Background
CXCL12 or stromal-derived factor-1 is a chemokine that binds to two receptors CXCR4 and CXCR7 and takes part in both physiological and pathological cell functions. The disruption of the ...CXCL12/CXCR4/CXCR7 chemokine axis is seen in various types of cancers.
Methods
We have immunohistochemically analyzed the expression of CXCL12 and its receptors in clear cell renal cell carcinoma patients. The study included 85 tissue samples. Since samples exhibited heterogeneity of expression intensity and staining localization (cytoplasmatic and membranous), histoscores were calculated, and their associations with clinicopathological parameters were analyzed.
Results
Both cytoplasmatic CXCR7 and CXCL12 histoscores were associated with greater tumour size, while CXCL12 staining was associated with a higher grade as well. Mortality was associated with tumour size and both membranous and cytoplasmatic CXCL12 histoscores. With each centimetre in tumour size, survival decreases 1.3 times, while CXCL12C histoscore higher than 73 was associated with 2.3 greater risk of mortality. CXCR4 histoscore could only be predicted by female gender and neither cytoplasmatic nor membranous CXCR4 expression was found to be a mortality predictor.
Conclusion
Our data suggest that regarding overall survival, CXCL12 could be considered a valuable prognostic marker.
CXCR4 and CXCR7 are chemokine receptors that bind with chemokine CXCL12 and influence various physiological and pathological processes. In renal cell carcinoma, their expression has been mostly ...associated with tumour aggressiveness. However, there are some contradictory results regarding the localization of immunohistochemical staining and predictive potential of these markers. The expression of CXCR4 and CXCR7 was immunohistochemicaly analyzed in 98 tumour samples, including 85 clear cell type (ccRCC) and 13 papillary type (pRCC). Depending on the staining localization (cytoplasmatic or membranous), intensity and percentage of stained cells, histoscores were calculated, and their association with clinicopathological parameters was analyzed. PRCC was associated with both CXCR7 and CXCR4 cytoplasmatic expression. We have also found that higher CXCR7 expression can be expected in tumours of greater size. In our study, mortality could be predicted by membranous CXCR7 histoscore, tumour size and pRCC type. With each centimetre in tumour size, survival decreases 1.2 times. CXCR7M histoscore higher by 50 units was associated with 1.5 greater risk of mortality. Neither membranous nor cytoplasmatic CXCR4 histoscore was found to be mortality predictor. Our data showed that CXCR7 could be considered as a valid prognostic marker regarding survival of RCC patients.
•CXCR7 expression in renal cell carcinoma is associated with poor OS.•CXCR7 expression in renal cell carcinoma increases with increasing tumour size.•Papillary renal cell carinoma type is associated with higher CXCR4 and CXCR7 expression
Disrupted NOTCH activity is a driving event in urothelial bladder cancer (UBC). After activation by hypoxia, the NOTCH3 receptor participates in tumor cell proliferation, acquisition of the ...epithelial-mesenchymal transition phenotype, and angiogenesis. The aim was to analyze the association of NOTCH3 expression with histopathological and clinical parameters, and to determine its predictive impact on the clinical outcome in UBC patients. The present research included 614 UBC samples incorporated in paraffin tissue microarrays, evaluated by immunohistochemistry for NOTCH3 expression. The accrual period was four years, while the follow-up period was two years. The membranous expression was semi-quantified (0-3), and the mean degree was 1.81±0.94. Criteria for semi-quantification the NOTCH3 expression were the intensity of the staining and the percentage of positive cells. The samples with negative (0) and weak (1) NOTCH3 immunohistochemical (IHC) score were considered negative, while the samples that showed moderate (2) and strong (3) expression were considered positive. Higher degree of positivity was associated with higher risk of cancer-specific mortality (p<0.001). Independent predictors for cancer-specific mortality were NOTCH3 expression and high stage (p<0.001). NOTCH3 expression was not a statistically significant predictor of recurrence-free survival (p=0.816). This study indicated that NOTCH3 is a predictor of poor outcome, suggesting that the NOTCH3 could be potentially reliable IHC marker for selecting the UBC patients that would require more intensive follow-up, especially if they diagnosed in higher stage, with divergent differentiation in pathological report, and without recurrences which would lead them to more frequent medical assessments.
Death receptor signalization that triggers the extrinsic apoptotic pathway and TGF-β1 have important roles in urothelial carcinogenesis, with a complex interplay between them. The aim of this ...research was to assess the association of death receptors DR4, DR5, and FAS as well as TGF-β1 immunohistochemical expression with the clinicopathological characteristics of urothelial bladder cancer (UBC) and to evaluate their prognostic significance. The decrease or loss of death receptors' expression was significantly associated with muscle-invasive tumors, while non-invasive UBC often retains the expression of death receptors, which are mutually strongly linked. High DR4 expression is a marker of low-grade tumors and UBC associated with exposition to known carcinogens. Conversely, TGF-β1 was significantly associated with high tumor grade and advanced stage. High expression of DR4 and FAS indicates longer overall survival. High TGF-β1 signifies an inferior outcome and is an independent predictor of adverse prognosis in UBC patients. This study reveals the expression profile of death receptors in UBC and their possible interconnection with TGF-β1 and indicates independent prognostic significance of high FAS and TGF-β1 expression in UBC, which may contribute to deciphering the enigma of UBC heterogeneity in light of the rapid development of novel and effective therapeutic approaches, including targeting of the TRAIL-induced apoptotic pathway.
Summary
During inflammation, lymphangiogenesis takes place to enhance the transport of filtered fluid, proteins, and immune cells. Dental pulp tissue is frequently exposed to inflammatory insults, ...but the lymphatic system of the pulp and its responses to injury have not been investigated in detail using specific lymphatic markers. The aim of this study was to evaluate and to compare the lymphatic system in health dental pulp and pulp with inflammation, and to establish whether lymphangiogenesis takes place during dental pulp inflammation.
Ten pulps with irreversibile pulpitis and eleven samples of healthy dental pulps were included in this study. All pulp samples were analyzed microscopically using the standard hematoxylin-eosin (HE) staining to detect the presence of inflammation. Immunohistochemical staining was performed using monoclonal anti-CD31 antibody (DAKO) at dilution 1:20. Microvessels identified by CD31, in which lumen the red blood cells were not detected, were considered as lymph vessels. Active areas of lymphangiogenesis (“hot spots”) were selected using low magnification. Images from five high power fields in the hot spot areas were recorded for each sample. Lymph vessels were counted using ImageJ program. The total number of lymph vessels so obtained was then divided by the number of the counted hot spots, and the result was used to denote the lymph vessel density.
The mean number of lymphatic vessels, detected by CD31, in the group without inflammation was significantly lower than in the group with inflammation (3.75 versus 13.58, t=7.093, p<0.001).
The present study established an increased number of lymphatic vessels in the inflamed human dental pulp suggesting that inflammation contributes to lymphangiogenesis.
During the past decade, a growing body of evidence has implied that cancer stem cells (CSCs) play an important role in the development of gastric cancer (GC). The notion that CSCs give rise to GC and ...may be responsible for invasion, metastasis, and resistance to treatment has profound implications for anti-cancer therapy. Recent major advances in the rapidly evolving field of CSCs have opened novel exciting opportunities for developing CSC-targeted therapies. Discovery of specific markers and signaling pathways in gastric CSCs (GCSCs), with the perfecting of technologies for identification, isolation, and validation of CSCs, may provide the basis for a revolutionary cancer treatment approach based on the eradication of GCSCs. Emerging therapeutic tools based on specific properties and functions of CSCs, including activation of self-renewal signaling pathways, differences in gene expression profiles, and increased activity of telomerase or chemoresistance mechanisms, are developing in parallel with advances in nanotechnology and bioengineering. The addition of GCSC-targeted therapies to current oncological protocols and their complementary application may be the key to successfully fighting GC.
The first line of defence in parasitic infection is the innate immune system. On the other hand, adaptive immune system posseses numerous mechanisams of hummoral and cellular immunity. Cellular ...immunity in a helminth infection is characterised by Th2 immune response. Considering the fact that the aim of a parasite is not to kill its host, the majority of parasites are highly addapted to the life inside the host, and succesefully avoid or limit its deffences. A special signifficance of the parasite as a potential pathogen is its possibility to escape immunity. Numerous helminths are releasing different substances that are acting as lymphocyte suppressors and macrophage inactivators and they are capable of destroying antibodies. They have a possibility of camouflage, sequestration and surface shell peeling with the aim to avoid immune response. Latest research in the field of immunology has revealed the significance of CD40 co-stimumlating protein of antigen presenting cells in the immune response to parasitic infection. Immune response in the course of parasitic infestion is important in pathogenesis of helminthioses.
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