Advances in paclitaxel combinations for treating cervical cancer

Introduction: Cervical cancer is the fourth common cancer in women worldwide. While, in the past, locally advanced stage disease was treated by pelvic radiotherapy, nowadays the National Cancer Institute strongly recommends chemoradiation protocols. Weekly cisplatin was previously the standard of care in this setting; however, the low response rate and the short median progression-free survival (PFS) of patients have led researchers to investigate combinatory regimens. Area covered: This article is based on literature searches up until April 2019, with current trial registers also analyzed. All data available on this topic has been summarized in this narrative review. Expert opinion: In recent years, it has been demonstrated that cisplatin-based doublets, and in particular, cisplatin plus paclitaxel, are superior to cisplatin as a monotherapy in terms of response rate and progression-free survival of patients with advanced cervical cancer. This double regime combined with bevacizumab is also considered the first-line option for metastatic or recurrent disease. Dose-dense paclitaxel in neo-adjuvant chemotherapy combinations is a promising option in patients with locally advanced cervical cancer. Exploration of novel biological therapies and in vitro combinations based on the use of paclitaxel is warranted

Homologous Recombination Deficiency in Ovarian Cancer: from the Biological Rationale to Current Diagnostic Approaches

The inability to efficiently repair DNA double-strand breaks using the homologous recombination repair pathway is defined as homologous recombination deficiency (HRD). This molecular phenotype represents a positive predictive biomarker for the clinical use of poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors and platinum-based chemotherapy in ovarian cancers. However, HRD is a complex genomic signature, and different methods of analysis have been developed to introduce HRD testing in the clinical setting. This review describes the technical aspects and challenges related to HRD testing in ovarian cancer and outlines the potential pitfalls and challenges that can be encountered in HRD diagnostics

Microbiome and PCOS: State-of-art and future aspects

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS has been postulated. Aim of this review is to summarize the available literature data about the relationship between microbiome and PCOS. A search on PubMed and Medline databases was performed from inception to November 20Most of evidence has focused on the connection of intestinal bacteria with sex hormones and insulin-resistance: while in the first case, a relationship with hyperandrogenism has been described, although it is still unclear, in the second one, chronic low-grade inflammation by activating the immune system, with increased production of proinflammatory cytokines which interfere with insulin receptor function, causing IR (Insulin Resistance)/hyperinsulinemia has been described, as well as the role of gastrointestinal hormones like Ghrelin and peptide YY (PYY), bile acids, interleukin-22 and Bacteroides vulgatus have been highlighted. The lower genital tract mi-crobiome would be affected by changes in PCOS patients too. The therapeutic opportunities include probiotic, prebiotics and synbiotics, as well as fecal microbiota transplantation and the use of IL-22, to date only in animal models, as a possible future drug. Current evidence has shown the involvement of the gut microbiome in PCOS, seen how humanized mice receiving a fecal transplant from women with PCOS develop ovarian dysfunction, immune changes and insulin resistance and how it is capable of disrupting the secondary bile acid biosynthesis. A future therapeutic approach for PCOS may involve the human administration of IL-22 and bile acid glycodeoxycholic acid

Diagnostic and prognostic role of TFF3, Romo-1, NF-кB and SFRP4 as biomarkers for endometrial and ovarian cancers: a prospective observational translational study

Purpose: This study aimed to evaluate trefoil factor 3 (TFF3), secreted frizzled-related protein 4 (sFRP4), reactive oxygen species modulator 1 (Romo1) and nuclear factor kappa B (NF-κB) as diagnostic and prognostic markers of endometrial cancer (EC) and ovarian cancer (OC). Methods: Thirty-one patients with EC and 30 patients with OC undergone surgical treatment were enrolled together with 30 healthy controls in a prospective study. Commercial ELISA kits determined serum TFF-3, Romo-1, NF-кB and sFRP-4 concentrations. Results: Serum TFF-3, Romo-1 and NF-кB levels were significantly higher in patients with EC and OC than those without cancer. Regarding EC, none of the serum biomarkers differs significantly between endometrial and non-endometrioid endometrial carcinomas. Mean serum TFF-3 and NF-кB levels were significantly higher in advanced stages. Increased serum levels of TFF-3 and NF-кB were found in those with a higher grade of the disease. Regarding OC, none of the serum biomarkers differed significantly among histological subtypes. Significantly increased serum levels of NF-кB were observed in patients with advanced-stage OC than those with stage I and II diseases. No difference in serum biomarker levels was found between those who had a recurrence and those who had not. The sensibility and specificity of these four biomarkers in discriminating EC and OC from the control group showed encouraging values, although no one reached 70%. Conclusions: TFF-3, Romo-1, NF-кB and SFRP4 could represent new diagnostic and prognostic markers for OC and EC. Further studies are needed to validate our results

Early invasive vulvar squamous cell carcinoma arising in a woman with vulvar pemphigus vulgaris and systemic lupus erythematosus

Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucous membranes. Genital involvement occurs when most other common sites are concurrently affected or are in remission. Systemic lupus erythematosus (SLE) is an autoimmune disease that may affect many parts of the body and the skin with occasional bullous lesions. Pemphigus vulgaris and SLE may be associated, albeit rarely. Here, we report the first case of a woman affected with SLE presenting with early invasive squamous cell carcinoma (SCC) arising from Pemphigus Vulgaris of the vulva

Dioxin and endometriosis: a new possible relation based on epigenetic theory

Endometriosis is a chronic disease characterized by the growth of endometrial-like glands and stroma outside the uterine cavity. Nowadays, the exact etiology of endometriosis is unclear and the interaction between a variety of environmental physical and chemical compounds may potentially promote the disease in women with an individual susceptibility. The first demonstration of a relation between an environmental factor and endometriosis was obtained with the chronic dietary exposure of a primate colony to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Besides the well-known dioxin’s pathway of action, several papers are focusing on the role of epigenetic mechanisms, a way through which the genome responds to the environment and can lead to permanent changes in gene expression until affecting the phenotypes or cause disease. In this review, we focus on the possible role of dioxin epigenetics modification in endometriosis

Unraveling a difficult diagnosis: The tricks for early recognition of ovarian cancer

Epithelial ovarian cancer (EOC) is the predominant type of ovarian cancer (OC). The 5-year survival of patients has improved over the last three decades, although the overall cure rate of OC if about 30%. Despite high response rates after initial chemotherapy, most patients with advanced ovarian cancer ultimately develop the recurrent disease because of resistance to chemotherapy. A proper early diagnosis and treatment of patients with ovarian cancer are urgently needed. Nowadays the diagnosis is performed by means of clinical symptoms and signs, often indicators of a disease already at an advanced stage, tumor markers (CA125 and HE4), transvaginal ultrasonography and imaging, very useful in distinguishing adnexal masses. Understand the nature of an adnexal mass is the primary point to begin the diagnosis of OC. Validated different model to approach and characterize adnexal pathology preoperatively are described, such as the International Ovarian Tumor Analysis (IOTA) and the Assessment of Different NEoplasias in the AdneXa (ADNEX) model. New tumor markers, such as PRSS8, FOLR1, KLK6/7, GSTT1, and miRNAs, are getting ahead and are worth noting for early detection of ovarian cancer. Despite the development of numerous ultrasound models for the diagnosis of adnexal masses and the analysis of different tumor markers, the early diagnosis of ovarian cancer is still difficult to practice. Moreover, identifying genetic risk alleles, such as germline BRCA1 and BRCA2 mutations, for ovarian cancer has had a significant impact on disease prevention strategies

Current and experimental drug therapy for the treatment of polycystic ovarian syndrome

Introduction: Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 8–13% of reproductive-age women. Irregular periods, hirsutism, or infertility are the most common clinical presentations of patients affected by PCOS. This syndrome is also linked to metabolic abnormalities such as type 2 diabetes, insulin resistance and obesity. The optimal therapeutic approach is still unknown. Areas covered: This narrative review offers an overview of the literature on current and experimental pharmacological options for treating PCOS and highlights ongoing clinical trials. Several electronic databases were searched and current research registers were analyzed to the present year. The papers selected for this review were critically analyzed, and all data available were summarized, organized, and explored to derive key information. Expert opinion: The main goal of PCOS treatment is to obtain a metabolic and hormonal balance. Optimal PCOS therapy should be direct to the reproductive abnormalities and the entire spectrum of endocrine and metabolic complications that appear to have a long-term negative impact on PCOS patient health, as in post-menopausal period. The discovery of new mechanisms in PCOS pathogenesis will offer the possibility of testing new drug classes