Experimental oncology最新文献

Aim: To study the activity of antitumor immunity effectors and to analyze possible mechanisms of peritoneal Mph M1/M2 repolarization of Balb/c mice under the influence of lectin from B. subtilis IMV B-7724 in the dynamics of the model tumor growth.

Materials and methods: Studies were performed on Balb/c mice; Ehrlich adenocarcinoma (АСЕ) was used as an experimental tumor. Lectin from B. subtilis IMV B-7724 was administered to ACE-bearing mice at a dose of 1 mg/kg of body weight, 10 times. Immunological testing was performed on days 21 and 28 after tumor grafting. The functional activity of peritoneal macrophages (Mph), natural killer (NK) cells, cytotoxic lymphocytes (CTL), and cytokine levels (IFN-γ, IL-4) were studied by the standard methods. mRNA expression levels of transcription factors STAT-1, STAT-6, IRF5, and IRF4 in Mph were evaluated.

Results: The administration of lectin from B. subtilis IMV B-7724 to mice with solid ACE led to the preservation of the initial functional state of peritoneal Mph M1 during the experiment. The bacterial lectin ensured the preservation of the cytotoxic activity of CD8+ T-lymphocytes and a significant (p < 0.05) increase in the NK activity (by 2.7 times compared to the intact animals and by 12.9 times compared to the untreated mice). A strong positive correlation was noted between the levels of the functional activity of Mph and CD8+ T-lymphocytes of animals with tumors and the indices of the antitumor effectiveness of bacterial lectin. The indirect polarization of Mph was evidenced by a strong positive correlation between the level of the NO/Arg ratio (which characterizes the direction of Mph polarization) and the cytotoxic activity of CD8+ T-lymphocytes, NK cells, and the expression of STAT1/STAT6 (the 21st day) and IRF5/IRF4 (the 28th day).

Conclusion: In ACE-bearing mice, repolarization of the peritoneal Mph toward M1 can occur not only due to the direct action of bacterial lectin on the cellular receptors but also with the involvement of other effectors of antitumor immunity (NK cells, T-lymphocytes). The transcription factors of the STAT and IRF signaling pathways are involved in the polarization process.

Background: The non-operative management of rectal adenocarcinoma (RA) after neoadjuvant chemoradiation therapy (nCRT) has gained increasing attention. The "Watch and Wait" ("W&W") strategy allows one to avoid surgery-related reduction in the quality of life due to permanent pelvic organ dysfunction or irreversible stoma. Still, the oncological safety of this strategy is under evaluation.

Aim: To share a single-center experience of the "W&W" strategy.

Materials and methods: The retrospective analysis of 125 patients who received nCRT in 2016-2021 was performed. Patients who met the European Society for Medical Oncology (ESMO, 2017) criteria of clinical complete response (cCR) and received non-operative management were analyzed.

Results: Ten patients (8%) were re-staged after nCRT as cCR and followed the "W&W" strategy. Patients' characteristics: 7 female, 3 male; mean age 67.3 years. Tumor characteristics: pre-treatment N+ was present in 7 cases; G1 adenocarcinoma in a majority of cases; mean tumor distance from the anal verge - 5.85 cm; mean tumor circumference - 71%; mean tumor length - 3.87 cm. The mean follow-up time was 30 months. Local regrowth or/and distant metastases developed in 3 cases. The 2-year disease-free survival was 70%.

Conclusions: Most of the patients following the "W&W" strategy have benefited. However, to reduce the number of relapses, it is necessary to perform a more careful selection of patients.

Virginal gigantomastia (VGM) is a benign disease of the breasts without a clearly established etiology. The treatment of VGM remains a problem. The conservative treatment is not effective while surgery is too traumatic. Most specialists recommend subcutaneous mastectomy with immediate implant reconstruction or reduction mammoplasty. The reduction mammoplasty with adjuvant hormone therapy is a variant of treatment of young patients with a risk of recurrence. We present a case of a patient with VGM who was operated in 2014. Reduction mammoplasty was performed. After 9 years, the patient had a relapse and second surgery, resection of the breasts with reduction mammoplasty. Tissues with cysts, fibrosis, hamartomas, and fibroadenomas were dissected. Histopathology revealed extensive fibrosis with hamartomas and fibroadenomas. The immunohistochemical examination of the breast tissue showed a high level (70%) of estrogen and progesterone receptors expression. We prescribed hormone therapy with tamoxifen 10 mg per day. Dynamic monitoring of the treatment result and control of the disease remission was carried out. Breast-conserving surgery performed in such patients can help alleviate the psychological, social, and physical disorders caused by VGM.

Background: Papillary thyroid carcinoma (PTC) is the most common type of well-differentiated thyroid cancer accounting for up to 80% of all thyroid neoplasms. Metastases to the regional lymph nodes (RLN) of the neck are a feature of its biological aggressiveness. The presence of psammoma bodies may be considered a pathomorphological feature of PTC in addition to the papillary structure of tumor and specific nuclear changes. The aim of the study was to evaluate a clinical value of psammoma bodies in the RLN of PTC patients.

Materials and methods: 91 patients with PTC who were surgically treated at the Verum Expert Clinic were enrolled in the study. The clinical and pathomorphological data were retrieved from the archival medical records.

Results: According to the results of the clinico-morphological analysis, 51 patients (56%) with PTC had metastases in the RLN of the neck, and 40 (44%) patients had no metastases. Among 51 patients with metastases in the RLN, in 4 patients psammoma bodies in the RLN and tumor tissue were identified. In 3 of these 4 patients, the size of the primary PTC tumor was less than 10 mm, but an aggressive cancer course such as significant number of metastases in the RLN or multifocal growth was found in all these cases.

Conclusions: The presence of psammoma bodies in RLN and primary PTC tumor could be suggested as a predictor of metastasis to lymph nodes. The detection of point echogenic foci in the lymph nodes by ultrasound at the preoperative stage is a sign of psammoma bodies. This finding can be useful for improving the efficacy in selection of surgical treatment tactics for the optimal neck dissection by planning neck dissection in the presence of such point echogenic foci at the preoperative stage and performing regular check-ups of the patients.

Background: Breast cancer (BCa) is one of the most common oncological diseases in women in Ukraine and worldwide, which determines the need to search for new diagnostic and prognostic markers. In this aspect, the study of multicellular proteins, in particular osteopontin (OPN) and osteonectin (ON), in BCа tissue is relevant. The aim of the work was to investigate the expression of SPP1 and SPARC at the mRNA and protein levels in BCa tissue and to assess their relationship with the main clinicopathological BCa characteristics and the survival rates of patients.

Materials and methods: The work was based on the analysis of the results of the examination and treatment of 60 patients with stage II-III BCa and 15 patients with breast fibroadenomas. SPP1 and SPARC mRNA levels were determined by real-time PCR. The study of the expression of protein products of the SPP1 and SPARC genes was carried out by the immunohistochemical method.

Results: We have established that the BCa tissue was characterized by 3.5 (p < 0.05) and 7.4 (p < 0.05) lower levels of SPP1 and SPARC mRNA, respectively, compared to the tissue of benign neoplasms, while OPN and ON expression levels were 1.6 (p < 0.05) and 5.6 (p < 0.05) times higher, respectively, compared to fibroadenoma tissue. The analysis of the relationship between the expression of SPP1 and SPARC at the protein and mRNA levels in BCa tissue and the main clinicopathological BCa characteristics revealed its dependence on the presence of metastases in regional lymph nodes, differentiation grade, and the molecular BCa subtype. Also, high expression levels of SPP1 and OPN were associated with worse patient survival rates.

Conclusion: The obtained results indicate the perspective of using SPP1 and SPARC expression indices in BCa tissue to assess the aggressiveness of the cancer course and optimize the tactics of treating patients.

Oncolytic peptides are derived from natural host defense peptides/antimicrobial peptides produced in a wide variety of life forms. Over the past two decades, they have attracted much attention in both basic research and clinical applications. Oncolytic peptides were expected to act primarily on tumor cells and also trigger the immunogenic cell death. Their ability in the tumor microenvironment remodeling and potentiating the anticancer immunity has long been ignored. Despite the promising results, clinical application of oncolytic peptides is still hindered by their unsatisfactory bioactivity and toxicity to normal cells. To ensure safer therapy, various approaches are being developed. The idea of the Ukrainian research group was to equip peptide molecules with a "molecular photoswitch" - a diarylethene fragment capable of photoisomerization, allowing for the localized photoactivation of peptides within tumors reducing side effects. Such oncolytic peptides that may induce the membrane lysis-mediated cancer cell death and subsequent anticancer immune responses in combination with the low toxicity to normal cells have provided a new paradigm for cancer therapy. This review gives an overview of the broad effects and perspectives of oncolytic peptides in anticancer immunity highlighting the potential issues related to the use of oncolytic peptides in cancer immunotherapy. We summarize the current status of research on peptide-based tumor immunotherapy in combination with other therapies including immune checkpoint inhibitors, chemotherapy, and targeted therapy.

Background: Paclitaxel is a highly effective chemotherapeutic agent used to treat breast, ovarian, and other cancers. At the same time, paclitaxel causes peripheral neuropathy as a side effect in 45%-70% of patients.

Aim: The aim of the study was to investigate the effect of paclitaxel-induced peripheral neuropathy on the development of pathological changes in the salivary glands of animals and to explore the possibility of correction of the identified changes with vitamin B/ATP complex.

Materials and methods: To simulate toxic neuropathy, animals were injected i/p with paclitaxel 2 mg/kg for 4 days. In order to correct the identified changes, rats were injected i/m with vitamin B/ATP complex (1 mg/ kg) for 9 days. In the homogenate of the submandibular salivary glands, α-amylase activity, total proteolytic activity, total antitryptic activity, the content of medium mass molecules, thiobarbituric acid reactive substances (TBARS), oxidatively modified proteins, and catalase activity were determined.

Results: A significant increase in the content of oxidatively modified proteins, medium mass molecules, and the content of TBARS and significant decrease in the activity of catalase and amylase were determined in the salivary glands of animals with toxic neuropathy compared to these parameters in intact animals. Administration of vitamin B/ATP complex for 9 days against the background of paclitaxel-induced neuropathy led to normalization of antitryptic activity and amylase activity, a significant decrease in the content of oxidatively modified proteins, medium mass molecules, and TBARS along with a significant increase in catalase activity in the salivary glands of animals compared to the untreated rats with neuropathy.

Conclusion: Paclitaxel-induced neuropathy caused the development of pathological changes in the salivary glands of rats, which was evidenced by a carbonyl- oxidative stress and impaired protein synthetic function. The correction with vitamin B/ATP complex restored the protein-synthetic function and the proteinase-inhibitor balance, suppressed the oxidative stress and normalized free radical processes in the salivary glands of rats.

Director of the R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the National Academy of Sciences of Ukraine, Doctor of Biological Sciences Professor Liubov Heorhiivna Buchynska celebrates her 75th anniversary   Liubov Heorhiivna Buchynska graduated from the Biological Department of the Taras Shevchenko State University in 1977 and has been working at the R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the National Academy of Sciences of Ukraine since 1977. In 1996, she became the Scientific Secretary of the Institute, in 2001 - the Deputy Director, and in 2021 - Director of the Institute. In 1989, L. Buchynska  received her PhD degree and in 2012,  she defended her doctoral thesis "Endometrioid cancer: taxonomy of genetic alterations of cancer cells and their role in determining malignancy potential" and received her doctoral degree in specialty "oncology". Since 2003, she has headed the Laboratory of Oncogenetics (nowadays - the Department of Genetics of Cancer and Oncohematology). In 2020, L. Buchynska was given the title of Professor in Biology.  Prof. L. Buchynska is a well-known Ukrainian scientist in the field of oncogenetics and cytomorphology. Her long-term studies are characterized by a multidisciplinary approach to solving the problems of cancer biology and genetics. The innovation component occupies an important place in the fundamental studies by Prof. L. Buchynska aimed at implementing technologies for early and differential diagnosis of the precancerous and cancerous processes and assessing  the course of the disease in patients with malignancies of the organs of the female reproductive system. Prof. L. Buchynska has authored more than 250 scientific papers and 7 patents of Ukraine. She is a co-author of three monographs. She pays special attention to research-and-organizational and educational activities and training of young researchers. She has supervised five PhD theses. For the last 10 years, she has been collaborating with the Bogomolets National Medical University lecturing biology.  Prof. L. Buchynska is the Deputy Editor-in-Chief of the "Experimental Oncology" and "Oncology" journals, a member of the Scientific Council on the Problems of Malignant Neoplasms, a member of the Board of the National Association of Ukrainian Oncologists and the Non-governmental Organization "Ukrainian Society for Cancer Research". Prof. L. Buchynska was awarded the Bogomolets Prize of the National Academy of Sciences of Ukraine and a Certificate of Merit of the National Academy of Sciences of Ukraine. She was decorated with the Medal of Honor of the National Academy of Sciences of Ukraine "For Scientific Achievements". Holding the helm of the Institute in difficult times for our country, Liubov Heorhiivna is doing her best for a noble goal - fighting cancer. The administration and staff of the Institute have a great pleasure to congratulate Liubov Heorhiivna on her 75th annive

Background: Molecules and cytokines can be targeted in cancer therapy. Transforming growth factor-beta (TGF-β) is a cytokine that acts on protein kinase receptors in the plasma membrane. The signaling pathway of TGF-β can trigger the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway, a signal transduction pathway important in cancer growth and development. However, this PI3K/AKT cascade can be inhibited by phosphatase and tensin homolog (PTEN) tumor suppressor genes.

Aim: To determine the inhibitory effect of Holothuria scabra methanol extract (HSE) on breast cancer growth through the TGF-β/PI3K pathways and PTEN tumor suppressor gene on a breast cancer (BC) mice model.

Materials and methods: Female C57BL6 mice were subcutaneously injected with carcinogen DMBA 1 mg/kg body weight (BW) and fed a high-fat diet (HFD). Mice were randomly divided into five groups (n = 6): negative control (NC) administered with a standard diet, positive control (PC) administered with DMBA and HFD, and three treatment groups (T1, T2, and T3) treated with HSE doses of 0.33, 0.66, and 0.99 g/kg BW for 12 weeks. TGF-β concentration in the blood serum of mice was assessed by ELISA and the PIK3CA and PTEN gene expression by qRT-PCR.

Results: The treatment with HSE resulted in a significant decrease in TGF-β concentrations in the blood sera of treatment groups T1 (35.31 ± 17.33), T2 (43.31 ± 17.42), and T3 (48.67 ± 20.94) pg/mL compared to the PC group (162.09 ± 11.60) pg/mL (p < 0.001). However, only HSE at a dose of 0.99 g/kg BW decreased the PIK3CA gene expression (p = 0.026), and at a dose of 0.66 g/kg BW increased the PTEN expression up to 4.93-fold.

Conclusion: HSE is capable of inhibiting the TGF-β/PIK3CA pathway and increasing the PTEN gene expression.

Aim: To study the prognostic value of the density of tumor-infiltrating lymphocytes (TILs) and its association with other clinical-morphological parameters in colon adenocarcinomas (CAC).

Materials and methods: 236 CAC samples were examined. TILs density was estimated as the percentage of tumor stromal area occupied by TILs. By the index of TILs density, the patients were divided into 3 groups: TILs 0-9% (n = 88); TILs 10-39% (n = 106); TILs > 40% (n = 42). Dependent on this index, their overall survival (OS) was analyzed.

Results: Kaplan - Meier curves revealed a significant (p < 0.001) difference in the OS for patients with different TILs infiltration intensities. Multivariate Cox's proportional hazard regression model analysis has confirmed that patients with moderate TILs density (HR 0.57, 95% CI 0.34-0.96, p = 0.035) had better OS rates compared to low TILs density. TILs were associated with the stage (p < 0.001), lymph node metastasis pN (p < 0.001), distant metastasis M (p < 0.001), and the patient's outcome (p < 0.001).

Conclusion: TILs can be considered an additional prognostic tool during regular histological examination and are strongly associated with the most significant clinical-morphological features of CAC.