Inhibin secretion in women with the polycystic ovary syndrome before and after treatment with progesterone

<p>Abstract</p> <p>Objectives</p> <p>It has been suggested that inhibin secretion is altered in women with the polycystic ovary syndrome (PCOS). However, the contribution of a preceding luteal phase has not been taken into account. The aim of the present study was to investigate whether progesterone in the context of a simulated luteal phase affects basal and FSH-induced inhibin secretion in women with PCOS and elevated LH.</p> <p>Methods</p> <p>Ten women with PCOS and 8 normally cycling women participated in an experimental procedure (Exp) involving the administration of a single injection of recombinant FSH (450 IU sc). In the women with PCOS, the procedure was performed before (Exp 1) and after a 20-day treatment with progesterone (Exp 2), while in the normal women on day 2 of the cycle (Exp 3). Inhibin A and B levels were measured in blood samples taken before and 24 hours after the FSH injection.</p> <p>Results</p> <p>Basal LH levels were significantly higher and inhibin A levels were significantly lower in the PCOS group compared to the control group, while inhibin B levels were comparable in the two groups. In the PCOS group, after treatment with progesterone inhibin A and LH but not inhibin B levels decreased significantly (p < 0.05). After the FSH injection, inhibin A and B levels increased significantly in the women with PCOS (Exp 1 and Exp 2) but not in the control women (Exp 3).</p> <p>Conclusions</p> <p>In women with PCOS, as compared to control women, the dissimilar pattern of inhibin A and inhibin B secretion in response to FSH appears to be independent of a preceding simulated luteal phase. It is possible that compared to normal ovaries, the PCOS ovaries are less sensitive to endogenous LH regarding inhibin A secretion and more sensitive to exogenous FSH stimulation in terms of inhibin A and inhibin B secretion.</p

Impact of Rehabilitation on Breast Cancer Related Fatigue: A Pilot Study

Breast cancer fatigue (BCF) is a complex and multidimensional condition characterized by a persistent sense of physical and/or mental stiffness, resulting in a substantial impairment of health-related quality of life in breast cancer survivors. Aim of this prospective cohort study was to evaluate the feasibility and the effectiveness of a 4-week rehabilitation protocol on BCF, muscle mass, strength, physical performance, and quality of life in breast cancer (BC) survivors. We recruited adult BC women with a diagnosis of BCF, according to the International Classification of Diseases 10 criteria, referred to the Outpatient Service for Oncological Rehabilitation of a University Hospital. All participants performed a specific physical exercise rehabilitative protocol consisting of 60-min sessions repeated 2 times/week for 4 weeks. All outcomes were evaluated at the baseline (T0), at the end of the 4-week rehabilitation treatment (T1), and at 2 months follow up (T2). The primary outcome measure was the Brief Fatigue Inventory (BFI); secondary outcomes included: Fat-Free Mass and Fat Mass, assessed by Bioelectrical Impedance Analysis (BIA); Hand Grip Strength Test (HGS); Short Physical Performance Battery (SPPB); 10-meter walking test (10 MWT); 6-min walking test (6 MWT); European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ\u2013C30). Thirty-six women (mean age: 55.17 \ub1 7.76 years) were enrolled in the study. Significant reduction of BCF was observed both after the 4-week rehabilitation treatment (T1) (BFI: 5.4 \ub1 1.6 vs. 4.2 \ub1 1.7; p = 0.004) and at the follow-up visit (T2) (BFI: 5.4 \ub1 1.6 vs. 4.4 \ub1 1.6; p = 0.004). Moreover, significant differences (p < 0.001) HGS, SPPB, 10 MWT, 6 MWT, and EORTC QLQ-C30 were found at T1, while at T2 all the outcome measures were significantly different (p < 0.05) from the baseline. The rehabilitation protocol seemed to be feasible, safe, and effective in reducing BCF, improving muscle mass and function, and improving HRQoL in a cohort of BC survivors. The results of this study could improve awareness of this underestimated disease, suggesting the definition of a specific therapeutic exercise protocol to reduce BCF

Immune microenvironment dynamics in breast cancer during pregnancy: impact of gestational age on tumor-infiltrating lymphocytes and prognosis

BackgroundBreast cancer during pregnancy (PrBC) is a rare condition known for its aggressive clinical behavior. The presence of tumor-infiltrating lymphocytes (TILs) has been shown to have a significant impact on the prognosis of these patients. Despite some biological characteristics of the tumor that may differ depending on the gestational age, little is known about the dynamics of the immune landscape within the tumor microenvironment (TME) in PrBC. Therefore, in this study, our objective was to gain comprehensive insights into the relationship between gestational age at breast cancer diagnosis and the composition of the TME.Methodsn = 108 PrBC were selected from our institutional registry and categorized based on the gestational age by trimester. For all cases, TILs were profiled according to the International TILs Working Group recommendations, and subtyped by CD4, CD8, and forkhead box P3 (FOXP3) immunohistochemistry. PD-L1 was tested according to the combined positive score (CPS) using the IHC 22C3 pharmDx assay, with a cutoff value of ≥10 for positivity. The statistical approach encompassed Fisher’s and Chi-squared tests, with appropriate adjustments for multiple comparisons, logistic regression models, and survival analyses based on the Kaplan–Meier method.ResultsThe proportion of patients with poorly differentiated (G3) neoplasms increased as the gestational age advanced (first trimester, n = 25, 56.8%; second trimester, n = 27, 69.2%; third trimester, n = 21, 87.5%; p = 0.03). The histologic subtypes as well as the hormone receptor (HR) and HER2 status did not show significant changes across different pregnancy trimesters. In the HR+/HER2– subtype, there was a higher proportion of tumors with high/moderate TILs in the early phases of pregnancy, similar to FOXP3 expression (TILs: first trimester, n = 10, 35.7%; second trimester, n = 2, 10.5%; third trimester, n = 0; p = 0.02; FOXP3: first trimester, n = 10, 40%; second trimester, n = 3, 15.8%; third trimester, n = 0; p = 0.03). The median follow-up for our cohort was 81 months. Patients who relapsed after a breast cancer diagnosis during the first trimester were more frequently PD-L1-negative, unlike those with no disease recurrence (n = 9, 100% vs. n = 9, 56.3%; p = 0.03; hormone therapy and n = 9, 100% vs. n = 7, 53.9%; p = 0.02; chemotherapy). No statistically significant differences were seen among the three trimesters in terms of survival outcome.ConclusionThe TME dynamics of HR+/HER2− PrBC vary based on gestational age, suggesting that immune tolerance expression during later gestational age could explain the increased aggressiveness of tumors diagnosed at that stage

Hydrotherapy (Project Hydriades)

Natural resources are being used for the maintenance of health. According to the Law 3498/2006 of the Greek Parliament the natural health spas must be validated for their therapeutic properties. The Association of Municipalities and Communities of Health Springs of Greece signed a contract with the Research Committee of the Aristotle University of Thessaloniki, Greece, in order to conduct the research programme: ‘Study for the documentation of the therapeutic properties of the thermomineral waters’. The main aim of the project is: (1) the study of biological and therapeutic parameters of the natural health sources, (2) the identification of the indications and contraindications of hydrotherapy. Aims parallel to the main ones have been also set

Improving HER2 testing reproducibility in HER2-low breast cancer

HER2 is a pillar biomarker in breast cancer, and it is assessed by immunohistochemistry (IHC) using a three-tier scoring system and reflex in situ hybridization (ISH) for IHC score 2+. Novel HER2-directed antibody-drug conjugates have demonstrated significant antitumor activity in breast cancers with low levels of HER2 expression, i.e. IHC score 1+ or ISH-negative IHC score 2+. Both primary and acquired resistance to anti-HER2 therapies remains a challenge in the treatment of breast cancers according to the HER2 positivity continuum. Thus, the ability to precisely discriminate among HER2-zero, HER2-low, and HER2-positive breast cancers is no longer a mere academic exercise. HER2 testing criteria, guidelines, and quality controls are re-gaining momentum for this new clinical need. Therefore, all preanalytical and analytical variables that might trouble the sensitivity and reproducibility of this test should be carefully considered to address all possible issues and open all possible therapeutic opportunities for breast cancer patients

The Value of Three-Dimensional Modeling on Repositioning and Soft Tissue Filling in Microsurgical Reconstruction of Secondary Mandibular Defects: A Retrospective Study

Purpose Secondary mandibular defect reconstruction is a challenging operation. It is performed rather rarely, as in most of the cases a primary reconstruction is preferable. Restoration of function and symmetry, in secondary reconstruction of mandibular defects, requires accurate repositioning of segments and appropriate soft tissue filling. The purpose of this study is to estimate the value of three-dimensional (3D) digital modeling to meet the above requirements, in secondary microsurgical reconstruction of mandibular defects. Methods Five cases of mandibular defects, with various degrees of asymmetry and dysfunction, were restored secondarily, with fibula flaps, after virtual reconstruction on a 3D model derived from their computed tomography, with the utilization of CAD-CAM software. Software reproduced symmetrical 3D models by mirroring the healthy side. Occlusion was restored by fine adjustments on 3D models and finally a reconstruction plate was pre-bent on them, prior to its sterilization for use in surgery. Three out of the five cases received an osteo-cutaneous flap, while in the other two patients, an osseous flap was used. Lower face symmetry, mouth opening, and main patient&apos;s complaints were evaluated pre-and postoperatively to assess the value of the 3D modeling. Results All flaps survived. Hematoma occurred in two patients and was resolved after evacuation. In two patients, a fistula observed, was attributed to screw loosening, and treated after a surgical debridement and screw replacement. Intraoral exposure in the posterior part of the fibula flap was recorded in one patient, possibly from wound dehiscence due to tension of the intraoral tissue, and successfully covered with an ipsilateral nasolabial flap. The resulting symmetry and function were satisfactory in all the patients. Conclusion Secondary mandibular defects are often related with cosmetic disfigurement, misalignment of mandibular segments, and mandibular malfunction. For the correction of mandibular continuity, symmetry, and restoration of function, preoperative 3D modeling may be an important tool, according to our results

Immunohistochemical Expression of Epithelial Cell Adhesion Molecule (EpCAM) in Salivary Gland Cancer: Correlation with the Biological Behavior

Salivary gland neoplasms comprise a diverse group of tumors with different biological behaviors and clinical outcomes. Understanding the underlying molecular alterations associated with these malignancies is critical for accurate diagnosis, prognosis, and treatment strategies. Among the many biomarkers under investigation, epithelial cell adhesion molecule (EpCAM) has emerged as a promising candidate in salivary gland cancer research. This article aims to provide a comprehensive overview of the differential expression of EpCAM in salivary gland cancer and its potential correlation with the biological behavior of these tumors. The clinical characteristics of 65 patients with salivary gland malignancy of different histopathological subtypes were included. We report the differential expression of EpCAM and the relationship between the clinical and histopathologic features of these tumors. Regarding the evaluation of the effect of EpCAM expression on survival, in our study, we showed that tumors with high EpCAM expression had reduced disease-free survival (DFS) and overall survival (OS) (p < 0.001) compared to patients with cancers with low EpCAM expression. In addition, the concurrent presence of perineural invasion and positive EpCAM expression appeared to be associated with shorter disease-free survival and overall survival. In conclusion, our study confirmed the prognostic value of detecting perineural invasion and EpCAM expression

Malignancies in Patients with Celiac Disease: Diagnostic Challenges and Molecular Advances

Celiac disease (CD) is a multiorgan autoimmune disorder of the chronic intestinal disease group characterized by duodenal inflammation in genetically predisposed individuals, precipitated by gluten ingestion. The pathogenesis of celiac disease is now widely studied, overcoming the limits of the purely autoimmune concept and explaining its hereditability. The genomic profiling of this condition has led to the discovery of numerous genes involved in interleukin signaling and immune-related pathways. The spectrum of disease manifestations is not limited to the gastrointestinal tract, and a significant number of studies have considered the possible association between CD and neoplasms. Patients with CD are found to be at increased risk of developing malignancies, with a particular predisposition of certain types of intestinal cancer, lymphomas, and oropharyngeal cancers. This can be partially explained by common cancer hallmarks present in these patients. The study of gut microbiota, microRNAs, and DNA methylation is evolving to find the any possible missing links between CD and cancer incidence in these patients. However, the literature is extremely mixed and, therefore, our understanding of the biological interplay between CD and cancer remains limited, with significant implications in terms of clinical management and screening protocols. In this review article, we seek to provide a comprehensive overview of the genomics, epigenomics, and transcriptomics data on CD and its relation to the most frequent types of neoplasms that may occur in these patients

Malignancies in Patients with Celiac Disease: Diagnostic Challenges and Molecular Advances

Celiac disease (CD) is a multiorgan autoimmune disorder of the chronic intestinal disease group characterized by duodenal inflammation in genetically predisposed individuals, precipitated by gluten ingestion. The pathogenesis of celiac disease is now widely studied, overcoming the limits of the purely autoimmune concept and explaining its hereditability. The genomic profiling of this condition has led to the discovery of numerous genes involved in interleukin signaling and immune-related pathways. The spectrum of disease manifestations is not limited to the gastrointestinal tract, and a significant number of studies have considered the possible association between CD and neoplasms. Patients with CD are found to be at increased risk of developing malignancies, with a particular predisposition of certain types of intestinal cancer, lymphomas, and oropharyngeal cancers. This can be partially explained by common cancer hallmarks present in these patients. The study of gut microbiota, microRNAs, and DNA methylation is evolving to find the any possible missing links between CD and cancer incidence in these patients. However, the literature is extremely mixed and, therefore, our understanding of the biological interplay between CD and cancer remains limited, with significant implications in terms of clinical management and screening protocols. In this review article, we seek to provide a comprehensive overview of the genomics, epigenomics, and transcriptomics data on CD and its relation to the most frequent types of neoplasms that may occur in these patients

Breast Cancer with Bone Metastasis: Molecular Insights and Clinical Management

Despite the remarkable advances in the diagnosis and treatment of breast cancer patients, the presence or development of metastasis remains an incurable condition. Bone is one of the most frequent sites of distant dissemination and negatively impacts on patient’s survival and overall frailty. The interplay between tumor cells and the bone microenvironment induces bone destruction and tumor progression. To date, the clinical management of bone metastatic breast cancer encompasses anti-tumor systemic therapies along with bone-targeting agents, aimed at slowing bone resorption to reduce the risk of skeletal-related events. However, their effect on patients’ survival remains controversial. Unraveling the biology that governs the interplay between breast neoplastic cells and bone tissue would provide means for the development of new therapeutic agents. This article outlines the state-of-the art in the characterization and targeting the bone metastasis in breast cancer, focusing on the major clinical and translational studies on this clinically relevant topic