Ассоциация рака молочной железы с онкогенными папилломавирусами: аргументы за и против

Possible breast cancer (BC) association with oncogenic human papilloma viruses (HPV) remains subject for discussion. DNA of these viruses was found in numerous BC samples in predominant majority of researches into the problem, that being the main argument in favour of their involvement into genesis of the given tumor. The principal objection to the opinion is that the HPV genomes number per a single cancer cell in HPV-positive BC is several orders of magnitude inferior to the similar indicator for cervical cancer. Urgency of the issue of possible BC association with oncogenic HPVs increases under the development of effective preventive vaccines against HPV infection. To clarify this matter the data might help either confirming or disproving the oncogenic HPV genome activity in DNA HPV-positive BC.Возможная ассоциация рака молочной железы (РМЖ) с онкогенными вирусами папилломы человека (ВПЧ) остается предметом дискуссий. В подавляющем большинстве исследований, посвященных данной проблеме, ДНК этих вирусов обнаружена во многих образцах РМЖ, что служит главным аргументом в пользу их причастности к развитию данной формы рака. Основное возражение против этой точки зрения – то, что количество геномов ВПЧ, приходящихся на одну опухолевую клетку в ВПЧ-положительном РМЖ, на несколько порядков уступает аналогичному показателю для рака шейки матки. Актуальность вопроса о возможной ассоциации РМЖ с онкогенными ВПЧ возрастает в условиях, когда созданы эффективные профилактические вакцины против ВПЧ-инфекции. Прояснению этого вопроса способствуют данные, подтверждающие или опровергающие активность генома онкогенных папилломавирусов в ДНК ВПЧ-положительном РМЖ

Ассоциация рака молочной железы с онкогенными папилломавирусами: обнаружение ДНК папилломавирусов в клетках рака молочной железы

Breast cancer is the most acute worldwide healthcare problem. Its incidence is rising. Development of this malignant tumor is associated with many risk factor, however primary cause of the disease stays usually obscure. Researches into breast cancer association with oncogenic papillomaviruses have been conducted for three decades, yet there is no definite conclusion on the problem. Actuality of the issue of breast cancer association with these viruses increases many times with the development of prophylactic vaccines against cervical cancer: in case such association does occur realistic perspective appears to prevent this extremely widespread cancer as well.Рак молочной железы – одна из острейших проблем здравоохранения во всем мире. Заболеваемость им растет. Развитие этого злокачественного новообразования связано со многими факторами риска, однако первопричина заболевания в большинстве случаев остается невыясненной. Исследования, посвященные ассоциации рака молочной железы с онкогенными папилломавирусами, проводятся на протяжении трех десятилетий, но однозначного заключения по данной проблеме пока нет. Актуальность вопроса об ассоциации с этими вирусами рака молочной железы многократно возрастает с появлением профилактических вакцин против рака шейки матки: в случае, если такая ассоциация имеет место, становится реальной перспектива предупреждения также и этой чрезвычайно распространенной формы рака

Ассоциирован ли рак предстательной железы с вирусами папилломы человека? Возвращаясь к нерешенной проблеме

Prostate cancer morbidity and mortality rates are steadily increasing in Russia and the world. The etiology of this cancer has not been adequately studied. In particular, the role of high-risk human papillomavirus types that are potent biological carcinogens in a number of other human organs remains unclear. Different laboratories worldwide continue to provide information, the authors of which make mutually exclusive conclusions regarding the involvement of these viruses in the genesis of prostate cancer. This review contains an analysis of the data available in the literature on the possible involvement of human papillomaviruses in prostate cancer.Заболеваемость раком предстательной железы и смертность от данного заболевания неуклонно возрастают. Этиология этой формы рака недостаточно изучена. Остается неясной роль вирусов папилломы человека типов высокого онкогенного риска, которые в ряде других органов человека являются сильными биологическими канцерогенами. Продолжают появляться сообщения из разных лабораторий мира, авторы которых делают взаимоисключающие выводы относительно участия этих вирусов в генезе рака предстательной железы. Обзор содержит анализ данных литературы, опубликованных преимущественно в последние годы, о возможном участии вирусов папилломы человека в возникновении рака предстательной железы

The specificity and patterns of staining in human cells and tissues of p16INK4a antibodies demonstrate variant antigen binding

The validity of the identification and classification of human cancer using antibodies to detect biomarker proteins depends upon antibody specificity. Antibodies that bind to the tumour-suppressor protein p16INK4a are widely used for cancer diagnosis and research. In this study we examined the specificity of four commercially available anti-p16INK4a antibodies in four immunological applications. The antibodies H-156 and JC8 detected the same 16 kDa protein in western blot and immunoprecipitation tests, whereas the antibody F-12 did not detect any protein in western blot analysis or capture a protein that could be recognised by the H-156 antibody. In immunocytochemistry tests, the antibodies JC8 and H-156 detected a predominately cytoplasmic localised antigen, whose signal was depleted in p16INK4a siRNA experiments. F-12, in contrast, detected a predominately nuclear located antigen and there was no noticeable reduction in this signal after siRNA knockdown. Furthermore in immunohistochemistry tests, F-12 generated a different pattern of staining compared to the JC8 and E6H4 antibodies. These results demonstrate that three out of four commercially available p16INK4a antibodies are specific to, and indicate a mainly cytoplasmic localisation for, the p16INK4a protein. The F-12 antibody, which has been widely used in previous studies, gave different results to the other antibodies and did not demonstrate specificity to human p16INK4a. This work emphasizes the importance of the validation of commercial antibodies, aside to the previously reported use, for the full verification of immunoreaction specificity

Protein p16 as a marker of dysplastic and neoplastic alterations in cervical epithelial cells

BACKGROUND: Cervical carcinomas are second most frequent type of women cancer. Success in diagnostics of this disease is due to the use of Pap-test (cytological smear analysis). However Pap-test gives significant portion of both false-positive and false-negative conclusions. Amendments of the diagnostic procedure are desirable. Aetiological role of papillomaviruses in cervical cancer is established while the role of cellular gene alterations in the course of tumor progression is less clear. Several research groups including us have recently named the protein p16(INK4a )as a possible diagnostic marker of cervical cancer. To evaluate whether the specificity of p16(INK4a )expression in dysplastic and neoplastic cervical epithelium is sufficient for such application we undertook a broader immunochistochemical registration of this protein with a highly p16(INK4a)-specific monoclonal antibody. METHODS: Paraffin-embedded samples of diagnostic biopsies and surgical materials were used. Control group included vaginal smears of healthy women and biopsy samples from patients with cervical ectopia. We examined 197 samples in total. Monoclonal antibody E6H4 (MTM Laboratories, Germany) was used. RESULTS: In control samples we did not find any p16(INK4a)-positive cells. Overexpression of p16(INK4a )was detected in samples of cervical dysplasia (CINs) and carcinomas. The portion of p16(INK4a)-positive samples increased in the row: CIN I – CIN II – CIN III – invasive carcinoma. For all stages the samples were found to be heterogeneous with respect to p16(INK4a)-expression. Every third of CINs III and one invasive squamous cell carcinoma (out of 21 analyzed) were negative. CONCLUSIONS: Overexpression of the protein p16(INK4a )is typical for dysplastic and neoplastic epithelium of cervix uteri. However p16(INK4a)-negative CINs and carcinomas do exist. All stages of CINs and carcinomas analyzed are heterogeneous with respect to p16(INK4a )expression. So p16(INK4a)-negativity is not a sufficient reason to exclude a patient from the high risk group. As far as normal cervical epithelium is p16(INK4a)-negative and the ratio p16(INK4a)-positive/ p16(INK4a)-negative samples increases at the advanced stages application of immunohisto-/cytochemical test for p16(INK4a )may be regarded as a supplementary test for early diagnostics of cervical cancer

ВПЧ-СТАТУС РАКА МОЧЕВОГО ПУЗЫРЯ, МОРФОЛОГИЧЕСКИЕ ХАРАКТЕРИСТИКИ ОПУХОЛИ И КЛИНИЧЕСКИЕ ОСОБЕННОСТИ ЗАБОЛЕВАНИЯ

The data of medical records of 101 patients with urothelial bladder cancer (BC) were compared with the results of laboratory detection of human papillomaviruses (HPV) in the tumor tissue samples taken from these patients during transurethral resection. DNA of HPV 16, the major type of the virus responsible for the occurrence of cervical cancer, was previously detected in 38 samples; and oncogenes E6 and E7 mRNA and HPV 16 E7 oncoprotein were found in 13 of these samples. Comparison of HPV-positive and HPV-negative groups revealed that HPV-positive BC showed higher cell anaplasia than HPV-negative one; moreover, primary cancer was HPV-positive more frequently than recurrent cancer. Sex, age, muscular layer invasion did not correlate with the HPV positivity of BC. Проведено сопоставление данных историй болезни 101 больного уротелиальным раком мочевого пузыря (РМП) с результатами лабораторной детекции вирусов папиллом человека (ВПЧ) в образцах опухолевой ткани, взятой у этих пациентов во время транс-уретральной резекции. Ранее ДНК ВПЧ-16, основного типа вируса, ответственного за возникновение рака шейки матки, была обнаружена в 38, а мРНК онкогенов Е6 и Е7 и онкобелок Е7 ВПЧ-16 – в 13 из этих образцов. При сравнении групп «ВПЧ-положительные» и «ВПЧ-отрицательные» выявлено, что ВПЧ-положительный РМП характеризуется более высокой степенью анаплазии клеток, чем ВПЧ-отрицательный, при этом первичный рак бывает ВПЧ-положительным чаще, чем рецидивный. Пол, возраст и инвазия в мышечный слой не коррелируют с ВПЧ-положительностью РМП.

Детекция с помощью полимеразной цепной реакции генетического материала вируса папилломы человека 16-го типа в операционном материале от больных раком предстательной железы

Background. The high rates of prostate cancer (PC) morbidity and mortality, as well as their high growth rates suggest that investigations of the nature of PC are of importance. The possible association of PC with high-risk human papillomaviruses (HPV) remains open.Objective: to examine surgically removed prostate tissue from patients with PC for HPV 16 type E7 oncogene, the main type of HPV being responsible for cervical cancer.Materials and methods. Polymerase chain reaction was used to test the prostate tissues removed from 17 patients with PC during radical prostatectomy. Cryopreserved (formalin- and paraffin- untreated) tumor samples were employed for better preservation of DNA. The multifocal growth pattern typical of PC was taken into account using microdissection to accumulate homogeneous prostate cancer, dysplastic, and intact epithelial cells.Results. HPV 16 type E7 oncogene DNA was detected in the samples from 7 patients with PC out of the 17 examinees, including all 5 cases where DNA had been isolated from the homogeneous regions of PC.Conclusion. The finding may suggest that HPV 16 is frequently present in the prostate glands of Russian patients with PC.Введение. Высокие показатели заболеваемости раком предстательной железы (РПЖ) и смертности от этой патологии, а также их высокие темпы роста свидетельствуют о важности изучения природы РПЖ. Вопрос о возможной ассоциации РПЖ с онкогенными вирусами папилломы человека (ВПЧ) остается открытым.Цель работы – изучение хирургически удаленной ткани предстательной железы у больных РПЖ на предмет присутствия в ней онкогена Е7 ВПЧ 16-го типа, основного типа ВПЧ, ответственного за возникновение рака шейки матки.Материалы и методы. Методом полимеразной цепной реакции протестированы удаленные при радикальной простатэктомии ткани предстательной железы 17 больных РПЖ. Для лучшей сохранности ДНК использовали криоконсервированные (не подвергавшиеся обработке формалином и парафином) образцы опухолей. Учитывали свойственный РПЖ мультифокальный характер роста, применив метод микродиссекций для накопления однородных клеток (рака, дисплазии, нормального эпителия железы).Результаты. ДНК онкогена Е7 ВПЧ 16-го типа обнаружена в материалах от 7 больных РПЖ из 17 обследованных, в том числе во всех 5 случаях, когда ДНК была выделена из гомогенных областей РПЖ.Заключение. Полученный результат позволяет предполагать, что ВПЧ 16-го типа нередко присутствует в предстательной железе российских больных РПЖ

ВИРУС ПАПИЛЛОМЫ ЧЕЛОВЕКА КАК ФАКТОР РИСКА ПРИ РАКЕ МОЧЕВОГО ПУЗЫРЯ

The paper reviews the data available in the literature on the possible involvement of human papillomavirus in the induction of bladder cancer (BC). The results of the authors studies in this area are summarized. The data obtained in clinical and experimental studies in vivo and in vitro count in favor of the idea that human papillomavirus may be implicated in the genesis of BC.Представлен обзор литературы по проблеме возможного участия вируса папилломы человека в индукции рака мочевого пузыря (РМП). Суммированы результаты собственных исследований в этой области. Данные, полученные на клиническом материале и экспериментальных моделях in vivo и in vitro, свидетельствуют в пользу точки зрения, согласно которой вирус папилломы человека может участвовать в генезе РМП

Is there an association between prostate cancer and human papillomaviruses? Returning to the unresolved problem

Prostate cancer morbidity and mortality rates are steadily increasing in Russia and the world. The etiology of this cancer has not been adequately studied. In particular, the role of high-risk human papillomavirus types that are potent biological carcinogens in a number of other human organs remains unclear. Different laboratories worldwide continue to provide information, the authors of which make mutually exclusive conclusions regarding the involvement of these viruses in the genesis of prostate cancer. This review contains an analysis of the data available in the literature on the possible involvement of human papillomaviruses in prostate cancer

PREVALENCE OF BLOOD CIRCULATION DISEASES AMONG WORKERS EXPOSED TO OCCUPATIONAL NOISE IN MINERAL EXTRACTION AND THEIR WORK-RELATEDNESS

The purpose of the study was to assess work-related diseases of blood circulation among workers occupationally exposed to noise in mineral extraction. Material and methods. Working conditions, health status of 1481 workers of leading occupations of oil and ore minerals extraction along with the assessment of cardio-vascular system functional state according to electrocardiography, eye fundus vessels, systemic microhemodynamics and blood microcirculation of bulbar conjunctiva have been studied. Results and discussion. Workers of these occupations are exposed to a complex of work environment and work process factors with occupational noise as a priority one. Blood circulation diseases are detected two times more frequently among workers than in the control group. Arterial hypertension frequency increases with age and work experience; a reliable increase is observed among individuals with work experience of 11-15 years and more than 15 years as compared to the group of workers with 6-10-year work experience and less than 5 years. On electrocardiographic examination, changes in the heart have been revealed in 54.2 % of workers engaged in ore extraction and 42.9 % of workers of oil extraction. Cerebrovascular diseases in most workers have been diagnosed along with arterial hypertension and atherosclerotic processes confirmed by changes in the eye fundus vessels. Thus, the elevated prevalence and an increase in arterial hypertension frequency due to work experience do not exclude potential impact of hazardous working conditions on its formation. The significant role of working conditions for arterial hypertension development has been established among operators of overhaul and underground repair of wells, drift miners, machinists of loading and delivery machines, aggregates and excavators. This is the foundation for the development of measures for creating safe working conditions and prevention of blood circulation diseases