Analysis of cancer incidence structure in the Republic of Uzbekistan

Relevance: Globocan reports 19.3 million new cases of malignant neoplasms in 2020 globally. Mammary gland cancer has become the most commonly diagnosed oncological pathology, followed by lung, colon and rectum, prostate, and stomach cancers. In Uzbekistan, malignant neoplasms of the breast, stomach, cervix, lungs, and brain dominate the structure of cancer incidence. The study aimed to analyze the cancer incidence trends and structure in the Republic of Uzbekistan in 2020. Results: In 2020, 21976 new cancer cases were registered in Uzbekistan. The ratio of men and women newly diagnosed with cancer was 0.7:1.4. Cancers of the breast, cervix, and ovary were the most common in women; cancers of the stomach, lung, and prostate — in men. Hemoblastoses were more common at a young age, breast cancer – at working age, and stomach cancer – at old age. Conclusions: The statistical information analysis showed that in 2020 the cancers of the mammary gland, stomach, and cervix were leading in the overall cancer structure, with significant differences in different age categories. This determines the need for further improvement of cancer care in Uzbekistan.

Analysis of cancer incidence structure in the Republic of Uzbekistan

Relevance: Globocan reports 19.3 million new cases of malignant neoplasms in 2020 globally. Mammary gland cancer has become the most commonly diagnosed oncological pathology, followed by lung, colon and rectum, prostate, and stomach cancers. In Uzbekistan, malignant neoplasms of the breast, stomach, cervix, lungs, and brain dominate the structure of cancer incidence. The study aimed to analyze the cancer incidence trends and structure in the Republic of Uzbekistan in 2020. Results: In 2020, 21976 new cancer cases were registered in Uzbekistan. The ratio of men and women newly diagnosed with cancer was 0.7:1.4. Cancers of the breast, cervix, and ovary were the most common in women; cancers of the stomach, lung, and prostate - in men. Hemoblastoses were more common at a young age, breast cancer – at working age, and stomach cancer – at old age. Conclusions: The statistical information analysis showed that in 2020 the cancers of the mammary gland, stomach, and cervix were leading in the overall cancer structure, with significant differences in different age categories. This determines the need for further improvement of cancer care in Uzbekistan.

Effects of Lapatinib on HER2-Positive and HER2-Negative Canine Mammary Carcinoma Cells Cultured In Vitro

HER2 is a prognostic and predictive marker widely used in breast cancer. Lapatinib is a tyrosine kinase inhibitor that works by blocking the phosphorylation of the receptor HER2. Its use is related to relatively good results in the treatment of women with HER2+ breast cancer. Thus, this study aimed to verify the effects of lapatinib on four canine primary mammary gland carcinoma cell cultures and two paired metastatic cell cultures. Cultures were treated with lapatinib at concentrations of 100, 500, 1000 and 3000 nM for 24 h and the 50% inhibitory concentration (IC50) for each cell culture was determined. In addition, a transwell assay was performed to assess the ability of lapatinib to inhibit cell migration. Furthermore, we verified HER2 expression by RT-qPCR analysis of cell cultures and formalin-fixed paraffin-embedded tissues from samples corresponding to those used in cell culture. Lapatinib was able to inhibit cell proliferation in all cell cultures, but it was not able to inhibit migration in all cell cultures. The higher the expression of HER2 in a culture, the more sensitive the culture was to treatment. This relationship may be an indication that the expression of HER2 may be a predictive factor and opens a new perspective for the treatment of primary and metastatic mammary gland cancer.

Maternal n-3 polyunsaturated fatty acids restructure gut microbiota of offspring mice and decrease their susceptibility to mammary gland cancer

Our previous studies revealed that maternal diet rich in n-3 polyunsaturated fatty acid (PUFA) is associated with decreased mammary cancer risk in offspring. However, the mechanism remains unclear. The present...

Leptin Modulates the Metastasis of Canine Inflammatory Mammary Adenocarcinoma Cells through Downregulation of Lysosomal Protective Protein Cathepsin A (CTSA)

Canine malignant mammary gland tumors present with a poor prognosis due to metastasis to other organs, such as lung and lymph node metastases. Unlike in human studies where obesity has been shown to increase the risk of breast cancer, this has not been well studied in veterinary science. In our preliminary study, we discovered that leptin downregulated cathepsin A, which is responsible for lysosomal-associated membrane protein 2a (LAMP2a) degradation. LAMP2a is a rate-limiting factor in chaperone-mediated autophagy and is highly active in malignant cancers. Therefore, in this study, alterations in metastatic capacity through cathepsin A by leptin, which are secreted at high levels in the blood of obese patients, were investigated. We used a canine inflammatory mammary gland adenocarcinoma (CHMp) cell line cultured with RPMI-1640 and 10% fetal bovine serum. The samples were then subjected to real-time polymerase chain reaction, Western blot, immunocytochemistry, and lysosome isolation to investigate and visualize the metastasis and chaperone-mediated autophagy-related proteins. Results showed that leptin downregulated cathepsin A expression at both transcript and protein levels, whereas LAMP2a, the rate-limiting factor of chaperone-mediated autophagy, was upregulated by inhibition of LAMP2a degradation. Furthermore, leptin promoted LAMP2a multimerization through the lysosomal mTORC2 (mTOR complex 2)/PH domain and leucine rich repeat protein phosphatase 1 (PHLPP1)/AKT1 (Serine/threonine-protein kinase 1) pathway. These findings suggest that targeting leptin receptors can alleviate mammary gland cancer cell metastasis in dogs.

Differential Impact of Calcitriol and Its Analogs on Tumor Stroma in Young and Aged Ovariectomized Mice Bearing 4T1 Mammary Gland Cancer

(1) Background: Vitamin D compounds (VDC) are extensively studied in the field of anticancer properties, including breast cancer. Previously, we showed that calcitriol and its analogs (PRI-2191 and PRI-2205) stimulate metastasis in 4T1 murine mammary gland cancer models in young mice, whereas the reverse effect was observed in aged ovariectomized (OVX) mice; (2) Methods: We determined the phenotype of monocytes/macrophages using FACS and examined the expression of selected genes and proteins by Real-Time PCR and ELISA; (3) Results: Activities of VDC are accompanied by an increase in the percentage of Ly6Clow anti-inflammatory monocytes in the spleen of young and a decrease in aged OVX mice. Treatment of young mice with VDC resulted in an increase of CCL2 plasma and tumor concentration and Arg1 in tumor. In later stage of tumor progression the expression of genes related to metastasis in lung tissue was decreased or increased, in old OVX or young mice, respectively; (4) Conclusions: Pro- or anti-metastatic effects of calcitriol and its analogs in young or aged OVX mice, respectively, can be attributed to the differences in the effects of VDC on the tumor microenvironment, as a consequence of differences in the immunity status of young and aged mice.

The importance of environmental exposure on selected xenoestrogens in the pathogenesis of breast cancer

Breast cancer is one of the most common types of cancer observed in women, and in its pathogenesis, in addition to endogenous estrogens, a significant role is played by xenoestrogens, which are present in the human life environment. It is a large group of exogenous compounds of diverse structure, not produced in the human body, which imitate the action of female sex hormones, especially estrogens, and in consequence affect the hormonal balance of the body. Despite the diverse structure, their common feature is the ability to interact with estrogen receptors. In this way they change the functioning of the endocrine system and, consequently, they can induce negative changes in the human body and effects on the health of both the parental generation and its offspring. Some xenoestrogens may cause tumor growth by stimulating cell proliferation, angiogenesis and metastasis. So far, such properties have been found for organic compounds, but also for some metal ions, referred to as metalloestrogens. For this reason, it is extremely important to know the sources of the presence and mechanisms of xenoestrogens in the pathogenesis of mammary gland cancer. The presented paper discusses the role of selected xenoestrogens, such as: bisphenol A, phthalates, parabens or cadmium, as a metalloestrogen. A wide range of xenoestrogens has been selected for the compounds given above, due to their importance in the pathogenesis of breast cancer and their widespread presence in the human environment, as well as to draw attention to the still-present problem of possible chronic environmental or occupational exposure of humans. The paper also explores the problem of the effect of xenoestrogens on the efficacy of breast cancer treatment, presenting possible xenoestrogen-drug interactions. It also explains how xenoestrogens present in foods (phytoestrogens) can affect the effectiveness of pharmacotherapy of breast cancer.