Immunoexpression of metalloproteinase 14 and tissue inhibitor of metalloproteinase 2 in colorectal carcinomas and lymph node metastases

Abstract Changes in metalloproteinase (MMP) and tissue inhibitor of metalloproteinases (TIMP) have been associated with tumor progression in colorectal cancer. However, the role of MMP-14 and TIMP-2 has yet to be determined. We investigated the differential expression of MMP-14 and TIMP-2 in colorectal carcinomas of the left and the right colon, as well as in mononuclear cells in primary tumors and their lymph node metastases. We performed an immunohistochemistry analysis of tumor samples obtained from 50 cases of colorectal cancer. We found that MMP-14 staining was positive in 100 % of cases, in contrast to normal mucosa (86 % positivity, P = 0.0451). Additionally, neoplastic cells showed a higher frequency of TIMP-2-positive staining (70 % versus 14 % of normal mucosa, P = 0.0004). Furthermore, MMP-14 expression in primary tumor-associated mononuclear cells was higher in cases without lymph node metastases (N0) in comparison to more advanced carcinomas (N1–N3) (P = 0.0353). MMP-14 and TIMP-2 expression was observed in neoplastic cells in primary tumors, with a higher frequency of increased expression of MMP-14 (82 %) than increased expression of TIMP-2 (22 %, P 
Source: Comparative Clinical Pathology - Category: Pathology Source Type: research

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ConclusionsTaking into consideration the central role of inflammation in the pathophysiology of CRC and the recognised connection between inflammatory events and cancer, these results enlighten the relevance of the phenolic constituents of pennyroyal as important pharmacological sources in the investigation of new treatment options for patients with inflammatory bowel diseases.Graphical abstract
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
We describe two patients with advanced non ‐small‐cell lung cancer (NSCLC), including one in whom the definitive diagnosis of pulmonary pleomorphic carcinoma (PPC) was made by histopathology of the resected tumour and another in whom the diagnosis of “favor adenocarcinoma containing sarcomatoid components” was made by tissue biopsy. Both were resistant to first line platinum‐based chemotherapy, but responded dramatically to second line nivolumab therapy. We present two cases of pulmonary pleomorphic carcinoma (PPC) treated with Nivolumab. A 57 ‐year‐old man presented with a 3.5‐cm mass in the left l...
Source: Respirology Case Reports - Category: Respiratory Medicine Authors: Tags: Case Report Source Type: research
Retinoblastoma binding protein 6 (RBBP6) is a cancer-related protein that has been implicated in the regulation of cell cycle and apoptosis. RBBP6 isoform 1 has been demonstrated to interact with two tumour suppressors, p53 and pRB. Isoform 1 been shown to regulate p53 through its ubiquitin ligase activity, thus implicating in cell cycle regulation and apoptosis. Isoforms 1 and 2 are multidomain proteins containing a domain with no name (DWNN) domain, a Zinc Finger, a RING Finger, an Rb-binding domain and a p53-binding domain. The RBBP6 isoform 3 comprises the DWNN domain only. Isoform 4 lacks the Rb-binding domain but its...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Review Article Source Type: research
In this study, we provide both correlative and functional evidence that senescent fibroblasts and an essential SASP factor, GDF15, induce physiological and molecular changes that promote the adenoma-carcinoma initiation and progression sequence in the colon. We assessed the role of senescence and the SASP in CRC formation. Using primary human colon tissue, we found an accumulation of senescent fibroblasts in normal tissues from individuals with advanced adenomas or carcinomas in comparison with individuals with no polyps or CRC. In in vitro and ex vivo model systems, we induced senescence using oxidative stress in c...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
Publication date: Available online 12 August 2019Source: Pharmacological ResearchAuthor(s): Christian BaillyAbstractTwenty-five years ago, the cytotoxic drug irinotecan (IRT) was first approved in Japan for the treatment of cancer. For more than two decades, the IRT prodrug has largely contributed to the treatment of solid tumors worldwide. Nowadays, this camptothecin derivative targeting topoisomerase 1 remains largely used in combination regimen, like FOLFIRI and FOLFIRINOX, to treat metastatic or advanced solid tumors, such as colon, gastric and pancreatic cancers and others. This review highlights recent discoveries in...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
In conclusion, the antibacterial and cytotoxic activities suggested that the novel antifungalmycin N2 was a promising active structure to be developed as new drug for treating infectious diseases and cancers. PMID: 31411045 [PubMed - as supplied by publisher]
Source: Natural Product Research - Category: Biochemistry Authors: Tags: Nat Prod Res Source Type: research
In this study, we examined the role of endogenously produced IL-33 in the colon-26 tumor model, in which involvement of the IL-33:ST2 pathway was negligible on the tumor side. We found that the generation of regulatory T cells (Tregs) and CD8+ T cells, and IFN-γ expression by both CD4+ and CD8+ T cells (T cell activation) were impaired in IL-33-deficient mice. Overall antitumor responses, assessed by tumor growth and IFN-γ expression by tumor-infiltrating CD8+ T cells, were also impaired, even after Treg adjustment prior to tumor inoculation. These results indicate that endogenous IL-33 augmented CD8+ T cell-me...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research
Abstract Hepatocyte nuclear factor 4-alpha (HNF4α) is a highly conserved member of nuclear receptor superfamily of ligand-dependent transcription factors that is expressed in liver and gastrointestinal organs (pancreas, stomach, and intestine). In liver, HNF4α is best known for its role as a master regulator of liver-specific gene expression and essential for adult and fetal liver function. Dysregulation of HNF4α expression has been associated with many human diseases such as ulcerative colitis, colon cancer, maturity-onset diabetes of the young, liver cirrhosis, and hepatocellular carcinoma. How...
Source: World Journal of Gastroenterology - Category: Gastroenterology Authors: Tags: World J Gastroenterol Source Type: research
Abstract Colorectal cancer (CRC) is one of the most common causes of cancer mortality in the world. The incidence is related to increases with age and western dietary habits. Early detection through screening by colonoscopy has been proven to effectively reduce disease-related mortality. Currently, it is generally accepted that most colorectal cancers originate from adenomas. This is known as the "adenoma-carcinoma sequence", and several studies have shown that early detection and removal of adenomas can effectively prevent the development of colorectal cancer. The other two pathways for CRC development ...
Source: Medicina (Kaunas) - Category: Universities & Medical Training Authors: Tags: Medicina (Kaunas) Source Type: research
In this study, the effects of sole and dual CTLA-4 and PD-L1 blockade were investigated in a microsatellite stable highly aggressive orthotopic mouse model of colon cancer. Dual CTLA-4 and PD-L1 inhibition resulted in tumor growth stagnation and completely blocked liver metastasis. Sole CTLA-4 and PD-L1 inhibition only moderately reduced metastatic spread of the colon cancer cells, though CTLA-4 blockade being superior to PD-L1 inhibition. Dual immune checkpoint blockade and sole CTLA-4 inhibition significantly increased intratumoral CD8+ and CD4+ T cells and reduced FOXP3+/CD4+ Treg cells. This was associated with increas...
Source: Neoplasia - Category: Cancer & Oncology Authors: Tags: Neoplasia Source Type: research
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