Endometriosis — insights into a multifaceted entity

   Firstly described at the end of nineteenth century, endometriosis remains an enigmatic disease, from etio­pathogenesis to specific markers of diagnosis and its ability to associate with malignancies. Our review has been designed from a historical perspective and steps up to an updated understanding of the disease, facilitated by relatively recent molecular and genetic progresses. Although the histopathological diagnosis is relatively simple, the therapy is difficult or ineffective. Experimental models have been extremely useful as they reproduce the human disease and allow the testing of different potential modulators or treatment options. Due to molecular resemblance to carcinogenesis, applications of anti-cancer agents are currently under scrutiny. The desired goal of an efficient therapy against symptomatic disease, along with associated infertility and malignancies, needs a deeper insight into the complex mechanisms involved in endometriosis initiation, development, and progres­sion. Current trends in genomic and proteomic approaches are useful for a more accurate classification and for the identification of new therapeutic targets

Periostin in ovarian carcinoma: from heterogeneity to prognostic value

Introduction. Periostin (POSTN), an extracellular matrix protein, is involved in tumor-associated extracellular matrix (ECM) remodeling. However, its potential value as a prognostic and/or predictive factor has not yet been confirmed. The present study aims to assess POSTN expression separately in tumor cells and stroma of different ovarian carcinoma (OC) histological types, and its relationship with clinicopathological features. Material and methods. 102 cases of different histological OC subtypes were immunohistochemically investigated, for POSTN expression assessment in both epithelial tumor cells and tumor stroma. Statistical analysis was performed to correlate POSTN profile with clinicopathological characteristics, therapeutic response, and survival. Results.  POSTN expression in epithelial tumor cells was significantly correlated with POSTN expression in tumor stroma. The expression of POSTN in tumor cells was associated with histological type, tumor type (type I and II), tumor recurrence, progression-free survival (PFS), and overall survival (OS), whereas stromal POSTN expression was significantly correlated with age, histological type, tumor type, grade, and stage, residual disease, tumor recurrence, response to chemotherapy, and OS. Survival analysis revealed significant differences of PFS and OS in patients with high POSTN expression in tumor cells and negative stromal POSTN expression compared to patients with low POSTN expression in tumor cells and positive stromal POSTN expression (PFS: hazard ratio (HR) = 2.11, 95% confidence interval (CI): 1.33–3.37, P = 0.002; OS: HR = 1.78, 95% CI: 1.09–2.89, P = 0.019). Conclusions. The comparative assessment of POSTN immunoexpression in two tumor compartments: in tumor cells and stroma, by use of different scoring systems revealed that higher stromal POSTN levels are evidently correlated with unfavorable clinical features and poorer prognosis, while POSTN expression in tumor cells seems to be associated with a better patient outcome

Multi-Faceted Role of Cancer-Associated Adipocytes in Colorectal Cancer

Colorectal cancer (CRC) is one of the most commonly diagnosed types of cancer, especially in obese patients, and the second cause of cancer-related death worldwide. Based on these data, extensive research has been performed over the last decades to decipher the pivotal role of the tumor microenvironment (TME) and its cellular and molecular components in CRC development and progression. In this regard, substantial progress has been made in the identification of cancer-associated adipocytes’ (CAAs) characteristics, considering their active role in the CCR tumor niche, by releasing a panel of metabolites, growth factors, and inflammatory adipokines, which assist the cancer cells’ development. Disposed in the tumor invasion front, CAAs exhibit a fibroblastic-like phenotype and establish a bidirectional molecular dialogue with colorectal tumor cells, which leads to functional changes in both cell types and contributes to tumor progression. CAAs also modulate the antitumor immune cells’ response and promote metabolic reprogramming and chemotherapeutic resistance in colon cancer cells. This review aims to report recent cumulative data regarding the molecular mechanisms of CAAs’ differentiation and their activity spectrum in the TME of CRC. A better understanding of CAAs and the molecular interplay between CAAs and tumor cells will provide insights into tumor biology and may open the perspective of new therapeutic opportunities in CRC patients

Synchronous, metachronous and metastatic tumors of the upper female genital tract

The occasional finding of simultaneous or metachronous multiple primary cancers in the upper genital tract may represent metastasis from one location to another or independent primary tumors. The overall survival of patients with simultaneous primary cancers of the ovary and uterus suggests multifocal rather than metastatic disease. Diagnosis relies upon conventional clinicopathological criteria. The distinction is important because the prognosis and treatment are different. Metastases to the female genital tract occur frequently in the ovary, sometimes the ovarian tumor being primarly manifested although the extragenital tumor remains occult. In perspective, global genetic profiling should determine the potential prognostic relevance of specific molecular alterations, by correlation of profiling data with patient outcome

Administration of valine, leucine, and isoleucine improved plasma cholesterol and mitigated the preatherosclerotic lesions in rats fed with hypercholesterolemic diet

Hypercholesterolemia has a major contribution to the occurrence and progression of atherosclerotic lesions. Recent studies report the involvement of branched-chain amino acids in cholesterol methabolism. The aim of this research was to evaluate the role of valine, leucine and isoleucine on the occurrence and progression of atherosclerosis in rats receiving hypercholesterolic diet. Material and methods: 50 male Wistar rats distributed into five groups with the following type of diets: group I (control) received standard diet; group II - cholesterol; group III - cholesterol and valine; group IV - cholesterol and leucine; group V - cholesterol and isoleucine. The experimental study was conducted over a period of 2 months. The animals were evaluated for the serum levels of total cholesterol at the beginning of the experiment, after 1 month and after 2 months. The collected tissue fragments of heart and aorta were prepared for the examination by optical microscopy in order to identify the atherosclerotic changes. Results: The most increased values of serum cholesterol were recorded in rats from group II (p=0.001), for the second and third evaluation. The histological examination showed early histopathological lesions on the vascular intima for the groups treated with cholesterol, valine, leucine, and isoleucine. These early changes (the occurrence of some superficial endothelial erosions, adhesion of erythrocytes and platelets) were correlated with the degree of the arterial wall damage, of the leukocytes adhesion to the arterial intima, and the discontinuities of the internal elastic lamina. Conclusion: The comparative study of the effects of the three essential amino acids revealed that valine induced a faster response than leucine and isoleucine on the improvement of biochemical parameters, but there were no significant differences between the three amino acids in terms of their protective ability, demonstrated by the histopathological lesion assessment

Angiosarcoma - molecular markers in histopathological diagnosis

Angiosarcoma of the breast represents an uncommon entity. This is a case report of a 36-year-old woman who had a primary angiosarcoma of the right breast. After detecting a mass in her breast, she underwent mastectomy. Routine histopathological techique, followed by immunohistochemistry for factor VIII, CD34, vimentin, desmin, and pan- cytokeratin were performed in order to obtain the positive and differential diagnosis. Six months after the surgery, the patient succumbed to multiple metastases. The clinical course corresponded to general poor prognosis of breast angiosarcoma. Vascular targeting approaches in modern therapies represent promising methods for improvement of angiosarcoma\'s prognosis

The impact of Human papilloma virus (HPV) infection on the development of cervical neoplasia

The genesis of uterine cervix carcinoma has as central etiology the active infection of human papilloma virus (HPV), especially high oncogenic risk subtypes. However, this is a necessary, but not sufficient cause of virtually all cases of cervical cancer worldwide. At present, the proportion of cervical carcinomas attributed to HPV infection is estimated at 99%. It is considered that the pathogenesis of cervical carcinoma is the result of the proliferation of one or, at most, a few HPV-infected cells. Invasive cervical cancer arises in cervical intraepithelial neoplasia, which in turn develops preferentially in squamous metaplasia of certain limited areas. These areas represent the most important morphologic characteristic in cervical intraepithelial neoplasia. It is still unknown the precise mechanism for the development of separate fields in HPV-related intraepithelial neoplasia and the variable susceptibility of reserve cells for different HPV genotypes. The goal of any cervical cancer screening test is to identify women who are at risk of cervical cancer development and to reassure others that do not belong to this category. Cervical cytology (Pap smears) were the primary screening tests. More recently, carcinogenic HPV DNA testing has been included as adjunctive test or as a primary screening test based on the central role of carcinogenic HPV infection in the development of cervical cancer. New biomarkers, including those that measure the interaction of host and virus, are being considered either as stand-alone molecular assays or in conjunction with cytology or carcinogenic HPV DNA testing to improve its sensitivity or specificity, respectively. .Profilactic HPV vaccination of women who are sexually active may provide protection against HPV-16 or HPV-18 infection which may lead to cytological abnormalities, precancer or cancer