Binary Proton Therapy of Ehrlich Carcinoma Using Targeted Gold Nanoparticles.

Proton therapy can treat tumors located in radiation-sensitive tissues. This article demonstrates the possibility of enhancing the proton therapy with targeted gold nanoparticles that selectively recognize tumor cells. Au-PEG nanoparticles at concentrations above 25 mg/L and 4 Gy proton dose caused complete death of EMT6/P cells in vitro. Binary proton therapy using targeted Au-PEG-FA nanoparticles caused an 80% tumor growth inhibition effect in vivo. The use of targeted gold nanoparticles is promising for enhancing the proton irradiation effect on tumor cells and requires further research to increase the therapeutic index of the approach.

Bismuth Nanoparticles Increase Effectiveness of Proton Therapy of Ehrlich Carcinoma.

We studied the antitumor activity of the combined use of local proton irradiation in two modes (10 and 31 Gy) with preliminary intra-tumoral injection of two types of bismuth nanoparticles differing in surface coating: coated with the amphiphilic molecule Pluronic-F127 or Silane-PEG (5 kDa)-COOH polymer. Nanoparticles were used in doses of 0.75 and 1.5 mg/mouse. In two independent series on experimental tumor model (solid Ehrlich carcinoma), bismuth nanoparticles of both modifications injected directly into the tumor enhanced the antitumor effects of proton therapy. Moreover, the radiosensitizing effect of bismuth nanoparticles administered via this route increased with the increasing the doses of nanoparticles and the doses of radiation exposure. In our opinion, these promising data obtained for the first time extend the possibilities of treating malignant neoplasms.

[Small cell neuroendocrine carcinoma of the endometrium]. / Melkokletochnaya neiroendokrinnaya kartsinoma endometriya.

The article describes a rare case of small cell neuroendocrine carcinoma of the endometrium in a 67-year-old woman. According to the literature, only about 90 such observations have been described worldwide. Histological examination revealed three necessary features: the small-cell nature of the tumor, the presence of epithelial and neuroendocrine markers. An IHC study revealed a positive expression of Syn, Chrom A, CD56, CK AE1/AE3 markers; the proliferative activity index was 70%.

[Detection of SARS-CoV-2 RNA in the mucosa of the appendices of children with COVID-19]. / Vyyavlenie RNK SARS-CoV-2 v slizistoi obolochke cherveobraznogo otrostka u detei s COVID-19.

Background. The novel coronavirus infection (COVID-19) often manifests in children as diarrhea, vomiting, abdominal pain, and some children develop acute appendicitis. To elucidate the role of SARS-CoV-2 in the development of acute appendicitis, a more detailed study of the presence of its genetic material in the tissue of the appendix. OBJECTIVE: Determination of SARS-CoV-2 RNA in appendices of children with COVID-19 by fluorescence in situ hybridization (FISH). MATERIAL AND METHODS: A retrospective analysis of case histories and morphological analysis using FISH of appendices of pediatric patients with established clinical diagnosis of acute appendicitis and confirmed infection with SARS-CoV-2 was performed. The material was divided into 3 groups: 1st -appendices obtained during appendectomy in children with established clinical diagnosis of «coronavirus infection¼ (COVID-19, PCR+) (n=42; mean age 10.8 years); 2nd - appendices of children (n=55; mean age 9.7 years) with acute appendicitis obtained before the onset of the COVID-19 pandemic; 3rd (control) group (n=38; mean age 10.3 years) - autopsy material of the appendices (intact). RESULTS: In all samples of the appendices of the 1st group, a positive SARS-CoV-2 viral RNA signal was noted in the cytoplasm of most epithelial cells and single immunocompetent cells. The signal intensity remained the same in all slides, regardless of age. In all samples obtained from patients without COVID-19 (groups 2 and 3), confocal microscopy did not reveal a signal, which indicates successful adaptation of the FISH method in this study and excludes the false positive results. CONCLUSION: In the epithelium of the appendices of children of different age with COVID-19, the FISH method revealed SARS-CoV-2 RNA, which does not exclude the association between viral invasion and the development of acute appendicitis.

Effect of Collagen and GelMA on Preservation of the Costal Chondrocytes' Phenotype in a Scaffold in vivo.

The aim of the study was to compare type I collagen-based and methacryloyl gelatin-based (GelMA) hydrogels by their ability to form hyaline cartilage in animals after subcutaneous implantation of scaffolds. Materials and Methods: Chondrocytes were isolated from the costal cartilage of newborn rats using 0.15% collagenase solution in DMEM. The cells was characterized by glycosaminoglycan staining with alcian blue. Chondrocyte scaffolds were obtained from 4% type I porcine atelocollagen and 10% GelMA by micromolding and then implanted subcutaneously into the withers of two groups of Wistar rats. Histological and immunohistochemical studies were performed on days 12 and 26 after implantation. Tissue samples were stained with hematoxylin and eosin, alcian blue; type I and type II collagens were identified by the corresponding antibodies. Results: The implanted scaffolds induced a moderate inflammatory response in both groups when implanted in animals. By day 26 after implantation, both collagen and GelMA had almost completely resorbed. Cartilage tissue formation was observed in both animal groups. The newly formed tissue was stained intensively with alcian blue, and the cells were positive for both types of collagen. Cartilage tissue was formed among muscle fibers. Conclusion: The ability of collagen type I and GelMA hydrogels to form hyaline cartilage in animals after subcutaneous implantation of scaffolds was studied. Both collagen and GelMA contributed to formation of hyaline-like cartilage tissue type in animals, but the chondrocyte phenotype is characterized as mixed. Additional detailed studies of possible mechanisms of chondrogenesis under the influence of each of the hydrogels are needed.

[Angiomyolipoma of the liver]. / Angiomiolipoma pecheni.

Angiomyolipoma of the liver is an extremely rare neoplasm, the number of reported cases of this disease is only about 600 worldwide. Morphological criteria for neoplasm verification present difficulties due to low occurrence and complexity of differential diagnostic search. In this regard, this observation is of interest to pathologists and physicians. A special feature of this tumor is the presence of three components: adipose, vascular and muscular with characteristic epithelioid cells. The article presents the clinical and morphological characteristics of liver angiomyolipoma in a 40-year-old woman. The diagnosis was confirmed by immunohistochemical study: a positive reaction with HMB45, Melan A, SMA, desmin, CD31, CD34; proliferative index was more than 25%.

[Influence of platelets growth factors on spermatogenesis after electronic irradiation]. / Vliyanie faktorov rosta trombotsitov na spermatogenez posle oblucheniya elektronami.

BACKGROUND: The number of cases of male infertility is steadily growing every year, and therefore it is necessary to develop new methods for the diagnosis and treatment of this disease. It is known that plasma enriched with platelets, the α-granules of which contain growth factors, possesses high regenerative activity; therefore, we can expect positive results from its use for the restoration of spermatogenic epithelium. OBJECTIVE: Morphological assessment of spermatogenesis after local ß-irradiation with a dose of 8 Gy and the introduction of growth factors. MATERIAL AND METHODS: Wistar rats (n=135) were divided into groups: I - Control, II - 8IR, III - 8IR+LP-PRP+IGF, IV - 8IR+LP-PRP, and V - LP-PRP. Spermatogenesis in animals of groups II, III, and IV was inhibited by a single local irradiation with 8 Gy electrons. Then, for 11 weeks, LP-PRP was injected intraperitoneally to rats III and IV, and in group III - additionally IGF-1. The testes were examined by light microscopy, computer morphometry, micro-CT, and Western blotting. RESULTS: After irradiation, a decrease in spermatogenic epithelium and the number of germ cells was observed up to sub- and total germinal aplasia, fibrosis and an increase in the expression of caspase-3. Against the background of LP-PRP+IGF administration, the decrease in the proportion of germ cells (hypospermatogenesis) was less pronounced. CONCLUSION: The introduction of growth factors and other biologically active substances released from the α-granules of LP-PRP platelets leads to a delayed decrease in the quantitative and qualitative indicators of spermatogenesis, and the additional administration of IGF-1 enhances the regenerative processes that counteract the development of the effects of electron irradiation with a dose of 8 Gy.

[Clinical and morphological characteristics of SARS-CoV-2-related myocarditis proven by the presence of viral RNA and proteins in myocardial tissue]. / Kliniko-morfologicheskaya kharakteristika SARS-CoV-2-assotsiirovannogo miokardita, podtverzhdennogo nalichiem RNK i belkov virusa v tkani miokarda.

OBJECTIVE: To investigate the clinical and morphological features of SARS-CoV-2-related myocarditis, by determining the presence of viral RNA and proteins in myocardial tissue. MATERIAL AND METHODS: The study was conducted to examine the material of 32 autopsies with a confirmed diagnosis of myocarditis. There were data of a morphological study, including a standard histological study, as well as immunohistochemical determination of the surface markers CD45, CD3, CD20, and CD68 cells of an inflammatory infiltrate and virus proteins (SARS-CoV-2 nucleocapsid protein and spike protein). Positive and negative control tests were carried out. In addition, coronavirus RNA was detected in the myocardium using a polymerase chain reaction. RESULTS: Polymerase chain reaction (PCR) revealed viral RNA in myocardial tissue. Viral proteins were identified in the macrophages of an inflammatory infiltrate and cardiomyocytes. CONCLUSION: The findings may suggest that the virus persists in the myocardium and chronic myocarditis develops.

[The specific immunophenotypic features of nasopharyngeal carcinoma]. / Immunofenotipicheskie osobennosti nazofaringeal'noi kartsinomy.

We have undertaken the retrospective analysis of the medical histories of 119 patients presenting with nasopharyngeal carcinoma (NPC) and the biopsy specimens obtained from them; the wereinvestigated with the use of the histological (staining of the micropreparations with hematoxylin and eosin) and immunehistochemical (monoclonal murine antibodies against Pan-cytokeratin, CK 5/6, EBV, CK7, CK19, p16) techniques. The study has demonstrated the presence of non-differentiated nasopharyngeal carcinoma in 97 patients, diffuse large-cell B-lymphoma in 18 ones, melanoma of the nasopharyngeal mucous membrane in 2, and nasopharyngeal rhabdosarcoma in 1 patient. The immunohistochemical study revealed co-expression of the markers of Epstein-Barr virus, Pan-cytokeratin, and CK 5/6 in the non-differentiated nasopharyngeal carcinoma .

[IDH1- and IDH2-mutations in brain glial tumors - the new antioncogenic mechanism]. / IDH1- i IDH2-mutatsii v glial'nykh opukholiakh golovnogo mozga - novyi antionkogennyi mekhanizm.

Mutant forms of the gene IDH1 progress significantly slower, have a lower risk of neoplastic transformation, and generally, mutations of this gene have a pronounced anti-oncogenic effect. At the same time, almost all mutations are quite stereotyped (98,9%) and occur in the same region of the gene - R132H mutations. IDH1 gene mutations is a complex multi-layered process, which is a completely new, not previously described anti-oncogene activation mechanism of intracellular protection. The reason that there is a mutation in the tumor cells is associated with de novo blocking differentiation processes and development of brain cells in the development process, as evidenced by severe cerebral hypoplasia in patients with congenital forms of this mutation. A completely new mechanism of antitumor protection has been described - stereotypical IDH1 gene mutation is a gene, in fact, is a key event, causing a cascade of further anti-oncogenic mechanisms in brain gliomas.

[New approach to diagnosis, immunophenotypic verification and prognostic prediction for renal angiomyolipoma].

Renal angiomyolipoma (AML) is a rare benign neoplasm of mesenchymal origin. AML incidence varies from 0.3 to 5%, while women suffer four times more often than men. In most cases, renal AML measures less than 4 cm, is asymptomatic and detected accidentally with computed tomography or ultrasound. A histological variant of AML need to be verified to choose management strategy and reduce the risk of complications. Histological and immunohistochemical assessment of biopsy and surgical specimens has an essential diagnostic value in determining the type and subtypes of renal neoplasms and the risk of malignancy. The study aimed to investigate pathomorphological and prognostic features (immunohistochemical characteristics) of renal AML. MATERIALS AND METHODS: Patients (n=42) with CT-detected renal neoplasms underwent partial nephrectomy. The majority (n=34) of patients was admitted to the hospital urgently, often without symptoms (n=23). The surgical specimens studied were examined using light microscopy and immunohistochemistry analysis with primary mouse monoclonal antibodies to HMB-45, Melan-A, -SMA, S-100 and SC (Novocastra, UK). RESULTS: All specimens showed morphological characteristics typical of AML and a positive response to antibodies against HMB-45 (ve +/3; 99.6+/-0.3%), Melan-A (ve + / 2, 89.6+/-4.3%) and SMA (ve + 2; 70.1+/-2.9%) and exhibited no staining with antibodies against S-100 and SK. CONCLUSION: Morphological study of renal AML shows that the tumor is benign, therefore partial nephrectomy, in our opinion, should be considered as an alternative to radical nephrectomy, including for sporadic giant renal AML.