Medical Oncology最新文献

Lung adenocarcinoma (LUAD), the predominant non-small cell lung cancer (NSCLC) subtype, faces major clinical challenges including poor prognosis and acquired drug resistance. This study integrates multi-omics analyses with in vitro functional validation experiments to systematically elucidate the molecular regulatory mechanisms of hyaluronan receptor (RHAMM/CD168) in LUAD development and its potential clinical translational value. Bioinformatics analysis based on public databases such as TCGA and GEO revealed that CD168 mRNA expression was significantly higher in LUAD tumor tissues compared to adjacent normal tissues. Kaplan-Meier survival analysis and multivariable Cox regression models confirmed that high CD168 expression was independently associated with significantly shorter overall survival (OS) and progression-free survival (PFS) after adjusting for confounding factors such as age, gender, and clinical stage. Moreover, high CD168 expression correlated with altered immune cell infiltration patterns and changes in immune checkpoint molecule expression, suggesting that CD168 may play a crucial role in modulating the immune-suppressive tumor microenvironment and affecting responses to immunotherapy. Functional experiments demonstrated that silencing CD168 significantly inhibited cell proliferation, migration, and invasion in LUAD cell lines (A549 and H1299), and promoted apoptosis, confirming its oncogenic function. Bioinformatics analysis constructed the "lncRNA (CYTOR)-miRNA (hsa-let-7c-5p)-CD168" regulatory axis, wherein CYTOR may function as a ceRNA to sequester hsa-let-7c-5p, thereby alleviating miRNA-mediated suppression of CD168. Furthermore, Western blot analysis revealed that silencing CD168 decreased the phosphorylation levels of ERK and MEK, suggesting that CD168 promotes LUAD progression in association with MAPK/ERK signaling pathway activity. In summary, CD168 may promote LUAD progression by reshaping the immunosuppressive microenvironment and enhancing malignant behavior, establishing it as a prognostic biomarker and a potential therapeutic target, particularly for immunotherapy combinations.

Cisplatin resistance severely limits the efficacy of chemotherapy for cervical cancer (CC), and its molecular mechanisms remain incompletely understood. While epigenetic alterations such as DNA methylation are recognized as important contributors, the upstream regulatory networks, particularly the role of long non-coding RNAs (lncRNAs), are still unclear. This study aimed to explore novel mechanisms influencing cisplatin resistance in cervical cancer. Cisplatin-resistant CC cells (HeLa and SiHa) were established. A comprehensive approach employing mRNA and lncRNA microarrays, RT-qPCR, methylation-specific PCR (MSP-PCR), chromatin immunoprecipitation, luciferase reporter assays, RNA pull-down, RNA immunoprecipitation, cellular functional assays, and a mouse subcutaneous xenograft tumor model was utilized. The study found that Kallikrein 10 (KLK10) expression was significantly downregulated in cisplatin-resistant CC cells due to promoter hypermethylation mediated by DNA methyltransferase 1 (DNMT1). LncRNA microarray analysis revealed that TMPO-AS1 was the most significantly upregulated lncRNA in resistant cells. Functional assays confirmed that TMPO-AS1 promoted cisplatin resistance, proliferation, migration, and invasion of CC cells. Mechanistically, TMPO-AS1 acted as a competitive endogenous RNA (ceRNA) by sponging miR-140-5p, thereby relieving its inhibitory effect on DNMT1 mRNA, upregulating DNMT1 expression, enhancing KLK10 promoter methylation, and leading to its silencing. In vivo experiments further demonstrated that silencing TMPO-AS1 inhibited tumor growth. This study unveils a novel TMPO-AS1/miR-140-5p/DNMT1/KLK10 regulatory axis that plays a critical role in cisplatin resistance in CC, providing a potential therapeutic target for overcoming chemoresistance.

Cancer continues to be one of the top killers worldwide. Traditional treatment strategies like chemotherapy, radiation, and surgery have non-specific treatment options with considerable side effects. Gene-based therapies using nucleic acids like siRNA, miRNA, and DNAzymes provide an alternative approach; however, issues with stability, delivery, and off-target effects continue to plague their clinical use. Niosomes, or non-ionic surfactant vesicles, provide a flexible and inexpensive alternative to circumvent many of these issues. This review will present the niosomal systems for nucleic acid delivery in cancer therapy. Niosomes have key advantages compared to traditional delivery vehicles due to their chemical stability and biocompatibility, and ease of surface modifications. Their ability to carry a range of nucleic acids and allow for endosomal escape makes niosomes ideal candidates for targeted, multimodal therapies. Critical therapeutic applications include co-delivery of nucleic acids with chemotherapeutic drugs to improve synergistic activity, reprogramming the tumor microenvironment to increase immune response, and bypassing mechanisms of tumor resistance. In addition, the incorporation of external triggers, such as magnetic and ultrasound responsive elements, provides precise spatiotemporal control over nucleic acid release. The review outlines exciting research improvements of niosomal formulations based on surface charge, ligand targeting, and new genetic payloads, underscoring the state-of-the-art potential of niosomes for personalized cancer treatments. niosomes showed low immunogenicity and good pharmacokinetics in preclinical research, suggesting they are highly translational and leading-edge for next-generation cancer treatments.

Colorectal cancer (CRC) remains a significant global health concern and is among the leading causes of cancer-related mortality. The disease often progresses to more advanced and treatment-resistant stages. By 2040, the incidence of CRC is projected to increase substantially worldwide, particularly in low- and middle-income countries. Despite the availability of various treatment modalities, CRC incidence remains elevated. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, represent a novel approach for CRC therapy and diagnosis. EVs possess distinct biological characteristics and exhibit both immunosuppressive and immunostimulatory properties within the tumour microenvironment. Tumour-derived EVs facilitate CRC progression and metastasis by transferring oncogenic proteins and microRNAs that promote epithelial-mesenchymal transition and alter recipient cell behaviour. Conversely, immune-derived EVs produced by dendritic cells, natural killer cells, T lymphocytes, B lymphocytes, and macrophages enhance anti-tumour immune responses and contribute to the elimination of cancer cells. Due to their stable encapsulation of nucleic acids, proteins, and lipids, EVs serve as highly sensitive and specific biomarkers for CRC diagnosis, prognosis, and therapeutic monitoring. Additionally, EVs have demonstrated both abscopal and bystander effects, highlighting their capacity to induce systemic antitumor responses. Recent advances in EV engineering, together with emerging technologies such as artificial intelligence, CRISPR/Cas9 genome editing, and chimeric antigen receptor (CAR)-T cell therapy, present new opportunities to optimise EV-based interventions and broaden their translational applications. Nevertheless, substantial challenges persist, including EV heterogeneity, technical barriers in isolation and characterisation, and limited understanding of their functional diversity. Addressing these limitations, particularly in the development of EV-based vaccines, enhancement of immunostimulatory properties, and further integration of artificial intelligence, will be essential for realising the full clinical potential of EVs in colorectal cancer management.

Skin cancer continues to be among the top malignancies diagnosed around the world, with rising incidence through the years. The cause of most deaths is the metastatic progression, which commonly limits the success of the treatments available. The commonly used methods of surgery, radiotherapy, and immunotherapy, photodynamic and conventional chemotherapy have improved the patient survival rates tremendously. However, the systemic toxicities and therapeutic resistance limit therapeutic efficacy of these treatments. Hence, developing targeted solutions is essential that tackle these concerns directly. Targeted exosomes as extracellular vesicles (EVs) are unique biological nanocarriers for the direct cell delivery of chemo, nucleic acids, and immune modifiers to tumor cells. The purpose of this review is to survey the literature and examine current exosome research in cancer has to offer, especially in relation to improving focused drug delivery, immune modification, tumor microenvironment (TME) alteration, and skin cancer immunotherapy. We describe evidence from preclinical and developing clinical studies showing the exosome-mediated delivery systems improve the bioavailability of a drug. This occurs through its specificity for tumors, mitigate the systemic toxicity of the drug, and neutralize the mechanisms of immune- and chemotherapy resistance. These new approaches to therapy represent a significant advancement in dermatologic oncology and are likely to improve prognosis and patients' quality of life.

Ashwagandha (W. somnifera), known for its broad health benefits, has shown potential in cancer prevention and treatment. The aim of this study was to investigate the potential effect of ashwagandha aqueous extract (ASH-AE) on cell proliferation and therapy resistance markers in hepatocellular carcinoma (HCC). An in vitro study was conducted using the HepG2 cell line. The HepG2 cells were divided into 4 groups according to the treatment regimen received. ASH-AE was extracted from the whole plant and characterized by GC-MS and HPLC. HepG2 cell viability was determined for all groups. The protein expression of cluster of differentiation 90 (CD90) was determined by flow cytometry technique. Also, the gene expression of Sonic Hedgehog (SHH), Patched 1(PTCH1) and ATP-binding cassette subfamily C1 (ABCC1) was assayed by qRT-PCR. The protein expression and localization of glioma-associated oncogene 1 (Gli1) in HepG2 cells were determined by immunocytochemistry (ICC) assay. The results indicated that ASH-AE either alone or in combination with sorafenib (SOR) significantly reduced HepG2 cell viability in a concentration dependent manner (P ˂0.001) with IC50 was 6.65 mg/ml for ASH-AE, 11.3 µM for SOR, and 5.6 mg/ml + 18.6 µM for ASH-AE in combination with SOR. Moreover, SOR significantly increased the percentage of CD90⁺ cells and Gli1 protein expression and nuclear translocation as well as ABCC1 gene expression compared to untreated cells. On the other hand, ASH-AE either alone or in combination with SOR significantly decreased the percentage of CD90⁺ cells and Gli1 expression and nuclear translocation as well as SHH, PTCH1 and ABCC1 gene expression compared to untreated cells and that treated with SOR. We concluded for the first time that the combination of SOR and ASH-AE generates antagonistic antitumor effect in HepG2 cells. Moreover, ASH-AE can inhibit proliferation of HepG2 cells and mitigate sorafenib-induced resistance-associated markers in HepG2 cells by targeting CD90⁺ cells via Hedgehog pathway modulation.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor, classified by the WHO as grade IV astrocytoma, with poor prognosis and limited treatment options. Extracellular vesicles (EVs) are lipid bilayer nanoparticles present in all biological fluids. They mediate intercellular communication by transferring proteins, lipids, mRNA, and miRNA. While their diagnostic potential in GBM has been explored, their role in diffuse glioblastoma invasion remains underinvestigated. In this study, human astrocytes (NHA) were treated with EVs isolated from GBM cell lines (U87-MG and A172), and phenotypic changes were assessed using proliferation assays (MTS, EdU), cell cycle analysis, RT-qPCR, TGM2 ELISA and western blot. The results demonstrated that GBM-derived EVs significantly contribute to astrocyte phenotypic alterations associated with invasion and metastasis. These findings highlight the importance of EV-mediated intercellular communication in GBM progression and suggest further in vivo studies to elucidate their role in central nervous system invasion.

Acute lymphoblastic leukemia (ALL), classified as a lymphoid neoplasm under the WHO 5th Edition Haematolymphoid Tumours system, is characterized by uncontrolled proliferation of immature B-cell precursors. Nanotechnology-based therapies are promising for hematologic malignancies because they modulate cellular pathways and improve drug delivery without directly targeting apoptotic proteins. This study investigates the effects of silver nanoparticles (Ag-NPs), known for their anti-cancer and oxidative stress-mediated cytotoxic properties, and ciprofloxacin, a fluoroquinolone with reported anti-leukemic activity, on apoptosis-related gene expression in NALM-6 B-cell progenitor ALL cells. Cells were treated with ciprofloxacin (25 µg/mL) or Ag-NPs (4 µg/mL), alone or combined, for 48 h, followed by MTT assay for viability, Annexin V-FITC/PI flow cytometry for apoptosis, and real-time PCR analysis of BAX, B-cell lymphoma 2 (Bcl-2), and Caspase-3 expression (normalized to glyceraldehyde-3-phosphate dehydrogenase [GAPDH]). Ciprofloxacin significantly increased pro-apoptotic BAX and Caspase-3 expression (p = 0.0001, p = 0.0113) while reducing anti-apoptotic Bcl-2 (p = 0.0013); Ag-NPs produced moderate apoptotic effects, whereas combination treatment enhanced apoptosis (31.0%, p = 0.0092) and further amplified gene modulation (e.g., BAX log2FC = 4.4531, p = 0.0036). These findings suggest that Ag-NPs may enhance upstream signaling and drug response rather than directly acting on apoptotic proteins, supporting their potential as nanotechnological co-therapeutics in B-cell ALL. Further mechanistic and in vivo studies are warranted.

Non-small cell lung cancer (NSCLC) is a metabolism associated disease which mainly depends on anaerobic glycolysis to produce the macromolecules needed for biosynthesis and rapid cell proliferation. Since the cancer cells depend on glycolysis for energy production, the development of drug targets that inhibit the glyco-metabolism will be a promising approach for the management of NSCLC. Plant derived phytocompounds have demonstrated anti-NSCLC activity by modulating the glycolytic pathway, thus curbing the energy requirement essential for the proliferation of cancer cells. In the current study, we explored the efficacy of farnesol in A549 lung adenocarcinoma cells using in vitro assays. Farnesol inhibited the viability of A549 cells to 50% at 21.5 µg/mL. Relative proteomic profiling via nano LC-MS/MS analysis identified 277 differentially expressed proteins in control and farnesol treated samples. Notably, PKM (FC = -3.911819), TKT (FC = -2.857373), ALDOA (FC = -4.8557) and LDH (FC = -2.624372) were downregulated exhibiting a strong interacting network in STRING analysis indicating suppression of anaerobic glycolysis. Furthermore, a decrease in the expression of GluIIβ, FBKP1A and apoptotic regulators such as LAP2 and ATP5F subunits suggest initiation of autophagy and apoptosis. AO/EtBr staining confirmed a late apoptotic shift while, DAPI staining revealed nuclear fragmentation at this concentration. Additionally, farnesol impaired mitochondrial ATP synthesis by reducing mitochondrial membrane potential (MMP) to 66% and elevated ROS levels to 54% creating a disturbance in mitochondrial stability. Overall, Farnesol significantly disrupts anaerobic glycolysis in A549 cells promoting cell death through mitochondrial dysfunction, oxidative stress, apoptosis and reducing cellular acidosis.

Venetoclax (VEN) is a B-cell lymphoma 2 (BCL-2) inhibitor approved for treatment in acute myeloid leukemia (AML). Human heavy chain ferritin (HFn) is a bio-inspired nanoparticle (NP) utilized to deliver multiple chemotherapies to tumor cells through CD71-mediated endocytosis. In this study, the efficacy of VEN/HFn NP was investigated for targeted delivery in AML. Recombinant HFn was expressed, purified, and characterized using SDS-PAGE, western blotting, and dynamic light scattering (DLS). VEN was encapsulated in HFn, and the resulting VEN/HFn NPs, along with the corresponding controls, were utilized to treat the AML cell lines THP-1 and K562. Cell proliferation, apoptosis, and CD71 and HLA-I expression levels were assessed using MTT and flow cytometry assays. The mRNA expression of IFN-β and BCL-2 was measured using Real-time PCR. Drug-nanoparticle interactions were analyzed using molecular docking. HFn NPs were successfully constructed with a 95% VEN encapsulation efficiency, supported by molecular docking simulations that indicated a strong binding affinity (-9.2 kcal/mol) and a thermodynamically stable complex. Functionally, both VEN/HFn and free VEN treatments significantly induced apoptosis and upregulated HLA-I and IFN-β expression in both cell lines. Also, BCL-2 expression was significantly reduced. Importantly, no significant differences in these effects were observed between the VEN/HFn and free VEN, confirming that encapsulation preserves the drug's activity. Our results indicate a promising and efficient strategy for the encapsulation and targeted delivery of venetoclax using HFn nanoparticles for AML patients. This delivery system can support co-delivery of various drugs and combination therapy of tumor cells.