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Siberian journal of oncology

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Vol 23, No 4 (2024)
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EPIDEMIOGICAL STUDIES

5-18 560
Abstract

The aim of the study was to assess the territorial patterns in cancer incidence and mortality among the population of the Far Eastern Federal District in the period 2013–2022. Material and Methods. Data from official reports of cancer services (form No 35, No. 7) processed using standard cancer statistics programs were presented. Results. In the east of the country, 31,822 new cancer cases were registered in 2022, which was 1.3 % more than in 2021. The average cancer incidence rate in males was 294.06 ± 5.05 per 100,000 (2020: 296.94 ± 4.66), with a decrease rate of 3.0 %. In females, the equivalent rate increased to 240.96 ± 5.73 per 100,000 (2020: 237.92 ± 6.26 per 100,000) with a rise of 6.3 %. Skin cancer was the most common malignancy (11.6 %) followed by trachea, bronchi, lung (11.5 %), breast (11.3 %) and colon (6.3 %) cancers. The percent of actively detected patients increased to 23.2 % (2013: 14.0 %) as did the index of accumulation of contingents – 7.3 (2013: 5.3). The number of patients with stage I–II cancer increased to 57.0 % (2013: 47.5 %), while the number of stage III-IV cancers decreased to 20.8 % (2013: 24.7 %). The number of morphologic studies (94.1 %) was lower than the average for RF (95.8 %). The proportion of patients registered for five or more years decreased to 57.2 % (RF: 58.2 %). The average cancer mortality rate in men was 174.99 ± 3.10 per 100,000 (2020: 181.76 ± 2.51 per 100,000). The average cancer mortality rate in women was lower than in men, being 91.34 ± 1.20 per 100,000 (2020: 93.71 ± 0.80о per 100,000). Cancers of trachea, bronchi and lung (20.0 %), stomach (8.9 %), colon (7.0 %) and breast (6.6 %) were the leading causes of mortality. Conclusion. The low level of active cancer detection did not significantly change the incidence rates during the study period. A greater volume of preventive measures with improvement of their quality will enable the primary health care system to detect cancer at early stages, form groups being at high risk for cancer development and, consequently, to reduce mortality rates. A prerequisite for improving medical care for cancer patients is the continuous training of professional staff and the use of modern diagnostic and treatment technologies.

19-31 427
Abstract

The aim of this study was to investigate the status of return to work and the influencing factors in patients with common cancers referring to three medical centers during the years 2020 to 2022. Material and Methods. In the present study (a retrospective cohort), all patients who visited three medical centers during the years 2020–2022 and were diagnosed with common cancers (non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, gastrointestinal cancers and sarcoma), were included in the study. Work ability index (WAI) was assessed based on selected questions from the WAI questionnaire. Hospital Anxiety and Depression Scale (HADS) was used to assess depression and anxiety, and Multidimensional Fatigue Inventory (MFI-20) was used to assess the level of fatigue. Then, the data obtained from individuals who returned to work were compared with those who did not return. Results. Out of 750 eligible patients, 135 individuals were enrolled in the study. 114 patients were male (84.4 %). The mean age of individuals was 50.2 ± 10.4 years. The most of individuals were diagnosed with gastric cancer (n=66, 48.9 %). After treatment, 36 (26.7 %) individuals returned to work, with the majority (24 individuals: 66.6 %) reporting a decrease in physical ability to do work. Sixty-six (73.3 %) patients did not return to work, with the most common reason being physical inability to work in 60 (66.6 %) individuals. Higher quality of life score was reported in individuals who returned to work. Conclusion. The rate of return to work was approximately 27 %. The return to work rate was highest among individuals with non-Hodgkin’s lymphoma and lowest among individuals with oesophageal cancer and Hodgkin’s lymphoma. The most influential factors affecting the return to work include disease recurrence and quality of life.

CLINICAL STUDIES

32-44 525
Abstract

Objective: to clarify the indications for the use of nephron-sparing technologies in surgical treatment of patients with retroperitoneal sarcomas. Material and Methods. The study included 64 patients with primary retroperitoneal sarcomas with kidney and renal pedicle invasion, who underwent surgical treatment in the Thoracic-abdominal Department of the P.A. Herzen Moscow Oncology Research Institute from 2010 to 2021. Twenty-one patients underwent nephrectomies, and 43 patients underwent nephron-sparing surgery. The morphological profile of sarcomas, age and gender of the patients, feasibility of using nephron-sparing technologies, postoperative complications, and long-term outcomes in patients of both groups were analyzed. Results. Forty-three patients with primary retroperitoneal sarcomas with invasion of the renal parenchyma, ureter, and renal pedicle underwent nephron-sparing surgery (precision mobilization of the kidney, ureter and vascular structures of the kidney from tumor tissue, kidney resection, ureteral stenting, resection of the renal vein orifices, resection of the ureters, and kidney autotransplantation). Postoperative complications were observed in 19.0 % of nephrectomy group patients (4 pts: II, IIIB, IV and V types according to Clavien–Dindo) and in 30.2 % of nephron-sparing group patients (15 pts: types II – 8, IIIA – 1, IIIB – 3, IV – 1). No statistical differences in the relapse-free period and survival time between two groups were observed. The 1-, 3- and 5-year survival rates were 84.1 %, 65.9 %, and 51.4 %, respectively. Multifactorial analysis showed that mortality increased significantly in patients over 64 years of age and was associated with both disease recurrence and concomitant pathology (p=0.009). There was also a trend toward decreased survival in patients with leiomyosarcoma (p=0.066). Conclusion. In retroperitoneal sarcomas, tumor resection with preservation of organs and structures not directly invaded by the tumor is the optimal surgical strategy. Nephron-sparing technologies do not worsen both immediate and long-term treatment outcomes. For leiomyosarcoma, tumor resection with nephrectomy is the most suitable approach.

LABORATORY AND EXPERIMENTAL STUDIES

45-53 539
Abstract

The aim of the study was to evaluate a prognostic significance of immunohistochemical parameters in serous ovarian carcinomas and their statistical relationships after neoadjuvant treatment to assess the development of tumor resistance to platinum-containing adjuvant polychemotherapy regimens. Material and Methods. An immunohistochemical study of tumor tissue was carried out in patients with high-grade serous ovarian cancer (stage IIIC–IV). The age of the patients ranged from 49–72 years. There were 59 patients who were sensitive and 22 patients who were resistant to platinum-containing adjuvant polychemotherapy. In the tissue of ovarian tumors obtained during surgery after noadjuvant polychemotherapy, we studied immunohistochemical indicators of proliferative activity (Ki67), expression of the DNA excision repair protein ERCC1 and proteins of the ABC transporter family – Pgp and BCRP, as well as statistical relationships between these indicators (Spearman’s rank correlation coefficient). Results. After effective neoadjuvant polychemotherapy, more pronounced signs of activity in the processes of proliferation, DNA repair and xenobiotic efflux were noted in serous ovarian carcinomas, which subsequently demonstrated resistance to platinum-containing polychemotherapy regimens compared to tumors that retained platinum sensitivity. Moreover, in 40 % of cases or more, there was a coincidence in the ranges of values of the studied parameters in tumors with different sensitivity to platinum drugs. The expression of transporter proteins greater than 60 % for BCRP and 65 % for Pgp was shown to precede the development of resistance to adjuvant treatment with carboplatin. In the studied groups, differences in the number and significance of statistical relationships between the variables were observed. The most significant differences were noted for the Ki67 – BCRP correlation, which had the opposite direction in groups with different sensitivity to adjuvant treatment with carboplatin. Conclusion. A comprehensive immunohistochemical analysis of highgrade serous ovarian carcinomas after neoadjuvant polychemotherapy, which further demonstrated different sensitivity to platinum-containing adjuvant regimens, was carried out, and the prognostic value of the studied parameters was assessed. The revealed critical levels of Pgp and BCRP expression in tumor tissue may have a prognostic value regarding the effect of adjuvant polychemotherapy. The results of the correlation analysis suggest a relationship between the development of platinum resistance and changes in the nature of the regulatory relationships between proliferative activity and transport processes in tumor tissue.

54-65 510
Abstract

Introduction. Tumor-associated macrophages (TAMs) are essential innate immune cells in the tumor microenvironment. TAMs can stimulate cancer cell proliferation and primary tumor growth, angiogenesis, lymphangiogenesis, cancer cell invasiveness in vessels and metastatic niche formation as well as support chemotherapy resistance. TAMs are phenotypically diverse both in various cancer localizations and in intratumoral heterogeneous compartments. Tumor-specific modeling of TAMs is necessary to understand the fundamental mechanism of pro- and anti-tumor activity, to test their interaction with existing therapies, and to develop TAM- targeted immunotherapy. Aim of study: To investigate cancer-specific transcriptomic features of ex vivo human TAM models. Material and Methods. Here we compared transcriptomic profiles of TAMs for breast, colorectal, ovarian, lung, and prostate cancers ex vivo. Human monocytes were isolated from buffy coats, and then stimulated by the tumor cell conditioned medium ex vivo. Using real-time PCR, we quantified the expression of key TAM biomarkers including inflammatory cytokines, scavenger-receptors, angiogenesis-regulating genes, and matrix remodeling factors. Results. PCR analysis allowed revealing cancer-specific expression profiles of modeled TAMs. By comparing the existing knowledge about TAM phenotypes in human tumors in vivo with the collected data, we discuss the advantages and limitation of ex vivo TAM models derived from human blood monocytes. Conclusion. Monocytes-derived macrophages stimulated with cancer cell-conditioned medium can, to a certain extent, allow modeling of cancer-specific programming of TAMs. Our model system is valuable to examine agents reprogramming key TAM pro-tumoral activities, and for the reproducible analysis of mechanistic events that program tolerogenic status of TAMs towards cancer cells.

66-76 435
Abstract

Radiotoxicity is a serious problem for patients undergoing radiotherapy, so the search for new radioprotective drugs to mitigate its effects is highly relevant. Radioprotectors should have a number of properties, including direct antioxidant action, reduction of oxidative stress, ability to induce DNA repair or inhibit apoptosis, and at the same time not cause their own side effects. Antioxidants based on lithium salts look promising in terms of their properties. The aim of study was to study the radioprotective properties of lithium pyruvate in vitro. Material and Methods. Relatively radiosensitive blood mononuclear cells and relatively radioresistant fibroblasts of 3T3L1 line were used as biomodels for x-ray exposure. Cells were incubated and irradiated in 96-well plates. Lithium pyruvate was used at a final concentration of 1.2 mM. Cells were irradiated at a dose rate of 15 mGy/s in the absorbed-dose range from 0 to 5 Gy using an x-ray unit (anode voltage: 160 kV, average current: 3.5 mA). Cell viability was assessed by MTT test and resazurin test. The evaluation of cell death variants and the level of oxidative stress were determined by cytofluorimetric method. Results. The cytoprotective effect of lithium pyruvate was established. Cytoprotection was manifested in the increased cell survival and decreased oxidative stress level under lithium pyruvate after x-ray in a wide range of absorbed doses. Relatively high efficiency was shown in relation to blood mononuclear cells with an increase in the viable fraction by 5–7 % and a decrease in oxidative stress level during irradiation in the range of 1.0–3.0 Gy. Apoptosis was found to be the main mechanism of cell death after irradiation. Lithium pyruvate reduced the level of apoptosis in cell population under irradiation and chemically induced oxidative stress. Conclusion. Radioprotective effect of lithium pyruvate under x-ray irradiation in vitro has been shown. Reduction of oxidative stress under the action of pyruvate provides a pathogenetic basis for the potential use of this compound as a radioprotector, which requires further studies on in vivo models.

77-85 445
Abstract

Background. Esophageal cancer is the eighth most common cancer in the world. The antitumor effects of medicinal plants have been shown as a therapeutic strategy to treat esophageal cancer. This study aimed to evaluate in vitro effects of Cuscuta epithymum extract on the survival and apoptosis of esophageal cancer cell line. Material and Methods. Here, the hydroalcoholic Soxhlet extract of C. epithymum plant was prepared. The cell viability of esophageal cancer cell line KYSE-30 was evaluated by MTT assay after 24 h treatment with concentrations of 50, 100, 200, 400, 600, 800 and 1000 μg/ml of the extract. Then, the apoptotic effect of extract was evaluated by flow cytometry using Propidium Iodide (PI) staining and sub-G1 peak analysis, and Annexin V-FITC/PI staining in cells treated with concentrations of 125, 250, 500 and 750 μg/ml as well as morphological change of healthy cells to apoptotic and necrotic form. Results. The hydroalcoholic extract of C. epithymum decreases the viability of KYSE-30 cells in a dose-dependent manner with an IC50 of 646 µg/ ml at 24 h. A significant increase was observed in the percentage of sub-G1 phase in cells treated with 500, 750, and 1000 μg/ml of C. epithymum extract for 24 h compared to the control group (p<0.01 and p<0.001). The results also showed a significantly enhanced the percentage of primary and secondary apoptotic cells compared to untreated cells. At concentrations of 250, 500, and 750 µg/ml, approximately 17, 33 and 45 % of cells was apoptotic. The apoptotic and necrotic cells morphology after treatment with 250 and 500 µg/ml of the extract was also confirmed by fluorescence microscopy. Conclusion. The findings showed the apoptotic effect of the hydroalcoholic extract of C. epithymum on KYSE-30 cells in vitro. The effect of this extract on the genes involved in apoptosis as well as the mechanism of action of this extract are recommended.

86-95 491
Abstract

Background. Integrins, as adhesion molecules, play a key role in the interaction of cells with the basal membrane and intercellular matrix. Numerous studies demonstrate evidence of increased expression of integrins on tumor cells in different types of cancer. Thus, β3 and αV integrins are associated with stem-like features of tumor cells, and β4 integrin as α6β4 heterodimer provides anchorage-independent survival of malignant mammary epithelial cells. However, all the described functions of integrins have been investigated exclusively on primary tumor cells. The functional significance and expression pattern of integrins on circulating tumor cells (CTCs) remains unclear. The aim of the study was to evaluate the β3, β4 and αvβ5 integrin expression on CTCs and its association with molecular subtype, stage and lymph node metastasis in breast cancer patients Material and Methods. The study included 22 patients with T1–4N0–3M0 invasive ductal breast carcinoma. Venous blood was taken from patients without neoadjuvant chemotherapy (group 1) and after neoadjuvant chemotherapy (group 2) in the volume of 12 ml into vacuum tubes with EDTA. The expression of CTC integrins including stemness features CD44/CD24, CD133 and ALDH1, and epithelial-mesenchymal transition (EMT) (N-cadherin) was evaluated by flow cytometry. Results. CTCs with β3+β4-αvβ5- and β3-β4+αvβ5+ phenotypes and stemness properties were associated with larger tumor size (T4) in breast cancer patients. The β3 integrin expression was associated with more aggressive molecular subtypes of breast cancer. Administration of neoadjuvant chemotherapy did not affect the expression pattern of β3, β4 and αvβ5 integrins in CTCs. Conclusion. In breast cancer, most CTCs expressed β3, β4 and αvβ5 integrins despite the lack of attachment to the basal membrane and intercellular matrix. The expression of the above integrins on CTCs was associated with breast cancer molecular subtype, stage and lymph node metastasis, and therefore its evaluation can be considered as one of the objectives of liquid biopsy study.

ONCOLOGY PRACTICE

96-107 673
Abstract

Introduction. An increasing number of patients of reproductive age get cancer and are highly interested in preserving fertility. Survival rates for cancer patients are improving. Methods of reproductive technologies are being improved to preserve the ability to bear children. Rehabilitation aimed to ensure a satisfactory quality of life takes on a new meaning, and with the development of new technologies, the level of possible assistance also changes. Today, rehabilitation measures for cancer patients of reproductive age should undoubtedly include all possible ways to preserve and restore fertility. Aim: preservation of fertility in patients with ovarian tumors. Material and Methods. After ovariectomy, the ovaries were transported to the embryology laboratory, where oocyte-cumulus complexes were extracted and subsequently matured using the OTO-IVM (ovarian tissue oocyte in vitro maturation) method. The resulting mature oocytes (Metaphase II) were cryopreserved by vitrification or, if a partner was available, fertilized by ICSI (intracytoplasmic sperm injection), the embryos were cultured to the blastocyst stage and also cryopreserved by vitrification. Cryopreserved oocytes and embryos can be used by patients after cancer treatment in assisted reproductive technology programs. Results. A total of 218 OCCs were recovered, 29.8 % were degraded oocytes (n=65). The proportion of OCC suitable for ripening was 153 (70.2 %). After 36 or 48 hours, 65 oocytes matured in 13 patients, which amounted to 42.5 % of oocytes without signs of degradation. In 11 patients the OCC was removed from the tumor-affected ovary. 149 oocytes were obtained, of which 50 (33.6 %) were oocytes with signs of degradation. The remaining 99 (66.4 %) of OCCs had satisfactory quality; after maturation, the Metaphase II stage reached in 49 (49.5 %) of oocytes. As a result, biological material was cryopreserved in 13 of 15 patients: 5 embryos and 60 oocytes.

108-116 645
Abstract

Objective: to determine the frequency and risk factors for postoperative pancreatic fistula (POPF) after gastrectomy. Material and Methods. From January 1, 2018 to October 31, 2023, 198 patients with stage I–III gastric cancer underwent gastrectomy with D2 lymphadenectomy at a Regional Oncological Dispensary. The characteristics of the studied patients were assessed according to a unified protocol. Statistically significant factors influencing the development of POPF were identified. Results. The incidence of POPF was 18.7 % (37/198). It was found that not all pancreatic fistulas were accompanied by acute pancreatitis. Among the patients with POPF, 5 had associated acute pancreatitis: 2 with mild, and 3 with moderate severity; no severe acute pancreatitis was observed. The statistically significant indicator for the occurrence of POPF was the neutrophil-lymphocyte index (p=0.033), in the absence of other infectious phenomena. In addition, the following significant factors were identified: lymphadenopathy of regional lymph nodes (p=0.037), tumor stage (T criterion) (p=0.002), splenectomy (p<0.001), and resection of the pancreas (p<0.001). Conclusion. The frequency of postoperative pancreatic fistulas after gastrectomy was 18.7 %. Statistically significant factors for the development of POPF include resection of the pancreas, splenectomy, lymph node status, tumor size, and depth of invasion. An additional indicator for the development of POPF is an increase in the neutrophil-lymphocyte index 1 day after surgery.

117-124 476
Abstract

Background. Approximately 50 % of cancer patients have pain in their daily lives, which is multifaceted sensation goes beyond basic biochemical signal of pain. Oral mucositis is one of the negative consequences with intense pain, discomfort, challenges in speaking and eating. These components collectively influence patient's total quality of life across mental, biological, social aspects. Biopsychosocial model (BPS) is an effective technique for understanding and addressing conceptualization and treatment of pain in cancer patients. The aim of this study is to assess efficacy of the BPS in managing post-cancer distress and potential to improve quality of life for individuals with cancer. Material and Methods. This study evaluated 30 cancer patients who completed radiotherapy and were referred from cancer hospital. The examination encompasses three distinct categories: biological, psychological, and social components. The biological aspect was documented based on mucosal lesions and VAS scores for individuals; followed by photo-biomodulation was given. Palliative care was provided in psychological aspect through implementation of exercise, meditation, music therapy. The social component encompasses community engagement, social activities, counseling services for family members. Patients were categorized into 3 groups – A, B, C. All three components were carefully evaluated and one-month follow-up was done. Results. The outcome derived from statistical analysis of the data collected from groups A, B, and C. When group A was compared to group B, there was 46 % increase in quality of life. When group C was compared to group A, 65 % of patients exhibited favorable quality of life. The average VAS score of patients decreased from 9.2 to 4.5 after Low-Level Laser Therapy (LLLT), demonstrating gradual decrease in discomfort. P value showed statistically significant (<0.05). Conclusion. Healthcare providers can enhance their treatment efficiency, addressing root cause of illness, and enhance overall well-being by incorporating BPS into their practice. Addressing the various elements of biological, psychological, and social factors would have beneficial effect on overall quality of life.

REVIEWS

125-140 584
Abstract

Background. DNA methylation is a crucial mechanism of epigenetic regulation of transcription. Disturbances in DNA methylation mechanism are associated with various malignancies such as acute myeloid leukaemia, breast cancer, prostate cancer, etc. Influencing the functional status of DNA methyltransferases (DNMTs) enzymes and TET family proteins (TETs), which regulate DNA methylation and demethylation, is the basis of epigenetic anticancer therapy approach. In this review, we have considered the challenges and prospects of nucleoside and non-nucleoside inhibitors of DNMTs as well as TETs inhibitors. The results of clinical trials on the efficacy of DNMTs inhibitors used individually and as part of combination chemotherapy conducted over the last 15 years are also evaluated. Material and Methods. Sources were searched in PubMed, ScienceDirect, Web of Science, eLibrary, CyberLeninka. More than 700 publications were used in the analysis, but the review included mainly works of the last 10 years. A number of articles published earlier than 2015 were used for historical reference. Results. The review provides information on current advances in the development and study of epigenetically active compounds whose action is aimed at the regulation of DNA methylation. Data on the in vitro and in vivo effects of agents considered for use in the therapy of various malignancies are presented. In addition, the data of clinical trials of the most promising epigenetic modulators are presented.

141-151 1503
Abstract

The aim of the study was to present various types of radiation that can increase the effectiveness of combined photodynamic therapy (PDT) for malignant and premalignant lesions. Material and Methods. The Web of Science, Scopus, MedLine, Library, and RSCI databases were used for finding publications on this topic, mainly over the last 10 years. Of 230 sources, 64 were included in the review. Results. Photodynamic therapy is a new cancer treatment technology that has become increasingly popular in recent years. It is often an alternative method of treating cancer when there is a high risk of side effects and complications during traditional treatments such as surgery, radiation therapy and chemotherapy. PDT requires a photosensitizer, light energy, and oxygen to create reactive oxygen species that destroy cancer cells. This review examines the basic principles and mechanisms of PDT used alone and in combination with other traditional therapies. Despite the fact that PDT is an effective and non-invasive cancer treatment, it has some limitations, such as low light penetration depth, ineffective photosensitizers and tumor hypoxia. Our study examines new strategies that use other energy sources, such as infrared- and x-rays, ultrasound, as well as electric and magnetic fields, to enhance the PDT effect and overcome its limitations. Great hopes are also associated with the use of a combination of PDT and neutron capture therapy (NСT). Currently, chlorin derivatives associated with boron carriers have been developed. They can be used for both fluorescence diagnostics and PDT, as well as for NСT. The synthesized compounds have a high selectivity of accumulation in the tumor. To date, encouraging preclinical results of high efficiency of combined use of NСT and PDT have already been obtained. Conclusion. Combination with various energy sources is a key factor for further development of PDT. Future research aimed at overcoming the limitations of PDT will contribute to unlocking the full potential of this technology in clinical practice.

152-161 845
Abstract

Purpose of the study: analysis of modern scientific data on the molecular mechanisms of the CRISPR-Cas9 system in gene editing, advantages and disadvantages in cancer research and the development of new treatment methods. Material and Methods. A comprehensive electronic search of relevant published studies was conducted in the scientific databases PubMed/MEDLINE, ScienceDirect, Wiley and Google Scholar published between 2014 and 2024. The search was tailored to the specific requirements of each database based on the following keywords: CRISPR-Cas9, sgRNA, genome editing, cancer immunotherapy, CAR-T. The search yielded 487 studies on the topic of interest, of which 54 were used to write the literature review. Additionally, the article discretely highlights the importance and challenges of CRISPR-Cas9 in the production of genetically engineered T cells for potential use in treating certain types of cancer. Results. Accordingly, CAR-T (chimeric antigen receptor T-cell) therapy is widely used as one of the main components of immunotherapy in the treatment of leukemia, lymphoma and some solid tumors. The development of programmed single guide RNAs (sgRNAs) and new modifications of the Cas9 protein has made the technology flexible and universal. CRISPR-Cas9 is often used to modify T and NK cells by designing antigen receptors to improve their sensory circuits with complex functionality capable of recognizing and killing tumor cells. At the same time, delivery of the finished ribonucleoprotein (Cas9+sgRNA) complex into the cell avoids the constitutive processes of transcription and translation, which ensures the fastest possible gene editing. Conclusion. In this review, we reviewed the scientific evidence highlighting the promising impact of CRISPR technologies in cancer research and treatment. CRISPR-Cas9 is considered a unique and effective technology in the field of genetic and biomolecular engineering.

162-171 452
Abstract

Administration of pharmaceuticals containing radioactive isotopes and capable of specific binding to certain proteins is one of the approaches used in the treatment or diagnosis of malignant tumors. High renal accumulation of radioactive compounds after administration of radioconjugates with molecular mass less than 70 KDa is of the challenges that need to be solved. The purpose of the study was to identify the most effective approaches to reduce the accumulation of radioactivity in the kidneys after administration of radioconjugates used for diagnostic imaging and targeted therapy for cancer. Material and Methods. We conducted a literature search on the topic of the review in the electronic databases PubMed, Scopus and Web of Science from 1987 to 2023, 82 articles were used for writing the review. Results. The review presents a description of approaches used to improve the biodistribution of radioconjugates, mainly in preclinical studies. The advantages and disadvantages of such techniques have been described. Conclusion. Reducing renal radioactivity using radioconjugates of molecules with molecular masses less than 70 KDa is a challenging but achievable task. It is concluded that the use of cleavable linkers in such radioconjugates is highly promising, since this approach does not change the pharmacokinetics of such drugs. It is noted that the advantage of introducing concomitant substances compared to changing the structure of radioconjugates is a lesser dependence on the characteristics of a particular radiopharmaceutical. This approach also does not require prior work to modify the radioconjugate, but has limited efficiency.

172-185 473
Abstract

Objective: to summarize the available data on the features of vascularization of endometrioid adenocarcinoma (EAC). Material and Methods. The search for relevant sources was performed in the “PubMed” database using the keywords “endometrium + cancer + angiogenesis”, “endometrium + cancer + angiogenesis + lymph”. Of the selected sources, 78 were included in this review. Results. Angiogenesis is an important and necessary stage in the pathogenesis of the appearance, progression and metastasis of EAC and, thus, the study of tumor vascularization provides an opportunity to improve diagnosis and personalized approach to treatment. Vascular density correlates with advanced stage of EAC, high grade of malignancy, myometrial invasion, cervical and adnexal lesions, vascular invasion, metastases to lymph nodes (LN), the presence of cancer cells in the peritoneal fluid, low overall survival and survival without tumor progression. There are publications that deny the connection of vascularization with the histological type of tumor, its grade, lymphovascular invasion, lymph node metastases, the depth of myometrial invasion, and these publications even prove that microvessel density is not an independent prognostic factor. So, there is still no consensus and final opinion, as evidenced by low or high vascularization of EAC. Recently, there are many drugs that affect both the processes of angiogenesis directly and the inducers and factors that control vascular growth. Unfortunately, all such drugs have a fairly high toxicity, and resistance to them very quickly develops. Conclusion. Despite numerous results of studies devoted to the study of the formation of blood vessels and isolated data on lymphangiogenesis in EAC, there is no data in the literature on studying changes in the vascularization of LN in gynecological cancer. However, proangiogenic and antiangiogenic factors are disseminated throughout the body and must exert their effects in distant organs and tissues. Based on changes in the vascularization of LN, it will apparently become possible to predict the activity of angiogenesis in the primary tumor, assess the prognosis of the disease, and the effectiveness of the treatment. In addition, significant expression of the vascular network in an enlarged lymph node biopsied for diagnosis may be a symptom of the development of a malignant tumor in the lymph collection region, even in the absence of metastases.

CASE REPORTS

186-193 2186
Abstract

Background. Triple-negative breast cancer is the most aggressive molecular subtype among breast malignancies. Due to the high proliferative activity of tumor cells and the lack of targets for targeted therapy, neoadjuvant chemotherapy plays the main role in complex treatment of this subtype. The optimal time to start neoadjuvant chemotherapy is defined as less than 8 weeks. Delays in time to treatment initiation may adversely affect treatment outcomes, as well as cause local or systemic disease progression. Achieving complete pathological response after neoadjuvant chemotherapy reduces the relative risk of relapse by more than 70 %, which, in turn, leads to a significant improvement in long-term survival of these patients. Description of the clinical case. A 32-year-old woman came to the clinic 15 months after being diagnosed with triple-negative breast cancer. The patient was treated with alternative medicine methods for 15 months, and upon admission to the hospital, the patient had pronounced local tumor growth with massive decay, tumor lysis syndrome and nutritional disorders. We decided to perform neoadjuvant chemotherapy: 12 cycles of weekly paclitaxel + carboplatin, followed by 4 cycles of dose-dense doxorubicin + cyclophosphamide. Chemotherapy resulted in a significant reduction in tumor size and improvement of health status of the patient. There were no clinically significant side effects requiring hospitalization or dose reduction. Upon completion of neoadjuvant treatment, the patient underwent mastectomy. The histological examination revealed a complete pathological response of the primary tumor and regional lymph nodes. The patient underwent adjuvant external beam radiation therapy. The patient is alive 3 years after diagnosis and 1.5 years after treatment completion. She plans delayed breast reconstruction with contralateral breast augmentation. Conclusion. This is a rare case of locally advanced triple-negative breast cancer with pathological complete response to neoadjuvant chemotherapy 15 months after diagnosis.

194-203 532
Abstract

Background. Currently, there is a steady trend towards an increase in the incidence of both synchronous and metachronous multiple primary malignant tumors (MPMT). However, metachronous polyneoplasia of the pancreatobiliary tract is relatively rare, and there have been very few reports on successful treatment of this malignancy. Case presentation. In September 2014, the patient K. was diagnosed with adenocarcinoma of the ampulla of Vater (T2N0M0, stage Ib) and underwent gastropancreatoduodenal resection with the creation of pancreatic-gastric anastomosis at the Abdominal Department of Cancer Research Institute of Tomsk National Research Medical Center. There were no complications in the postoperative period. At a 6.5-year followup, no evidence of disease progression was found. In April 2021, a follow-up examination conducted at the Cancer Research Institute revealed a large lesion on the distal part of the pancreatic stump with no clinically significant manifestations. Diagnosis of MPMT was confirmed by transgastric endoscopic ultrasound-guided biopsy. Histological and immunohistochemical examinations revealed undifferentiated ductal carcinoma of the pancreas. Considering the metachronous tumor localization, pancreatic stump extirpation with resection of the posterior wall of the stomach and splenectomy was performed. No complications occurred in the postoperative period. The patient received replacement therapy for exocrine pancreatic insufficiency and individual correction of carbohydrate metabolism. At a 15-month follow-up, liver metastases were detected, and palliative chemotherapy was administered. The patient died 6 months later due to disease progression. The survival time was 99 months after the first surgery and 21 months after the second surgery. Conclusion. We report a rare case of metachronous cancers of the ampulla of Vater and pancreatic stump developed with an interval of 6.5 years. The patient underwent successful curative resections consecutively. The overall survival time from the date of diagnosis was 99 months.



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