΅ΠΊΡΠ» ΠΈΠ³ΡΠ°ΡΡ Π³Π»Π°Π²Π½ΡΡ ΡΠΎΠ»Ρ Π² ΠΏΡΠΈΠΎΠ±ΡΠ΅ΡΠ΅Π½ΠΈΠΈ ΠΈΠ½Π²Π°Π·ΠΈΠ²Π½ΠΎΠ³ΠΎ ΠΈ ΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ
ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»Π° Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎ ΡΡΠ°Π½ΡΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½Π½ΡΠΌΠΈ ΡΠΏΠΈΡΠ΅Π»ΠΈΠ°Π»ΡΠ½ΡΠΌΠΈ ΠΊΠ»Π΅ΡΠΊΠ°ΠΌΠΈ. Π¦Π΅Π»Ρ: ΠΎΡΠ΅Π½ΠΊΠ° ΡΠΎΠ»ΠΈ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΡΠΈΠ½Π΄Π΅ΠΊΠ°Π½Π°-1
ΠΈ Π-ΠΊΠ°Π΄Π³Π΅ΡΠΈΠ½Π° Π² ΡΠΊΠ°Π½ΠΈ ΡΠΈΡΠΎΠ²ΠΈΠ΄Π½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ Π² Π½ΠΎΡΠΌΠ΅ ΠΈ ΠΏΡΠΈ ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΠΈ. ΠΠ΅ΡΠΎΠ΄Ρ: ΠΎΠ±ΡΠ°Π·ΡΡ ΡΠΊΠ°Π½ΠΈ Π΄Π»Ρ ΠΈΠΌΠΌΡΠ½ΠΎΠ³ΠΈΡΡΠΎΡ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π²Π·ΡΠ»ΠΈ Ρ 55 Π±ΠΎΠ»ΡΠ½ΡΡ
ΡΠ°ΠΊΠΎΠΌ ΡΠΈΡΠΎΠ²ΠΈΠ΄Π½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ (Π©Π), 40 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² β Ρ Π°Π΄Π΅Π½ΠΎΠΌΠΎΠΉ Π©Π, 40 β Ρ Π³ΠΈΠΏΠ΅ΡΠΏΠ»Π°ΡΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ
ΠΏΡΠΎΡΠ΅ΡΡΠ°ΠΌΠΈ Π©Π, ΠΊΠΎΠ½ΡΡΠΎΠ»Π΅ΠΌ ΡΠ»ΡΠΆΠΈΠ»ΠΈ 20 ΠΎΠ±ΡΠ°Π·ΡΠΎΠ² Π½Π΅ΠΈΠ·ΠΌΠ΅Π½Π΅Π½Π½ΠΎΠΉ ΡΠΊΠ°Π½ΠΈ Π©Π (Π°ΡΡΠΎΠΏΡΠΈΡ). Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ:
ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ ΡΠΈΠ½Π΄Π΅ΠΊΠ°Π½Π°-1 ΠΈ Π-ΠΊΠ°Π΄Π³Π΅ΡΠΈΠ½Π° Π² Π½ΠΎΡΠΌΠ°Π»ΡΠ½ΡΡ
ΡΠΎΠ»Π»ΠΈΠΊΡΠ»ΡΡΠ½ΡΡ
ΡΠΏΠΈΡΠ΅Π»ΠΈΠ°Π»ΡΠ½ΡΡ
ΠΊΠ»Π΅ΡΠΊΠ°Ρ
Π©Π Π²ΡΡΠ°ΠΆΠ΅Π½Π° ΠΈΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΠΎ,
Ρ ΠΏΡΠ΅ΠΈΠΌΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠΉ Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΠ΅ΠΉ Π² Π±Π°Π·ΠΎΠ»Π°ΡΠ΅ΡΠ°Π»ΡΠ½ΠΎΠΉ ΠΌΠ΅ΠΌΠ±ΡΠ°Π½Π΅. ΠΠ΅ ΠΎΡΠΌΠ΅ΡΠ°Π»ΠΈ ΡΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
ΡΠ°Π·Π»ΠΈΡΠΈΠΉ Π² ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ
ΠΎΠ±Π΅ΠΈΡ
ΠΌΠΎΠ»Π΅ΠΊΡΠ» ΠΏΡΠΈ Π³ΠΈΠΏΠ΅ΡΠΏΠ»Π°ΡΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠΎΡΠ΅ΡΡΠ°Ρ
ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ Π°Π΄Π΅Π½ΠΎΠΌΠ°ΠΌΠΈ Π©Π. ΠΠ΄Π½Π°ΠΊΠΎ ΡΠ°ΠΊΠΎΠ²Π°Ρ Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎ ΡΠ½ΠΈΠΆΠ΅Π½Π°
Π² ΠΎΠ±ΡΠ°Π·ΡΠ°Ρ
Π²ΡΡΠΎΠΊΠΎΠ΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ ΠΊΠ°ΡΡΠΈΠ½ΠΎΠΌΡ ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ Π½ΠΎΡΠΌΠ°Π»ΡΠ½ΡΠΌ ΡΠΏΠΈΡΠ΅Π»ΠΈΠ΅ΠΌ Π©Π (p = 0,0001 ΠΈ p = 0,032
ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ), Π° ΡΠ°ΠΊΠΆΠ΅ ΠΏΡΠΈ Π½ΠΈΠ·ΠΊΠΎΠ΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΌ ΠΈ Π°Π½Π°ΠΏΠ»Π°ΡΡΠΈΡΠ΅ΡΠΊΠΎΠΌ ΡΠ°ΠΊΠ΅ ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ Π²ΡΡΠΎΠΊΠΎΠ΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΡΠΎΠ²Π°Π½Π½ΡΠΌΠΈ
ΠΎΠΏΡΡ
ΠΎΠ»ΡΠΌΠΈ Π©Π (p = 0,0037 Π΄Π»Ρ ΡΠΈΠ½Π΄Π΅ΠΊΠ°Π½Π°-1 ΠΈ p = 0,075 Π΄Π»Ρ Π-ΠΊΠ°Π΄Π³Π΅ΡΠΈΠ½Π°). ΠΡΠ²ΠΎΠ΄Ρ: ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ
ΡΠΈΠ½Π΄Π΅ΠΊΠ°Π½Π°-1 ΠΈ Π-ΠΊΠ°Π΄Π³Π΅ΡΠΈΠ½Π°, ΡΠΎΠΏΡΠΎΠ²ΠΎΠΆΠ΄Π°ΡΡΠ΅Π΅ΡΡ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ΠΌ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΊ Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΠ°ΡΠΈΠΈ, ΠΌΠΎΠΆΠ΅Ρ Π±ΡΡΡ ΡΠ°ΡΡΡΡ
ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠ° ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ Π©Π
Proteome Profiling of Breast Tumors by Gel Electrophoresis and Nanoscale Electrospray Ionization Mass Spectrometry
We have conducted proteome-wide analysis of fresh surgery specimens derived from breast cancer patients, using an approach that integrates size-based intact protein fractionation, nanoscale liquid separation of peptides, electrospray ion trap mass spectrometry, and bioinformatics. Through this approach, we have acquired a large amount of peptide fragmentation spectra from size-resolved fractions of the proteomes of several breast tumors, tissue peripheral to the tumor, and samples from patients undergoing noncancer surgery. Label-free quantitation was used to generate protein abundance maps for each proteome and perform comparative analyses. The mass spectrometry data revealed distinct qualitative and quantitative patterns distinguishing the tumors from healthy tissue as well as differences between metastatic and non-metastatic human breast cancers including many established and potential novel candidate protein biomarkers. Selected proteins were evaluated by Western blotting using tumors grouped according to histological grade, size, and receptor expression but differing in nodal status. Immunohistochemical analysis of a wide panel of breast tumors was conducted to assess expression in different types of breast cancers and the cellular distribution of the candidate proteins. These experiments provided further insights and an independent validation of the data obtained by mass spectrometry and revealed the potential of this approach for establishing multimodal markers for early metastasis, therapy outcomes, prognosis, and diagnosis in the future. Β© 2008 American Chemical Society
Dysplasia of the Upper Aerodigestive Tract Squamous Epithelium
Dysplasia of the oral, laryngeal and oropharyngeal stratified squamous epithelia is a microscopically defined change that may occur in clinically identifiable lesions including erythroplakia, leukoplakia and erythroleukoplakia, lesions that convey a heightened risk for carcinomatous progression. Dysplastic lesions have been classified microscopically according to degree of cytologic atypia and changes in architectural patterns, usually on a three part or four part gradation scale. Vocal cord epithelial lesions are graded according to either the Ljubljana or the World Health Organization (WHO) system whereas oral dysplasias are generally classified according to WHO criteria. Cytologically atypical cells are considered to represent precancerous changes predicting an increase risk for carcinomatous transformation. Inter- and intra-rater reliability studies among pathologists have disclosed low correlation coefficients for four part grading systems, whereas improved agreement is achieved (kappa correlation values) using the Ljubljana systems. Evidence forwarded by some studies supports the prognostic value of progressively severe dysplastic changes for carcinomatous transformation; however, some studies indicate that the presence of a clinically defined lesion without microscopic evidence of dysplasia also connotes increased risk for carcinomatous transformation. Loss of heterozygosity (LOH) at 3p and 9p microsatellite domains, DNA ploidy analysis and nuclear image analyses may have predictive value as molecular and histomorphological biomarkers
Metallothionein genes: no association with Crohn's disease in a New Zealand population
Metallothioneins (MTs) are excellent candidate genes for Inflammatory Bowel Disease (IBD) and have previously been shown to have altered expression in both animal and human studies of IBD. This is the first study to examine genetic variants within the MT genes and aims to determine whether such genetic variants have an important role in this disease. 28 tag SNPs in genes MT1 (subtypes A, B, E, F, G, H, M, X), MT2, MT3 and MT4 were selected for genotyping in a well-characterized New Zealand dataset consisting of 406 patients with Crohn's Disease and 638 controls. We did not find any evidence of association for MT genetic variation with CD. The lack of association indicates that genetic variants in the MT genes do not play a significant role in predisposing to CD in the New Zealand population
Gastric adenocarcinoma in a patient re-infected with H. pylori after regression of MALT lymphoma with successful anti-H. pylori therapy and gastric resection: a case report
BACKGROUND: Helicobacter pylori (H. pylori) has been etiologically linked with primary gastric lymphoma (PGL) and gastric carcinoma (GC). There are a few reports of occurrence of both diseases in the same patient with H. pylori infection. CASE PRESENTATION: We report a patient with PGL in whom the tumor regressed after surgical resection combined with eradication of H. pylori infection. However, he developed GC on follow up; this was temporally associated with recrudescence / re-infection of H. pylori. This is perhaps first report of such occurrence. CONCLUSIONS: Possible cause and effect relationship between H. pylori infection and both PGL and GC is discussed. This case also documents a unique problem in management of PGL in tropical countries where re-infection with H. pylori is supposed to be high
Expression of p21WAF1 in AstlerβColler stage B2 colorectal cancer is associated with survival benefit from 5FU-based adjuvant chemotherapy
In several, but not all, previous studies, positive p21WAF1 expression has been suggested as an indicator of a good prognosis in patients with stage III/IV colorectal cancer. However, it is not known whether the same is true for stage B2 patients. The purpose of this study is to assess the influence of p21WAF1 expression in tumor cells on disease-free survival (DFS) and overall survival (OS) of AstlerβColler stage B2 and C patients with colorectal cancer who underwent 5-fluorouracil-based adjuvant chemotherapy. Nuclear p21WAF1 was detected by immunohistochemistry in tissue microarrays from 275 colorectal cancers. The expression of p21WAF1 was associated with DFS (pβ=β0.025) and OS (pβ=β0.008) in the subgroup of stage B2 patients that was treated with adjuvant chemotherapy. In multivariate analysis, it remained the only independent prognostic parameter in relation to DFS and OS (pβ=β0.035 and pβ=β0.02, respectively). In the subgroup of 72 stage B2 patients with positive p21WAF1 expression but not in the subgroup of 61 stage B2 patients with negative p21WAF1 expression, adjuvant chemotherapy was associated with better DFS (85% 5-year survival versus 65% without chemotherapy, pβ=β0.03) and OS (96% versus 82%, pβ=β0.014). In the combined stage B2 and C group of patients treated with adjuvant chemotherapy, positive p21WAF1 expression was also associated with better DFS and OS (pβ=β0.03, pβ=β0.002, respectively). Expression of p21WAF1 in colorectal tumor cells identifies a subgroup of AstlerβColler stage B2 patients who could benefit significantly from 5FU-based chemotherapy and may improve the selection of patients for adjuvant chemotherapy
Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats
BACKGROUND: It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. METHODS: To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein): pregnant (N), tumor-bearing (WN), pair-fed rats (Np). Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine): leucine (L), tumor-bearing (WL) and pair-fed with leucine (Lp). Non pregnant rats (C), which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. RESULTS: Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. CONCLUSIONS: Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones
Application of functional genomics to primate endometrium: insights into biological processes
Endometrium is a dynamic tissue that responds on a cyclic basis to circulating levels of the ovarian-derived steroid hormones, estradiol and progesterone. Functional genomics has enabled a global approach to understanding gene regulation in whole endometrial tissue in the setting of a changing hormonal milieu. The proliferative phase of the cycle, under the influence of estradiol, has a preponderance of genes involved in DNA synthesis and cell cycle regulation. Interestingly, genes encoding ion channels and cell adhesion, as well as angiogenic factors, are also highly regulated in this phase of the cycle. After the LH surge, different gene expression profiles are uniquely observed in the early secretory, mid-secretory (window of implantation), and late secretory phases. The early secretory phase is notable for up-regulation of multiple genes and gene families involved in cellular metabolism, steroid hormone metabolism, as well as some secreted glycoproteins. The mid-secretory phase is characterized by multiple biological processes, including up-regulation of genes encoding secreted glycoproteins, immune response genes with a focus on innate immunity, and genes involved in detoxification mechanisms. In the late secretory phase, as the tissue prepares for desquamation, there is a marked up-regulation of an inflammatory response, along with matrix degrading enzymes, and genes involved in hemostasis, among others. This monograph reviews hormonal regulation of gene expression in this tissue and the molecular events occurring therein throughout the cycle derived from functional genomics analysis. It also highlights challenges encountered in using human endometrial tissue in translational research in this context
Infiltrating ductal and lobular breast carcinomas are characterised by different interrelationships among markers related to angiogenesis and hormone dependence
To obtain a more integrated understanding of the different breast cancer phenotypes and to investigate whether bio-molecular profiles can distinguish between specific histotypes, we explored the interrelations among several biologic variables indicative of, or related to, hormone dependence, proliferation and apoptosis control, and angiogenesis in ductal and lobular carcinomas, the most common histotypes. Oestrogen and progesterone receptors, tumour proliferative activity, the expression of cyclin A, p16ink4A, p27kip1, p21waf1, p53, bcl-2, and levels of vascular endothelial growth factor and hypoxia-inducible factor-1Ξ± (HIF-1Ξ±) were evaluated in 190 in ductal and 67 lobular carcinomas. Our findings support the hypothesis that in ductal and lobular carcinomas are two distinct, partially phenotypically unrelated entities, the latter being characterised by the presence of features indicative of differentiation such as oestrogen receptors, low proliferation and lack of p53 expression and associated with low vascular endothelial growth factor content compared to angiogenesis in ductal carcinomas. Conversely, no significant difference was found between lobular carcinomas and in ductal carcinomas considering the frequency distribution of PgR-positive cases, cyclin-dependent kinase inhibitors acting at the G1/S boundary, bcl-2 and HIF-1Ξ± protein expression. Although both generally defined as hormone responsive, in ductal and lobular carcinomas are also characterised by biologic patterns in which proteins related to hormone responsiveness, cell-cycle control, apoptosis and angiogenesis were differently associated. This finding suggests the need to refine breast cancer characterisation in order to provide detailed information about individual tumours, or subsets of tumours, that will help in defining optimal treatment approaches
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