Experimental oncology最新文献

Aim: To evaluate the clinical and morphological features of breast cancer (BC) of the luminal B subtype in young women to determine biological aggressiveness, response to neoadjuvant chemotherapy, and prognosis.

Materials and methods: A retrospective study included luminal B subtype BC patients under 40 years of age (n = 108) and over 55 years (n = 101) treated at the National Cancer Institute. All patients received neoadjuvant chemotherapy according to the ddAC-12T regimen. TNM stages, tumor differentiation grade, Ki-67 expression, hormone receptor status, response to the neoadjuvant chemotherapy (NAC) (RECIST 1.1), pathomorphology grade (Miller - Payne), disease-free (DFS) and overall survival (OS) were analyzed.

Results: Patients of the younger age group were more likely to have G3 tumors (68% vs. 45%), high Ki-67 levels >35% (72% vs. 50%), and lymph node involvement (71% vs. 59%). The median estrogen receptor expression was 35% in the young patients vs. 65% in the older patients. Complete histological response to NAC was achieved in 26% of the young patients (vs. 9% in the older group). Five-year RFS in the young women was 82.4% vs. 94.1% in the older group.

Conclusions: The luminal B subtype of BC in the young women is characterized by the higher proliferative activity, lower hormonal sensitivity, and more frequent lymph node involvement. Despite the response to NAC, this group demonstrates the worse DFS. The results confirm the need for personalized treatment strategies and improved early diagnosis programs in young patients.

Capillary hemangiomas (CH) are benign proliferative vascular neoplasms commonly present in skin and soft tissues but rarely found intracranially. We describe a case of a 14-year-old male patient with histologically proven CH of the optic nerve, who underwent surgical resection of the lesion due to progressive visual loss. Imaging studies revealed a cystic-solid formation in the suprasellar region lateralized to the right and located above the pituitary gland. This case shows that CH may originate from the optic nerve, leading to its gradual compression and causing optic neuropathy. While the correct differential diagnosis on the MRI may be difficult, surgical treatment is warranted in cases of progressive visual decline.

Background: Evidence-based screening strategies can substantially reduce colorectal cancer (CRC) mortality. While colonoscopy is the gold standard, its invasiveness renders it less preferable as an initial screening tool. A two-step approach using a non-invasive fecal immunochemical test (FIT) followed by a confirmatory colonoscopy is gaining favor. A novel FIT that simultaneously detects fecal hemoglobin (F-Hb) and fecal transferrin (F-Tf) demonstrates variable diagnostic performance.

Aim: This study compared the diagnostic performance of four screening strategies using three FITs with different cutoffs for F-Hb and F-Tf to detect neoplastic lesions in patients with suspected CRC.

Materials and methods: We conducted a cross-sectional study involving suspected CRC patients aged ≥ 18 at Hasan Sadikin Hospital, Bandung, from March 2023 to August 2023. The study included 72 clinically suspected CRC patients who underwent colonoscopy. We compared four CRC screening strategies using FITs designated as FIT-I (F-Hb ≥ 10 ng/mL), FIT-II (F-Hb ≥ 50 ng/mL), FIT-IIIa (F-Hb ≥ ≥ 100 ng/mL or F-Tf ≥ 40 ng/mL), and FIT-IIIb (F-Hb ≥ 100 ng/mL and F-Tf ≥ 40 ng/mL).

Results: The FIT-IIIb strategy, which requires positive results for both markers, yielded the highest diagnostic performance for detecting neoplastic lesions, with 60.0% sensitivity, 96.6% specificity, a 93.8% positive predictive value, and a 73.7% negative predictive value.

Conclusion: A dual-marker FIT detecting both F-Hb and F-Tf is a promising and effective screening tool for CRC. Future research should explore its implementation in broader populations and potential impacts on screening guidelines.

Aim: To investigate neurofunctional parameters of motor nerves in breast cancer (BCa) patients with paclitaxelinduced peripheral neuropathy (PIPN) and to determine the feasibility of using alpha-lipoic acid (ALA) in combination with ipidacrine hydrochloride (IPD) for PIPN prevention.

Materials and methods: The study included 100 patients with BCa stages II-IV, who were treated with polychemotherapy (PCT) according to the AT (paclitaxel, doxorubicin) or ET (paclitaxel, epirubicin) scheme in the neoadjuvant, adjuvant, or palliative regimens. Patients were randomized into two groups (n = 50 in each): group I received PCT only; group II - PCT in combination with ALA + IPD. Electroneuromyographic (ENMG) studies of the motor fibular and tibial nerves were performed before the start of chemotherapy and after the 3rd and 6th cycles of PCT.

Results: Comparison of ENMG parameters of the motor nerves of the lower extremities of BCa patients before the start of PCT with these parameters after 3 and 6 PCT cycles indicated a slightly pronounced but significant decrease in the M-response and partly the nerve conduction velocity, which progressed with an increase in the cumulative dose of paclitaxel. Despite this, the average values of ENMG parameters remained within normal limits even after 6 cycles of PCT. The detected changes indicated a tendency toward axonal damage and mild myelinopathy. Significantly higher M-response rates of motor nerves were found in patients of group II compared to group I only after 6 cycles of PCT with paclitaxel.

Conclusion: The use of ALA and IPD improves the functional state of the axons in patients with BCa treated with paclitaxel.

Background: The effect of the inhibitors of glycolysis and oxidative phosphorylation on the altered metabolism of neoplasms is considered a promising method of antitumor therapy. However, most studies on the antimetastatic activity of such inhibitors focus on analyzing their effect on the migratory and invasive characteristics of cells. Meanwhile, the survival of circulating metastatic cells and their resistance to anoikis are critically important factors in metastasis.

Aim: To carry out a comparative study of sodium oxamate (SOX) and metformin (MTF) effects on the survival, proliferative activity, and metabolic plasticity of the low-metastatic variant of Lewis lung carcinoma (LLC/R9) cells under their anchorage-independent growth.

Materials and methods: Cell death, apoptosis, cell cycle distribution, reactive oxygen species (ROS) production, glucose and lactate levels, and vimentin expression in LLC/R9 cells under their anchorage- independent growth were assessed following SOX and MTF treatments.

Results: The cytotoxicity of inhibitors was manifested in a significant decrease in the number of viable LLC/R9 cells and an increase in the number of dead and apoptotic cells, the effects being more pronounced for MTF. In the case of SOX treatment, a correlation was observed between an increase in the percentage of apoptotic cells and ROS level and a decrease in the glucose consumption rate (GCR). MTF increased GCR and the number of apoptotic cells, without changes in ROS levels. Incubation with MTF resulted in a significant twofold increase in the percentage of cells in the S phase due to a decrease in the fraction of cells in the G1/G0 and G2/M phases of the cell cycle.

Conclusions: Unlike SOX, the cytotoxic effect of MTF on de-adhesive cells was directly related to disrupting energy homeostasis and cell cycle regulation rather than by oxidative stress. Their combined application could potentially reinforce metabolic stress in circulating tumor cells, simultaneously weakening glycolytic and oxidative compensatory pathways, thereby limiting metastatic competence.

Background: Infiltration of the tumor microenvironment by macrophages plays a key role in the progression of breast cancer (BC), modulating tumor growth, angiogenesis, immunosuppression, and metastasis. However, the association between macrophage infiltration levels and the clinicopathological characteristics of BC, including the molecular subtype of the neoplasm and receptor status, remains insufficiently studied.

Aim: To investigate the relationship between macrophage infiltration in BC tissue and the extent of tumor spread as well as the molecular profile of the neoplasms.

Materials and methods: Using immunohistochemistry, the level of infiltration of tumor tissue by CD68+ (total macrophages) and CD163+ (M2 phenotype macrophages) tumor-associated macrophages (TAMs) was assessed in the postoperative samples from 67 patients with BC stage I-II.

Results: The level of CD68+ macrophage infiltration in BC tissue was associated with the disease stage (p = 0.004), tumor size (T category) (p = 0.026), and the presence of metastases in regional lymph nodes (p = 0.047). The highest number of CD163+ M2-like macrophages was recorded in poorly differentiated BC tissue (p = 0.024) and in neoplasms of the basal-like molecular subtype (p = 0.023). The lowest numbers of both CD68+ and CD163+ macrophages were detected in HER2/neu-positive tumors (p = 0.023). The data indicated that BC tumors classified as T2 and N1-N3 were characterized by an increased content of M1-polarized macrophages, whereas in basal-like BC and poorly differentiated tumors (G3), the M2 macrophage subpopulation predominated. This contributed to the formation of an immunosuppressive tumor phenotype and indicated the potential prognostic significance of macrophage infiltration in malignant breast neoplasms.

Conclusions: The topology and quantitative characteristics of macrophage infiltration in tumor tissue are closely associated with the extent of BC spread and the molecular profile of the neoplasms. The CD68+/CD163+ cell ratio may reflect the balance between antitumor and immunosuppressive mechanisms within the microenvironment and be considered a potential prognostic marker.

Angiosarcoma of the breast is a rare malignant tumor and accounts for 1% of all soft tissue tumors of the breast. Breast angiosarcoma caused by previous radiation therapy more frequently affects older women with a history of breast cancer. The standard treatment for such patients is radical surgery, but there are still many debatable questions regarding the treatment of these malignant tumors. The purpose of this article is to review the medical literature on angiosarcomas associated with radiotherapy and describe a case as an example.

Chronic stress is one of the key exogenous factors that can significantly affect tumor cell biology by disrupting the regulation of the tumor microenvironment (TME), thereby promoting the manifestation of the malignant process. Activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system induced by stressors leads to the secretion of glucocorticoids and catecholamines, which contribute to the deregulation of microenvironmental components that determine the aggressiveness of malignant neoplasms. This review systematizes the current views on the impact of stress-induced signals on the immune, stromal, vascular, and metabolic components of the TME and analyzes their contribution to the formation of an aggressive tumor phenotype. Particular attention is given to the interplay between neurohumoral stress, the gut, and the intratumoral microbiome, forming a complex networked environment supporting tumor progression. Advancing the understanding of molecular interactions between stress mediators and cellular elements of the TME will provide a foundation for developing innovative therapeutic strategies targeting not only the tumor itself but also minimizing the adverse effects of stress on individual components of the TME.

Genitourinary cancers, including prostate, bladder, and renal cancers, represent a significant global health burden due to their high prevalence and resistance to conventional therapies. A critical aspect of cancer progression is metabolic reprogramming, which not only fuels uncontrolled growth but also profoundly influences programmed cell death pathways and the tumor immune microenvironment. This review synthesizes current research on the intricate roles of long non-coding RNAs (lncRNAs) in modulating three emerging forms of regulated cell death - cuproptosis, ferroptosis, and disulfidptosis - within the context of genitourinary malignancies. We discuss how specific lncRNA signatures are implicated in the regulation of these metabolic cell death pathways, affecting cancer cell proliferation, migration, and invasion. Furthermore, we explore the compelling association between these lncRNA expression patterns and the characteristics of the tumor immune microenvironment, highlighting their potential as prognostic biomarkers and indicators for stratifying patient responses to immunotherapy. The evidence presented underscores the multifaceted functions of lncRNAs in cancer metabolism and immunity, positioning them as promising therapeutic targets and informative biomarkers for precision oncology in genitourinary cancers.

Background: Breast cancer (BC) accounts for about 30% of cancers in women, with a mortality rate of around 15%. HER2- positive BC, an aggressive subtype, represents 15-20% of all BC cases. High-dose vitamin C has shown antitumor effects by increasing reactive oxygen species in cancer cells without significant toxicity.

Aim: This study aimed to explore an in vitro dual treatment using ascorbyl palmitate (AP), a lipophilic vitamin C derivative, and trastuzumab, an HER2 receptor blocker.

Materials and methods: HER2-positive SK-BR-3 BC cells were treated with AP, trastuzumab, or their combination. The cell survival MTT assay, apoptosis, and cell cycle phase analysis were conducted using flow cytometry, while mRNA and protein expression were assessed using RT-qPCR and Western blot methods. Ki-67 expression was evaluated by immunofluorescence assay.

Results: AP reduced cell viability in a time- and dose-dependent manner, and its combination with trastuzumab further decreased cell viability. A cytometric analysis showed enhanced apoptosis after combination treatment. mRNA analysis revealed upregulated TP53 mRNA expression, along with upregulation of BAX, CYCS, CASP3, and CASP8 gene expression, while the BCL-2 and BCL2L1 genes were downregulated, further supporting the induction of apoptosis. The antiproliferative effectiveness of the combination therapy was demonstrated by a Western blot assay, which showed suppression of phospho-P38, ERK1/2, and PI3K protein synthesis.

Conclusion: These results underscore the potential effects of combining AP and trastuzumab in BC treatment, guiding future therapeutic strategies.