Morphologic Subtypes of Hepatocellular Carcinoma

Tumor growth cascade is a complicated and multistep process with numerous obstacles. Until recently, evidences have shown the involvement of microRNAs (miRNAs) in tumorigenesis and tumor progression of various cancers, including colorectal cancer (CRC). In this study, we explored the role of miR-194 and its downstream pathway in CRC. We acquired data through miRNA microarray profiles, showing that the expression of miR-194 was significantly suppressed in CRC tissues compared with corresponding noncancerous tissues. Decreased miR-194 expression was obviously associated with tumor size and tumor differentiation, as well as TNM stage. Both Kaplan–Meier and multivariate survival analysis showed that downregulated miR-194 was associated with overall survival. Moreover, functional assays indicated that overexpression of miR-194 in CRC cell lines inhibited cell proliferation both in vitro and in vivo. In addition, using dual-luciferase reporter gene assay, we found MAP4K4 was the direct target of miR-194. Silenc...

https://www.tandfonline.com/doi/pdf/10.1080/15384101.2015.1007767

MiR-194, commonly repressed in colorectal cancer, suppresses tumor growth by regulating the MAP4K4/c-Jun/MDM2 signaling pathway

Background Idiopathic granulomatous mastitis (IGM) is a rare chronic inflammatory disease of the breast with unknown aetiology. Its treatment is controversial and the recurrence rate is high. The objectives of this study were to examine the demographic, sociocultural and clinical characteristics observed among a large cohort of IGM patients from Turkey and to identify factors related to the recurrence of IGM. Methods The study was designed as a multicentre retrospective study including 22 breast centres in Turkey. A total of 720 IGM patients are included in the study. Patient data were obtained from the patient's files and electronic records based on the study protocol. Patients' demographic, clinical, radiological, treatment and recurrence of IGM related characteristics were recorded. Results Our results revealed a statistically significant association between IGM recurrence and history of pregnancy, breastfeeding, breast infection and smoking (P 0.05). Conclusion Our findings show that history of pregnancy, breastfeeding, breast infection and smoking were the risk factors for IGM recurrence. As current treatment methods did not affect IGM recurrence, recurrence-related factors, such as breast infection and smoking, should be considered to eliminate while focusing on less invasive local treatment research.

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Factors related to recurrence of idiopathic granulomatous mastitis: what do we learn from a multicentre study?

On the Role of Galectin-3 in Cancer Metastasis : From the Bench to the Clinic and Back

// Arundhati Jana 1 , Nancy L. Krett 1 , Grace Guzman 2 , Ahmer Khalid 1 , Ozkan Ozden 1 , Jonas J. Staudacher 1 , Jessica Bauer 1 , Seung Hyun Baik 1 , Timothy Carroll 1 , Cemal Yazici 1 and Barbara Jung 1 1 Division of Gastroenterology and Hepatology, University of Illinois Medical College, Chicago, IL 60612, USA 2 Department of Pathology, University of Illinois Medical College, Chicago, IL 60612, USA Correspondence to: Barbara Jung, email: bjung@uic.edu Keywords: activin, NFkB, colon cancer, MDM2, migration Received: September 07, 2016     Accepted: February 09, 2017     Published: March 18, 2017 ABSTRACT Colorectal cancer (CRC) remains a common and deadly cancer due to metastatic disease. Activin and TGFB (TGFβ) signaling are growth suppressive pathways that exert non-canonical pro-metastatic effects late in CRC carcinogenesis. We have recently shown that activin downregulates p21 via ubiquitination and degradation associated with enhanced cellular migration independent of SMADs. To investigate the mechanism of metastatic activin signaling, we examined activated NFkB signaling and activin ligand expression in CRC patient samples and found a strong correlation. We hypothesize that activation of the E3 ubiquitin ligase MDM2 by NFkB leads to p21 degradation in response to activin treatment. To dissect the link between activin and pro-carcinogenic NFkB signaling and downstream targets, we found that activin but not TGFB induced activation of NFkB leading to increased MDM2 ubiquitin ligase via PI3K. Further, overexpression of wild type p65 NFkB increased MDM2 expression while the NFkB inhibitors NEMO-binding domain (NBD) and Bay11-7082 blocked the activin-induced increase in MDM2. In conclusion, in colon cancer cell migration, activin utilizes NFkB to induce MDM2 activity leading to the degradation of p21 in a PI3K dependent mechanism. This provides new mechanistic knowledge linking activin and NFkB signaling in advanced colon cancer which is applicable to targeted therapeutic interventions.

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NFkB is essential for activin-induced colorectal cancer migration via upregulation of PI3K-MDM2 pathway.

Pathologic evaluation of the appendix after appendectomy is routine and can occasionally identify unexpected findings The aim of the present study was to determine the incidence and type of pathologic diagnoses found in appendectomy specimens at our institution The clinicopathological data of 1627 patients who underwent appendectomies for presumed acute appendicitis from January 2008 to October 2014 were reviewed retrospectively There were 986 men and 641 women (sex ratio M/F = 15) aged between 16 months and 90 years (mean = 30 years) All patients underwent appendectomy (either open or laparoscopic) Histological examination of the surgical specimen showed acute inflammation of the appendix in 1455 cases (8942 %), fibrosed appendix in 37 cases (227 %), and Enterobius vermicularis (n = 23) In 101 cases (62 %), the appendix was histologically normal Incidental unexpected pathological diagnoses were noted in 57 appendectomy specimens They included pinworm (n = 23), mucinous neoplasms (n = 12), neuroendocrine tumors (NET) (n = 8), adenocarcinoma (n = 2), granulomatous inflammation (n = 5), tuberculosis (n = 2), hyperplastic polyp (n = 1), tubular adenoma (n = 1), diverticulitis (n = 1), endometriosis (n = 1), and actinomycosis (n = 1) The routine histopathological examination of the appendix is of value for identifying unsuspected conditions requiring further postoperative management Gross examination alone does not appear to be a good indicator of an unexpected finding on microscopic exam It is recommended that in order to avoid misdiagnoses, all appendices should be histopathologically examined

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Unexpected Histopathological Findings in Appendectomy Specimens: a Retrospective Study of 1627 Cases.

One of the most important pathways which are frequently affected in colorectal cancer is p53/ (MDM2)/p14ARF pathway. We aim to determine the methylation pattern of p14/ARF in relation to mutation of p53. This correlation was studied to investigate whether their alterations could be considered as a predictor factor of prognosis in colorectal cancer and whether it can be useful in early-stage diagnosis. Statistical analyses show that p14/ARF hypermethylation was correlated with rectum location (p = 0.004), primary TNM stage (p = 0.016), and advanced Astler–Coller stage (p = 0.024). The RT-PCR that revel 31 % of patients did not express p14/ARF mRNA or at very low level. A high concordance between CpG hypermethylation and the low levels (p < 0.005) was shown. In addition, our analyses demonstrate that patients with mutation in the p53 gene have a lack of the protein expression (p < 0.005). This category with negative expression of p53 had a shorter survival rate (p < 0.005). On the one hand, MSP pattern of p14/ARF were correlated with a lack of p53 expression (p = 0.007). We found that p53/p14ARF pathway was frequently deregulated among our patients. In our study, we demonstrate that hypermethylation of p14/ARF occurs early during CRC tumorogenesis. However, we did not find correlation between p14/ARF and survival. These results suggest that p14/ARF methylation pattern may constitute a predictor factor of CRC in early stage but it could not be considered as a prognostic factor. On the other hand and because of the reversibility of the methylation mechanism, it may be appropriate to target the demethylation of p14/ARF to develop new drogues for CRC.

/pdf/biological-significance-of-promoter-hypermethylation-of-p14-3j7djsvbes.pdf

Biological significance of promoter hypermethylation of p14/ARF gene: Relationships to p53 mutational status in Tunisian population with colorectal carcinoma

Background: Cystic neoplasms of the pancreas are rare and constitute approximately 0.5% of all pancreatic neoplasms. Aims: The study was to describe clinicopathological features of pancreatic cystic tumors. Patients and Methods: In our retrospective study, we reviewed 10 cases of pancreatic cystic neoplasms that were diagnosed at the pathology department of Mongi Slim hospital over a 14-year period (2000-2013). We adopted the latest World Health Organization (WHO) classification (2010) in grouping all tumors. Results: There were one male and nine female patients (sex ratio M/F = 1:9) aged between 21 and 68 years (mean = 37.5 years). The most common clinical presentation was epigastric and abdominal pain ( n = 6) followed by vomiting ( n = 3). Abdominal computed tomography (CT) scan disclosed a cystic lesion of the pancreas ranging in size between 2 and 10 cm (mean = 6.75 cm). All patients underwent surgical treatment. Histopathological examination of the surgical specimen established the diagnosis of solid pseudopapillary neoplasm ( n = 2), serous cystic neoplasm ( n = 2), mucinous cystadenoma ( n = 4), mucinous cystadenocarcinoma ( n = 1), and intraductal papillary mucinous neoplasm with invasive carcinoma ( n = 1). Conclusion: Better understanding of pancreatic cystic neoplasms is essential for clinicians to make accurate diagnosis and to provide the best management for patients.

Pancreatic cystic neoplasms.

Resume Introduction. – Les facteurs pronostiques jouent un role important en oncologie clinique, ils permettent au clinicien de selectionner les patients pour un traitement donne. Ces facteurs sont nombreux quand il s'agit des adenocarcinomes colorectaux. Dans cette etude, les auteurs analysent en uni- et multivariee les differents facteurs pronostiques ayant conditionne la survie d'une serie de 150 adenocarcinomes colorectaux reseques. Materiel et methodes. – Il s'agit d'une etude retrospective monocentrique realisee entre janvier 1990 et decembre 2002. Les 150 patients inclus etaient âges en moyenne de 58 ans (mediane de 61 ans) avec un sex-ratio (hommes/femmes) de 1,4. Dans tous les cas l'adenocarcinome etait confirme par les biopsies et l'examen histologique definitif de la piece operatoire. Sur le plan histologique, il etait bien differencie dans 69 cas (46 %), moyennement differencie dans 50 cas (33,3 %) et indifferencie dans 17 cas (11,3 %). Il y avait une composante colloide muqueuse ou adenocarcinome mucineux dans 14 cas (9,4 %). Resultats. – L'adenocarcinome etait de siege colique dans 84 cas (56 %) et rectal dans 66 cas (44 %). Une extension locoregionale etait retrouvee dans 18 cas (12 %) et a distance dans 45 cas (30 %), a type de metastases hepatiques dans 37 cas (82,2 %), de metastases pulmonaires dans huit cas (17,8 %) et de metastases a la fois hepatiques et pulmonaires dans six cas. Selon la classification de Dukes six patients(4 %) etaient stade I TNM, 61 stade II TNM (40,7 %), 51 stade III (34 %) et 32 stade IV TNM (34 %). Une chimiotherapie adjuvante etait realisee dans 60 cas des cancers coliques (a partir d'un stade II TNM). Une radiotherapie neoadjuvante etait realisee chez 33 patients porteurs d'un adenocarcinome rectal a la dose de 45 Gy. Une chimiotherapie systemique adjuvante etait realisee chez cinq patients porteurs d'un adenocarcinome rectal. Avec un recul moyen de 46 mois (extremes 5 a 96 mois), 35 sont perdus de vu, 52 patients sont decedes (Dix deces postoperatoires) et 63 sont vivants a la date de point. La survie mediane globale est de 20 mois avec un intervalle de confiance (IC 95 %) allant de 18,2 a 21,9 mois. Les taux de survie, tous stades confondus, a un an et cinq ans sont respectivement de 92,8 et 26,3 %. Differents facteurs pronostiques etaient identifies en analyse univariee apres analyse de la survie selon Kaplan-Meier et comparaison des taux de survie par le test du Log-rank ( p

Survie et facteurs pronostiques des adénocarcinomes colorectaux : étude analytique uni- et multifactorielle de 150 cas

IntroductionMDM2 was originally identified as an oncoprotein that binds to p53 and inhibits p53-mediated transactivation. Scientists have described functional single-nucleotide polymorphisms (SNP) in the MDM2 gene. They showed that the genotype of SNP 309 induces an increase in the level of MDM2 pro

Sabeh Mzabi

Papers

Unexpected Histopathological Findings in Appendectomy Specimens: a Retrospective Study of 1627 Cases.

Biological significance of promoter hypermethylation of p14/ARF gene: Relationships to p53 mutational status in Tunisian population with colorectal carcinoma

Pancreatic cystic neoplasms.

Survie et facteurs pronostiques des adénocarcinomes colorectaux : étude analytique uni- et multifactorielle de 150 cas

Impact of MDM2 polymorphism: increased risk of developing colorectal cancer and a poor prognosis in the Tunisian population.