Activation and Functions of Col6a1+ Fibroblasts in Colitis-Associated Cancer.

Cancer-associated fibroblasts (CAFs) comprise a group of heterogeneous subpopulations with distinct identities indicative of their diverse origins, activation patterns, and pro-tumorigenic functions. CAFs originate mainly from resident fibroblasts, which are activated upon different stimuli, including growth factors and inflammatory mediators, but the extent to which they also maintain some of their homeostatic properties, at least at the earlier stages of carcinogenesis, is not clear. In response to cytokines, such as interleukin 1 (IL-1) and tumor necrosis factor (TNF), as well as microbial products, CAFs acquire an immunoregulatory phenotype, but its specificity and pathophysiological significance in individual CAF subsets is yet to be determined.

The lncRNA Sweetheart regulates compensatory cardiac hypertrophy after myocardial injury in murine males.

After myocardial infarction in the adult heart the remaining, non-infarcted tissue adapts to compensate the loss of functional tissue. This adaptation requires changes in gene expression networks, which are mostly controlled by transcription regulating proteins. Long non-coding transcripts (lncRNAs) are taking part in fine-tuning such gene programs.

Fendrr synergizes with Wnt signalling to regulate fibrosis related genes during lung development via its RNA:dsDNA triplex element.

Long non-coding RNAs are a very versatile class of molecules that can have important roles in regulating a cells function, including regulating other genes on the transcriptional level. One of these mechanisms is that RNA can directly interact with DNA thereby recruiting additional components such as proteins to these sites via an RNA:dsDNA triplex formation. We genetically deleted the triplex forming sequence (FendrrBox) from the lncRNA Fendrr in mice and found that this FendrrBox is partially required for Fendrr function in vivo.

First genome-wide association study of esophageal atresia identifies three genetic risk loci at , //, and .

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci.

Col6a1/CD201 mesenchymal cells regulate intestinal morphogenesis and homeostasis.

Intestinal mesenchymal cells encompass multiple subsets, whose origins, functions, and pathophysiological importance are still not clear. Here, we used the Col6a1 mouse, which targets distinct fibroblast subsets and perivascular cells that can be further distinguished by the combination of the CD201, PDGFRα and αSMA markers. Developmental studies revealed that the Col6a1 mouse also targets mesenchymal aggregates that are crucial for intestinal morphogenesis and patterning, suggesting an ontogenic relationship between them and homeostatic PDGFRα telocytes.

Fibroblast Reprogramming in Gastrointestinal Cancer.

Gastrointestinal cancers are a significant cause of cancer mortality worldwide and have been strongly linked with chronic inflammation. Current therapies focus on epithelial/cancer cells; however, the importance of the tumor microenvironment in the development and treatment of the disease is also now well established. Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment, and are actively participating in tumor initiation, promotion and metastasis.

Human exome and mouse embryonic expression data implicate ZFHX3, TRPS1, and CHD7 in human esophageal atresia.

Introduction: Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) occurs approximately 1 in 3.500 live births representing the most common malformation of the upper digestive tract. Only half a century ago, EA/TEF was fatal among affected newborns suggesting that the steady birth prevalence might in parts be due to mutational de novo events in genes involved in foregut development.

BRACHYURY directs histone acetylation to target loci during mesoderm development.

T-box transcription factors play essential roles in multiple aspects of vertebrate development. Here, we show that cooperative function of BRACHYURY (T) with histone-modifying enzymes is essential for mouse embryogenesis. A single point mutation (T) results in decreased histone 3 lysine 27 acetylation (H3K27ac) at T target sites, including the locus, suggesting that T autoregulates the maintenance of its expression and functions by recruiting permissive chromatin modifications to putative enhancers during mesoderm specification.

Identification and Functional Characterization of Hypoxia-Induced Endoplasmic Reticulum Stress Regulating lncRNA (HypERlnc) in Pericytes.

Rationale: Pericytes are essential for vessel maturation and endothelial barrier function. Long noncoding RNAs regulate many cellular functions, but their role in pericyte biology remains unexplored.

Objective: Here, we investigate the effect of hypoxia-induced endoplasmic reticulum stress regulating long noncoding RNAs (HypERlnc, also known as ENSG00000262454) on pericyte function in vitro and its regulation in human heart failure and idiopathic pulmonary arterial hypertension.

Roles for long non-coding RNAs in physiology and disease.

While the vast majority of the genome is transcribed into RNA, only a small fraction of these transcripts have protein-coding potential. A large fraction of the transcribed RNA belongs to the class known as long non-coding RNAs (lncRNAs). Several recent studies have shown that at least some of these lncRNA transcripts represent functional RNA molecules.

A novel nomogram to predict the probability of prostate cancer on repeat biopsy.

Purpose: We developed a predictive model that incorporates clinical data and prostate specific antigen kinetic from general practice to detect prostate cancer in patients with a previously negative prostate biopsy.

Materials And Methods: From January 2001 to January 2007 data on 419 men who underwent repeat prostate biopsy with 12 or more cores were used to develop the nomogram. From February 2007 to June 2007 data on 63 men with the same criteria were used to validate the nomogram.

Intranodal myofibroblastoma: a case report and review of literature.

Intranodal myofibroblastoma is rare benign spindle cell neoplasm of lymph node, first described in 1989, that can be confused with other spindle cell tumor. Immunohistochemical and ultrastructural analysis are essential for a correct diagnosis. We reported a typical case of intranodal myofibroblastoma in a 72-year-old female, which is, to our knowledge, the 64th case described in literature.

High grade prostatic intraepithelial neoplasia with squamous differentiation.

An unusual variant of prostatic intraepithelial neoplasia with prominent and extensive squamous differentiation is described. The lesion was identified in the transition zone of a 79 year old man with a three year history of increasing urinary obstructive symptoms and a clinical diagnosis of benign prostatic hyperplasia who underwent simple prostatectomy. Two years after surgery, prostatic biopsies showed atrophy and mild chronic inflammation, with no evidence of malignancy.

A case of medullary sponge kidney (Cacchi-Ricci disease) mimicking a renal mass.

Medullary sponge kidney (MSK) is an uncommon benign congenital disorder, generally asymptomatic. In symptomatic patients the diagnosis is usually made by excretory urography performed in the most frequent complications such as renal stones, urinary tract infections and haematuria. Excretory urography can be very characteristic, showing cystic collections of ectatic collecting ducts like "bunches of grapes" or "bouquet of flowers".

Bladder carcinosarcoma: a case observation.

Carcinosarcoma of the bladder is a very unusual neoplasm that arises more frequently in males with a greater incidence in the seventh decade of life. There are no patognomonic clinical findings or symptoms to address its presence. Symptoms, as for other bladder cancers, are fundamentally represented by haematuria and dysuria.

[An autopsy case of neonatal lactic acidosis].

Defects in mitochondrial enzymes, such as pyruvate dehydrogenase and cytochrome oxidase, cause hereditary disorders which lead to modifications in cellular pH due to the accumulation of pyruvate and lactic acid. Mitochondrial diseases include severe neonatal diseases and less severe forms of adult diseases. We report the case of lactic acidosis in a newborn girl who was delivered at 36 weeks of gestation and who died 3 months after birth.

[Meconium peritonitis and feto-fetal transfusion syndrome].

A case of twin-to-twin transfusion syndrome with intrauterine death of one twin and meconium peritonitis and intravascular disseminated coagulation in the other twin is reported. Meconium peritonitis follows to bowel perforation, caused by segmental severe hypoplasia of muscular layer. The Authors suggest that this structural alteration of bowel wall could be an expression of inequal distribution of some cells between the two twins, during embrional development.

[Immunohistochemical and ultrastructural study of a case of carcinosarcoma (biphasic sarcomatoid carcinoma) of the lung with rhabdomyoblastic differentiation].

Histologic, immunohistochemical and ultrastructural features of a case of carcinosarcoma of the lung are described. The biphasic pattern of this neoplasm is characterized by the presence of a carcinomatous component that corresponds to an adenosquamous carcinoma, and a sarcomatous component with rhabdomyoblastic differentiation. Since the biphasic sarcomatoid carcinoma has an aggressive clinical behaviour, immunohistochemical expression of prognostic markers, such as Ki-67 and p53 is evaluated to individuate differences between the carcinomatous and the sarcomatous components of the tumor.

[Renal lymphoma: an atypical mass in search of characterization].

We report the case of a B cell, renal non-Hodgkin lymphoma come to our attention due to urologic symptoms. A review of the literature is provided and it is discussed the differential diagnosis with renal cell carcinoma.

[Total anomalous pulmonary venous drainage. Description of a case].

A case of total anomalous pulmonary venous drainage (TAPVD) is reported, which according to Darling classification corresponded to infradiaphragmatic type (type III) and is associated to pulmonary arterial thrombosis and infarctions. It's emphasized the need of an accurate dissection of cardiovascular system in perinatal necropsies, specially in cases of sudden infant death. By an appropriate dissection, cardiovascular malformations can be recognized.

[Comparative study of endocrine differentiation in early and advanced stomach carcinoma].

To comparatively evaluate the frequency of the neuroendocrine differentiation in the early and in the advanced stage of the disease, 189 gastric carcinomas (67 early gastric cancers and 122 advanced gastric cancers) were studied by immuno-histochemistry using a monoclonal antibody against chromogranin A (CgA). CgA-positive tumor cells were detected in 55 of 189 gastric carcinomas (29.1%).

[The histopathological and microbiological aspects in a model of acute acalculous cholecystitis: an experimental study].

The early stages of acute acalculous cholecystitis (ACC) have been difficult to investigate due to the animal models developed and utilized over the past years. A new model of animal AAC induced by intra-abdominal sepsis is presented. Under general anesthesia 35 guinea pigs underwent laparotomy.