Genetic and therapeutic landscapes in cohort of pancreatic adenocarcinomas: next-generation sequencing and machine learning for full tumor exome analysis.

About 7% of all cancer deaths are caused by pancreatic cancer (PCa). PCa is known for its lowest survival rates among all oncological diseases and heterogenic molecular profile. Enormous amount of genetic changes, including somatic mutations, exceeds the limits of routine clinical genetic laboratory tests and further stagnates the development of personalized treatments. We aimed to build a mutational landscape of PCa in the Russian population based on full exome next-generation sequencing (NGS) of the limited group of patients. Applying a machine learning model on full exome individual data we received personalized recommendations for targeted treatment options for each clinical case and summarized them in the unique therapeutic landscape.

[Clinical, morphological, and prognostic features of papillary thyroid carcinoma with different BRAF mutational status assessed by immunohistochemistry]. / Klinicheskie, morfologicheskie i prognosticheskie osobennosti papilliarnogo raka shchitovidnoi zhelezy s razlichnym statusom BRAF, ustanovlennym immunogistokhimicheskim metodom.

The somatic mutation in BRAFT1799A (BRAFV600E), the data on the prognostic role of which are contradictory, is one of the most common molecular genetic abnormalities in the cells of papillary thyroid carcinoma (PTC). OBJECTIVE: To investigate the association of the immunoexpression of mutant BRAF in PTC with different morphological characteristics and long-term treatment results in patients. MATERIAL AND METHODS: Information on inpatients with PTC was obtained from the database of the Pathology Department, A.F. Tsyb Medical Radiology Research Center (a branch of the National Medical Radiology Research Center, Ministry of Health of the Russia). The paraffin-embedded blocks of surgically removed primary, metastatic, and recurrent PTC tissues were cut and stained with hematoxylin and eosin and anti-mutant BRAF monoclonal antibodies. The results of immunohistochemical tests were assessed and the frequency of BRAF immunoexpression was analyzed in relation to various clinical and morphological parameters of tumor growth, the pattern and volume of treatment in the patients, by taking into account its long-term results (the presence or absence of tumor recurrence and metastases in the postoperative period). RESULTS: The expression of mutant BRAF (BRAF+) was noted in 29 (39.3%) of the 74 cases of PTC. The BRAF+ group differed from the BRAF group by a higher proportion of male patients, older age, advanced clinical stage of carcinoma, a predominance of papillary structure of tumors, and a higher frequency of their recurrence and/or metastases in the postoperative period. CONCLUSION: The immunohistochemical assessment of BRAF status opens up a possibility to predict local recurrence and metastases in the postoperative period in patients treated for PTC.

[High-grade thyroid cancer].

The paper analyzes the data available in the literature on the morphological and prognostic features of relatively rare high-grade thyroid cancer. It shows the difficulties and unsolved problems of morphological diagnosis and the possibilities of current methods for immunohistochemical and molecular genetic studies to determine the malignant potential of the tumor and prognosis.

[A rare case of concurrent follicular and columnar cell variants of papillary thyroid carcinoma].

The paper describes a rare case of concurrent two different histological (follicular and columnar cell) variants of papillary carcinoma in one thyroid with columnar cell metastases to the lymph nodes and femoral bone. There are morphological features of and differences in BRAF status in the cells of two variants of papillary thyroid carcinoma.

[Characteristics of a clinical course of immune cytopenias with a high titer of autoantibodies to the microsomal antigen of the thyroid gland]. / Osobennosti klinicheskogo techeniia immunnykh tsitopenii, soprovozhdaiushchikhsia povyshennym titrom autoantitel k mikrosomal'nomu antigenu shchitovidnoi zhelezy.

AIM: To ascertain the role of high antibodies (Ab) titers to microsomal antigen (MA) of the thyroid in clinical manifestations of cytopenic syndromes. MATERIAL AND METHODS: Clinical data are presented on 144 patients with depressed hemopoiesis having different levels of thyroid Aab. RESULTS: When the titer was significantly elevated (41% patients with immune cytopenias), hematological malignancies run with recurrences, remission is rare. Treatment of the thyroid pathology improves hematological indices in some cases though does not reduce titers of Ab thyroid MA. CONCLUSION: Detection of autoimmune pathology of the thyroid is necessary not only for specification of the concurrent process diagnosis but also for initiation of adequate combined treatment.

[Autoantibodies to the thyroid gland in hemoblastoses and cytopenias]. / Autoantitela k shchitovidnoi zheleze pri gemoblastozakh i tsitopeniiakh.

AIM: To study the level of thyroid antibodies (TAB) in blood diseases. MATERIAL AND METHODS: TAB levels dynamics was studied in 413 patients with hematological diseases. RESULTS: Increased incidence of cases with high Ab titer to thyroid microsomal antigen was found. High and moderate titers were revealed in 33% of all examinees, including 41%, 22%, 32% and 29% among patients with immune cytopenia, chronic lymphoid leukemia, generalized mature-cell lymphoma and myeloproliferative diseases, respectively. These high and moderate titers were rather stable. In 15% patients Ab were elevated insignificantly, this rise being unstable. CONCLUSION: Stable high titers of antibodies to thyroid antigens point to increased incidence rates of concomitant autoimmune hyroiditis in patients with blood diseases.

[Postradiation recovery of hematopoiesis in mice affected by Neogen (IEW)]. / Postradiatsionnoe vosstanovlenie krovetvoreniia u myshei pod vliianiem neogena (IEW).

The effect of the synthetic peptide IEW (Neogen) with immunomodulating properties on postradiation recovery of haemopoiesis was investigated. We have shown that Neogen is a potential stimulator of haemopoiesis. The administration of Neogen after irradiation shortened duration of period of the recovery of the compartment of CFU-S-8 and the amount of bone marrow cells. The comparision of the effects of Neogen and GM-CSF (Leucomax) and G-CSF (Granocyte 34) have shown that the targets for these agents are probably different: polypotent CFU-S-for Neogen, and CFU-GM-for GM-CFS. Based on the results, we suggested the mechanism of Neogen effects on heamopoiesis.

[The protective effect of thermal treatment before irradiation on CFUs from bone marrow of mice: a potential involvement of heat shock proteins]. / Zashchitnyi éffekt predradiatsionnoi termicheskoi obrabotki myshei na KOEs ikh kostnogo mozga: vozmozhnoe uchastie belkov teplovogo shoka.

It was studied on mice how prior whole body hyperthemia affects a colony-forming ability of bone marrow after gamma-irradiation. It was found that heating of the animals (42 degrees C, 10 min) 18-22 h before their total irradiation (4 Gy) increases 2-fold the level of CFUs8 and CFUs12 determined in the spleen exotest. The induced radioresistance correlated with accumulation of heat shock proteins, HSP70 and HSP25, in tissues of preheated mice. Injection of quercetin (a selective inhibitor of the heat shock protein synthesis) 0.5 h before the heating fully abolished both the subsequent heat shock protein accumulation and the rise in CFUs populations as compared with control. It is suggested that heat shock proteins, whose expression increases in response to hyperthermia, can play a role of endogenous radioprotectors. Possible mechanisms of their protective action under irradiation are discussed.

[Radiation damage of the thyroid gland as a probable cause of increased incidence of non-Hodgkin lymphoma and other hematologic diseases]. / Radiatsionnoe povrezhdenie shchitovidnoi zhelezy kak veroiatnaia prichina uvelicheniia chastoty nekhodzhkinskikh limfom i drugikh gematologicheskikh zabolevanii.

Th distribution of autoimmune thyroiditis in the patients with diseases of blood system was investigate. The attribute of autoimmune thyroiditis was revealed by the detection of antimicrosomal antibodies. It was established that the autoimmune thyroiditis are more often in patients with various hematological diseases than in control group. It is supposed that the increase in frequency of some hematological diseases in residents suffered from the Chernobyl accident can be defined not only by the influence of the radiation on blood system, but also can be connected with damage to thyroid glands.

[A comparative study of the immunological (antimicrosomal antibodies) and cytogenetic indices of children living in radioactively contaminated areas of Bryansk Province]. / Sravnitel'noe izuchenie immunologicheskikh (antimikrosomal'nykh antitel) i tsitogeneticheskikh pokazatelei u detei, prozhivaiushchikh na radioaktivno zagriaznennykh territoriakh Brianskoi oblasti.

The chromosome dicentric aberrations in the lymphocytes and levels of antibodies to human thyroid microsomal antigen in the serum of the children lived in the area of Bryansk Province suffered from the Chernobyl accident was examined. Correlation between those tests was not estimated: the autoantibodies were revealed in group with dicentrics and without those in 4.0% and 4.5% of cases correspondingly. Antimicrosomal antibodies were revealed more frequently (5.0%) and in higher titers in the children from the more polluted Bryansk Province than in those from Kaluga Province (3.1%). These data can testify about the role of inside radiation of thyroid gland in appearance of autoimmune thyroiditis signs.

[The probable sequelae of thyroid damage from radioactive iodine during the Chernobyl accident]. / Veroiatnye posledstviia povrezhdeniia radioaktivnym iodom shchitovidnoi zhelezy v period Chernobyl'skoi avarii.

An important peculiarity of the Chernobyl catastrophe is the discharge into the atmosphere of tremendous amount of radioactive iodine and, as a result, selective damage of the thyroid in children from the affected areas. The most dangerous consequence is the thyroid cancer. The analysis of the situation when children's thyroids were subjected to irradiation shows that tumors can most frequently develop as late as 20-30 years after irradiation. There are reasons to believe that tumors are induced by low dose of irradiation. The most important factor in development of pathologies is for sure the age of the children of the moment of irradiation. A well-known consequence of the impact of radiation on the thyroid is the lymphocyte thyroiditis. The interest to this pathology is determined by the fact that it substantially increases the probability of development of various haematologic diseases (lympho- and myeloproliferative neoplasms).

[Antibodies to the thyroid microsomal antigen in children and adolescents subjected to radiation exposure as a result of the accident at the Chernobyl Atomic Electric Power Station]. / Antitela k mikrosomal'nomu antigenu shchitovidnoi zhelezy u detei i podrostkov, podvergshikhsia radiatsionnomu vozdeistviiu v rezul'tate avarii na Chernobyl'skoi AES.

For evaluation of the possibility of the appearance of autoimmune thyroiditis in children and juveniles lived in the areas of Kaluga Province [correction of region] suffered from the Chernobyl accident the content of antibodies to human thyroid microsomal antigen was investigated. Percentage of positive sera varied from 4.8% to 1.2% during 6 years. There is significant difference in the frequency of the antibody appearance between persons suffered from radioactive iodine and unsuffered ones. Correlation between levels of antimicrosomal antibodies and radiation dose obtained from incorporated radioactive iodine was not estimated.

[Immunologic methods in epidemiologic monitoring of population, affected by radioactive iodine as a result of the accident at the Chernobyl nuclear plant]. / Immunologicheskie metody v épidemiologicheskom monitoringe naseleniia podvergshegosiavozdeistviiu radioaktivnogo ioda v rezultate avarii na ChAES.

Ultrasound investigations of the thyroid gland and determinations of microsomal antibodies have been performed in persons who lived in the town of Korosten (Zhitomir Region) during the Chernobyl accident. A high correlation has been found between ultrasound and immunological results. The immunological screening of the population suffered from the Chernobyl disaster might be successfully used for the autoimmune thyroiditis detection. These data complete those obtained by the ultrasound tests.