Effects of Fractionated Radiation Exposure on Vimentin Expression in Cervical Cancers: Analysis of Association with Cancer Stem Cell Response and Short-Term Prognosis.

Elucidation of the mechanisms for the response of cancer stem cells (CSCs) to radiation exposure is of considerable interest for further improvement of radio- and chemoradiotherapy of cervical cancer (CC). The aim of this work is to evaluate the effects of fractionated radiation exposure on the expression of vimentin, which is one of the end-stage markers of epithelial-mesenchymal transition (EMT), and analyze its association with CSC radiation response and short-term prognosis of CC patients. The level of vimentin expression was determined in HeLa, SiHa cell lines, and scrapings from the cervix of 46 CC patients before treatment and after irradiation at a total dose of 10 Gy using real-time polymerase chain reaction (PCR) assay, flow cytometry, and fluorescence microscopy.

Prognostic Value of Serum Transferrin Analysis in Patients with Ovarian Cancer and Cancer-Related Functional Iron Deficiency: A Retrospective Case-Control Study.

(1) Background: There are no reliable and widely available markers of functional iron deficiency (FID) in cancer. The aim of the study was to evaluate the role of transferrin (Tf) as a marker of cancer of the ovary (CrO) and related FID. (2) Methods: The study groups consisted of 118 patients with CrO and 69 control females.

HPV Status and Individual Characteristics of Human Papillomavirus Infection as Predictors for Clinical Outcome of Locally Advanced Cervical Cancer.

This study is aimed at searching for an informative predictor of the clinical outcome of cervical cancer (CC) patients. The study included 135 patients with locally advanced cervical cancer (FIGO stage II-III) associated with human papillomavirus (HPV) 16/18 types or negative status of HPV infection. Using logistic regression, we analyzed the influence of the treatment method, clinical and morphological characteristics, and the molecular genetic parameters of HPV on the disease free survival (DFS) of patients treated with radiotherapy or chemoradiotherapy.

Radiation Response of Cervical Cancer Stem Cells Is Associated with Pretreatment Proportion of These Cells and Physical Status of HPV DNA.

Radio- and chemoresistance of cancer stem cells (CSCs) is considered as one of the possible causes of adverse results of chemoradiotherapy for various malignancies, including cervical cancer. However, little is known about quantitative changes in the CSC subpopulation in the course of treatment and mechanisms for individual response of CSCs to therapy. The purpose of the study was to evaluate the association of radiation response of cervical CSCs with clinical and morphological parameters of disease and features of human papillomavirus (HPV) infection.

Correlation of Radiation Response of Cervical Cancer Stem Cells with Their Initial Number before Treatment and Molecular Genetic Features of Papillomavirus Infection.

The proportion of CD44CD24 cancer stem cells (CSC) was determined in cervical scrapings of 41 patients with squamous cell carcinoma of the uterine cervix before treatment and after irradiation in a total focal dose of 10 Gy. The relationship of quantitative changes in the CSC population with such parameters of papillomavirus infection as genotype, viral load, and physical status of HPV DNA (the absence or presence of HPV DNA integration into the cell genome and the degree of integration) was studied. Single- and multi-factor analysis revealed 2 independent indicators affecting the radiation response of CSC: initial number of these cells before treatment and physical status of HPV DNA.

Quantitative Changes in the Population of Cancer Stem Cells after Radiation Exposure in a Dose of 10 Gy as a Prognostic Marker of Immediate Results of the Treatment of Squamous Cell Cervical Cancer.

Prognostic significance of the proportion of cancer stem cells in cervical scrapings from 38 patients with uterine cervical cancer before treatment and after irradiation in a total dose of 10 Gy was assessed for immediate results of radio- and combined chemoradiotherapy evaluated by the degree of tumor regression in 3-6 months after the treatment. Cancer stem cells were detected as cells with CD44+CD24low immunophenotype by flow cytometry. The proportion of cancer stem cells in patients with the complete tumor regression decreased by on average 2.

The Presence of Human Papillomavirus DNA Integration is Associated with Poor Clinical Results in Patients with Third-Stage Cervical Cancer.

The presence of virus DNA integration into the cell genome was studied for 47 primary HPV16-positive patients with morphologically verified stage III cervical cancer. By using ROC analysis, the patients were divided into two groups: with and without HPV DNA integration into the host cell genome. The differences between the groups by the histological type, degree of tumor differentiation, and primary response to therapy were statistically insignificant.

The Content of ROS in Blood Lymphocytes of Healthy Individuals, Individuals Irradiated as a Result of Chernobyl Disaster and Patients with Prostate Cancer.

The ROS concentration and proliferation activity (Ki67 expression.marker) have been studied in the periphery blood lymphocytes of Moscow and Obninsk citizens, donors, Chernobyl disaster liquidators, inhabitants of the region contaminated after Chernobyl disaster (Klincy) and individuals with prostate cancer. It was shown that ROS concentration in lymphocytes of the liquidators and residents of the polluted region was lowered.

[Frequency of Lymphocytes with Mutations at the Locus of T-Cell Receptor in Residents of Radiation Polluted Bryansk Region 28 Years after the Chernobyl Nuclear Power Plant Accident].

The aim of this study is to assess the level of somatic mutagenesis according to the frequency of lymphocytes bearing mutations at the locus of T-cell receptor (TCR) in the residents of the Bryansk region contaminated with radionuclides as a result of the Chernobyl accident. The study was :conducted in 2014 in two regional centers - Klintsy and Novozybkov (average¹³⁷Cs pollution density of 322 and 708 kBq/m²,.respectively).

Association of the apolipoprotein E 2 allele with concurrent occurrence of endometrial hyperplasia and endometrial carcinoma.

Genes encoding proteins with antioxidant properties may influence susceptibility to endometrial hyperplasia (EH) and endometrial carcinoma (ECa). Patients with EH (n = 89), EH concurrent with ECa (n = 76), ECa (n = 186), and healthy controls (n = 1110) were genotyped for five polymorphic variants in the genes involved in metabolism of lipoproteins (APOE Cys112Arg and Arg158Cys), iron (HFE Cys282Tyr and His63Asp), and catecholamines (COMT Val158Met). Patients and controls were matched by ethnicity (all Caucasians), age, body mass index (BMI), and incidence of hypertension and diabetes.

[The risk of neoplastic processes transformation in cervix uteri].

There was performed a comparative analysis of quantitative load and physical status of human papillomavirus (HPV) type 16 in groups of patients with cervical intraepithelial neoplasia (CIN)--25 people and cervical cancer (CC)--85 people. According to the analysis there were selected criteria appropriate to a combination of adverse factors that characterized HPV- infection and at the same time estimated both quantitative load and physical status of the virus: high viral load (> 6,5 lg copies of HPV DNA per 100000 cells) in episomal form or low load (< 6,5 lg copies of HPV DNA per 100000 cells) in integrated form of the virus. According to calculations a relative chance of appearing of CC in CIN patients with unfavorable combination of factors was 7,5 times higher than in other patients.

[The significance of physical status of human papillomavirus type 16 for predicting the effectiveness of invasive cervical cancer treatment].

For the 83 patients with HPV 16-cancer of the cervix (cervical cancer) I-III stages it was performed a comparative analysis of primary tumor response to therapy, the clinical outcome of the disease for 3-5 years after radical treatment and an evaluation of the possible contribution in these rates of the physical status of the virus. It was shown that total tumors regression in the early stages of the observation predominate in patients with "high-integrated" virus DNA (the degree of integration > 50%) of compared with a group of patients with episomal and "low-integrated" form of the virus, but in a distant periods (3-5 years) in the first group predominate an adverse outcome of disease. This pattern is true for tumors of stage I-III, and for less common--I-II stages.

[Infection with high-risk human papillomavirus and prognosis of cervical carcinoma].

Real-time polymerase chain reaction procedure was used to evaluate bioptic tumor samples from patients suffering cervical carcinoma (CC) stages I-IV. Out of 110 patients, high-risk human papillomavirus (HPV) infection was identified in 98 (89.1%), HPV type 16--63, HPV type 18--10 and HPV type 45--5.

[The polymorphism of catechol-O-methyltransferase (COMT) and hemochromatosis (HFE) genes in the radiocontaminated regions residents with different chromosome aberration frequency].

The association between polymorphisms in genes COMT, HFE that takes part in oxidative stress regulation, and chromosome aberration frequency in lymphocytes was assessed in 278 female residents of radiation polluted regions of Central Russia: Bryansk (322 kBk/m2) and Tula Districts (137Cs - 171 kBk/m2). The C187G, G845A genotyping of HFE and G1947A (H/L) of COMT was done by means of polymerase chain reaction-restriction fragment length polymorphism. Studied population was divided into 3 subgroups by level of chromosome aberrations per cell (0-2, 3-4, >5).

[The association of TCR-mutant cells with DNA polymorphism in women residing in radiation polluted regions of the Russian Federation].

Using flow-cytometric method the frequency of lymphocytes beaming mutations at T-cell receptor (TCR) locus was assessed in women residing in radiation polluted regions of Bryansk and Tula Districts. Simultaneously genotyping of the 8 polymorph loci for genes involved in detoxication of xenobiotics and oestrogen metabolism was carried out. The increased TCR-mutant cell frequency was found to be characteristic of homozygotes of the low activity appropriated enzymes for 3 loci (HFE187, GSTM1 and MTHFR) at least.

[Mechanisms of detoxification efficiency of new enterosorbent in combined radiation pathology].

Studies with rats and white mice demonstrated that combined radiation injury (CRI) comes to reducing protease activity in small intestine tissues. In liver tissue the activity of cathepsine D increased under the action of new enterosorbent--clay of Kaluga deposit ("CKD"). In blood serum of the damaged animals the amount of histogenic toxins--middle mass molecules (MMM) and oligopeptides decreased after "CKD" administration.

[Somatic mutagenesis at T-cell receptor locus in inhabitants of radiation polluted regions as a result of the Chernobyl disaster].

In the period of 2001-2004, frequency of cells bearing mutations at T-cell receptor (TCR) locus was assessed in 553 inhabitants of radiation polluted regions of the Russian Federation and 154 unexposed control persons. The inhabitants were divided into three groups according to age at the moment of the Chernobyl disaster and 137Cs pollution density: 1) in utero, 37-555 kBq/m2; 2) 0-14 years old, 20-555 kBq/m2; 3) 18 and more years old, highest 137Cs density (185 more than 555 kBq/m2). The most intense changes of the TCR-mutant cell frequency were observed in the group of persons exposed to ionizing radiation in utero.

Frequency of hemochromatosis gene (HFE) mutations in Russian healthy women and patients with estrogen-dependent cancers.

Possible association between the C282Y and H63D mutations in the HFE gene and estrogen-dependent cancer risk was assessed. Genotyping was performed using PCR amplification followed by digestion of products with specific restrictases. In a population of 260 healthy women (permanent residents of the southwest European Russia), mutant allele frequencies at the C282Y and H63D sites were evaluated as 3.

Effect of irradiation on colony-forming ability of stem cells from patients with ovarian cancer.

In patients with ovarian cancer, the colony-forming capacity and radiosensitivity of clonogenic tumor cells from the primary node and metastases (ascites) differed considerably.

[Various aspects of individualized planning of computerized radiotherapy for uterine and ovarian cancer].

The study was concerned with radiotherapy planning using individual data on tissue volume to be treated. The investigation used criteria based on correlations of TDF, actual volume identified by ultrasound, computed and magnetic resonance tomography and dose fractionation regime. As a result, grave complication rates dropped 3 times including cases of locally advanced tumors, non-traditional dose fractionation and advanced regimens of polychemotherapy.

Prognostic significance of S-phase fraction detected by antithymidine antibodies in epidermoid cervix carcinomas.

Purpose: To assess the predictive value of pretreatment proliferative activity of epidermoid cervix carcinoma cells with respect to short- and long-term results of radiotherapy.

Methods And Materials: The proliferative activity of 25 epidermoid cervix carcinomas was evaluated as the immunofluorescent labeling index (LI) by rabbit antithymidine antibodies reacting specifically with single-stranded DNA of replication forks in S-phase cells. The short-term clinical outcome was estimated at 3-6 months after treatment by visual and palpatory examination.

[Thermoradiotherapy of cancer of the endometrium].

The paper is concerned with the consideration of technical potentialities of local UHF-hyperthermia with regard to combined radiotherapy of endometrial cancer. The authors performed comparative analysis of thermoradiotherapy of a tumor and adjacent normal tissues and of combined radiotherapy as an independent method. The results of this investigation have shown that a decrease in a single focal dose per fraction, taking into account the DMF of hyperthermia in thermoradiotherapy, the same therapeutic effect on a tumor being preserved like in radiotherapy, reduces the frequency of radiation reactions of adjacent normal organs and tissues.

[Long-term results of combined radiation therapy of cancer of the cervix].

The authors presented 5-year results of combined radiation therapy of 217 patients with stage I-II cervical cancer using 60Co high energy sources on the Agat-B unit for intracavitary irradiation. Intracavitary therapy with fractions of 10 and 5 Gy was compared. No significant correlation was found between a therapeutic effect and a fraction value.