Objective: Lung cancer is a leading cause of cancer-related mortality, primarily due to its high metastatic potential, particularly to the brain and bones. Brain metastases significantly challenge clinical management, impacting treatment efficacy and patient survival, while bone metastases cause severe complications such as pathological fractures and hypercalcemia. Understanding the clinico-pathological factors influencing these metastases is essential for improving patient outcomes. Materials and Methods: This study examined a cohort of 158 patients with primary lung cancer treated at the Cheikh Zaid International University Hospital in Rabat, Morocco. Clinical data, including demographic information, smoking status, and histological and molecular characteristics, were collected. The incidences of bone and brain metastases were analyzed. Statistical analysis was performed using Excel and Jamovi software, with qualitative variables expressed as frequencies and quantitative variables as central tendencies. Associations between variables were evaluated using Chi-square and Fisher's exact tests, with a significance threshold set at p < 0.05. Results: Bone metastases were identified in 31 patients (19.6%) via bone scintigraphy, while brain metastases were confirmed in 29 patients (18.4%) through cerebral MRI. No significant differences were observed between males and females or among different age groups. However, smoking was significantly associated with bone metastases (p = 0.034), with smokers exhibiting a higher incidence. A significant association was found between brain metastases and the adenocarcinoma histological subtype (p = 0.001), indicating that specific tumor characteristics influence metastatic patterns. No significant correlation was observed between molecular status and the occurrence of metastases. Conclusions: This study underscores the importance of clinico-pathological factors in lung cancer metastasis. Smoking is significantly correlated with bone metastases, while adenocarcinoma is closely linked with brain metastases. These findings highlight the need for personalized management strategies and improved data documentation to enhance clinical care.
Objective: This study aimed to evaluate the anticancer activity of cryptotanshinone (CPT) in estrogen and progesterone receptor-positive (ER+/PR+) MCF-7 breast cancer cells and to determine whether delivery via the filamentous M13 bacteriophage enhances CPT's functional effect, with a focus on FOXM1 gene expression. Materials and Methods: MCF-7 cells were treated with CPT across a concentration range to establish dose-response behavior and calculate IC50 values at 24 and 48 h using an MTT viability assay. For phage-mediated delivery, cells were exposed to M13 alone, free CPT, CPT co-administered with M13 without loading, and preformed M13-CPT complexes, followed by MTT-based viability assessment. FOXM1 messenger ribonucleic acid (mRNA) levels were quantified at 24 and 48 h by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and normalized to a housekeeping gene using Delta Ct-based analysis. Results: CPT decreased cell viability in a dose- and time-dependent manner, yielding IC50 values of 19.82 & micro;M at 24 h and 16.14 & micro;M at 48 h. CPT also suppressed FOXM1 expression, with a stronger inhibitory effect at 48 h rather than at 24 h. M13 alone did not produce a meaningful change in viability. Compared with free CPT and the non-loaded CPT+M13 mixture, M13-CPT induced a markedly greater reduction in cell viability. In addition, Annexin V-fluorescein isothiocyanate/propidium iodide (V-FITC/PI) analysis showed that CPT increased apoptosis, with a stronger effect in the M13-CPT group than free CPT. Conclusions: CPT reduces MCF-7 cell viability and downregulates FOXM1 expression, and delivery through M13 bacteriophage further enhances in vitro cytotoxic efficacy without requiring additional targeting ligands.
The osteosarcoma tumor microenvironment has both cellular and non-cellular components. Among the cellular components, both immune and non-immune cells can be derived. The immune cells include infiltrating T lymphocytes, B cells, and dendritic cells, while the non-immune cells include macrophages and cancer-associated fibroblasts. The extracellular matrix, blood vessels, and all cytokines and chemokines are included in the non-cellular portion. Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is up-regulated during the early stages of tumor formation due to an induced hypoxic drive. Tumor suppression, progression, or relapse may result from the interplay of various elements in the tumor microenvironment. Tumor suppression occurs when immune cells cooperate to eliminate cancer cells, whereas tumor formation occurs when an immunosuppressive microenvironment is created. Tumor growth or recurrence might result from some components of the tumor microenvironment releasing chemicals that hinder other immune cells from defending the tumor. T regulatory cells release the inhibitory cytokines interleukin (IL)-10 and IL-35, produce bioactive transforming growth factor beta (TGF-(3), and induce death in effector T cells. Macrophages and dendritic cells produce HIF-1 alpha, which directly reduces tumor cells' vulnerability to doxorubicin (DOX)-induced apoptosis. Doxorubicin, narasin, ifosfamide, cisplatin, methotrexate, gemcitabine, etoposide, carboplatin, and cyclophosphamide have all been used to treat osteosarcoma. Modest doses of doxorubicin are recommended because of the cardiotoxic effects alone, but these leave some cancer cells alive. This review explicitly describes how the changes in the tumor microenvironment contribute specifically to doxorubicin resistance and how doxorubicin-resistant cells affect the components in the tumor microenvironment.
Objective: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of chemotherapeutic agents used in the treatment of cancer patients. Peripheral Neuropathy (PN) may arise due to the disease itself or as a consequence of treatment with chemotherapeutic agents, such as proteasome inhibitors, platinum-based compounds, and vinca alkaloids, which are widely known as CIPN. However, the underlying mechanisms of CIPN remain poorly understood. The objective of this study was to investigate the presence of CIPN in a rat model and identify potential biomarkers associated with the induction of neuronal damage and consequent neuropathy. Materials and Methods: CIPN was induced in experimental rats by administering Bortezomib (BTZ), Cisplatin (CIS), and Vincristine (VIN). The onset and progression of CIPN in these rats were assessed by the Hot and Cold plate experiments. The ELISA method was used to measure the levels of neuronal damage-related biomarkers NSE, S100B, and inflammatory biomarkers IL-6, TNF alpha, and IL-10 using plasma and sciatic nerve, collected from the experimental rats. Results: Our findings revealed significant alterations in body weight, as well as abnormal responses in the hot plate and cold plate tests, which are indicative of CIPN. Our results showed a significant increase in NSE, S100B, IL-6, and TNF alpha levels in the plasma of rats that showed symptoms of CIPN. However, the IL-10 levels were elevated in the sciatic nerve and plasma of the CIPN rats. Conclusion: These findings suggest that NSE, S100B, IL-6, TNF alpha, and IL-10 could serve as biomarkers for detecting CIPN induced by chemotherapeutic agents. Further research is necessary to fully understand the roles of these biomarkers in the development and progression of CIPN.
cell lung cancer (NSCLC) remains the most frequently diagnosed malignancy and the leading cause of cancer-related death worldwide. Although targeted therapies for actionable alterations and immune checkpoint inhibitors (ICIs) have improved outcomes, clinical benefit is highly heterogeneous, with frequent primary non-response and early acquired resistance. This unmet need has intensified the search for robust prognostic factors and predictive biomarkers. The human microbiota has emerged as a relevant candidate within this landscape, given its central role in immune modulation, systemic inflammation, epithelial barrier integrity, and the production of bioactive metabolites. Increasing evidence supports a gut-lung axis in NSCLC, with dysregulated intestinal and airway microbial profiles associated with aggressive phenotypes, metastatic patterns, and survival endpoints. Mechanistically, dysbiosis may influence tumor progression and therapy response through microbe-associated molecular pattern signaling and metabolite-driven effects on antigen presentation, interferon pathways, and regulatory T-cell balance, ultimately reshaping the tumor microenvironment. In immunotherapy, baseline gut microbiome features and iatrogenic perturbations have been linked to reduced ICI efficacy, while microbiota-restoring strategies such as fecal microbiota transplantation can rescue anti-PD-1 activity in translational models. Importantly, emerging data extend the relevance of the microbiome to oncogene-addicted NSCLC: baseline fecal signatures have been associated with the efficacy and gastrointestinal toxicity of Epidermal Growth Factor Receptor-tyrosine kinase inhibitors (EGFR-TKIs), and experimental microbiota perturbation can suppress EGFR-TKIs' antitumor effects, whereas microbiota-supporting interventions may enhance response. Despite promising signals, inter-study variability and confounding exposures limit comparability. This narrative short review is based on a non-systematic search of PubMed/MEDLINE, Embase, and Scopus focused on NSCLC microbiome/gut-lung axis and outcomes with ICIs and EGFR-TKIs. Prospective, well-controlled multi-omics studies integrating microbiome, metabolome, immune profiling, and rigorous clinical annotation are needed to validate actionable signatures and define microbiota-informed strategies to optimize NSCLC treatment.
Thioether analogs of vitamin K3 (VK3) promote the generation of reactive oxygen species (ROS) and enhance the expression of the apoptosis-inducing receptor Fas and its ligand, thereby inducing apoptosis through activation of mitogen-activated protein kinase (MAPK) and caspase-3. They can also induce apoptosis without generating ROS by maintaining phosphorylation via inhibition of mitochondrial or tyrosine and serine/threonine phosphatases involved in intracellular signal transduction. Moreover, VK3 analogs have been shown to upregulate death receptor 5 (DR5) and induce apoptosis in human leukemia-derived cells through the intracellular DR signaling pathway. In this study, we aimed to investigate the effect of the VK3 analog 2-(2-mer-captoethanol)-3-methyl-1,4-naphthoquinone (CPD5) on the expression of factors acting further upstream in this signaling pathway. Materials and Methods: Apoptosis induction in human leukemia-derived cells following CPD5 treatment was examined by assessing intracellular protein expression levels using Western blotting. The analyzed proteins were factors involved in apoptosis signaling upstream of DR5. Results: Treatment with CPD5 (10 & micro;M) activated caspase-3 and caspase-8 and increased the expression of DR5. Further investigation of upstream signaling revealed elevated levels of tumor necrosis factor alpha-related apoptosis-inducing ligand (TRAIL), which acts on death receptors. Expression of the TRAIL-cleaving enzyme was also increased. Conclusions: These findings indicate that CPD5 acts on the TRAIL-cleaving enzyme in leukemia-derived cells, leading to the excessive release of soluble TRAIL (sTRAIL) and subsequent apoptosis via DR5. By elucidating its upstream effects and site of action, CPD5 can be proposed as a potential anti-tumor agent.
Pitfalls in 18F Fluorodeoxy-glucose Positron Emission Tomography Computed Tomography (18F FDG PET-CT) can mislead PET readers to interpret images incorrectly, particularly in oncologic staging and restaging. Although FDG uptake reflects increased glucose metabolism, it is not specific for malignancy. Hibernoma, a rare benign tumor arising from brown adipose tissue, may show intense FDG avidity and closely mimic metastatic disease, representing an important diagnostic pitfall. Case Presentation: A 45-year-old man with stage IIIB non-small cell lung carcinoma (NSCLC) underwent PET-CT for post-treatment re-staging. An incidental, false-positive FDG-avid fatty lesion was found in the right gluteal region. Follow-up 18F FDG PET-CT showed partial remission of the right upper lobe lung mass and mediastinal lymphadenopathy, but metastatic lesions progressed in the left upper lobe and T12 vertebra. The prior right gluteal fatty lesion showed altered glucose metabolism with FDG avidity, suspicious for metastasis. A biopsy of the right gluteal lesion confirmed a hibernoma. The patient was started on the standard doses of the cyclophosphamide, doxorubicin, and etoposide (CAE) regimen (1,000 mg/m2 cyclophosphamide, 60 mg/ m2 doxorubicin, and 50 mg/m2 vincristine) for six cycles, at 4-week intervals. The patient opted for conservative treatment with maintenance dose chemotherapy tablets (erlotinib 150 mg once/day). Conclusions: An appropriate 18F FDG PET-CT characterization of a hibernoma in a patient with NSCLC may avert futile treatment, as it potentially resembles a false-positive malignant lesion.
Objective: N6-methyladenosine (m6A) methylation regulators are critical for cancer progression, but published data on the mechanism of m6A modification in tumor microenvironment (TME) cell infiltration of colorectal cancer (CRC) remains limited. This study aimed to investigate the correlation between m6A modification patterns and CRC TME heterogeneity and explore their prognostic significance and guiding value for immunotherapy. Materials and Methods: RNA expression profiles and clinical data of CRC were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Unsupervised clustering was performed to evaluate m6A modification patterns of23 m6A methylation regulators in 983 CRC samples, and their associations with TME cell infiltration characteristics were systematically analyzed. Gene Ontology (GO) and gene set variation analysis (GSVA) explored underlying mechanisms, while principal component analysis (PCA) constructed an m6A score to quantify modification patterns. Results: m6A methylation regulators showed high genetic and expression heterogeneity in CRC, leading to three distinct modification patterns. These patterns closely matched three immunophenotypes (immune rejection, immune inflammation, and immune desert) and exhibited distinct biological functions. Univariate and multivariate Cox regression indicated m6A score as an independent prognostic factor (HR=1.010, 95% CI: 1.002-1.019; HR=1.009, 95% CI: 1.000-1.017). Low m6A scores correlated with higher tumor mutation load, PD-L1/CTLA-4 expression, and poor survival. In the CTLA-4 immunotherapy cohort, high m6A scores were associated with significantly better immune response and clinical benefit (p=3.4e-06). Conclusions: m6A methylation modification patterns are key drivers of TME heterogeneity and complexity in CRC. Exploring the relationship between m6A modification patterns and TME aids in formulating CRC immunotherapy strategies and provides valuable prognostic guidance.
Objective: This study aimed to explore the potential prognostic value and immunoregulatory roles of C-X-C motif chemokine ligand 10 (CXCL10) in ovarian cancer through bioinformatics analysis to identify potential biomarkers for personalized immunotherapy strategies. Materials and Methods: We integrated Genotype-Tissue Expression (GTEx) normal ovarian tissues (n=88) and The Cancer Genome Atlas (TCGA) ovarian cancer samples (n=427) to screen differentially expressed genes using DESeq2 (version 1.42.0) and limma (version 3.40.2) packages. Protein-protein interaction networks (PPI) were constructed via Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape (version 3.10.1). Survival analysis was performed with Kaplan-Meier method and pathway enrichment was analyzed through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). Immune infiltration was assessed using Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm. Validation was conducted using GEO datasets (GSE10971, GSE14407, GSE18520) and experimental verification through quantitative PCR (qPCR), Western blot, and Cell Counting Kit-8 (CCK-8) assays in ovarian cancer cell lines. Results: CXCL10 expression was significantly upregulated in ovarian cancer tissues compared to normal tissues (p<0.001) and showed correlation with T-cell and macrophage infiltration (p<0.001). Patients with low CXCL10 expression had poor prognosis (HR < 1), while co-expression with immune checkpoint molecules programmed cell death protein 1 (PDCD1), T cell immunoreceptor with Ig and ITIM domains (TIGIT), and forkhead box P3 (FOXP3) was associated with longer survival. Functional enrichment analysis revealed that CXCL10 was significantly enriched in immune-related pathways including lymphocyte-mediated immune response and antigen presentation. Correlation analysis demonstrated strong associations between CXCL10 and immune checkpoint genes including PDCD1 and CTLA-4 (p<0.05). The time-dependent ROC analysis showed limited individual prognostic capability with AUC values of 0.446 for CXCL10, 0.478 for PDCD1, 0.435 for TIGIT, and 0.455 for FOXP3. Experimental validation confirmed that CXCL10 overexpression inhibited A2780 and SKOV3 cell proliferation (p<0.01) and enhanced the efficacy of anti-PD-1 antibodies. Conclusions: Our findings suggest that CXCL10 may serve as a potential prognostic biomarker and immunotherapeutic target for ovarian cancer. The results indicate possible clinical applications in patient stratification and combination immunotherapy strategies, though further mechanistic studies and clinical validation are warranted.
Immune checkpoint inhibitor (ICI) combination therapy has higher efficacy than ICI monotherapy but is associated with a high grade 3 or 4 immune-related adverse event (irAE) incidence. Since ICI treatment is performed in outpatient settings, irAE monitoring is challenging. We elucidated risk factors for early irAE detection and prevention. Patients and Methods: We retrospectively investigated factors related to irAE severity and their impact on survival in patients with non-small cell lung cancer (NSCLC) receiving nivolumab plus ipilimumab at our center from January 2020 to December 2022. Results: Baseline platelet count and platelet-to-lymphocyte ratio (PLR) were higher in the grade 3 or higher group than in the grade 2 or lower group (median, 314 & times; 103/& micro;L and 288 vs. 227 & times; 103/& micro;L and 150; p = 0.035 and 0.010, respectively). irAE grade and number of multisystem irAEs were positively correlated; 83% of patients in the grade 3 or higher group had multisystem irAEs. Using a PLR cutoff of 204 (determined using receiver operating characteristic curves), all patients with grade 3 or higher irAEs were in the PLR >= 204 group, representing 66.7% of patients. Severe irAE presence was associated with prolonged overall survival (OS) (p = 0.081). Progression-free survival and OS were longer in patients with multisystem irAEs than in those without (p = 0.004 and 0.016, respectively). Conclusions: Multisystem irAEs are associated with a better prognosis in patients with NSCLC receiving nivolumab plus ipilimumab. Determining platelet count and PLR immediately before this regimen may help predict the occurrence of severe irAEs.
Objective: Studies on the relationship between vitamin D receptor (VDR) polymorphisms and Prostate Cancer (PCa) have shown conflicting results. Therefore, we conducted a meta-analysis of case-control studies to investigate a possible association between VDR (single-nucleotide polymorphisms) SNPs and PCa risk. Materials and Methods: Our aim was to evaluate separately how the 6 known VDR gene SNPs TaqI (T>C), FokI (C>T), BsmI (G>A), Cdx2 (G>A), ApaI (G>T) and Poly-A (L/S) affect PCa in the general population and in ethnic subgroups of prostate cancer patients. Databases including Medline, Scopus, and Web of Science were searched. Studies meeting the inclusion criteria were reviewed in an updated meta-analysis using Revman 5.4.1 and Stata 16.0 software. The methodological quality of each study was assessed using the Newcastle-Ottawa scale. Fixed or random effect models were used to summarize odds ratios (ORs) with 95% CIs according to heterogeneity. Sensitivity analyses and meta-regression analyses were performed to identify potential sources of heterogeneity. Results: A total of 65 studies fulfilled the inclusion criteria. The overall results indicated a positive association between Poly-A polymorphism and PCa risk, especially in the Caucasian population. However, in subgroup analysis by ethnicity, TaqI polymorphism was associated with increased risk of PCa in the Caucasian and Arab subgroups under the contrasting allelic and dominant genetic models. For ApaI polymorphism, our results show a significant positive association with PCa risk in Caucasian and Asian men under additive and recessive genetic models, respectively. Notably, the recessive, dominant and contrasting allelic models of the FokI polymorphism show a higher risk of developing PCa in Caucasian and mixed men, respectively. Conversely, the Cdx2 and BsmI polymorphisms showed no apparent association with PCa risk either in the overall results or in the subgroup analysis by ethnicity. Conclusions: The results suggest that the VDR gene TaqI (T>C), FokI (C>T), ApaI (G>T), and Poly-A (L/S) SNPs are associated with PCa risk. Further large and well-designed studies are needed to confirm this conclusion.
Objective: The effectiveness of exercise in addressing sleep disturbance and improving survival outcomes among advanced cancer survivors remains inconsistent. To evaluate and synthesize the effectiveness of exercise on sleep disturbance and survival in advanced cancer survivors. Materials and Methods: Databases of the Cochrane Library, PubMed, PsycINFO, CINAHL, EMBASE, and China National Knowledge Infrastructure (CNKI) were searched. A total of 12 randomized controlled trials (RCTs) were included. A total of 12 RCTs with 1313 participants of advanced cancer survivors were included. Outcomes were assessed using the revised Cochrane risk-of-bias tool in RevMan. A random-effects model was used, and the re-sults are presented as summary standardized mean differences (SMDs) with their 95% confidence intervals (CIs). To explore sources of heterogeneity, a meta-regression was conducted using Stata 15.0. Results: Meta-analysis revealed a significant inverse association between exercise levels and subjective sleep quality (SMD =-0.42, 95% CI:-0.70 to-0.13). Meta-regression identified a significant moderating effect of gender proportion on exercise's impact on sleep disturbance (95% CI: 0.36 to 1.32, p = 0.002). Subgroup analysis indicated that exercise significantly reduced sleep disturbance, specifically in cohorts with <= 50% female participation (SMD =-0.63, 95% CI:-0.92 to-0.34). Conversely, pooled data showed no significant effect of exercise interventions on overall survival in advanced cancer survivors. Conclusions: Long-term exercise should help improve sleep, especially for male patients with advanced can-cer. The impact of exercise intervention on survival should be assessed not only at advanced stages of cancer, but also from early exercise habits. More evidence is needed from randomized trials of exercise interventions on survival in advanced cancer survivors.
cancer, particularly non-small cell lung cancer (NSCLC), remains a major therapeutic challenge, with cisplatin resistance limiting clinical efficacy. The study under discussion identifies miR-150-3p as a tumor suppressor and cisplatin sensitizer that acts through direct downregulation of AKT2, thereby enhancing chemotherapy responsiveness. Using TCGA data and functional assays in A549 and H358 cells, the authors demonstrate antiproliferative and antimigratory effects of miR-150-3p, together with potentiation of cisplatin cytotoxicity. These findings highlight the PI3K/AKT pathway as a central mediator of drug resistance and underscore the potential of miRNA-based therapeutic strategies. Nonetheless, important limitations restrict translational applicability: reliance on only two cell lines fails to capture NSCLC heterogeneity, while tumor-microenvironment and systemic factors remain unexplored. Emerging evidence indicates that host-microbiota interactions, microbial metabolites, and iatrogenic factors such as antibiotics or proton pump inhibitors may critically modulate PI3K/AKT signaling and thereby influence cisplatin response. Moreover, challenges related to miRNA delivery and functional redundancy among AKT isoforms raise further concerns for clinical translation. Taken together, while the study provides strong evidence that miR-150-3p can sensitize NSCLC cells to cisplatin via AKT2 targeting, future research integrating in vivo models, microbiome profiling, and mechanistic dissection of AKT isoforms is required to fully assess its therapeutic potential.
Objective: Kidney cancer represents 5% of all adult malignancies in men and 3% in women. The most common type is clear cell renal cancer, representing about 70-80% of the total. The medical approach to renal cancer has changed in the last few years, especially with the use of immunotherapy and tyrosine kinase inhibitors. Case presentation: We present a case of a 48-year-old man, affected by clear cell renal cell carcinoma, detected in 2014. After nephrectomy surgery, clinical-instrumental follow-up was initiated. After only one year, a recurrence of bone disease was documented. Therefore, different types of treatments were undertaken, including systemic therapy with anti-VEGF and immunotherapy. The last treatment was Lenvatinib. Besides these, loco-regional treatments were used, which provided good disease control over time. Results: We analyzed the case of a patient who survived for 10 years after being diagnosed with clear cell renal cell carcinoma. During these years, the patient underwent 5 lines of treatment and several loco-regional treatments. The use of drugs such as Sunitinib and Cabozantinib allowed good control of the disease while also maintaining a good quality of life. We finally offered our patient treatment with Lenvatinib, based on a study comparing the latter with Everolimus and the combination of the two. Lenvatinib treatment, which started in July 2023 and ended in February 2024, helped to further increase survival and maintain a good quality of life. Conclusions: The case we presented is an example of how, with a good succession of systemic and loco-regional treatments and multidisciplinary and tailored approaches, long survival can be achieved while also maintaining a good quality of life.
Objective: The aldo-keto reductase (AKR) superfamily catalyzes the NAD(P)H-dependent reduction of aldehydes to less reactive alcohols, playing a critical role in detoxification and cellular redox homeostasis. AKR family members have been increasingly implicated in tumor progression across various cancers. However, the functional role and mechanism of AKR7A2 in hepatocellular carcinoma (HCC) progression remain poorly understood. Here, we identified an essential role of AKR7A2 in HCC progression. Materials and Methods: The expression of AKR7A2 was analyzed in HCC tissues and human cell line models via immunohistochemistry (IHC) and Western blotting. The influence of AKR7A2 on HCC proliferation, migration, and invasion was assessed through CCK-8, colony formation, and Transwell assays. Potential molecular mechanisms were explored through bioinformatics analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Results: We found that AKR7A2 expression was upregulated and significantly associated with poor prognosis. Elevated AKR7A2 expression was also linked to resistance to radiotherapy and sorafenib treatment. Knockdown of AKR7A2 suppresses HCC cell proliferation, migration, and invasion. Bioinformatics analysis further demonstrated that expression of AKR7A2 was positively correlated with oxidative phosphorylation (OXPHOS), mitochondrial biogenesis, PPARG expression, and tumor-associated macrophage polarization. Conclusions: Taken together, our results indicate that AKR7A2 promotes HCC cell proliferation, migration, and invasion through PPARG-mediated OXPHOS and tumor-associated macrophage polarization. Therefore, AKR7A2 represents a promising therapeutic target for the treatment of HCC.
Objective: The aim of this study is to evaluate the clinicopathological features and prognostic impact of breast cancer harboring germline BRCA1/2 mutation. Materials and Methods: This cross-sectional study was conducted on early and de novo metastatic BRCA mutant female breast cancer patients diagnosed at King Salman Medical City, Medina region, Kingdom Saudi Arabia (KSA), since 2022. A germline BRCA1/2 mutation was confirmed from blood samples by a next-generation sequencing test. Results: Median age of diagnosis was 35 years old (35-60), and family history of breast cancer was present in 33.3%. Sixty-six percent of patients were in an early stage; however, 34% of patients had de novo metastatic diseases; 22.2% of them had central nervous system (CNS) involvement. On follow-up of early breast cancer patients, 30% developed contralateral breast cancers, 21% developed ipsilateral disease, while 57% developed distant metastasis. Triple-Negative Breast Cancer (TNBC) was found in 45% of these BRCA1/2 mutant breast cancer patients, which was more prevalent in BRCA1 carriers accounting for 75% of cases. No differences were found in the toxicity due to breast radiation between BRCA1 and BRCA2 patients regarding skin dermatitis, pigmentation, breast or chest wall oedema, and telangiectasia. Most of the de novo metastatic patients were BRCA2 mutant vs. BRCA1 (66.5% vs. 33.5%). Median progression-free survival (PFS) of all BRCA BRCA-mutated patients was 13 months. However, BRCA1 patients showed longer PFS (median; 20 vs. 12 months, p p=0.4). Median overall survival (OS) of all BRCA mutants was 23 months, with better OS in BRCA1 mutant patients (median OS: 25 vs. 19 months, p p=0.3). Conclusions: To our knowledge, this is the first cross sectional study investigating the clinical and prognostic value of germline BRCA1/2 mutation in breast cancer in our locality. Germline BRCA1/2 carriers presented with more aggressive disease and poor outcomes. Germline BRCA2 mutant patients were more often diagnosed at an advanced stage and showed poorer PFS and OS compared to their BRCA1 mutation carriers counterparts.
Objective: It is well-established that the fluid attenuated inversion recovery (FLAIR) sequence is superior for visualizing leptomeningeal lesions. However, in clinical practice, contrast-enhanced T1-weighted imaging (T1WI) is routinely used to image leptomeningeal metastasis (LM) because of its greater sensitivity , specificity. Potential misestimation may arise from interference by adjacent fat tissues. In this study, we aimed to compare the diagnostic efficacy of contrast-enhanced T1WI-Fat saturation (T1WI-FS) vs. contrast-enhanced T2WI-FLAIR-FS for detecting LM. Patients and Methods: Patients diagnosed with LM by either clinical evaluation or cerebrospinal fluid (CSF) cy- tology were included. Contrast-enhanced T1WI-FS and T2WI-FLAIR-FS were performed sequentially in all cases. Results: Contrast-enhanced T2WI-FLAIR-FS demonstrated superior LM visibility (p p < 0.0001) and depicted le- sions more clearly ( p < 0.0001) than contrast-enhanced T1WI-FS. Conclusions: Contrast-enhanced T2WI-FLAIR-FS demonstrated superiority over contrast-enhanced T1WI-FS for LM imaging.
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. Despite significant advancements in immunotherapy and targeted therapy, chemotherapy remains the cornerstone of treatment for advanced NSCLC patients. Cisplatin, a widely used chemotherapeutic agent, exerts its effects by inducing apoptosis through DNA interaction. However, most patients eventually develop resistance to cisplatin. MicroRNA (miRNA)-based therapies have shown great potential in overcoming cisplatin resistance. While miR-150-3p has demonstrated tumor-suppressive effects in various cancers, its impact on cisplatin sensitivity in NSCLC remains unclear. Materials and Methods: Microarray analysis was performed to detect miRNA expression changes in NSCLC cells following cisplatin treatment. The prognostic value of miR-150-3p and its differential expression between normal and tumor tissues were analyzed using The Cancer Genome Atlas (TCGA) database. The effects of miR-150-3p overexpression in A549 and H358 cells were validated using CCK8 assay, colony formation assay, wound healing scratch assay, and transwell migration assay. Luciferase reporter assay was conducted to identify the target genes of miR-150-3p. Results: MiR-150-3p was significantly upregulated in NSCLC cells after cisplatin treatment, and its high expression was associated with improved prognosis in NSCLC patients. Overexpression of miR-150-3p suppressed cell proliferation, colony formation, wound healing capacity, and migration in A549 and H358 cells. Exogenous miR-150-3p enhanced the anti-proliferative and anti-migratory effects of cisplatin. MiR-150-3p overexpression downregulated AKT2 expression. Luciferase reporter assays confirmed that miR-150-3p directly binds to the 3' untranslated region (3'UTR) of AKT2. Conclusions: This study reveals that miR-150-3p enhances cisplatin efficacy in NSCLC cells by targeting AKT2.
The Gasdermin (GSDM) protein family plays a pivotal role in inducing pyroptosis, a form of programmed cell death. Pyroptosis is closely associated with the initiation, progression, and prognosis of various cancer types. However, the relationship between GSDMS expression and breast cancer, as well as the underlying molecular mechanisms, remains insufficiently characterized. Materials and Methods: In this study, we conducted a comprehensive analysis of GSDMS expression in breast cancer using multiple databases, including UALCAN, BC-GenExMiner, OncoPrint, TIMER, Kaplan-Meier, TIMER 2.0, cBioPortal, DiseaseMeth 3.0, and OncoLnc. Furthermore, the analysis was confirmed online using the R package. Results: Except for GSDMA, all other GSDMS family members exhibited differential expression between breast tumor tissues and adjacent normal tissues. The expression patterns of these genes were significantly correlated with distinct clinical features of breast cancer. Genetic alterations, including missense mutations, deletions, amplifications, and deep deletions, were the primary contributors to changes in the GSDMA-E and PJVK genes, with mutation frequencies ranging from 0.90% to 19.00%. Elevated expression levels of GSDMD and PJVK were associated with improved patient prognosis. Additionally, members of the GSDM family showed strong correlations with immune cell infiltration, particularly lymphocytes, within breast cancer tissues. DNA methylation analysis revealed hypomethylation of GSDMC, GSDMD, and PJVK in breast cancer tissues, whereas hypermethylation was observed for GSDMA and GSDME. Conclusions: Our findings indicate that GSDMD and PJVK are potential therapeutic targets and prognostic biomarkers in breast cancer. This study enhances our understanding of the roles of GSDMS family members in breast cancer and provides critical insights for clinicians in the development of targeted therapies and treatment strategies.
Anthriscus sylvestris (AS), a traditional medicinal herb, has emerged as a potential anti-cancer functional food. This study aimed to explore its anti-tumor mechanisms, focusing on colon cancer, using network pharmacology and experimental validation. Materials and Methods: Active components of Anthriscus sylvestris were screened via the TCMSP database (OB >= 30%). Network pharmacology identified 91 shared targets between Anthriscus sylvestris and anti-tumor activity. Protein-protein interaction (PPI) networks, GO/KEGG analyses, and molecular docking were performed. In vitro experiments assessed the effects of Anthriscus sylvestris petroleum ether extract on STAT3 activity in HT29 colon cancer cells. Results: Three key active components (dihydroanhydropodorhizol, dimethylmatairesinol, and (+)-hinokinin) were identified. Molecular docking revealed strong binding affinities (e.g., -7.84 kcal/mol for (+)-hinokinin-ESR1). KEGG enrichment highlighted pathways like FoxO and STAT3 signaling. In HT29 cells, AS extract concentration-and time-dependently suppressed STAT3/p-STAT3 protein expression (e.g., 80 mu g/ml reduced STAT3 to 21.37% of control) and inhibited STAT3 DNA-binding activity (80 mu g/ml: 21.37% inhibition). Conclusions: Anthriscus sylvestris exerts anti-colon cancer effects by targeting STAT3 signaling, supported by network pharmacology and experimental validation. Its petroleum ether extract demonstrates significant therapeutic potential, providing a scientific foundation for developing AS-based anti-cancer foods or drugs.
