RESUMEN
The proportion of CD44+CD24low 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. The increase in the CSC proportion after radiation exposure was observed 4.5-fold more often in patients with an initially low proportion of CSC (<3%) than that in other patients (p=0.001). The CSC proportion increased by on average 3% after irradiation in patients with complete integration of HPV 16/18 DNA and decreased by 3.8 % in patients with partial integration or no integration (p=0.03).
Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Células Madre Neoplásicas/efectos de la radiación , Neoplasias del Cuello Uterino/radioterapia , Adulto , Anciano , Alphapapillomavirus , Antígeno CD24/biosíntesis , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/virología , Cuello del Útero/virología , ADN Viral/metabolismo , Femenino , Genotipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Receptores de Hialuranos/biosíntesis , Persona de Mediana Edad , Biología Molecular , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/genética , Tolerancia a Radiación , Resultado del Tratamiento , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/virología , Carga Viral , Integración Viral , Adulto JovenRESUMEN
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 2.2±1.1% after irradiation, while in patients with partial regression this indicator increased by on average 3.3±2.3% (p=0.03). Multiple regression analysis revealed two independent indicators affecting tumor regression: the stage of the disease (which is quite expected) and change in the proportion of cancer stem cells after the first irradiation sessions (R=0.60, p<0.002 for the model in the whole). The proportion of cancer stem cells before the treatment did not have prognostic significance.
Asunto(s)
Células Madre Neoplásicas/efectos de la radiación , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/radioterapia , Femenino , Citometría de Flujo , Humanos , Receptores de Hialuranos/metabolismo , Inmunofenotipificación , Pronóstico , Análisis de Regresión , Neoplasias del Cuello Uterino/metabolismoRESUMEN
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. Virus DNA integration more than 7-fold reduced 5-year relapse-free survival and 1.7-fold reduced overall survival rate in comparison with patients without HPV DNA integration (p=0.0002 and p=0.05, respectively). The relative risk of adverse outcome of the disease in patients with the presence of HPV16 DNA integration increases by 4 times over a period of less than 3 years (Ñ=0.0006) at high AUC level. The probability of earlier progression of the disease in patients with of HPV DNA integration calculated according to the Cox proportional hazards model was 85.5% (hazard ratio 5.96; p=0.002). Thus, the results suggest that the presence of HPV16 DNA integration into the cell genome is an independent factor in predicting clinical outcome of advanced cervical cancer and can serve as an effective criterion for the individual choice of treatment tactics for the patients.
Asunto(s)
ADN Viral/genética , Papillomaviridae/genética , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/genética , Neoplasias del Cuello Uterino/patología , Femenino , Humanos , Recurrencia Local de Neoplasia/genética , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/virología , Integración Viral/genética , Integración Viral/fisiologíaRESUMEN
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). The average frequency of the TCR-mutant cells in the total group of examined residents of the Bryansk region (n = 237) was not significantly different from that in the group of agematched control persons living in un- contaminated areas (n = 146): 3.8 x 10â»4 vs 3.5 x 10â»4, respectively (p = 0.84). However, after separation of examinees into 3 groups depending on age at the start of irradiation (at.the moment of the Chernobyl acci- dent) it was found that the average frequency of the TCR-mutant cells in the persons exposed in utero was 1.6 higher than that in the control group (p = 0.04). Proportion of persons with an increased frequency of the mutant cells (more than the age norm of this indicator) among prenatally exposed population reached 23.8%; which was about.4 times higher than in the control group (p = 0.04). Proportion of persons with an increased frequency of the TCR-mutant cells in group "0-17 years at the start of irradiation", was about 2 times higher than in controls, but this difference was not statistically significant (8.0% vs 4.3%, respectively, p = 0.33). In the third group "18 or more years old at the start of irradiation" we could not register the difference in the average frequency of theTCR mutant cells or the proportion of persons with an increased frequency of these cells in comparison with the age-matched control group. In general, comparison with earlier data shows that age-related regularities of somatic mutagenesis established 15-18 years after the Chernobyl accident persist at a later date (after 28 years in this study).
Asunto(s)
Accidente Nuclear de Chernóbil , Linfocitos/efectos de la radiación , Mutagénesis/efectos de la radiación , Receptores de Antígenos de Linfocitos T/genética , Adolescente , Adulto , Anciano , Radioisótopos de Cesio/toxicidad , Aberraciones Cromosómicas/efectos de la radiación , Femenino , Humanos , Persona de Mediana Edad , Mutación/efectos de la radiación , Liberación de Radiactividad Peligrosa , Contaminantes Radiactivos/toxicidad , Receptores de Antígenos de Linfocitos T/efectos de la radiación , Adulto JovenRESUMEN
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. But in lymphocytes of patients with tumors the ROS content was higher in comparison with the control. The cell content with Ki67 expression in lymphocytes of the individuals resided in the polluted region and tumor patients was lowered.
Asunto(s)
Accidente Nuclear de Chernóbil , Linfocitos/patología , Neoplasias de la Próstata/sangre , Especies Reactivas de Oxígeno/sangre , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Antígeno Ki-67/sangre , Linfocitos/efectos de la radiación , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/patología , Especies Reactivas de Oxígeno/efectos de la radiaciónRESUMEN
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.
Asunto(s)
Transformación Celular Neoplásica , Cuello del Útero/patología , Cuello del Útero/virología , Papillomavirus Humano 16/aislamiento & purificación , Infecciones por Papillomavirus/complicaciones , Displasia del Cuello del Útero/virología , Neoplasias del Cuello Uterino/virología , Adulto , Anciano , ADN Viral/aislamiento & purificación , Femenino , Papillomavirus Humano 16/genética , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Infecciones por Papillomavirus/virología , Pronóstico , Riesgo , Neoplasias del Cuello Uterino/patología , Carga ViralRESUMEN
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. It is assumed that the integration of HPV16 DNA into the cellular genome may serve as an independent predictor of clinical outcome of cervical cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia , Genoma Humano , Papillomavirus Humano 16/patogenicidad , Infecciones por Papillomavirus/complicaciones , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/terapia , Adulto , Anciano , Investigación sobre la Eficacia Comparativa , ADN Viral/análisis , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Papillomavirus Humano 16/genética , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Infecciones por Papillomavirus/virología , Compuestos de Platino/administración & dosificación , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , Pronóstico , Resultado del Tratamiento , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virologíaRESUMEN
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. One of genotypes 31.33, 35, 39, 52, 58, 59 was established in 8 and a combination of several genotypes of the virus--12 patients. Frequency of remission in CC patients associated with HPV type 16 who had survived 3 years was significantly higher than in the same category associated with HPV type 18 (p=0.03). Relapse frequency and mortality rates in patients with tumors associated with one of viruses 31.33, 35, 39, 52, 58 or 59 were higher as compared with HPV type 16--associated cases 2 years (p=0.03) or 3 years on (p=0.11), respectively. A similar trend was established for squamous-cell tumors stages 1 and 2 (p=0.07) (p=0.12), respectively. No difference was observed in efficacy of therapy for infection with one or a combination of several genotypes of high-risk HPV. Hence, the genotype of virus is believed to be a factor of prognosis in CC early cancers. However, a definitive conclusion cannot be reached until results of a larger body of evidence and longer follow-up are available.
Asunto(s)
Alphapapillomavirus/aislamiento & purificación , Infecciones por Papillomavirus/complicaciones , Infecciones Tumorales por Virus/complicaciones , Neoplasias del Cuello Uterino/virología , Adulto , Anciano , Alphapapillomavirus/genética , ADN Viral/aislamiento & purificación , Femenino , Genotipo , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/aislamiento & purificación , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Pronóstico , Factores de Riesgo , Infecciones Tumorales por Virus/virologíaRESUMEN
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). There was shown statistically significant difference in distribution of COMTand HFE genotypes between the groups. The high frequency of chromosome aberrations (> or = 5%) was associated with homozygotes of the high activity COMT G/G and HFE CC. Heterozygotes for G1947A COMT and C187G HFE reveal negative association with the high frequency of chromosome aberrations and correspond to "resistance factors".
Asunto(s)
Catecol O-Metiltransferasa/genética , Accidente Nuclear de Chernóbil , Aberraciones Cromosómicas , Antígenos de Histocompatibilidad Clase I/genética , Proteínas de la Membrana/genética , Traumatismos por Radiación/genética , Adulto , Radioisótopos de Cesio/toxicidad , Femenino , Frecuencia de los Genes , Proteína de la Hemocromatosis , Humanos , Leiomioma/genética , Estrés Oxidativo/genética , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple , Federación de Rusia , Neoplasias Uterinas/genéticaRESUMEN
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. This tendency was statistically significant in case of deletion polymorphism of the GSTM1 gene: TCR-mutant cell frequency of the homozygous carriers of a deletion at the GSTM1 locus was (4.63 +/- 0.18) x 10(-4) while it was (4.05 +/- 0.15) x 10(-4) in other groups of persons. The greatest mutant cell frequency was observed in carriers of the minor allele 4889G of the locus CYP1A. More often the increased values of the TCR-mutant cells (outside range "3sigma") were determined in women with genotypes A/G or G/G of the locus CYP1A1 (25%) than in carries of the normal genotype A/A (1.6%) (OR = 20.6; p = 0.0002). The comparison of the groups of women with reproductive system diseases reveals significant elevation in the mean TCR-mutant cell frequency in inhabitants of the most radiation polluted region among others.
Asunto(s)
Exposición a Riesgos Ambientales , Linfocitos/inmunología , Contaminantes Radiactivos , Receptores de Antígenos de Linfocitos T/genética , Citocromo P-450 CYP1A1/genética , ADN/genética , Femenino , Citometría de Flujo , Enfermedades de los Genitales Femeninos/genética , Enfermedades de los Genitales Femeninos/inmunología , Genotipo , Glutatión Transferasa/genética , Proteína de la Hemocromatosis , Antígenos de Histocompatibilidad Clase I/genética , Humanos , Recuento de Linfocitos , Proteínas de la Membrana/genética , Mutación , Polimorfismo Genético , Federación de RusiaRESUMEN
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. An effective fixation and withdrawal of bacteria from the bowl of the affected animals took place. The survival level of mice in 30 days after CRI comprised 20% as compared with 60% in the case of "CK D" administration. It is supposed that the increase of survival after "CKD" administration is the result of enhancement of macrophage detoxification in liver, determined on the increase of activity of cathepsine D (lysosomal protease), elimination of MMM and normalization of gut microflora.
Asunto(s)
Silicatos de Aluminio/administración & dosificación , Enteroadsorción , Péptido Hidrolasas/metabolismo , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Traumatismos Experimentales por Radiación/enzimología , Animales , Catepsina D/metabolismo , Arcilla , Intestino Delgado/efectos de los fármacos , Intestino Delgado/enzimología , Intestino Delgado/microbiología , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Ratones , Traumatismos Experimentales por Radiación/microbiología , Ratas , Ratas WistarRESUMEN
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. The mean frequency of the mutant cells was higher in the first group than in age-matched control group by about 1.5-fold: 4.0 x 10(-4) vs 2.7 x 10(-4) accordingly (p < 0.0001). Elevation in the mean TCR-mutant cell frequency was less expressed in group of inhabitants aged 0-14 years at the moment of irradiation start: 1.3-fold increase in comparison to age-matched control (3.8 x 10(-4) vs 2.9 x 10(-4), p = 0.0002). It was not found significant differences in mutant cell frequencies between control group and adults consisting in the third group (18 and more years old at the moment of the Chernobyl accident). The changes of the TCR-mutant cell frequency in persons exposed in pre- and postnatal periods differ not only quantitatively, but qualitatively. In the fist case all persons react to irradiation by increasing number of the TCR-mutant cells in some degree. In the second case - only a part of population. Proportion of reacting persons depends on age at the start of irradiation and, perhaps, on dose absorbed. The TCR-mutant frequency was significantly higher in persons with benign tumors of different localizations and nodules in thyroid gland than in persons without this pathology.
Asunto(s)
Accidente Nuclear de Chernóbil , Exposición a Riesgos Ambientales , Contaminación Ambiental , Genes Codificadores de los Receptores de Linfocitos T , Neoplasias/genética , Contaminantes Radiactivos/toxicidad , Análisis Citogenético , Femenino , Humanos , Masculino , Mutagénesis , Mutación , Federación de RusiaRESUMEN
In patients with ovarian cancer, the colony-forming capacity and radiosensitivity of clonogenic tumor cells from the primary node and metastases (ascites) differed considerably.
Asunto(s)
Células Madre Hematopoyéticas/patología , Células Madre Hematopoyéticas/efectos de la radiación , Neoplasias Ováricas/patología , Neoplasias Ováricas/radioterapia , Diferenciación Celular/efectos de la radiación , Ensayo de Unidades Formadoras de Colonias , Femenino , Hematopoyesis/efectos de la radiación , HumanosRESUMEN
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.
Asunto(s)
Neoplasias Ováricas/radioterapia , Traumatismos por Radiación/prevención & control , Radioterapia Asistida por Computador/métodos , Neoplasias Uterinas/radioterapia , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Traumatismos por Radiación/etiología , Radioterapia/efectos adversos , Planificación de la Radioterapia Asistida por Computador/métodos , Resultado del TratamientoRESUMEN
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. Three-year follow-up data were obtained through hospital charts and correspondence with referring physicians for only 19 patients. RESULTS: There was no statistically significant association between LI and such conventional prognostic factors as clinical stage. The LI value of cervix carcinomas was significantly associated with complete regression at 3-6 months after radiotherapy and 3-year disease-free survival. Complete regression at 3-6 months was observed in 87.5% patients with fast proliferating tumors (LI > 7.0%), and only in 41.2% patients with slowly proliferating tumors (p = 0.03). Probability of 3-year disease-free survival was 85.7% in patients with fast proliferating tumors and 50.0% in those with slowly proliferating tumors (p = 0.05). CONCLUSIONS: The immunofluorescent LI of epidermoid cervix carcinoma is able to provide prognostic information on short-term tumor response to radiotherapy and disease-free survival.
Asunto(s)
Carcinoma de Células Escamosas/patología , Fase S , Neoplasias del Cuello Uterino/patología , Adulto , Anciano , Anticuerpos , Carcinoma de Células Escamosas/radioterapia , División Celular , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Timidina/análisis , Neoplasias del Cuello Uterino/radioterapiaRESUMEN
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.
Asunto(s)
Hipertermia Inducida , Neoplasias Uterinas/terapia , Terapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Uterinas/radioterapiaRESUMEN
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. Nevertheless irradiation of 5 Gy was found more preferable as it was less frequently accompanied by complications of the adjacent organs.