The chemokine-like peptide, chemerin, stimulates chemotaxis in several cell types. In this study we examined the expression of putative chemerin receptors in gastric cancer and the action of chemerin on cancer cell migration and invasion. Immunohistochemical studies of gastric tumors identified expression of two putative receptors, chemokine-like receptor-1 (CMKLR1) and G-protein coupled receptor 1(GPR1), in cancer cells; there was also some expression in stromal myofibroblasts although generally at a lower intensity. The expression of both receptors was detected in a gastric cancer cell line, AGS; chemerin itself was expressed in cultured gastric cancer myofibroblasts but not AGS cells. Chemerin stimulated (a) morphological transformation of AGS cells characterized by extension of processes and cell scattering, (b) migration in scratch wound assays and (c) both migration and invasion in Boyden chamber chemotaxis assays. These responses were inhibited by two putative receptor antagonists CCX832 and α-NETA. Inhibition of receptor expression by siRNA selectively reduced CMKLR1 or GPR1 and inhibited the action of chemerin indicating that both receptors contributed to the functional response. Using a proteomic approach employing stable isotope dynamic labeling of secretomes (SIDLS) to selectively label secreted proteins, we identified down regulation of tissue inhibitors of metalloproteinease (TIMP)1 and TIMP2 in media in response to chemerin. When cells were treated with chemerin and TIMP1 or TIMP2 the migration response to chemerin was reduced. The data suggest a role for chemerin in promoting the invasion of gastric cancer cells via CMKLR1 and GPR1at least partly by reducing TIMP1 and TIMP2 expression. Chemerin receptor antagonists have potential in inhibiting gastric cancer progression.
Matrix metalloproteinase (MMP)‐7, unlike many MMPs, is typically expressed in epithelial cells. It has been linked to epithelial responses to infection, injury, and tissue remodeling including the progression of a number of cancers. We have now examined how MMP‐7 expression changes in the progression to esophageal adenocarcinoma (EAC), and have studied mechanisms regulating its expression and its functional significance. Immunohistochemistry revealed that MMP‐7 was weakly expressed in normal squamous epithelium adjacent to EAC but was abundant in epithelial cells in both preneoplastic lesions of Barrett's esophagus and EAC particularly at the invasive front. In the stroma, putative myofibroblasts expressing MMP‐7 were abundant at the invasive front but were scarce or absent in adjacent tissue. Western blot and ELISA revealed high constitutive secretion of proMMP‐7 in an EAC cell line (OE33) that was inhibited by the phosphatidylinositol (PI) 3‐kinase inhibitor LY294002 but not by inhibitors of protein kinase C, or MAP kinase activation. There was detectable proMMP‐7 in cultured esophageal myofibroblasts but it was undetectable in media. Possible metabolism of MMP‐7 by myofibroblasts studied by proteomic analysis indicated degradation via extensive endopeptidase, followed by amino‐ and carboxpeptidase, cleavages. Myofibroblasts exhibited increased migration and invasion in response to conditioned media from OE33 cells that was reduced by MMP‐7 knockdown and immunoneutralization. Thus, MMP‑7 expression increases at the invasive front in EAC which may be partly attributable to activation of PI 3‐kinase. Secreted MMP‐7 may modify the tumor microenvironment by stimulating stromal cell migration and invasion.
Background Prostatic diseases such as inflammation, benign prostatic hyperplasia, and tumors are prime causes of mortality and morbidity in males. The prevalence of these lesions increases with advancing age. The second most common cancer among males is prostate cancer, next to lung cancer worldwide. Aim The present study was undertaken with the aim of studying the clinicopathological characteristics of prostate lesions in surgical specimens Methods The present study was a retroprospective study. A total of 212 prostate surgical specimens were included. Information provided in the requisition form regarding age, type of prostatic biopsy and clinical presentation, and histopathological diagnosis was taken into consideration and recorded. All specimens were fixed in 10% neutral buffered formalin and 5μ sections were stained with hematoxylin and eosin stain (H&E stain). Relevant clinical data including age, the presenting complaints, and S.PSA values were recorded. Data were collected and analyzed using simple statistical methods with Microsoft Excel 2016. Results Out of 212 cases analyzed, 161 (76%) were transurethral resection of prostate (TURP) TUPR specimens, 38 (18%) were trucut needle biopsies, and 13 (6%) were open prostatectomy specimens. The youngest patient was 48 years old while the oldest patient was 90 years old with a mean of 71.7 ± 8.2 years. Of the total 212 surgical specimens, 174 (82%) cases were of benign prostatic hyperplasia (BHP), and 38 (18%) were prostatic adenocarcinoma (PAC). Also, 94 (44.3%) of BPH and carcinoma of the prostate cases were most common in the seventh decade of life (61-70 years). Difficulty in micturition was the most common presentation 82 (39%). A maximum number of the BPH cases 81 (46.5%) had the prostate-specific antigen range of 0 to 4 ng/mL. The highest value of serum PSA was noted among the PAC patients in the range of > 80 ng/mL. Out of 38 cases of prostatic adenocarcinoma, moderately differentiated (Gleason scores 7) was the most common core and was seen in 42.1% of the PAC cases. Conclusion The present study showed that the most frequently encountered prostatic lesion was BHP, commonly seen in the age group of 61 to 70 years. The PAC was common among males of more than 60 years. Histopathological examination is the best diagnostic tool for PAC
Background: Colorectal carcinoma (CRC) is the most common and one of the main causes of mortality and morbidity globally among gastrointestinal tract tumors. A benign polyp is the first step in the multistage pathogenesis of colorectal cancer, which eventually progresses to an adenoma and a carcinoma. Wnt/ βeta-catenin signaling pathway plays an initiating and rate-limiting role in colorectal tumorigenesis. Aim of the work: To evaluate the association between the immunohistochemistry (expression of E-cadherin, and β-catenin with the histopathological grade, and stage of colorectal cancer. Materials and Methods: The study was retrospectively collected from the archives of the Department of Pathology in Tobruk Medical Center. Eighty-two histopathologically confirmed cases of adenomas (n = 48) (tubular, villous, and tubulovillous), and colorectal adenocarcinoma (Mucinous, and Non-mucinous) (n = 34) were included in this study over two years (2021-2023). The histopathological diagnosis, grade, and staging of the tumors were obtained. While clinical information was obtained from medical records and pathology reports. immunohistochemical staining was performed for all the cases using E-cadherin and β-catenin antibodies, and the results were analyzed. Results: A total of 82 patients were studied out of these, 51(62.2%) patients were male, whereas 31 (37.8%) were females with a male: female ratio of 1.6:1. Age ranged from 30 years to 80 years. The mean age was the mean age of 52.9 (SD±15.8). A high prevalence of adenoma cases was observed in the age group 30– 40 years. The peak incidence for both types of colorectal carcinoma was in 61-70 years. By scoring the intensity of β-catenin there are significant correlation of β-catenin expression with tumor grade, stage, lymph node metastasis, and types of adenomas. The intensity of staining of E-cadherin in 48 cases of adenomas was showing high expression in 39 cases (81.3%), and low expression in only 9 cases (18.7%). While, the majority of the patients with CRC (58.8%) had low expression of E-cadherin levels, and (41.2%) had high expression. Conclusion: Our findings imply that E-cadherin and β-catenin may contribute to the invasion and progression of colorectal cancer, which may serve as prognostic indicators for colorectal carcinoma
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