Critical evaluation of how and when to include anthracyclines in preoperative chemotherapy is becoming more relevant in an era when the molecular genetic approach not only allows for the development ...of biologically targeted therapeutics, but also implies the ability to select the patients likely to benefit from certain cytotoxic agents. Changes in the copy number aberration (CNA) landscape of luminal B HER2- negative (HER2-) breast cancer (BC) during anthracycline-based neoadjuvant chemotherapy (NAC) regimens were studied in order to identify groups of potential CNA markers of objective response and CNA markers for predicting the development of hematogenous metastasis. Comparison of CNA frequencies depending on the response to NAC showed that objective response was observed in a larger number of deletions in the 11q22.3 and 11q23.1 loci (p = 0.004). Comparison of CNA frequencies in groups of patients after treatment showed that hematogenous metastasis was observed with a greater number of amplifications in the 9p22.2 locus (p = 0.003) and with a greater number of deletions in the 9p21.3 locus (p = 0.03). Potential predictive CNA markers of objective response and prognostic CNA markers of hematogenous metastasis in anthracycline- based NAC regimens have been identified.
Purpose
This review is devoted to assessing the prevalence of human papillomavirus (HPV) in lung cancer (LC) in the world. HPV is recognized as the etiological factor of cervical cancer, however, ...there is widespread evidence that this virus is detected not only in gynecological carcinomas, but also in tumors of other organs, in particular the upper respiratory tract and digestive tract.
Materials and methods
A search was conducted to a depth of 29 years in the PubMed, Web of Science, Scopus, databases. The review includes 95 articles.
Results
Of all the analyzed studies (9195 patients), 12 works showed a complete absence of HPV in the biological material in patients with LC. The absence of a virus among lung cancer patients has been established for Canada, the Netherlands and Singapore. The highest average percent of occurrence of this virus is shown for such countries as: Brazil, Korea, Greece and Taiwan (more than 40%). But the highest percentage of HPV occurrence by region is observed in Latin America (33.5%), followed by the Asian countries (31%), in European countries the frequency is 18%. Interestingly, the highest occurrence of high oncogenic types (16 and 18) is observed in Asia (40.3%), then in Latin America (33.6%), Europe (25.6%) and North America (15.4%). Low-oncogenic types (6 and 11) are also predominantly observed in Asia (39.9%), while in Europe and North America 30% and 12.8%, respectively. A meta-analysis of the prevalence of HPV was conducted using Comprehensive Meta-Analysis 3.0. Program, which included 26 studies, the results of which revealed: the prevalence of HPV infection in tumor lung tissue was compared with normal lung tissue OR (95% CI) = 5.38 (3.21–9.00)
p
< 0.0001, significance was also found for Chinese studies OR = 6.3, 95% CI 3.42–11.53,
p
< 0.0001, I2 = 71.8% and for nine studies in Europe OR = 6.3, 95% CI 1.8–22.18,
p
= 0.004, I2 = 51.0%. However, given the fact that the frequency of occurrence of HPV in lung tumor tissue varies greatly, a question may arise about the real role of HPV in LC carcinogenesis, which makes further research relevant and promising.
Many factors are involved in carcinogenesis of the ovary, such human genetic and physiological characteristics as lifestyle, existing diseases of the reproductive system, and, as suggested, the human ...papillomavirus (HPV).
It is well known that the human papillomavirus virus of high carcinogenic risk (HCR) plays a crucial role in the onset and development of cervical cancer, as well as cases of HPV positive breast cancer and endometrial cancer. The data on the presence of HPV in ovarian cancer are ambiguous: the researchers claim that there is no complete effect of the virus on the development of this type of cancer, and the detection of HPV in 60–80% of tumors. In this regard, there is a need to systematize the currently available research results on this controversial issue and conduct a meta-analysis of the association of HPV infection with the risk of ovarian cancer.
•HPV is found in ovarian cancer in 28.6% of cases, while in the samples of the control group the virus was detected in 8.8%.•Among patients from Europe, the prevalence of HPV in ovarian cancer was 31.2%. Among patients from Asia - 22.5%.•Europeans have a lower relative risk of developing ovarian cancer with HPV infection than Asians (RR 1.87 versus 3.61).
Evolution and natural selection of tumoral clones in the process of transformation and the following carcinogenesis can be called natural clonal evolution. Its main driving factors are internal: ...genetic instability initiated by driver mutations and microenvironment, which enables selective pressure while forming the environment for cell transformation and their survival. We present our overview of contemporary research dealing with mechanisms of carcinogenesis in different localizations from precancerous pathologies to metastasis and relapse. It shows that natural clonal evolution establishes intratumoral heterogeneity and enables tumor progression. Tumors of monoclonal origin are of low-level intratumoral heterogeneity in the initial stages, and this increases with the size of the tumor. Tumors of polyclonal origin are of extremely high-level intratumoral heterogeneity in the initial stages and become more homogeneous when larger due to clonal expansion. In cases of chemotherapy-induced clonal evolution of a tumor, chemotherapy becomes the leading factor in treatment. The latest research shows that the impact of chemotherapy can radically increase the speed of clonal evolution and lead to new malignant and resistant clones that cause tumor metastasis. Another option of chemotherapy-induced clonal evolution is formation of a new dominant clone from a clone that was minor in the initial tumor and obtained free space due to elimination of sensitive clones by chemotherapy. As a result, in ~20% of cases, chemotherapy can stimulate metastasis and relapse of tumors due to clonal evolution. The conclusion of the overview formulates approaches to tumor treatment based on clonal evolution: in particular, precision therapy, prediction of metastasis stimulation in patients treated with chemotherapy, methods of genetic evaluation of chemotherapy efficiency and clonal-oriented treatment, and approaches to manipulating the clonal evolution of tumors are presented.
Intratumor heterogeneity inherent in the majority of human cancers is a major obstacle for a highly efficient diagnosis and successful prognosis and treatment of these diseases. Being a result of ...clonal diversity within the same tumor, intratumor heterogeneity can be manifested in variability of genetic and epigenetic status, gene and protein expression, morphological structure, and other features of the tumor. It is most likely that the appearance of this diversity is a source for the adaptation of the tumor to changes in microenvironmental conditions and/or a tool for changing its malignant potential. In any case, both processes result in the appearance of cell clones with different undetermined sets of hallmarks. In this review, we describe the heterogeneity of molecular disorders in various human tumors and consider modern viewpoints of its development including genetic and non-genetic factors of heterogeneity origin and the role of cancer stem cells and clonal evolution. We also systematize data on the contribution of tumor diversity to progression of various tumors and the efficiency of their treatment. The main problems are indicated in the diagnosis and therapy of malignant tumors caused by intratumor heterogeneity and possible pathways for their solution. Moreover, we also suggest the key goals whose achievement promises to minimize the problem of intratumor heterogeneity and to identify new prognostic, predictive, and target markers for adequate and effective treatment of cancer.
We studied the effect of technogenic radiation on the degree of promoter methylation in genes involved in apoptosis in blood lymphocytes of workers exposed to long-term γ-radiation during their ...professional activities. Blood samples for the analysis were obtained from 11 conventionally healthy men aged from 54 to 71 years (mean 66 years), workers of the Siberian Group of Chemical Enterprises working experience from 27 to 40 years (mean 30 years); the external exposure dose was 175.88 mSv (158.20-207.81 mSv). In all examined subjects, the degree of methylation of the promoters of apoptosis-related genes ranged from 0.22 to 50.00%. A correlation was found between the degree of methylation of
BCLAF1
promoters (
p
=0.035) with the age of workers,
BAX
promoters (
p
=0.0289) with high content of aberrant cells, and
APAF1
promoters (
p
=0.0152) with increased number of dicentric chromosomes. A relationship was found between the dose of external irradiation and the degree of methylation of gene promoters of
BAD
(
p
=0.0388),
BID
(
р
=0.0426), and
HRK
(
р
=0.0101) genes.
To study the peculiarities of ecological relationships of breast cancer (BC) cell lines MCF-7, BT-474 and MDA-MD-231 under co-culturing conditions.
Three BC cell lines: luminal A - MCF-7, luminal B - ...BT-474 and triple-negative - MDA-MD-231 were co-cultured pairwise. Immunocytochemistry was used to differentiate the cell lines in the wells. The effect of the cell-free culture medium on the growth rate of the alternate cell line in the pair was also evaluated.
It was shown that when BT-474 cells were co-cultured with MCF-7 and BT-474 cells were co-cultured with MDA-MD-231, two types of ecological interactions could be observed: commensalism and amensalism, respectively. While the cells do not interact with each other in contact, the supernatants of single cultures of MCF-7 and MDA-MD-231 exert the same effect on BT-474 as co-cultivation of BT-474 with these cells.
The paracrine mechanism of intercellular interaction between different human BC cell lines has been demonstrated. The models used in population ecology can be applicable to identify the types of interaction between cell lines.
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