MUC-1 expression in pleomorphic adenomas using two human milk fat globule protein membrane antibodies (HMFG-1 and HMFG-2)

Pleomorphic adenoma (PA) is the most common salivary gland tumor and its microscopic features and histogenesis are a matter of debate. Human milk fat globule protein membrane (HMFG) monoclonal antibodies (MoAbs) comprise a set of antibodies against the mucin 1 (MUC-1) protein detected in several salivary gland tumors. Objective The aim of this study was to assess the immunoexpression of the PA neoplastic cells to MUC-1 protein using HMFG-1 and HMFG-2 MoAbs, contrasting these results with those from normal salivary gland tissue. Material and Methods Immunohistochemical detection of MUC-1 protein using HMFG-1 and HMFG-2 MoAbs was made in 5 mm thick, paraffin embedded slides, and the avidin-biotin method was used. Results Positivity to HMFG-1 and HMFG-2 MoAbs was found in ductal, squamous metaplastic and neoplastic myoepithelial cells, keratin pearls and intraductal mucous material. Two kinds of myoepithelial cells were identified: classic myoepithelial cells around ducts were negative to both MoAbs, and modified myoepithelial cells were positive to both MoAbs. This last cellular group of the analyzed tumors showed similar MUC-1 immunoexpression to ductal epithelial cells using both HMFG antibodies. Intraductal mucous secretion was also HMFG-1 and HMFG-2 positive. Conclusions Our results showed there are two kinds of myoepithelial cells in PA. The first cellular group is represented by the different kinds of neoplastic myoepithelial cells and is HMFG-positive. The second one is HMFG-negative and represented by the neoplastic myoepithelial cells located around the ducts

MUC1, MUC2, MUC4, MUC5AC, Cdx2: immunohistochemical characteristics in polyps and adenocarcinoma of distal colon

Aim – to study MUC1, MUC2, MUC4, MUC5AC, Cdx2 immunohistochemical expression in polyps and adenocarcinoma of distal colon. Materials and methods. Pathomorphological and immunohistochemical studies of biopsies from 30 patients, which underwent colonoscopy with polypectomy, and surgical material from 30 patients, which underwent surgery for colorectal adenocarcinoma, were carried out. Results. Distal colonic polyps are different from unchanged mucosa by increased MUC-1 expression. Maximum expression levels of the marker are observed in serrated adenomas, which are characterized by high MUC-1 expression level. Median of MUC-1 expression in adenocarcinoma is greater than that in unchanged mucosa, however, less than in polyps. Comparative analysis of data of the study of MUC2 expression indicates that the maximum expression of the marker is characteristic of unchanged mucous membrane. Polyps are distinguished by lower MUC2 expression levels; among them, highest expression levels are observed in hyperplastic polyps, lesser – in serrated adenomas and adenomas. Distal colonic carcinoma has extremely low median of MUC2 expression. The highest levels of MUC4 expression are observed in hyperplastic polyps, somewhat lower – in unchanged mucosa. Serrated adenomas, adenomas and adenocarcinomas differs by lower MUC4 expression levels. The minimum level of the marker expression is observed in serrated adenomas. In polyps MUC5AC expression levels are greater than in adenocarcinoma. Expression of this marker is not detected in unchanged mucosa. The maximum median of MUC5AC expression is observed in serrated adenomas, which are characterized by high level of the marker expression, somewhat lower – in adenomas, and more lower in hyperplastic polyps. High Cdx-2 expression level characterizes serrated adenomas and adenocarcinoma. The average Cdx-2 expression level is observed in adenomatous polyps, hyperplastic polyps, and unchanged mucosa, with the medians of the marked expression decreasing in that sequence. Conclusions. Distal colon polyps are characterized by increased MUC1 and Cdx-2 expression levels, with parallel decrease of MUC2 expression level and aberrant MUC5AC expression. At the same time, serrated adenomas are distinguished by the greatest deviations of the studied markers expression levels. Adenocarcinoma of the distal colon, compared with polyps, is characterized by decrease of MUC1, MUC2 and MUC5AC expression levels

MUC-1 gene is associated with prostate cancer death: a 20-year follow-up of a population-based study in Sweden

Anti-adhesion mucins have proven to play an important part in the biology of several types of cancer. Therefore, we test the hypothesis that altered expression of MUC-1 is associated with prostate cancer progression. We retrieved archival tumour tissue from a population-based cohort of 195 men with localised prostate cancer (T1a-b, Nx, M0) that has been followed for up to 20 years with watchful waiting. Semi-automated, quantitative immunohistochemistry was undertaken to evaluate MUC-1 expression. We modelled prostate cancer-specific death as a function of MUC-1 levels accounting for age, Gleason grade and tumour extent, and calculated age-adjusted and multivariate adjusted hazard ratios (HR). Men that had tumours with an MUC-intensity lower or higher than normal tissue had a higher risk of dying in prostate cancer, independent of tumour extent and Gleason score (HR 5.1 and 4.5, respectively). Adjustment for Gleason grade and tumour stage did not alter the results. Men with a Gleason score ⩾7 and MUC-1 deviating from the normal had a 17 (RR=17.1 95% confidence interval=2.3–128) times higher risk to die in prostate cancer compared with men with Gleason score <7 and normal MUC-1 intensity. In summary, our data show that MUC-1 is an independent prognostic marker for prostate cancer death

The study of the expression of muc-1 in gastric carcinomas and its correlation with the clinico-pathological variables

Worldwide, Gastric cancer is the second most common type of cancer. Of the gastric cancer, adenocarcinoma is the most common malignancy. It comprises over 90% of all gastric cancers. Gastric mucins are synthesized by gastric epithelial cells which are cytoprotective. Mucins are glycoprotein with high molecular weight, which are membrane bound or secreted products synthesized by secretory epithelial cells. Mucins in general are classified as neutral and acidic. Normal gastric mucin is of neutral type. In neoplastic transformation of gastric mucosa, the neutral mucin production is decreased.. More than 15 mucin genes have been identified. MUC-1 expressed in tumor may function as an anti-adhesion molecule that inhibits cell to cell adhesion, inducing the release of cells from the tumor. In these manners MUC-1 expression may be associated with invasive or metastatic properties of tumor cells, resulting in poor prognosis for patients with gastric carcinoma showing MUC-1 expression. In the study period of 2 years from June 2013-June 2015, Gastric cancer had a peak incidence in the age group of 51 – 60 years, with the mean age of 55.5 years with 70% - in males and 30% in females. Males predominate in the ratio of 2 .3 : 1 . On immunohistochemistry with MUC1,the expression was membranous / cytoplasmic positivity (graded as 1+, 2+, 3+, Negative) which was seen in 64% of cases. An increase in expression of MUC1 positivity was seen with increasing age and intestinal type of gastric adenocarcinomas

A novel ex vivo lung cancer model based on bioengineered rat lungs

Introduction: Two-dimensional cell cultures have contributed substantially to lung cancer research, but 3D cultures are gaining attention as a new, more efficient, and effective research model. A model reproducing the 3D characteristics and tumor microenvironment of the lungs in vivo, including the co-existence of healthy alveolar cells with lung cancer cells, is ideal. Here, we describe the creation of a successful ex vivo lung cancer model based on bioengineered lungs formed by decellularization and recellularization.Methods: Human cancer cells were directly implanted into a bioengineered rat lung, which was created with a decellularized rat lung scaffold reseeded with epithelial cells, endothelial cells and adipose-derived stem cells. Four human lung cancer cell lines (A549, PC-9, H1299, and PC-6) were applied to demonstrate forming cancer nodules on recellularized lungs and histopathological assessment were made among these models. MUC-1 expression analysis, RNA-seq analysis and drug response test were performed to demonstrate the superiority of this cancer model.Results: The morphology and MUC-1 expression of the model were like those of lung cancer in vivo. RNA sequencing revealed an elevated expression of genes related to epithelial-mesenchymal transition, hypoxia, and TNF-α signaling via NF-κB; but suppression of cell cycle-related genes including E2F. Drug response assays showed that gefitinib suppressed PC-9 cell proliferation equally well in the 3D lung cancer model as in 2D culture dishes, albeit over a smaller volume of cells, suggesting that fluctuations in gefitinib resistance genes such as JUN may affect drug sensitivity.Conclusions: A novel ex vivo lung cancer model was closely reproduced the 3D structure and microenvironment of the actual lungs, highlighting its possible use as a platform for lung cancer research and pathophysiological studies

IMMUNOPHENOTYPIC CHARACTERISTICS OF INFLAMMATORY BREAST CANCER

The investigation enrolled 31 patients with inflammatory breast cancer (IBC) treated at the N. N. Blokhin Cancer Research Center from 2006 to 2008. IBC is diagnosed on the basis of signs of rapid progression, such as localized or generalized breast induration, red- ness and edema. IBC accounts for less than 5% of all diagnosed breast cancers and is the most lethal form of primary breast cancer. We studied tumor markers of the immunophenotype of IBC and levels and subpopulations of immunocompetent tumor-infiltrating cells. We found that expression of HLA-DR is in negative correlation with MUC-1 expression and lymphoid cells tumor infiltration is asso- ciated with the increase in T-cell subpopulations

Labeling of Anti-MUC-1 Binding Single Chain Fv Fragments to Surface Modified Upconversion Nanoparticles for an Initial in Vivo Molecular Imaging Proof of Principle Approach

In vivo optical Imaging is an inexpensive and highly sensitive modality to investigate and follow up diseases like breast cancer. However, fluorescence labels and specific tracers are still works in progress to bring this promising modality into the clinical day-to-day use. In this study an anti-MUC-1 binding single-chain antibody fragment was screened, produced and afterwards labeled with newly designed and surface modified NaYF4:Yb,Er upconversion nanoparticles as fluorescence reporter constructs. The MUC-1 binding of the conjugate was examined in vitro and in vivo using modified state-of-the-art small animal Imaging equipment. Binding of the newly generated upconversion nanoparticle based probe to MUC-1 positive cells was clearly shown via laser scanning microscopy and in an initial proof of principal small animal optical imaging approach

Intestinal anti-inflammatory effects of artichoke pectin and modified pectin fractions in the dextran sulfate sodium model of mice colitis. Artificial neural network modelling of inflammatory markers

Anti-inflammatory properties of artichoke pectin and modified fractions (arabinose- and galactose-free) used at two doses (40 and 80 mg kg−1) in mice with colitis induced by dextran sulfate sodium have been investigated. Expression of pro-inflammatory markers TNF-α and ICAM-I decreased in groups of mice treated with original and arabinose-free artichoke pectin while IL-1β and IL-6 liberation was reduced only in mice groups treated with original artichoke pectin. A decrease in iNOS and TLR-4 expression was observed for most treatments. Intestinal barrier gene expression was also determined. MUC-1 and Occludin increased in groups treated with original artichoke pectin while MUC-3 expression also increased in arabinose-free pectin treatment. Galactose elimination led to a loss of pectin bioactivity. Characteristic expression profiles were established for each treatment through artificial neural networks showing high accuracy rates (≥90%). These results highlight the potential amelioration of inflammatory bowel disease on mice model colitis through artichoke pectin administration.This work has been funded by MICINN of Spain, Projects AGL2014-53445-R and AGL2017-84614-C2-1-R. Carlos Sabater thanks his FPU Predoc contract from Spanish MECD (FPU14/ 03619)

Intestinal anti-inflammatory effects of artichoke pectin and modified pectin fractions in the dextran sulfate sodium model of mice colitis. Artificial neural network modelling of inflammatory markers

Anti-inflammatory properties of artichoke pectin and modified fractions (arabinose- and galactose-free) used at two doses (40 and 80 mg kg−1) in mice with colitis induced by dextran sulfate sodium have been investigated. Expression of pro-inflammatory markers TNF-α and ICAM-I decreased in groups of mice treated with original and arabinose-free artichoke pectin while IL-1β and IL-6 liberation was reduced only in mice groups treated with original artichoke pectin. A decrease in iNOS and TLR-4 expression was observed for most treatments. Intestinal barrier gene expression was also determined. MUC-1 and Occludin increased in groups treated with original artichoke pectin while MUC-3 expression also increased in arabinose-free pectin treatment. Galactose elimination led to a loss of pectin bioactivity. Characteristic expression profiles were established for each treatment through artificial neural networks showing high accuracy rates (≥90%). These results highlight the potential amelioration of inflammatory bowel disease on mice model colitis through artichoke pectin administration.This work has been funded by MICINN of Spain, Projects AGL2014-53445-R and AGL2017-84614-C2-1-R. Carlos Sabater thanks his FPU Predoc contract from Spanish MECD (FPU14/ 03619)