Ovarian sclerosing stromal tumor mimicking malignancy: case series and literature review.

BACKGROUND: Sclerosing stromal tumors (SST) are rare ovarian neoplasms that often appear as solid unilateral tumors of the ovary with no specific clinical or radiological presentation. The definitive treatment is surgical removal. CASE PRESENTATION: Our article presents four cases of female patients with sclerosing stromal ovarian tumor with clinical characteristics mimicking malignant ovarian lesions. Interestingly, two of our cases had elevated levels of inhibin B. All patients were treated with surgery (oophorectomy) and had no disease recurrence. CONCLUSION: Tumors' macroscopic features are usually non-specific and often suggestive of possible malignancy, therefore diagnosis is always based on histopathological report.

The Co-Expression of Estrogen Receptors ERα, ERß, and GPER in Endometrial Cancer.

Estrogens have important roles in endometrial cancer (EC) and exert biological effects through the classical estrogen receptors (ERs) ERα and ERß, and the G-protein-coupled ER, GPER. So far, the co-expression of these three types of ERs has not been studied in EC. We investigated ERα, ERß, GPER mRNA and protein levels, and their intracellular protein distributions in EC tissue and in adjacent control endometrial tissue. Compared to control endometrial tissue, immunoreactivity for ERα in EC tissue was weaker for nuclei with minor, but unchanged, cytoplasmic staining; mRNA and protein levels showed decreased patterns for ERα in EC tissue. For ERß, across both tissue types, the immunoreactivity was unchanged for nuclei and cytoplasm, although EC tissues again showed lower mRNA and protein levels compared to adjacent control endometrial tissue. The immunoreactivity of GPER as well as mRNA levels of GPER were unchanged across cancer and control endometrial tissues, while protein levels were lower in EC tissue. Statistically significant correlations of estrogen receptor α (ESR1) versus estrogen receptor ß (ESR2) and GPER variant 3,4 versus ESR1 and ESR2 was seen at the mRNA level. At the protein level studied with Western blotting, there was significant correlation of ERα versus GPER, and ERß versus GPER. While in clinical practice the expression of ERα is routinely tested in EC tissue, ERß and GPER need to be further studied to examine their potential as prognostic markers, provided that specific and validated antibodies are available.

Genetic variability in GLP-1 receptor is associated with inter-individual differences in weight lowering potential of liraglutide in obese women with PCOS: a pilot study.

PURPOSE: The weight lowering potential of glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) is inter-individually different and clinically unpredictable. The potential role of genetic variability of GLP-1R on body weight response to GLP-1 RAs in obese women with polycystic ovary syndrome (PCOS) has not yet been evaluated. METHODS: Fifty-seven obese women with PCOS (aged 30.7 ± 7.0, BMI 38.6 ± 5.3 kg/m(2)) were assigned to liraglutide 1.2 mg QD s.c. for 12 weeks and classified as strong responders regarding weight loss if they lost 5% or more of their initial body weight. They were genotyped for common GLP-1R single nucleotide polymorphisms (SNPs) rs6923761 and rs10305420. Changes of measures of obesity were measured before and at the end of the treatment. RESULTS: Twenty out of 57 subjects were strong responders and lost 7.38 ± 1.74 compared to 2.11 ± 2.17 kg lost in poor responders. Carriers of at least one polymorphic rs10305420 allele had poor treatment response compared to carriers of two wild type alleles (OR = 0.27, 95% CI = 0.09-0.85, P = 0.025). Carriers of at least one polymorphic rs6923761 allele tended to have stronger treatment response compared to carriers of two wild type alleles (OR = 3.06, 95% CI = 0.96-9.74, P = 0.058). Fasting glucose and glucose after oral glucose tolerance test (OGTT) comparably decreased in both groups when compared to baseline, whereas no within treatment differences were found in androgen profile. Gastrointestinal adverse events were transit and balanced between strong and poor responders. CONCLUSIONS: GLP-1R rs10305420 polymorphism explained some of the inter-individual differences in response to liraglutide regarding weight loss in obese PCOS women.

Characterising umbilical abdominal wall endometriosis as a distinct subgroup of abdominal wall endometriosis - retrospective cohort study.

Abdominal wall endometriosis (AWE) is one of the rarest forms of endometriosis. Little is known about differences between umbilical AWE (U-AWE) and non-umbilical AWE (non-U-AWE) patients. This retrospective cohort study included patients treated for AWE at tertiary endometriosis centre between 2012 and 2020. Patients were divided into two groups - umbilical AWE and non-umbilical AWE.We identified 14 U-AWE and 45 non-U-AWE patients who mostly had lesions in caesarean section scar (38, 64.4%), rarely at other locations (7, 11.9%). Infertility rates for U-AWE patients and non-U-AWE patients were 57.1% and 17.8%, respectively. Concurrent or previous peritoneal endometriosis was noted in 85.7% of U-AWE and 24.4% of non-U- AWE patients. In addition, U-AWE patients and non-UAWE patients significantly differed in following: parity, number of previous caesarean sections, lesion size, prevalence of concurrent or previous deep infiltrating endometriosis, bleeding from abdominal wall, cyclic pain, continuous pain.Infertility and pelvic endometriosis were more prevalent in U-AWE patients. Our data suggests that U-AWE may be a specific marker for a patient highly prone to pelvic endometriosis and subsequent infertility. Findings suggests that clinician should consider comprehensive evaluation of U-AWE patients.

Streptococcal pharyngitis in a Child, Complicated with a Necrotizing Myositis: Diagnosis, Management and Follow-Up.

BACKGROUND Group A streptococcus is a common cause of pharyngitis and can also cause a wide variety of invasive infections, including necrotizing soft-tissue infections. The presented case is one of the rare occurrences of necrotizing soft-tissue infection as a consequence of hematogenous spread and is the first described pediatric case of streptococcal myositis that was clearly preceded by pharyngitis. CASE REPORT A 2.5-year-old boy, previously healthy, fell ill 3 days before admission with high-grade fever, diffuse erythematous truncal rash and, later, with pain in the left lower leg. The next day, scarlet fever was diagnosed, and he was started on oral penicillin V. In the following 2 days, the fever and pain in the leg did not subside; edema and redness of the left shin appeared. On admission, he was febrile and had tachycardia, and the mouth examination was consistent with bacterial pharyngitis. The left shin was grossly edematous, with diffuse bluish skin discoloration. Empiric antibiotic treatment with benzylpenicillin and clindamycin was started. An ultrasound scan of the left shin revealed extensive myonecrosis. Urgent fasciotomy was done, and necrotic muscles were surgically excised. CONCLUSIONS Streptococcal necrotizing myositis is exceedingly rare. Due to potentially life-threatening complications and a need for urgent surgical intervention, clinicians must have a low threshold of suspicion, even in atypical pathogenesis and presentation.

Overview of Immune Checkpoint Inhibitors in Gynecological Cancer Treatment.

In the last ten years, clinical oncology has been revolutionized by the introduction of oncological immunotherapy, mainly in the form of immune checkpoint inhibitors (ICIs) that transformed the standard of care of several advanced solid malignancies. Using ICIs for advanced gynecological cancers has yielded good results, especially for endometrial cancer. In ovarian or cervical cancer, combining ICIs with other established agents has shown some promise. Concurrently with the clinical development of ICIs, biomarkers that predict responses to such therapy have been discovered and used in clinical trials. The translation of these biomarkers to clinical practice was somewhat hampered by lacking assay standardization and non-comprehensive reporting of biomarker status in trials often performed on a small number of gynecological cancer patients. We can expect increased use of ICIs combined with other agents in gynecological cancer in the near future. This will create a need for reliable response prediction tools, which we believe will be based on biomarker, clinical, and tumor characteristics. In this article, we review the basic biology of ICIs and response prediction biomarkers, as well as the latest clinical trials that focus on subgroup effectiveness based on biomarker status in gynecological cancer patients.

Models including preoperative plasma levels of angiogenic factors, leptin and IL-8 as potential biomarkers of endometrial cancer.

Background: The diversity of endometrial cancer (EC) dictates the need for precise early diagnosis and pre-operative stratification to select treatment options appropriately. Non-invasive biomarkers invaluably assist clinicians in managing patients in daily clinical practice. Currently, there are no validated diagnostic or prognostic biomarkers for EC that could accurately predict the presence and extent of the disease. Methods: Our study analyzed 202 patients, of whom 91 were diagnosed with EC and 111 were control patients with the benign gynecological disease. Using Luminex xMAP™ multiplexing technology, we measured the pre-operative plasma concentrations of six previously selected angiogenic factors - leptin, IL-8, sTie-2, follistatin, neuropilin-1, and G-CSF. Besides basic statistical methods, we used a machine-learning algorithm to create a robust diagnostic model based on the plasma concentration of tested angiogenic factors. Results: The plasma levels of leptin were significantly higher in EC patients than in control patients. Leptin was higher in type 1 EC patients versus control patients, and IL-8 was higher in type 2 EC versus control patients, particularly in poorly differentiated endometrioid EC grade 3. IL-8 plasma levels were significantly higher in EC patients with lymphovascular or myometrial invasion. Among univariate models, the model based on leptin reached the best results on both training and test datasets. A combination of age, IL-8, leptin and G-CSF was determined as the most important feature for the multivariate model, with ROC AUC 0.94 on training and 0.81 on the test dataset. The model utilizing a combination of all six AFs, BMI and age reached a ROC AUC of 0.89 on both the training and test dataset, strongly indicating the capability for predicting the risk of EC even on unseen data. Conclusion: According to our results, measuring plasma concentrations of angiogenic factors could, provided they are confirmed in a multicentre validation study, represent an important supplementary diagnostic tool for early detection and prognostic characterization of EC, which could guide the decision-making regarding the extent of treatment.

A bistable genetic switch based on designable DNA-binding domains.

Bistable switches are fundamental regulatory elements of complex systems, ranging from electronics to living cells. Designed genetic toggle switches have been constructed from pairs of natural transcriptional repressors wired to inhibit one another. The complexity of the engineered regulatory circuits can be increased using orthogonal transcriptional regulators based on designed DNA-binding domains. However, a mutual repressor-based toggle switch comprising DNA-binding domains of transcription-activator-like effectors (TALEs) did not support bistability in mammalian cells. Here, the challenge of engineering a bistable switch based on monomeric DNA-binding domains is solved via the introduction of a positive feedback loop composed of activators based on the same TALE domains as their opposing repressors and competition for the same DNA operator site. This design introduces nonlinearity and results in epigenetic bistability. This principle could be used to employ other monomeric DNA-binding domains such as CRISPR for applications ranging from reprogramming cells to building digital biological memory.