Παρασκευή 25 Δεκεμβρίου 2015

Pelvic MRI findings in relapsed prostate cancer after radical prostatectomy

Little is known about the clinical impact of using multiparametric MRI to plan early salvage radiotherapy after radical prostatectomy. We aimed to evaluate the incidence and location of recurrence based on pel...

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Contemporary reviews on cancer treatment



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Cytotoxic drugs: past, present and future



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The number of polyploid giant cancer cells and epithelial-mesenchymal transition-related proteins are associated with invasion and metastasis in human breast cancer

Abstract

Background

Previously, we reported that polyploid giant cancer cells (PGCCs) induced by cobalt chloride (CoCl2) could have generated daughter cells with strong invasiveness and migration capabilities via asymmetric divisions. This study compared the expression of epithelial-mesenchymal transition (EMT)-related proteins, including E-cadherin, N-cadherin, and vimentin, between PGCCs and their daughter cells, and control breast cancer cell lines MCF-7 and MDA-MB-231. The clinicopathological significance of EMT-related protein expression in human breast cancer was analyzed.

Methods

Western blot was used to compare the expression levels of E-cadherin, N-cadherin, and vimentin in breast cancer lines MCF-7 and MDA-MB-231, between PGCCs with budding daughter cells and control breast cancer cells. Furthermore, 167 paraffin-embedded breast tumor tissue samples were analyzed, including samples obtained from 52 patients with primary breast cancer with lymph node metastasis (group I) and their corresponding lymph node metastatic tumors (group II), 52 patients with primary breast cancer without metastasis (group III), and 11 patients with benign breast lesions (group IV). The number of PGCCs was compared among these four groups.

Results

The number of PGCCs increased with the malignant grade of breast tumor. Group IIhad the highest number of PGCCs and the differences among group I, II, III and IV had statistically significance (P =0.000). In addition, the expression of E-cadherin (P = 0.000), N-cadherin (P = 0.000), and vimentin (P = 0.000) was significantly different among the four groups. Group II exhibited the highest expression levels of N-cadherin and vimentin and the lowest expression levels of E-cadherin.

Conclusions

These data suggest that the number of PGCCs and the EMT-related proteins E-cadherin, N-cadherin, and vimentin may be valuable biomarkers to assess metastasis in patients with breast cancer.



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Obesity is associated with insulin resistance but not skeletal muscle dysfunction or all-cause mortality

Abstract

Recent work has found that older adults with obesity and systemic inflammation have associated metabolic dysfunction but do not have associated lower lean mass or strength. However, this lean mass estimate may be inflated with obesity, given that 15 % of adipose tissue is composed of fat-free tissue. The primary purpose of this study was to investigate, in a nationally representative sample of adults, whether obese adults with chronic systemic inflammation (unhealthy) have differences in lean mass, muscle strength, and insulin resistance when compared to normal weight individuals without elevated levels of systemic inflammation (healthy). A secondary objective was to determine whether these potential differences were moderated by physical activity and to determine if these groups had a differential risk for all-cause mortality. Our findings suggests that the unhealthy group was associated with higher upper body lean mass (β = 823; 95 % confidence interval (CI) 637–1010; P < 0.001), lower body lean mass (β = 2724; 95 % CI 2291–3158; P < 0.001), and strength (β = 34.6; 95 % CI 13.5–55.7; P = 0.003) compared to the healthy group despite having systemic inflammation and correcting for fat-free adipose tissue. However, the unhealthy group was associated with insulin resistance (odds ratio (OR) = 16.1; 95 % CI 2.7–96.1; P = 0.005) although this finding was attenuated in those physically active (OR = 8.5; 95 % CI 2.43–30.15; P = 0.003). Despite this metabolic dysfunction, there was no difference in all-cause mortality risk between groups (hazard ratio (HR) = 1.16 (95 % CI 0.69–1.96; P = 0.54)) suggesting that higher amounts of lean mass and strength may be protective of premature mortality.



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Πέμπτη 24 Δεκεμβρίου 2015

The relationship between circulating 25-hydroxyvitamin D and survival in newly diagnosed advanced non-small-cell lung cancer

Abstract

Background

Serum 25-hydroxyvitamin D [25(OH)D], the major circulating form of vitamin D used for evaluating the vitamin D status of patients, has been associated with survival in a variety of cancers with conflicting evidence. We aimed to investigate this association in newly diagnosed advanced non-small-cell lung cancer (NSCLC) patients.

Methods

This was a consecutive cohort of 359 newly diagnosed stages III-IV NSCLC patients who underwent a baseline serum 25(OH)D evaluation prior to receiving any treatment at our institution between January 2008 and December 2010. We used the vitamin D categories of "deficient (<20 ng/ml)" and "not deficient (> = 20 ng/ml)". Cox regression was used to evaluate the prognostic significance of serum 25(OH)D after adjusting for relevant confounders.

Results

Mean age at diagnosis was 57.4 years. Of the 359 patients, 151 (42.1 %) were deficient in vitamin D at the time of diagnosis. The median survival in deficient and not deficient cohorts was 11.7 and 12.8 months respectively (p = 0.06). Season of diagnosis, performance status, smoking status and hospital location significantly predicted vitamin D status. On univariate Cox analysis, gender, stage of disease, hospital location, histologic subtype, subjective global assessment (SGA), performance status, smoking status, body mass index and serum albumin were significantly associated with survival (p <0.05 for all). On multivariate Cox analysis, six variables demonstrated statistically significant associations with survival: stage of disease, hospital location, histologic subtype, SGA, smoking status and serum albumin (p <0.05 for all). Serum vitamin D, which was borderline significant in univariate analysis, lost its significance in multivariate analysis.

Conclusions

We found season of diagnosis, performance status and smoking history to be predictive of vitamin D status. Consistent with previously published research in advanced NSCLC, we did not find any significant association between pre-treatment serum 25(OH)D and survival in our patients.



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Role of HLA-G and extracellular vesicles in renal cancer stem cell-induced inhibition of dendritic cell differentiation

Abstract

Background

Tumor immune-escape has been related to the ability of cancer cells to inhibit T cell activation and dendritic cell (DC) differentiation. We previously identified a tumor initiating population, expressing the mesenchymal marker CD105, which fulfills the criteria for definition as cancer stem cells (CD105+ CSCs) able to release extracellular vesicles (EVs) that favor tumor progression and metastases. The aim of the present study was to compare the ability of renal CSCs and derived EVs to modulate the behavior of monocyte-derived DCs with a non-tumor initiating renal cancer cell population (CD105- TCs) and their EVs.

Methods

Maturation of monocyte-derived DCs was studied in presence of CD105+ CSCs and CD105- TCs and their derived EVs. DC differentiation experiments were evaluated by cytofluorimetric analysis. T cell proliferation and ELISA assays were performed. Monocytes and T cells were purified from peripheral blood mononuclear cells obtained from healthy donors.

Results

The results obtained demonstrate that both CD105+ CSCs and CD105- TCs impaired the differentiation process of DCs from monocytes. However, the immune-modulatory effect of CD105+ CSCs was significantly greater than that of CD105- TCs. EVs derived from CD105+ CSCs and in less extent, those derived from CD105- TCs retained the ability to impair monocyte maturation and T cell activation. The mechanism has been mainly related to the expression of HLA-G by tumor cells and to its release in a form associated to EVs. HLA-G blockade significantly reduced the inhibitory effect of EVs on DC differentiation.

Conclusions

In conclusion, the results of the present study indicate that renal cancer cells and in particular CSCs and derived EVs impair maturation of DCs and T cell immune response by a mechanism involving HLA-G.



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