Placental markers of miscarriage

Successful implantation involves a high degree of development of spiral arteries, combined with high proliferative activity, which ensures the formation of a healthy placenta, full uterine-placental circulation, and the birth of a healthy child. The placenta is the unique organ of the biological monitoring, the mirror of pregnancy. Identification of placental markers of miscarriage is a promising direction for preventing reproductive losses. The aim of the work is to identify the markers of miscarriage and premature labor in the structures of the chorion and placenta. Materials and methods. The main group included tissue samples of the 22 chorions and 64 placentas after termination of current pregnancy from women with a history of reproductive losses. The control group included tissue samples of the 20 chorions after artificial abortion and 20 placentas after physiological pregnancy and birth. The placenta was examined according to the protocol (form No. 013-1/0). The expressions of VEGF, CD31/PECAM1, CD105/Endoglin/TGFβ 1/3 Receptor, Bcl-2α Ab-1, TNF-α, CD45/T200/LCA, CD56/NCAM1 were studied in the structures of chorion and placenta by immunohistochemistry. Results. Based on histological and immuno-histochemical study of chorion and placenta samples in women with reproductive history and termination of the current pregnancy, it was established that embryo-endometrial dysfunction is the cause of miscarriage in the first trimester, and inflammation is the precondition of preterm birth; markers of miscarriage and premature labor in the structures of the chorion and placenta have been identified. Conclusions. The markers of miscarriage are pathomorphological changes in endometrium and chorion combined with high expression of TNF-α and NK-CD56, low expression of CD31/PECAM1, negative expression of VEGF to indicate a violation of cytotrophoblast invasions. The markers of inflammation and premature labor are structural and functional changes of placenta in combination with moderate expression of TNF-α in syncytium, high expression of NK-CD56 in villous stroma, high expression of CD45/T200/LCA in the decidual membrane.

Extrapulmonary small cell carcinoma. Literature review

The review shows the features of rare tumors extrapulmonary small cell carcinomas (EPSCC). The possible approaches for the treatment of this unfavorable group of tumors are discussed. EPSCC can occur in every organ. The clinical course and morphology of EPSCC are similar to small lung cell carcinoma (SCLC). EPSCC belongs to the group of low-grade neuroendocrine tumors with high proliferative activity. There are a small number of publications in the literature concerning EPSCC. Basically, these publications concerning the various clinical cases with comments. Most often, EPSCC occurs in the female genital tract, gastrointestinal tract, genitourinary SCC and known cases of SCC of the head and neck. The cases concerning SCC in other organs are also described. For the treatment of EPSCC are usually applied guidelines developed for SCLC, and several publications on the use of immunotherapy in the treatment of EPSCC have already appeared. The analysis of the available literature let us suggest EPSCC is a big problem that requires a more in-depth study and consensus guidelines adoption for the management of these patients.

Immunophenotyping of intraepithelial lymphocytes in canine chronic enteropathy and intestinal T-cell lymphoma using endoscopic samples

Human enteropathy-associated T-cell lymphoma (EATL) is considered to be derived from intraepithelial lymphocytes (IELs); however, the origin of canine intestinal T-cell lymphoma (ITCL) remains unclear. Histological, immunohistochemical, and clonality examinations were performed using endoscopically collected canine duodenum samples of mucosal lesions of chronic enteropathy (CE; 73 cases) and ITCL without transmural neoplastic mass lesions (64 cases). Histopathological examinations revealed the intraepithelial accumulation of lymphocytes (called “intraepithelial lymphocytosis”) in 54/73 CE cases (74%) and the epitheliotropism of neoplastic lymphocytes in 63/64 ITCL cases (98%). Immunohistochemically, IELs in CE with intraepithelial lymphocytosis (IEL+CE) were diffusely immunopositive for CD3, with scattered immunopositivity for CD5, CD8, CD20, and granzyme B (GRB). The percentage of CD8+ in CD3+ IELs was significantly lower in IEL+CE than in CE without intraepithelial lymphocytosis (IEL−CE). Double-labeling immunohistochemistry revealed a high percentage of GRB expression in CD8− IEL among IEL+CE. Among 64 ITCL cases, CD3 was immunopositive in 64 (100%), CD5 in 22 (34%), CD8 in 8 (13%), CD20 in 12 (19%), CD30 in 13 (20%), and GRB in 49 (77%). In CD3+ cells, Ki67 immunopositivity was highest in ITCL, intermediate in IEL+CE, and lower in IEL−CE. A clonal TCR gene rearrangement was detected in 1/19 IEL−CE cases (5%), 15/54 IEL+CE (28%), and 38/58 ITCL (66%). These results indicate that the immunophenotype of canine ITCL (CD8−GRB+) is similar to that of the increased IELs in CE. The high proliferative activity and clonality of T cells in IEL+CE suggest that canine ITCL originates from these IELs, similar to human EATL.

Nodular fasciitis: USP6-associated neoplasia through multiple pathways

Even though nodular fasciitis (NF) is benign and self-limited nature, the presentations of clinical, ultrasonographic, and pathological features have been described as mimicking sarcoma. Erickson-Johnson et al. suggested that ubiquitin-specific protease 6 (USP6) transcriptional upregulation may be the driving force behind the high proliferative activity and growth of NF. When the lesion showed the proliferative findings of the margin on both ultrasonography (US) and pathology, accompanied by clinically rapid growth, self-limited and/or regress course, NF could be strongly suggested as previously described. In this article, the author reviews the current knowledge of NF as USP6-associated neoplasia and also describes the therapeutic strategy in NF. In addition to the presentations of clinical, ulrtrasonographic, and pathological appearances of NF, the evaluation of percentage of USP6 break-apart FISH signals reflecting lifetime and mitotic counts in NF may be a potential procedure for accurate diagnosis in particularly young NF. It is putative that the inhibition of USP6-related genes might be the potential therapeutic strategies for the extremely rare malignant nodular fasciitis.

Zic1 advances epaxial myotome morphogenesis to cover the neural tube via Wnt11r

The dorsal axial muscles, or epaxial muscles, are a fundamental structure covering the spinal cord and vertebrae, as well as mobilizing the vertebrate trunk. To date, mechanisms underlying the morphogenetic process shaping the epaxial myotome are largely unknown. To address this, we used the medaka zic1/zic4-enhancer mutant Double anal fin (Da), which exhibits ventralized dorsal trunk structures resulting in impaired epaxial myotome morphology and incomplete coverage over the neural tube. In wild type, dorsal dermomyotome (DM) cells, progenitors of myotomal cells, reduce their proliferative activity after somitogenesis and subsequently form unique large protrusions extending dorsally, potentially guiding the epaxial myotome dorsally. In Da, by contrast, DM cells maintain the high proliferative activity and form mainly small protrusions. By combining RNA- and ChIP-sequencing analyses, we revealed direct targets of Zic1 which are specifically expressed in dorsal somites and involved in various aspects of development, such as cell migration, extracellular matrix organization and cell-cell communication. Among these, we identified wnt11r as a crucial factor regulating both cell proliferation and protrusive activity of DM cells. We propose that the dorsal movement of the epaxial myotome is guided by DM cells and that Zic1 empowers this activity via Wnt11r to achieve the neural tube coverage.

Phyllodes tumor and its malignization into invasive ductal carcinoma − a case report

Introduction: Phyllodes tumors of the breast are rare and very distinct types of mammary neoplasms. They are characterized by their biphasicity, i.e. the presence of stromal and epithelial components at the same time. Malignancy is determined by the degree of stromal differentiation. The coexistence of the malignant epithelial component is a very rare phenomenon. Dozens of cases of simultaneous phyllodes tumor and epithelial malignancy have been reported so far. Nevertheless, the biological nature of this process is still an unexplained and a controversial topic. Case report: In this paper, we present a case of a patient with a suddenly enlarging lesion in the breast. According to the first surgical resection, a diagnosis of high-grade malignant phyllodes tumor was made with fibrosarcoma differentiation, stromal overgrowth and suppression of the epithelial component. Examination of scar resistence in early postoperative period revealed a triple-negative invasive low-differentiated breast carcinoma with very high proliferative activity, thus malignization of the epithelial component of the tumor occurred. Shortly, a diagnosis of second recurrence was made, treatment included axillary lymph node dissection (ALND) with a negative histological findings. The patient underwent complex adjuvant chemotherapy and radiotherapy and remained disease free 3 years after the surgery. Conclusion: Coexistence of phyllodes tumor and the breast carcinoma is very rare. The article describes the first published case, which documents the subsequent development of invasive low-differentiated ductal carcinoma immediately after resection of high-grade phyllodes tumor. Treatment and prognosis are generally determined by the characteristics of the carcinomatous component.

AB0757 ON THE ISSUE OF DIFFERENTIAL DIAGNOSIS OF PANNICULITIS

Background:Diagnosis of panniculitis (Pn) is associated with significant difficulties due to the variety of etiological factors, which include panniculitis-like T-cell lymphoma (PLTСL) – a rare variant of non-Hodgkin lymphoma.Objectives:to study clinical and laboratory features of PLTСL in rheumatology.Methods:Over 8 years PLTСL was diagnosed in 10 patients (9 women and 1 man, average age 37.2 ± 7.4) who were referred to V.A. Nasonova Research Institute of Rheumatology with a diagnosis of erythema nodosum or panniculitis. In addition to general clinical study, serum concentrations of α-1 antitrypsin, amylase, lipase, ferritin, creatine phosphokinase, immunological parameters (ANF-Hep2, dsDNA, C3 and C4 complements, CRP, ANCA, Scl-70, antibodies to cardiolipins G and M) were determined, and positron emission tomography combined with computed tomography (PET-CT), histological and immunohistochemical examination (IHC) of the biopsy sample of skin with subcutaneous fat from the affected areas were performed.Results:The clinical picture of PLTСL was characterized by generalized red-crimson moderately painful (VAS pain intensity 45mm) subcutaneous nodes on the upper limbs and trunk (100%), face (60%) and lower extremities (75%), without ulceration and oily fluid leakage. A “trembling saucer” symptom was evident in 75% of the observed cases. All patients had febrile fever. No enlargement of the lymph nodes of the liver and spleen was observed. The blood test revealed leukopenia (up to 2.0·x 109 /l) in 50% of cases, an increase in ESR and CRP by three or more times in 100% of cases. The biochemical blood test demonstrated an increase in LDH activity by two or more times in all patients. PET-CT in 100% of cases revealed an intense accumulation of 18F-FDG in the nodes which correlated with a high proliferative activity index. The morphological picture resembled lobular panniculitis without vasculitis. Tumor lymphocytes had an immunophenotype of cytotoxic T-lymphocytes: CD3+, CD8+, granzyme B+. To confirm the tumor nature of the infiltrate the rearrangements of the T-cell receptor genes were studied. Glucocorticoid therapy (23.5±9.6 mg/day) was ineffective which required polychemotherapy in most patients.Conclusion:PLTСL presents a complex diagnostic task that requires a multidisciplinary approach to verify the diagnosis and treatment tactics.Disclosure of Interests:None declared

The condition of piglet immune system during post-weaning period depending on the sex and stress-reactivity

The immune system of 90-day old piglets of SM-1 Novosibirsk breed piglets depends on sex and stress-reactivity. Stress-reactivity was measured using halothane test. The immunologic testing was performed 30 days after weaning. Our results show that overall piglet immune system demonstrated high proliferative activity of T- and B- immunocompetent cells with active formation of mature active T-and B-lymphocytes and did not show signs of immunosuppression. Compared to guilts, barrows had higher concentration of leucocytes, T-and B-lymphocytes, killer-supressor T-cells, activated and poorly differentiated T-lymphocytes. Gilts had higher production of inductor-helper T-cells, IgM and IgG when compared to barrows. Stress-resistant piglets had higher concentration of B-lymphocytes, IgM and IgG whereas stress-sensitive piglets had higher concentration of T-lymphocytes, supressor-killer T-cells and thymus T-lymphocytes. Gilts had higher concentration of inductor-helper T-cells than killer-supressor T-cells. Gilts overall had intensive antibody synthesis, however, stress-resistant gilts had higher IgG synthesis compared to stress-sensitive gilts. In barrows immature T-lymphocytes differentiated mainly into killer-supressor T-cells. The adaptivity of barrow immune system was characterized by high circulatory B-lymphocytes and IgM. Stress-sensitive barrows had lower antibody synthesis levels and higher T-lymphophoesis compared to stress-resistant barrows.

Actin-like protein 6A/MYC/CDK2 axis confers high proliferative activity in triple-negative breast cancer

Background Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with high proliferative activity. TNBC tumors exhibit elevated MYC expression and altered expression of MYC regulatory genes, which are associated with tumor progression and poor prognosis; however, the underlying mechanisms by which MYC retains its high expression and mediates TNBC tumorigenesis require further exploration. Methods ACTL6A regulation of MYC and its target gene, CDK2, was defined using Co-IP, mass spectrometry and ChIP assays. To study the role of ACTL6A in TNBC, we performed soft-agar, colony formation, flow cytometry and tumor formation in nude mice. CDK2 inhibitor and paclitaxel were used in testing combination therapy in vitro and in vivo. Results ACTL6A bound MYC to suppress glycogen synthase kinase 3 beta (GSK3β)-induced phosphorylation on MYC T58, which inhibited ubiquitination of MYC and stabilized it. Moreover, ACTL6A promoted the recruitment of MYC and histone acetyltransferase KAT5 on CDK2 promoters, leading to hyperactivation of CDK2 transcription. ACTL6A overexpression promoted, while silencing ACTL6A suppressed cell proliferation and tumor growth in TNBC cells in vitro and in vivo, which was dependent on MYC signaling. Furthermore, co-therapy with paclitaxel and CDK2 inhibitor showed synergistic effects in tumor suppression. Notably, ACTL6A/MYC/CDK2 axis was specifically up-regulated in TNBC and high expression of ACTL6A was correlated to shorter survival in patients with TNBC. Conclusions These findings reveal a novel mechanism by which ACTL6A prolongs the retention of MYC in TNBC and suggest that pharmacological targeting ACTL6A/MYC/CDK2 axis might have therapeutic potential in patients with TNBC.

Introduction to in vitro culture of Ginkgo biloba (Linnaeus, 1771)

The purpose of this research was to introduce Ginkgo biloba into culture, to study the composition and properties of its biologically active compounds. Methods. We researched the optimal growth conditions for obtaining a viable tissue culture, such as: concentration of phytohormones and other organic and nonorganic substances in Murashige – Skoog medium and light hours. The effectiveness of the standard method of sodium hypochloride sterilization of young leaves and vegetative buds also was verified. As a result, of conducting the experiment we were able to grow a living callus from leaves of G. biloba. Based on this result we can conclude that these conditions are acceptable for high proliferative activity of the plant. We were studied the effect of phytohormones NAA, at a concentration of 0.5 ml and 6-BAP, at a concentration of 2.5 ml. Also, was selected the ideal planting material for callus production – young leaves that were more sensitive to treatment with hypochloride. This research serves as the foundation for future research not only for our laboratory, but also for other research groups. The callus can be used to clone specimens of G. bilobain greenhouses. It will be use to extract and study unique chemical compounds, such as ginkgolides, bilobalides and various terpenes, contained in the extract of plants of this group.