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We present two cases of family members (first cousins) with short extremities caused by a novel variant of COL2A1 gene (NM_001844.5). Case 1 description: A 29-year-old woman presented in her first pregnancy for a second trimester anomaly scan at 23 weeks of gestation. Fetal long bones were measured below the third centile for gestational age. Follow-up scans revealed fetal long bone growth deceleration. Initial genetic work-up was negative and the rest of the maternal follow-up was unremarkable. A male baby weighing 3180 g was delivered at 39 weeks and 4 days of gestation. Case 2 description: A 33-year-old pregnant woman presented for a routine second trimester anomaly scan at 20 weeks and 4 days of gestation. All fetal measurements were appropriate for the gestational age. The routine growth scan performed at 32 weeks showed fetal long bone measurements below the third centile for gestational age, while the follow-up growth scan at 36 weeks and 4 days of gestation revealed consistent, below the third centile, fetal long bone growth. Given that the fetuses of these two cases were related (first cousins), whole exome sequencing (WES) was performed on Case 2. WES revealed a novel heterozygous missense variant c.1132G>A (p. Gly378Ser) of COL2A1 gene (NM_001844.5). Subsequently, targeted genetic sequencing for the variant was performed on Case 1 and the same novel variant was found. Targeted sequencing revealed the same variant in the mother of Case 1 and the father of Case 2 (siblings). A female baby weighing 3200 g was delivered at 40 weeks and 4 days of gestation. © 2022 by the authors.

Despite the advances in the field of reproductive medicine, implantation failure represents a challenging condition affecting 10–30% of patients subjected to in vitro fertilization (IVF). Research has focused on the identification of molecules playing crucial roles in endometrial receptivity, with the aim of designing predictive tools for efficient detection of the implantation window. To that end, novel molecular genomic and transcriptomic approaches have been introduced as promising tools to enable personalized approaches with the aim of optimizing embryo transfer dating. However, the clinical value of these approaches remains unclear. The aim of this study is to provide a systematic review and critical analysis of the existing evidence regarding the employment of commercially available novel approaches to evaluate endometrial receptivity. An Embase and PubMed/Medline search was performed on 1 February 2022. From the 475 articles yielded, only 27 were included and analyzed. The considerable heterogeneity of the included articles indicates the uniqueness of the implantation window, showcasing that the optimal time for embryo transfer varies significantly between women. Moreover, this study provides information regarding the technical aspects of these advanced molecular tools, as well as an analysis of novel possible biomarkers for endometrial receptivity, providing a basis for future research in the field. © 2022 by the authors.

OBJECTIVE: Endometrial cancer is increasingly prevalent in western societies and affects mainly postmenopausal women; notably incidence rates have been rising by 1.9% per year on average since 2005. Although the early-stage endometrial cancer can be effectively managed with surgery, more advanced stages of the disease require multimodality treatment with varying results. In recent years, endometrial cancer has been extensively studied at the molecular level in an attempt to develop effective therapies. Recently, a family of compounds that alter epigenetic expression, namely histone deacetylase inhibitors, have shown promise as possible therapeutic agents in endometrial cancer. The present review aims to discuss the therapeutic potential of these agents. MATERIALS AND METHODS: This literature review was performed using the MEDLINE database; the search terms histone, deacetylase, inhibitors, endometrial, targeted therapies for endometrial cancer were employed to identify relevant studies. We only reviewed English language publications and also considered studies that were not entirely focused on endometrial cancer. Ultimately, sixty-four articles published until January 2018 were incorporated into our review. RESULTS: Studies in cell cultures have demonstrated that histone deacetylase inhibitors exert their antineoplastic activity by promoting expression of p21WAF1 and p27KIP1, cyclin-dependent kinase inhibitors, that have important roles in cell cycle regulation; importantly, the transcription of specific genes (e.g., E-cadherin, PTEN) that are commonly silenced in endometrial cancer is also enhanced. In addition to these abstracts effects, novel compounds with histone deacetylase inhibitor activity (e.g., scriptaid, trichostatin, entinostat) have also demonstrated significant antineoplastic activity both in vitro and in vivo, by liming tumor growth, inducing apoptosis, inhibiting angiogenesis and potentiating the effects of chemotherapy. CONCLUSIONS: The application

With a lifetime risk estimated to be one in eight in industrialized countries, breast cancer is the most frequent type of cancer among women worldwide. Patients are often treated with anti-estrogens, but it is common that some tumors develop resistance to therapy. The causation and progression of cancer is controlled by epigenetic processes, so there is an ongoing interest in research into mechanisms, genes and signaling pathways associating carcinogenesis with epigenetic modulation of gene expression. Given the fact that histone deacetylases (HDACs) have a great impact on chromatin remodeling and epigenetics, their inhibitors have become a very interesting field of research. Aim: This review focused on the use of HDAC inhibitors as anticancer treatment and explains the mechanisms of therapeutic effects on breast cancer. We anticipate further clinical benefits of this new class of drugs, both as single agents and in combination therapy. Molecules such as suberoylanilide hydroxamic acid, trichostatin A, suberoylbis-hydroxamic acid, panobinostat, entinostat, valproic acid, sodium butyrate, SK7041, FTY720, N-(2-hydroxyphenyl)-2-propylpentanamide, Scriptaid, YCW1, santacruzamate A and ferrocenyl have shown promising antitumor effects against breast cancer. HDAC inhibitors consists an attractive field for targeted therapy against breast cancer. Future therapeutic strategies will include combination of HDAC inhibitors and chemotherapy or other inhibitors, in order to target multiple oncogenic signaling pathways. More trials are needed.

Malignant melanoma of the vagina is a rare, aggressive malignancy of poor prognosis. It principally affects post-menopausal women, with a mean age of 57 years, and the factors that contribute to its appearance are not well known. The first case of primary malignant vaginal melanoma was reported in 1887 and modern literature has noted about 500 cases, globally. Vaginal melanomas constitute 0.3% of all malignant melanomas and fewer than 3% of all vaginal carcinomas. To date there is no clear consensus regarding treatment. An early, accurate diagnosis and prompt investigation is essential in reaching appropriate treatment decisions. We present a clinical case of primary vaginal melanoma and review the literature briefly, presenting the current treatment plans and updates of this rare gynecological malignancy. Considerations, epidemiology, associated risk factors, response to therapy and expected outcome are also discussed. Conclusion: Primary malignant vaginal melanoma is a rare but aggressive melanoma that affects women in their 6th and 7th decade of life. The tumor appears as a dark node or spindle but can also be amelanotic. The size of the tumor is indicative of the prognostic factors. Surgery seems to be the only efficient treatment. Postoperative adjuvant therapy might help in preventing recurrence of the tumor. The survival rate is largely dependent on nodal and distant metastasis of the disease after initial tumor resection. There is a dire need to form a proper therapeutic regime to control this disease.

Triple-negative breast cancer (TNBC) lacks expression of estrogen receptor (ER), progesterone receptor (PR) and HER2 gene. It comprises approximately 15-20% of breast cancers (BCs). Unfortunately, TNBC's treatment continues to be a clinical problem because of its relatively poor prognosis, its aggressiveness and the lack of targeted therapies, leaving chemotherapy as the mainstay of treatment. It is essential to find new therapies against TNBC, in order to surpass the resistance and the invasiveness of already existing therapies. Given the fact that epigenetic processes control both the initiation and progression of TNBC, there is an increasing interest in the mechanisms, molecules and signaling pathways that participate at the epigenetic modulation of genes expressed in carcinogenesis. The acetylation of histone proteins provokes the transcription of genes involved in cell growth, and the expression of histone deacetylases (HDACs) is frequently up-regulated in many malignancies. Unfortunately, in the field of BC, HDAC inhibitors have shown limited effect as single agents. Nevertheless, their use in combination with kinase inhibitors, autophagy inhibitors, ionizing radiation, or two HDAC inhibitors together is currently being evaluated. HDAC inhibitors such as suberoylanilidehydroxamic acid (SAHA), sodium butyrate, mocetinostat, panobinostat, entinostat, YCW1 and N-(2- hydroxyphenyl)-2-propylpentanamide have shown promising therapeutic outcomes against TNBC, especially when they are used in combination with other anticancer agents. More studies concerning HDAC inhibitors in breast carcinomas along with a more accurate understanding of the TNBC's pathobiology are required for the possible identification of new therapeutic strategies.

Primary fallopian tube carcinoma (PFTC) is a rare gynaecological tumour that accounts for 0.14-1.8% of genital malignancies. The most common age of occurrence is between 40 and 65 years, and the mean age is 55 years. The factors that contribute to its appearance are not well known. Population studies show that the mean incidence of PFTC is 3.6 per million women per annum. Overall survival percentages for patients with PFTC are generally low, in the range of 22-57%. Pre-operative diagnosis is-rare and PFTC is usually confirmed by a pathologist, but earlier diagnosis with early clinical manifestation and prompt investigation improves the prognosis. Both PFTC and epithelial ovarian cancer (EOC) are treated with similar surgical and chemotherapy methods. Studies have shown that the prognosis for PFTC is worse than that for EOC or other primary gynaecological tumours. This article reviews and presents the current updates of this rare gynaecological malignancy. (C) 2013 Elsevier Ireland Ltd. All rights reserved.