Wspolczesna Onkologia-Contemporary Oncology最新文献

Introduction: This study aimed to investigate the role of ALKBH5 in the proliferation, invasion, and MUC1 expression of U251 glioblastoma cells, using both in vitro and in vivo methodologies.

Material and methods: This study investigated the role of ALKBH5, an RNA demethylase, in regulating the proliferation, invasion, and ferroptotic sensitivity of U251 glioblastoma cells, with a focus on its interplay with MUC1, a transmembrane glycoprotein implicated in tumour progression and stress responses.

Results: Using in vitro and in vivo models, we demonstrate that ALKBH5 knockdown significantly inhibits U251 cell proliferation, invasion, and tumour growth, while its overexpression enhances these oncogenic properties. ALKBH5 regulates MUC1 expression, with MUC1 overexpression that rescues the inhibitory effects of ALKBH5 knockdown on cell viability and invasion. We uncover a novel link between ALKBH5 and ferroptosis, i.e. that ALKBH5 knockdown sensitises U251 cells to ferroptotic cell death through modulation of MUC1-mediated lipid peroxidation and iron metabolism pathways. In vivo studies reveal reduced tumour growth and Ki-67 expression in ALKBH5 knockdown models with decreased MUC1 levels in tumour tissues.

Conclusions: The results highlight ALKBH5 as a critical regulator of glioblastoma progression and ferroptotic sensitivity, with MUC1 acting as a key downstream effector. Our findings provide new insights into the molecular mechanisms that drive glioblastoma aggressiveness and propose ALKBH5 and MUC1 as promising therapeutic targets for combating this lethal disease.

Small intestinal bacterial overgrowth (SIBO) is defined by an abnormal proliferation of colon-specific bacteria in the small intestine, whereas intestinal methanogen overgrowth (IMO) manifests with an increase of methane-producing archaea, specifically Methanobrevibacter smithii. Both conditions can disrupt gastrointestinal motility and manifest with various clinical symptoms. Small intestinal bacterial overgrowth appears to increase the risk of malnutrition and negatively affect malabsorption of essential nutrients such as vitamin B₁₂ and fat-soluble vitamins. This concern is particularly relevant for cancer patients as malnutrition can adversely affect treatment outcomes and mortality rates. Small intestinal bacterial overgrowth prevalence is 2.5-22% in the general population, with significantly higher rates observed in cancer patients, depending on a study, 65% of gastric and colorectal cancer patients, 63.3% of pancreatic cancer patients compared to 13.3% in healthy controls. Gastrointestinal complications, particularly in cases of gastrointestinal cancers, can arise from both the disease itself and its treatment. Managing symptoms becomes more challenging when SIBO occurs as its symptoms are often ambiguous and overlap with those of other conditions. This review summarizes the current state of knowledge on SIBO and IMO in gastrointestinal cancers. Current knowledge on SIBO and IMO, particularly in gastrointestinal cancer, is limited by the lack of validated diagnostic standards, evidence-based nutritional guidelines, and a focus on symptom control rather than underlying mechanisms. There is a need for research on recurrence despite treatment, as well as studies specifically targeting SIBO and IMO in cancer rather than as comorbidities. Future efforts should prioritize developing reliable diagnostics, understanding recurrence mechanisms, and exploring personalized therapies and nutritional interventions.

Introduction: Ovarian serous cystadenocarcinoma (SCA), a deadly gynecologic cancer, often goes undetected until the late stages. Tissue proteomics unveils disease heterogeneity, enhancing tumor classification and enabling personalized treatments tailored to individual expression profiles.

Material and methods: Tissue samples from 46 serous ovarian tumors were quantified using label-free liquid chromatography-tandem mass spectrometry. We identified 80 proteins differentiating SCA from borderline tumors, 277 distinguishing SCA from benign tumors, and 195 between borderline and benign tumors. Ingenuity pathway analysis revealed increased cell proliferation and RNA processing in SCA and borderline tumors compared to benign tumors, with SCA showing greater oxidative phosphorylation than borderline tumors.

Results: Our comparative analysis indicates that upregulated (ASS1 - argininosuccinate synthase 1, CAPS, PPA1, BCAT1, MCM4) and downregulated proteins (MUC5B, SLC4A1, tenascin-XB - TNXB, carbonic anhydrase 1, hemoglobin β) may offer a robust panel for distinguishing SCA from benign and borderline ovarian tumors, potentially aiding in early diagnosis and disease monitoring. The cancer-associated proteins pyridoxal dependent decarboxylase domain containing 1 (AUC: 0.83, 95% CI: 0.66-1), GFPT1 (AUC: 0.84, CI: 0.70-0.89), and HYOU1 (AUC: 0.84, CI: 0.70-0.98) significantly differentiated between low-grade (LGSCA) and high-grade serous cystadenocarcinoma (HGSCA). Low-grade SCA showed significantly greater levels of MZB1 (log₂ fold change (FC): -1.951, p-value: 0.0258), CRABP2 (FC: -2.34, p-value: 0.0016), and BCAM (FC: -1.945, p-value: 0.0197) than borderline cancers.

Conclusions: Argininosuccinate synthase 1 and TNXB showed potential as markers of disease progression. Elevated ASS1 was observed in borderline, LGSCA, and HGSCA tumors compared to benign tumors, while TNXB levels progressively declined from benign to borderline, LGSCA, and HGSCA tumors. Our study pinpoints critical biomarkers in serous ovarian tumors for HGSCA progression.

Introduction: This study investigated the prognostic significance of interleukin-6 (IL-6) in predicting infection severity and mortality among patients with acute myeloid leukemia (AML). Given the high susceptibility of AML patients to infectious complications, the study aimed to evaluate IL-6 as a superior biomarker compared to C-reactive protein (CRP) and procalcitonin (PCT).

Material and methods: A retrospective analysis was conducted on 84 AML patients who developed infectious complications during treatment. Biomarkers, including IL-6, CRP, and PCT, were measured at the onset of infection, and infection severity was graded on a scale from 1 to 5. Statistical me-- thods, including Spearman's rank correlation and one-way analysis of variance (ANOVA), were applied to determine relationships between biomarker levels, infection severity, and mortality. Multivariate logistic regression was employed to assess the predictive value of IL-6 for mortality, adjusting for demographic and hematological factors.

Results: IL-6 levels exhibited the strongest correlation with infection severity and mortality (odds ratio 2.45, 95% CI: 1.80-3.33) compared to CRP and PCT. The relationship was particularly pronounced in middle-aged patients (41-60 years). While CRP and PCT also increased with infection severity, IL-6 demonstrated superior predictive power, especially in severe and fatal cases.

Conclusions: IL-6 is a reliable prognostic biomarker for infection severity and mortality in AML patients, outperforming traditional inflammatory markers. Routine IL-6 monitoring could enable early identification of high-risk patients, facilitating timely interventions and improving outcomes. These findings support the integration of IL-6 monitoring into standard care protocols for AML patients with infectious complications.

Cancer is one of the leading causes of death worldwide, accounting for approximately 9.6 million deaths annually - 1 in 6 deaths globally. Recent advancements in nanoscience have highlighted the potential of nanomaterials in healthcare applications. Among these, iron oxide nanoparticles (IONPs) stand out due to their magnetic properties, semiconductor behavior, biocompatibility, biodegradability, and low toxicity. These characteristics make them highly valuable in multifunctional biomedical applications, including: magnetic hyperthermia for cancer therapy; targeted drug delivery to minimize chemotherapy side effects; cell labeling and tracking; and bioimaging techniques. This mini-review focuses on the latest developments in IONPs for cancer therapy, evaluating recent research on size, synthesis methods, and biomedical/electrochemical applications of coated, drug-loaded, and targeted nanoparticles. By compiling and comparing key findings, this paper serves as a comprehensive reference for researchers and scientists working on the multidisciplinary applications of nanomaterials.

Grey zone lymphoma (GZL) is a rare and aggressive B-cell lymphoma, exhibiting features of both diffuse large B-cell lymphoma and classical Hodgkin's lymphoma (cHL). Due to its rarity, especially in paediatric patients, no standardized treatment protocols exist. The disease presents diagnostic challenges and limited treatment options. Recent studies suggest that immune checkpoint inhibitors, such as pembrolizumab, may offer a promising treatment for refractory cases. A 15.5-year-old male initially presented with huge mediastinal tumour, fluid in the pleural cavity, enlargement of supraclavicular lymph nodes, left subclavian and diaphragmatic nodes and lung infiltration. Initial histopathological examination suggested cHL, but after progression on the first-line therapy (EuroNet-PHL-C2 protocol), biopsy confirmed mediastinal GZL. Despite further chemotherapy (COP, R-COPADM, R-CYM, R-CYVE, R-ICE), the disease continued to progress. Pembrolizumab was introduced after further progression. Following eight months of the treatment, positron emission tomography scans showed a complete metabolic response. The patient underwent autologous stem cell transplantation and continued pembrolizumab for 27 months, maintaining stable small residual tumour with a complete metabolic response. This case highlights the diagnostic challenges and treatment difficulties in paediatric GZL. Pembrolizumab, a programmed death 1 inhibitor, demonstrated efficacy in a heavily pretreated patient with refractory disease. Although pembrolizumab is widely used in adults, this successful application in paediatric GZL suggests its potential as a therapeutic option for this rare lymphoma subtype also in children and adolescents. Pembrolizumab occurred to be effective in refractory paediatric GZL, supporting the need for further studies to assess its safety and efficacy in larger cohorts.

Introduction: Lactate dehydrogenase (LDH) is an intracellular enzyme the concentration of which in the serum of melanoma patients is a commonly used biomarker for detecting recurrence, monitoring the effectiveness of ongoing systemic treatment, and for determination of prognosis.

Material and methods: In this report we evaluated the clinical value of elevated LDH during adjuvant BRAF (dabrafenib) and MEK (trametinib) inhibitors in 23 patients after resection of stage III cutaneous, BRAF-mutated melanoma.

Results: The treatment was administered for one year or until disease progression or unactable toxicity. In all patients, an increase in LDH was observed during treatment, of whom 18 patients had an increase to values above the upper limit of normal, while 4 patients had an increase within normal limits. After discontinuation of dabrafenib with trametinib, a decrease in LDH levels was observed in all patients except one, in whom treatment was discontinued due to disease progression. The increase in LDH was not associated with disease progression. Hypotheses explaining the increase in LDH include, among others, the immunomodulatory effect of BRAF and MEK inhibitors and the effect of drugs in question on the MAPK pathway in wild-type BRAF cells.

Conclusions: Information on the common increase in LDH in patients undergoing adjuvant therapy with dabrafenib with trametinib will avoid additional imaging studies in many situations and may prevent unnecessary emotional stress for patients.

Introduction: Glioblastoma (GBM) is the most aggressive primary brain tumour in adults. Systemic immunometabolic alterations are increasingly implicated in its pathogenesis, yet sex- and age-specific patterns remain unclear, especially in Uzbekistan. To characterize circulating cytokine and biochemical profiles in newly diagnosed GBM patients and assess sex- and age-related differences.

Material and methods: This cross-sectional study included 26 GBM patients (18 females, 8 males) and 26 matched healthy controls. Serum interleukin (IL)-10, IL-1β, IL-6, tumor necrosis factor-α, and IFN-γ were measured by enzyme-linked immunosorbent assay, and biochemical parameters (alkaline phosphatase, alanine aminotransferase - ALT, aspartate aminotransferase - AST, bilirubin, calcium, magnesium, iron, creatinine, uric acid, lactate dehydrogenase - LDH, phosphorus) were analysed by automated assays. Data were evaluated using ANOVA, t-tests, correlations, and principal component analysis (p < 0.05).

Results: No sex-based differences were observed (p > 0.05). Older patients had higher uric acid (p = 0.029) and borderline elevated IL-10 (p = 0.048) levels. Pro-inflammatory cytokines correlated with metabolic markers (ALT, AST, uric acid, LDH) and bilirubin correlated with iron/LDH.

Conclusions: Glioblastoma-related immunometabolic profiles are influenced mainly by tumour-intrinsic factors rather than sex, while age contributes to metabolic shifts. These findings provide novel regional data and support cytokine-biochemical profiling for biomarker development.

Introduction: The cytokine interleukin-11 (IL-11) binds on its target cells to a membrane-bound IL-11R, which results in homodimerization of the signal-transducing β-receptor gp130. Recent studies have uncovered a pro- inflammatory role in several diseases, including different tumor entities, and mouse models have revealed a crucial role of the IL-11/IL-11R axis in gastric cancer. However, studies regarding human gastric cancer are sparse, and whether the results obtained in mouse models also hold true in the human situation is little investigated.

Material and methods: We analyzed gene expression of IL11RA, IL11, IL6R, IL6 and IL6ST in different gastric tumor and immune cell lines. Furthermore, we stimulated these cell lines with exogenous cytokines and determined intracellular signaling. Finally, we analyzed gene expression data of gastric tumor patients and correlated them with overall patient survival.

Results: This study showed that different gastric tumor cell lines respond to IL-6 classic and trans-signaling, but only slightly to stimulation with IL-11. We observed that monocyte-like cell lines expressed high levels of IL-6R and responded to IL-6, but not to stimulation with IL-11. Using gene expression data, we found that IL11RA and IL11 are not overexpressed in human gastric cancer tissue and do not correlate with patient survival. However, low IL6 expression is associated with higher overall survival.

Conclusions: We provided evidence for IL-6 but not IL-11 signaling in gastric tumor cells and demonstrated that IL6 expression in gastric tumors is associated with overall survival of patients.

Introduction: Treating a child with cancer in a family is a challenge that can have an impact on mental health. The study consists of determining the prevalence of psychological distress of parents of cancer children and exploring its correlations with their coping strategies.

Material and methods: The survey was conducted between March and July 2023 among parents or guardians of children with cancer. The data collection tool was a version of the general health questionnaire (GHQ12) to estimate the prevalence of psychological distress and the coping orientation to problems experienced, to explore coping strategies. The correlation between the mean GHQ12 score and adaptation strategies is assessed through bivariate analyses and multiple regression.

Results: 232 parents or guardians of children participated in the study. The average GHQ12 score (0-36) was 22 ±6.83. Regarding coping strategies, religion was the most frequently used strategy. The general health questionnaire score showed significant negative correlations with active coping strategies with r = -0.14; p = 0.03, and acceptance with r = -0.51; p < 0.001, and significant positive correlations with denial with r = 0.25; p < 0.001, and self-blame with r = 0.24; p < 0,001. In multivariate analysis, acceptance (β = -1.9, p < 0.001) and denial stra- tegy (β = 0.46, p = 0.02) are predictive factors of psychological distress.

Conclusions: The study highlights the significant impact of coping strategies on the psychological distress experienced by parents of children undergoing cancer treatment in Morocco, by facilitating a more resilient adaptation and improved psychological well-being. These findings could form the basis for the development of culturally adapted mental health support programs for parents in simi-lar contexts.