Experimental oncology最新文献

Background: Malignant diffuse gliomas (MG) of the brain (WHO grade 3-4) are highly aggressive primary tumors of central nervous system (CNS), spreading rapidly by infiltrating healthy brain tissue. In the majority of cases, tumor relapse occurs. The prognostic significance of pre-surgery factors, such as inflammatory markers, particularly, the peripheral blood counts in patients with MG is discussed and remains controversial. The aim of this study was to assess the relationship between the blood cell ratios and overall survival (OS) and relapse-free survival (RFS) in MG patients.

Materials and methods: The data on 59 MG patients were analyzed: 41 cases of primary (newly diagnosed) MG (astrocytoma (A-III, WHO grade 3, n = 8) and glioblastoma (GB, WHO grade 4, n = 33)) and 18 cases of recurrent MG (recurrent A-III (WHO grade 3, n = 7) and recurrent GB (WHO grade 4, n = 11)). Blood cell counts (peripheral blood leukocytes (PBL), platelets (Pt), neutrophils (Neu), lymphocytes (Ly), monocytes (Mo)) and NLR (Neu/Ly ratio), PLR (Pt/Ly ratio), MLR (Mo/Ly ratio), and systemic immune-inflammation index (SII)) in the preoperative period (prior to re-resection in cases of recurrent MG) were evaluated. The Kaplan - Meier and Cox regression analyses of OS/RFS were performed. The potential association between the blood counts and ratios PLR (≤146 vs. >146), NLR (≤4 vs. >4), MLR (≤0.27 vs. >0.27), SII (≤906 vs. >906), as well as sex (female vs. male) and age (≤60 vs. >61) with OS and RFS were analyzed.

Results: PBL and Neu counts, as well as NLR and SII indices, in patients with primary and recurrent GB in the pre-operative period significantly exceeded the reference values (p < 0.02). PBL, Neu, and SII significantly correlated with tumor grade. In patients with primary A-III and GB, longer OS tended to be associated with high PLR, NLR, MLR, and SII values, while in patients with recurrent GB, longer OS tended to be associated with low values of these ratios. Patients with recurrent A-III and GB showed a significant association between low pre-surgery NLR, SII and better RFS while patients with recurrent GB - significant association between low pre-surgery MLR and better RFS. Significant association between OS and sex of patients with both primary and recurrent GB was shown.

Conclusions: The results obtained suggest the possible prognostic significance of PLR, NLR, MLR, and SII values in the treatment outcomes of MG patients.

Background: Gastrointestinal stromal tumors of the stomach (GIST) are relatively rare, and in 65% of cases, their primary localization is the stomach wall. Considering that the incidence of GIST is 1.2 cases per 10⁵ people per year, not all aspects of the treatment and diagnostic tactics are sufficiently studied. The aim of the study was to examine the possibilities of modern methods of preoperative verification of GIST of the stomach and the effectiveness of their surgical treatment using minimally invasive technologies.

Materials and methods: We analyzed the results of surgical treatment using minimally invasive technologies for 24 GIST patients with tumor localization in the stomach wall treated in the clinic of the Bogomolets National Medical University in 2017-2025. Histological and immunohistochemical analyses of the biopsy and surgical materials were performed.

Results: The choice of a method for performing gastric resection depended on the localization and size of the tumor, and the type of its growth. Of 17 (70.8%) patients with the exophytic type of GIST growth, 13 (54.2%) patients had significant difficulties with verification of the tumor in the gastric wall during laparoscopic revision.

Conclusion: The results of the study are consistent with international data and emphasize the need for morphological typing and the use of immunohistochemical markers for accurate diagnosis, risk stratification, and selection of further treatment tactics for patients with GIST of the stomach.

Background: Resistance of the advanced breast cancer (aBC) to hormone therapy and chemotherapy due to hyperactivated PI3K-pathway caused by mutations in the PIK3CA gene is a major treatment problem. Combining pegylated liposomal doxorubicin (PLD) with mild magnetothermy (MT) and letrozole could improve the efficacy of treatment. The aim was to assess the effect of combined treatment with PLD, MT, and letrozole on the survival of patients with luminal B postmenopausal aBC with mutations in the PIK3CA gene.

Material and methods: The aBC postmenopausal patients who progressed on a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and an aromatase inhibitor (AI) or neoadjuvant chemotherapy (ACT) were included in the study. Group 1 included 20 patients, treated with PLD + MT every 28 days (4 courses) and letrozole (daily per os, 4 months). Group 2 included 20 patients, who received the same treatment without letrozole. By PIK3СА status, each group included 10 patients with a mutant PIK3СА and 10 patients with a wild-type gene.

Results: Application of PLD + MT in combination with letrozole demonstrated improved progression-free survival (PFS) compared to PLD + MT alone. In group 1, the median PFS was 10.6 months (95% CI, 7.4-11.9 months) compared to a median PFS of 8.9 months (95% CI, 6.1-9.7 months) in group 2 (p = 0.005). In the sensitivity analyses, PFS of patients with wild-type PIK3CA in the first cohort was 10.1 months (95% CI, 8.7-11.1 months) compared to 8.4 months (95% CI, 7.0-10.4 months) in groups 1 and 2 respectively (p = 0.004), by 1:1 greedy nearest neighbor matching.

Conclusion: PLD with local MH in combination with letrozole was more effective irrespective of the PIK3CA gene status in postmenopausal aBC patients.

Background: Prostate cancer (PCa) remains a leading cause of cancer-related deaths among men. While PSA screening has reduced mortality, the lack of its specificity and limitations of biopsy necessitate alternative diagnostic approaches.

Aim: To evaluate the aggressiveness of PCa using an infrared (IR) imaging technique to improve PCa detection and treatment planning.

Materials and methods: We conducted a study using IR imaging on formalin-fixed paraffin-embedded prostate tissue samples from 60 patients who underwent radical prostatectomy. An IR-sensitive CCD camera, a holder for the sample, and an IR irradiation source (LED 850 nm) are parts of the experimental setup. Custom software was used to analyze tissue samples. For each aggressiveness group (low, intermediate, high; n = 20 per group), the ratio of average illumination (RAI) between malignant and healthy regions was calculated.

Results: RAIs between malignant area and healthy areas for different aggressiveness levels (mean ± 95% CI) were low-aggressiveness [6.8-7.2], intermediate [5.2-6.1], and high-aggressiveness [4.4-5.0]. These intervals did not overlap. The control (benign) tissues showed RAI > 7.5. The method demonstrated a sensitivity of 88% and specificity of 91% in distinguishing highly aggressive tumors.

Conclusion: IR imaging reliably differentiates PCa aggressiveness, with non-overlapping RAI intervals for each group. This technique may enhance early detection and guide personalized treatment strategies.

Background: Liver resection remains a gold standard for the treatment of colorectal liver metastases; however, radiofrequency ablation (RFA) may serve as an alternative for patients with contraindications to resection or within parenchymasparing strategies. The aim of this study was to analyze treatment outcomes, prognostic factors, and survival after RFA of intraparenchymal colorectal liver metastases.

Materials and methods: A retrospective analysis was performed on 33 patients with colorectal liver metastases who underwent RFA between 2013 and 2023. The ablation was carried out using the Cool-tip RF Ablation System E Series (Covidien) with a maximum output power of 200 W and internally cooled monopolar needles with a 3 cm active tip, under intraoperative ultrasound guidance.

Results: Patients were stratified according to survival status. Group 1 (n = 23) included patients who underwent RFA and were alive at the time of analysis; Group 2 (n = 10) included those who died of disease progression. The survival was significantly influenced by the presence of synchronous metastases (21.7% vs 100.0%, p < 0.001), metachronous metastases (78.3% vs 0, p < 0.001), and median time to progression (18 (78.3%) vs 1 (10.0%), p = 0.0004). No significant effect was found for sex, age, primary tumor localization or morphology, number of chemotherapy lines before ablation, maximal size and number of metastases, type of surgery for the primary tumor, or the presence of comorbidities.

Conclusion: RFA in the treatment of colorectal liver metastases is a safe alternative for the unresectable lesions or within parenchyma-sparing strategies. However, liver resection should be considered a priority option when technically feasible. Combining resection and RFA expands the range of patients eligible for radical intervention, potentially improving disease-free and overall survival rates. These findings are limited by baseline group disparities. Randomized or propensity-matched studies are needed to confirm RFA efficacy and define the target population most likely to benefit.

A unique observation of the successful complex treatment of a rare and clinically complex metastatic mediastinal paraganglioma is presented. It has been shown that neoadjuvant intra-arterial regional chemotherapy with the subsequent surgical removal of the tumor can be an effective method of choosing treatment for malignant metastatic mediastinal paraganglioma.

Background: Phagocytosis occurs in almost all cell types of multicellular organisms. Based on their efficiency, cells are classified as professional or non-professional phagocytes, with cancer cells belonging to the latter. This property of cancer cells underlies the formation of "cell-in-cell" structures, the high frequency of which is often associated with invasion and metastasis of malignant tumors.

Aim: To investigate the ability of Lewis lung carcinoma (LLC) cells to perform non-professional phagocytosis and to analyze how this process depends on cancer cell growth conditions.

Materials and methods: A low-metastatic variant of LLC cells (LLC/R9) was used. Phagocytic activity was examined under anchorage- dependent and anchorage-independent growth conditions, in both standard and glucose-free culture media, using fluorescent latex beads (1.0 μm in diameter).

Results: LLC/R9 cells demonstrated phagocytic activity, which increased nearly fourfold under anchorage-independent conditions, irrespective of E-cadherin expression. Glucose deprivation reduced the percentage of bead-engulfing cells by more than twofold under both growth conditions, while increasing the number of beads internalized per cell. This indicates a pronounced heterogeneity within the cancer cell population in their sensitivity to phagocytic activation under glucose deficiency.

Conclusions: Non-small cell lung cancer LLC/R9 cells are capable of phagocytosis, which is markedly enhanced under anchorage-independent growth and only weakly influenced by glucose deprivation.

Background: Breast cancer (BC) is the most frequently diagnosed malignancy among women in Libya; however, limited data are available on the immunohistochemical (IHC) profiles of BC in the region. This study aimed to characterize BC cases in Western Libya based on clinical, pathological, and IHC features.

Materials and methods: Thirty formalin-fixed paraffin-embedded BC tissue samples were collected from the patients at the National Cancer Institute in Sabratha, Libya, between January and April 2024. IHC staining for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 was performed.

Results: Patients' age ranged from 24 to 63 years (mean 44.60 ± 10.23), with the 44-53-year group being the most frequent (33%). Invasive ductal carcinoma was the most common subtype (74%), especially grade 3 (47%). Most tumors were ER-positive (78.6%), PR-positive (67.9%), and HER2-negative (67.9%), with low Ki-67 expression in 53.6% of cases. HER2 score 0 was most prevalent (40%). Mean PR expression was the highest in grade 2 tumors (53.0 ± 32.2), whereas Ki-67 in grade 3 tumors (51.1 ± 29.7). Significant associations were found between ER status and mean corpuscular hemoglobin (p = 0.039) and mastectomy status and mean cell hemoglobin concentration (p = 0.031).

Conclusion: The findings highlight the predominance of hormone receptor-positive and HER2-negative tumors in this Libyan cohort.

The tumor microenvironment (TME) plays a critical role in tumor survival, progression, and metastasis. Нypoxia level, as an integral parameter of TME, occupies a central place in the regulation and control of all events occurring in TME. The review focuses on the findings obtained by the authors during the study of the hypoxia impact on the processes related to some microenvironmental factors in order to identify its prognostic significance regarding the course of the disease. It was shown that most microenvironmental factors are largely associated with hypoxia and involved in the processes of the tumor response to therapy. Their significance in the development of minimal residual disease and in the processes that can be affected by adipose tissue is also discussed. Therapeutic strategies based on the tumor's distinctive properties should be more highly selective in relation to the tumor, allowing the highest possible therapeutic gain for a more favorable prognosis of the disease outcome and overall survival of patients with gastric cancer. The literature data on the subject are also discussed.

Background: Lectins are carbohydrate-binding proteins with diverse biological activities, and they are increasingly recognized for their potential in cancer diagnostics and therapy. Aim of the study was to investigate the cytostatic and cytotoxic effects of the bacterial lectin of Bacillus subtilis IMV B-7724 on breast cancer (BC) cell lines of different molecular subtypes.

Materials and methods: Experiments were performed on the T47D (luminal A), MCF‑ 7 (luminal B), and MDA-MB-468 (basal, triple-negative) cell lines. Cytotoxicity was assessed by crystal violet staining and LC₅₀/LC₃₀ determination. Cytomorphological alterations were analyzed using the Romanowsky - Giemsa staining and ImageJ morphometry. A flow cytometry was applied to evaluate the cell cycle distribution and apoptosis (Annexin V/PI assay). The expression of proliferation and apoptosis regulators (Ki-67, p53, BCL-2, BAX) was examined by immunocytochemistry.

Results: The lectin exerted dose-dependent cytotoxicity across all tested cell lines, with LC₅₀ values ranging between 351-419 μg/mL. The morphological analysis revealed subtype-specific alterations, including cell rounding, nuclear condensation, and decreased cytoplasmic volume, indicative of the apoptotic process. The flow cytometry showed distinct cell cycle arrest patterns: S-phase accumulation in T47D, G2/M blockade in MCF‑ 7, and combined S- and G2/M-phase arrest in MDA-MB-468. The viability assays confirmed a significant reduction of live cells, predominantly through late apoptosis and necrosis, with the strongest effect observed in T47D cells. The immunocytochemistry demonstrated a marked downregulation of Ki-67 and BCL-2, increased p53 expression, and BAX upregulation in MCF‑ 7 cells, whereas T47D cells displayed a paradoxical BAX suppression despite the apoptotic features.

Conclusions: Lectin of B. subtilis IMV B-7724 exerts multifaceted effects on BC cells of different molecular subtypes, including the suppression of cell proliferation, activation of apoptosis, and cell cycle modulation. The observed differences between the BC cell lines suggest that the lectin efficacy depends on both the molecular profile of the cells and the mode of apoptosis regulation (p53-dependent or p53-independent), warranting further studies to identify key targets.