PREDICTORS AND PREMORBID CONDITIONS OF THE DEVELOPMENT OF FEMALE GENITAL CANCER, IN PARTICULAR ENDOMETRY CANCER AND BREAST CANCER

Objective: to review a new potential diagnostic criteria for predictors and premorbid conditions of female genital cancer, including endometrial cancer and breast cancer. Materials and methods. Bibliographic, information-analytical methods were used in the work. Sources of information were data from the scientific literature on the topic of the study, modern gadleins, a review of randomized controlled trials. Results. The results of epidemiological studies suggest that the increased risk of cancer of the female reproductive system is the presence of obesity and type 2 diabetes. Potential mechanisms of their association are hyperinsulinemia, hyperglycemia, chronic inflammation, and insulin resistance. Because insulin is a major regulator of cell metabolism and is a tissue growth factor, hyperinsulinemia increases the risk of cancer. Hyperinsulinemia is associated with increased secretion of androgens by the ovaries and decreased levels of the protein that binds sex hormones, leading to higher concentrations of biologically active estrogens, which are also known to be risk factors for female genital cancer. In recent years, PFAA profiles have been found to be significantly altered in cancer and type 2 diabetes. Because cancer cells require certain amino acids to synthesize DNA, tumor growth factors, build new blood vessels, and duplicate all of their protein content, changes in PFAA profiles can be used as biomarkers of disease and different types of cancer at different stages. Conclusions. With the growing incidence of cancer, the issue of early diagnosis and detection of cancer in the pre-clinical stages remains relevant. Protein metabolism in cancer remains unclear and requires further research using a larger sample size. In addition, the biological mechanisms by which amino acids may contribute to the risk and progression of cancer or other premorbid conditions need to be elucidated. Determining the exact mechanism underlying changes in PFAA profiles has great potential for cancer diagnosis and treatment.

Combined treatment for female genital cancer

Obstetric and gynecological clinic of Kazan GIDUV for 40 years of its activity in the treatment of uterine cancer, as a rule, used combined therapy. In the first 2 decades, during the operation, attention was focused on the removal of parametric tissue. Experience has shown the insufficiency of such an intervention for long-term recovery. Relapses were frequent in the stump of the vagina, pelvic tissue, and lymph nodes.

Risks and cancer associations of metachronous and synchronous multiple primary cancers: a 25-year retrospective study

Background The situation of patients developing multiple primary cancers is becoming more frequent and graver. This study investigated the risks of developing second primary cancers that are related to first primary cancers, and the interval times of synchronous and metachronous multiple primary cancers. Patients and methods Retrospective data were retrieved from 109,054 patients aged ≥18 who were diagnosed with a first solid cancer and registered at Siriraj Cancer Center between 1991 and 2015. A two-month period between first- and second- primary cancers was used to differentiate metachronous and synchronous multiple primary cancers. The combinations of subsequent cancers and relative risks (RRs) of having multiple primary cancers versus having single primary cancer for the top-ten first and second primary cancers were examined. The RR was adjusted for age of the first primary cancer. A survival analysis of the time to second-primary-cancer development was performed. Results Multiple primary cancers were found in 1785 (1.63%) patients. Most (70.87%) second primary cancers occurred after 2 months of first breast, skin, colorectal, lung, head and neck, liver, male genital cancer–prostate, thyroid, and female genital cancer–non-uterine cancers, resulting in those cancers being classified as metachronous multiple primary cancer. After adjustment for age at first diagnosis, head and neck cancers had the highest metachronous association with second esophageal cancers (RR, 25.06; 95% CI, 13.41–50.77). Prostate cancer and second colorectal cancer also demonstrated a high metachronous association (RR, 2.00; 95% CI, 1.25–3.05). A strong synchronous association was found between uterine and ovarian cancers (RR, 27.77; 95% CI, 17.97–43.63). The median time from the first uterine cancer to second-cancer development was 55 days. Conclusions The top-ten most frequent multiple primary cancers were the following: breast; liver; head and neck; colorectal; male genital cancer–prostate; skin; female genital cancer–uterine; thyroid; lung; and female genital cancer–non-uterine. Second primary cancers showed specific associations that depended on the first primary cancer. Physicians should be cognizant of the most common combinations and the interval times of metachronous and synchronous multiple primary cancers.

SIRT5 is the desuccinylase of LDHA as novel cancer metastatic stimulator in aggressive prostate cancer

Prostate cancer (PCa) is the most commonly diagnosed genital cancer in men worldwide. Among patients who developed advanced PCa, 80% suffered from bone metastasis, with a sharp drop in the survival rate. Despite great efforts, the details of the mechanisms underlying castration-resistant PCa (CRPC) remains unclear. SIRT5, an NAD+-dependent desuccinylase, is hypothesized to be a key regulator of various cancers. However, compared to other SIRTs, the role of SIRT5 in cancer has not been extensively studied. Here, we showed significantly decreased SIRT5 levels in aggressive PCa cells relative to the PCa stages. The correlation between the decrease in the SIRT5 level and the patients survival rate was also confirmed. Using quantitative global succinylome analysis, we characterized a significant increase of lysine 118 succinylation (K118su) of lactate dehydrogenase A (LDHA), which plays a role in increasing LDH activity. As a substrate of SIRT5, LDHA-K118su significantly increased the migration and invasion of PCa cells and LDH activity in PCa patients. This study investigated the reduction of SIRT5 and LDHA-K118su as a novel mechanism involved in PCa progression. It can also be proposed as a new target that can prevent castration-resistant PCa progression, which is key to PCa treatment.

The use of in vivo dosimetry within the combined treatment of uterine body cancer

Relevance: Radiotherapy is the standard post-surgery treatment in patients with uterine cancer. However, radiotherapy affects 90.0–100.0% of the volume of risk organs. Information on the actual dose delivered to critical structures is needed to ensure the quality of radiotherapy. The purpose of this study was to determine the impact of the type of ionizing radiation on the dose load on the rectal mucosa using in vivo dosimetry. Results: At the first and tenth sessions of treatment using a cobalt apparatus, the in vivo dosimetry showed that the minimum value of the dose received during the tenth cycle was higher by 0.1 Gy. That is, the deviations from the planned dose were less at the same maximum values. Both the average value and the median during the tenth cycle were also moderately higher. The relative difference between the dose planned and received during the tenth cycle was higher than during the first cycle by an average of 1.12575%, with a median of 0.82214. When conducting radiotherapy using a linear accelerator, the average and median values were higher in the second measurement despite almost identical minimum and maximum values. The relative difference between the planned and received doses during the tenth cycle was higher than during the first cycle by an average of 0.55619%, with a median of 0.42948. Conclusion: The conducted study showed an intro- and interindividual variability of in vivo dosimetry results during radiotherapy of genital cancer patients. In vivo dosimetric control showed that the relative difference between the doses calculated and received by the rectal mucosa upon reaching of 20.0 Gy dose in comparison to the first irradiation cycle were twice higher on the ROCUS-AM cobalt apparatus vs. the Clinac 600 C linear accelerator. The data obtained during the investigation indicates the need to develop innovative approaches to topometric preparation of genital cancer patients and to continue their dosimetric monitoring to establish the causes of discrepancies in the results.

The use of in vivo dosimetry within the combined treatment of uterine corpus cancer

Relevance: Radiotherapy is the standard post-surgery treatment in patients with uterine corpus cancer. However, radiotherapy affects 90.0–100.0% of the volume of risk organs. Information on the actual dose delivered to critical structures is needed to ensure the quality of radiotherapy. The purpose of this study was to determine the impact of the type of ionizing radiation on the dose load on the rectal mucosa using in vivo dosimetry. Results: At the first and tenth sessions of treatment using a cobalt apparatus, the in vivo dosimetry showed that the minimum value of the dose received during the tenth cycle was higher by 0.1 Gy. That is, the deviations from the planned dose were less at the same maximum values. Both the average value and the median during the tenth cycle were also moderately higher. The relative difference between the dose planned and received during the tenth cycle was higher than during the first cycle by an average of 1.12575%, with a median of 0.82214. When conducting radiotherapy using a linear accelerator, the average and median values were higher in the second measurement despite almost identical minimum and maximum values. The relative difference between the planned and received doses during the tenth cycle was higher than during the first cycle by an average of 0.55619%, with a median of 0.42948. Conclusion: The conducted study showed an intro- and interindividual variability of in vivo dosimetry results during radiotherapy of genital cancer patients. In vivo dosimetric control showed that the relative difference between the doses calculated and received by the rectal mucosa upon reaching of 20.0 Gy dose in comparison to the first irradiation cycle was twice higher on the ROCUS-AM cobalt apparatus vs. the Clinac 600 C linear accelerator. The data obtained during the investigation indicates the need to develop innovative approaches to topometric preparation of genital cancer patients and to continue their dosimetric monitoring to establish the causes of discrepancies in the results.

Investigation of Genital System Cancers Prevalencein Isfahan, Iran

Background: Previous publication reported a significant disparity of genital cancer incidence between genders. The aim of this study is to investigate period prevalence (PP) and incidence (Irs) of genital cancer in Isfahan/Iran. Methods: Information equivalent to those collected by the USA Surveillance, Epidemiology, and End Results (SEER) program was obtained from the Isfahan Cancer Registry. Period prevalence (PP) was calculated per 100.000 persons. The cancer sites studied were defined according to the International Classification of Diseases (ICD-O; Third Edition) and recorded by topography code. Results: Between the years 2011 to 2015, among all registered cases (3024 cases), 60% applied to the male genital system. The mean (SD) age at diagnosis was higher for men 69.4 (14.7) than women 57.8 (15) (t-test; P<0.006). The calculated PP was significantly (Chi-squared test; P<0.001) higher in males (71.5) than females (49.6) per 100.000 in Isfahan Province. Conclusions: The PP for ovarian cancer in female and prostate cancer in male was higher than for other genital tumors. To facilitate early diagnosis for better management, we recommend that health-care plans for Isfahan Province/Iran place a greater focus on pharmacotherapy and environmental factors in cancer control.