Medical Oncology最新文献

Triple negative breast cancer (TNBC), a highly aggressive and heterogeneous subtype of breast cancer, lacks an effective targeted therapy. Conventional medication has limited efficacy in treating TNBC, which highlights the potential of developing therapeutic agents from natural bioactive compounds. This study aimed to investigate the cytotoxicity of prodelphinidin (PD), an anthocyanin found in purple sweet potato, in human MDA-MB-231 and MDA-MB-436 cells. The results showed that PD selectively inhibited human breast cancer, particularly TNBC. Furthermore, PD demonstrated significant dose- and time-dependent inhibition of MDA-MB-231 and MDA-MB-436 cell activity. Flow cytometry and western blot analysis revealed that PD induced cell apoptosis by down-regulating Bcl-2, activating caspase-3/9, and cleaving PARP. Additionally, PD treatment upregulated the expression of p-elF2α, GRP78, and CHOP, indicating the involvement of endoplasmic reticulum stress (ERS). PD treatment also increased the production of reactive oxygen species (ROS) and decreased superoxide dismutase (SOD) activity in TNBC cells. The cytotoxicity of PD reduced significantly by pre-treatment with caspase inhibitors (Ac-DEVD-CHO and Z-LEHD-FMK). In conclusion, PD effectively inhibited the proliferation and induced apoptosis in TNBC cells through the activation of ROS and endoplasmic reticulum stress.

Macrophages are key tumor microenvironment (TME) regulators, exhibiting remarkable plasticity that enables them to either suppress or promote cancer progression. Emerging evidence highlights the critical role of macrophage-derived long non-coding RNAs (lncRNAs) in shaping tumor immunity, influencing macrophage polarization, immune evasion, angiogenesis, metastasis, and therapy resistance. This review comprehensively elucidates the functional roles of M1- and M2-associated lncRNAs, detailing their molecular mechanisms and impact on cancer pathogenesis. In summary, elucidating the roles of lncRNAs derived from macrophages in cancer progression offers new avenues for therapeutic strategies, significantly improving patient outcomes in the fight against the disease. Further research into the functional significance of these lncRNAs and the development of targeted therapies is essential to harness their potential fully in clinical applications. We further explore their potential as biomarkers for cancer prognosis and therapeutic targets for modulating macrophage activity to enhance anti-cancer immunity. Targeting macrophage-derived lncRNAs represents a promising avenue for precision oncology, offering novel strategies to reshape the TME and improve cancer treatment outcomes.

Gastric cancer (GC) continues to be a major health issue globally due to its high rates of both occurrence and mortality. Despite advancements in treatment, the outlook for those affected remains poor, highlighting the critical need for new diagnostic and treatment methods. Nanotechnology, especially nanoparticles, is emerging as a crucial innovation in cancer care by improving imaging, targeting drug delivery, and enhancing early detection. These nanoparticles are also enhancing the effectiveness of treatments like phototherapy, chemotherapy, and immunotherapy. Notably, they show potential in addressing infections like Helicobacter pylori (H. pylori), which is known to increase the risk of developing GC. This review underscores the pivotal role of nanotechnology in enhancing the integrated management of GC, offering a basis for future advancements in the field.

The role of cancer cell metabolic reprogramming in the formation and maintenance of cancer stem cells (CSCs) has been well established. This reprogramming involves alterations in the metabolic pathways of cancer cells, leading to the acquisition of stem cell-like properties such as self-renewal and differentiation. This study aimed to investigate the potential effects of bone marrow mesenchymal stem cells (BM-MSCs) on the enrichment of breast CSCs. Exosomes (Exo) and conditioned media (CM) were isolated from BM-MSCs for use in this experimental study. The impact of BM-MSCs-Exo and BM-MSCs-CM on the expression of stemness genes NANOG and OCT-4, as well as CD24 and CD44 markers, was assessed in MCF-7 and MDA-MB-231 cell cultures to identify CSCs. Furthermore, the effects of BM-MSCs-Exo and BM-MSCs-CM on cancer cell metabolism were evaluated by examining changes in glycolysis, the pentose phosphate pathway (PPP), and amino acid profiles. Additionally, the influence of BM-MSCs-Exo and BM-MSCs-CM on tumor growth in vivo was also investigated. The analysis of stemness marker expression in cells treated with BM-MSCs-Exo and BM-MSCs-CM revealed an increase in stemness characteristics compared to the control group. Furthermore, the examination of changes in cell metabolism following these treatments showed alterations in glycolysis, PPP, and amino acid metabolism pathways. Additionally, it was demonstrated that BM-MSCs-Exo and BM-MSCs-CM can promote tumor growth in mice following transplantation of 4T1 cells. These findings suggest that BM-MSCs-Exo and BM-MSCs-CM can enrich the population of CSCs in MCF-7 and MDA-MB-231 cells by targeting metabolic pathways, however, further studies are required to elicit the exact mechanisms of these phenomena.

The aim of the present study is to investigate the proliferative or apoptotic effects of different doses and durations of Royal jelly (RJ) on serous type epithelial ovarian cancer, which is the most common epithelial ovarian cancer. For this purpose, cells of the Skov-3 human ovarian adenocarcinoma cell line were grown in McCoy medium and seeded in 6-well plates. RJ was prepared as a stock solution (1000 mg RJ/10 ml dH₂O) and 1, 5, 10, 20, and 50 mg/ml RJ doses from the prepared stock solution were added to the medium for 24, 48, and 72 h incubated. After the treatment of RJ, the cell viability test (Tripan Blue), Ki-67 to determine the proliferative effect, cleaved-Caspase-3 and cleaved PARP expressions to determine its apoptotic effect were examined by immunocytochemical and immunofluorescence methods. In addition, findings were supported by the TUNEL method. As a result of the experiments, it was determined that 1 mg/ml and 24 h treatment of RJ did not affect cell proliferation and apoptosis, but generally, 50 mg/ml of RJ for 72 h inhibited proliferation in cancer cells and induced apoptosis. The use of royal jelly both monotherapeutically and in combination as an alternative treatment for ovarian cancer may provide the basis for new experimental protocols.

Prunetin (PRU), a naturally occurring flavonoid, has gained recognition for its wide-ranging therapeutic benefits, though its anticancer properties have yet to be extensively reviewed. This study explores the potential of PRU in targeting critical molecular pathways involved in tumor progression, including oxidative stress, apoptosis, cell cycle regulation, and metastasis. Data were compiled from reputable sources, including PubMed, Springer Link, Scopus, Wiley Online, Web of Science, ScienceDirect, and Google Scholar. The findings emphasize PRU's ability to mitigate oxidative stress, promote apoptosis, and regulate the cell cycle in cancer cells. Its anti-inflammatory and anti-angiogenic properties further enhance its effectiveness against cancer. Mechanistic studies reveal that PRU suppresses oncogenic pathways such as PI3K/Akt/mTOR (Phosphoinositide 3-kinase/Protein kinase B/Mammalian target of rapamycin) while activating tumor-suppressor mechanisms. Experimental models show that PRU effectively inhibits cancer cell proliferation and metastasis. Additionally, PRU exhibits favorable pharmacokinetics, demonstrating high intestinal absorption (95.5%), good Caco-2 permeability, and metabolism via CYP1A2, CYP2C19, CYP2C9, and CYP3A4, though it has poor blood-brain barrier (BBB) permeability and limited aqueous solubility, posing challenges for systemic bioavailability. Beyond its anticancer properties, PRU displays broad pharmacological relevance, including anti-inflammatory, cardioprotective, neuroprotective, anti-obesity, and osteoprotective effects, mediated through pathways, such as NF-κB, MAPK, and AMPK. Toxicological studies indicate a favorable safety profile, with low cytotoxicity in normal cells and no significant toxicity at high doses in preclinical models. While clinical evidence on PRU remains limited, studies on structurally related isoflavones suggest promising therapeutic potential, necessitating further clinical trials to establish its efficacy and safety in humans.

The Forkhead box M1 (FOXM1) gene-mediated Wnt signaling pathway plays a significant role in the development and growth of glioblastoma multiforme (GBM), an exceptionally aggressive form of brain cancer. Our research explores the crucial involvement of the FOXM1 gene, a key transcription factor within the Wnt signaling pathway using bioinformatics techniques in both GBM and glioma stem cells (GSCs). Elevated FOXM1 gene expression is strongly associated with poor patient survival in GBM. Furthermore, FOXM1 gene expression is correlated with stemness-related factors, such as SOX2 and SOX9, which act as key drivers in the progression of cancer stem cells. Moreover, we specifically look into the direct associations of the FOXM1 gene with angiogenetic-related factors, metabolic genes, metastatic genes, pluripotency-related factors, immune cell infiltration, transcriptional networks, and functional category enrichment analysis, shedding light on the intricate molecular mechanisms involved in GBM initiation and progression. Additionally, our research identifies FOXM1-targeting miRNAs, revealing their potential as therapeutic candidates with implications for patient survival rates and DNA methylation patterns of the FOXM1 gene, uncovering insights into its epigenetic regulation. This knowledge contributes to a comprehensive understanding of the molecular landscape and potential avenues for developing more effective therapeutic approaches against GBM and GSCs.

Autophagy and the Warburg effect are two common pathways in pancreatic ductal adenocarcinoma (PDAC). To date, the reciprocal effects of these pathways have not yet been elucidated. Therefore, this study was designed to investigate the relationship between these factors in vitro and may provide therapeutic targets in the future. The Mia-Paca-2 and AsPc-1 cell lines were cultured under normal conditions. To achieve autophagy, starvation was induced by Hank's balanced salt solution (HBSS), whereas autophagy was inhibited by 3-methyladenine (3-MA). The Warburg effect is mimicked by lactic acid, and the Warburg effect is inhibited by oxamate, the main inhibitor of lactate dehydrogenase. Cell viability was checked through the MTT assay method. Autophagy was checked via evaluation of Beclin-1 via western blotting. The amount of lactic acid was also measured with a lactate dehydrogenase (LDH) assay kit. The cells were incubated with different concentrations of 3-MA, lactic acid and oxamate. The viability of AsPc-1 cells decreased, and the IC₅₀ values were 1195 µM, 23.06 mM and 8.617 mM for 3-MA, lactic acid and oxamate, respectively. Similarly, the IC₅₀ values of Mia-Paca-2 were 873.9 µM, 35.9 mM and 26.74 mM for 3-MA, lactic acid and oxamate, respectively. Our data revealed that starvation increased the expression of the autophagy-related protein Beclin-1 (P value < 0.05); however, 3-MA significantly reduced its expression (P value < 0.05). In addition, lactic acid alone did not affect the expression level of Beclin-1 (P value > 0.05), but oxamate treatment increased its expression (P value < 0.05). We also showed that starvation reduced lactic acid levels, but an autophagy inhibitor, 3MA, significantly increased lactic acid production (P value < 0.05). Our findings showed that lactic acid alone has no significant effect on autophagy and that oxamate induces autophagy, possibly because of caloric restriction. On the other hand, autophagy inhibits lactic acid production, whereas the inhibition of autophagy leads to increased lactic acid production.

Cervical cancer signifies a global health concern and is a major cause of cancer mortality in women worldwide. Dysregulation of apoptotic pathway and cell cycle play a role in cancer development. Aberrant signalling pathways leads to complex mechanisms leading to the severity. Bleomycin is an anti-tumor glycopeptide molecule which exhibits impressive cytotoxicity in cancer cells. However, its modulating significance on TGF-β induced cell cycle arrest and apoptosis in cervical cancer remains elusive. We confirmed the cytotoxicity, anti proliferative effect of bleomycin in HeLa cells. Meanwhile, bleomycin also led to the suppression of cell migration, invasion. Relative gene expression quantification for cell cycle regulatory, apoptotic, and TGF-β member's genes was done by qRT-PCR. Bleomycin markedly downregulated the expression of cyclin A2, cyclin B1 and cell cycle arrest at G₂/M phase in vitro. Dual AO/EB and Propidium iodide staining was done to evaluate early and late apoptosis in cervical cancer cells. Bleomycin prompts early and late apoptosis in cervical cancer cells by chromatin condensation and blebbing. Mechanistically, bleomycin activates TGF-β induced p21 cascade by upregulation of GADD45A and GDF11, stabilizing p53, to induce cell cycle arrest and apoptosis. Bleomycin induces DNA damage triggering TGF-β pathway. This study can broaden our understanding of the signalling mechanisms that could develop effective strategies for cancer therapy. Elucidation of these pathways in cervical cancer may ultimately lead to novel and more effective treatments. Here, we highlight apoptosis-inducing drug as a therapeutic strategy to regulate the process of carcinogenesis, and regulating apoptosis could benefit cancer treatment and prevention.

Epithelial ovarian cancer (EOC) is the second leading cause of death among women with gynecological cancers, particularly in high-income countries. Despite significant advancements in molecular oncology and an initially positive response to primary chemotherapy, the development of drug resistance remains a major challenge in the effective management of EOC. Consequently, there is an urgent need for innovative biological markers that can enable early diagnosis and provide more accurate predictions of recurrence risk in ovarian cancer patients. This study investigated the expression profiles of seven specific long noncoding RNAs (lncRNAs)-SNHG7, TUG1, XIST1, PRLB, TLR8-AS1, ZFAS1, and PVT1-associated with epithelial ovarian cancer and their relationship with drug resistance. To achieve this, drug-resistant subtypes of aggressive EOC cell lines, including carboplatin/paclitaxel-resistant OVCAR3 and SKOV3 lines, were developed. The expression profiles of the selected lncRNAs were quantitatively analyzed using RT-qPCR across various ovarian cancer cell lines and in serum samples from 25 patients before chemotherapy, six months after treatment, and 23 healthy controls. The findings revealed that the target lncRNAs were significantly upregulated under drug-resistant conditions and in post-chemotherapy serum samples, suggesting their involvement in a complex regulatory network. These results highlight the critical roles of lncRNAs in the progression and treatment response of EOC, positioning them as potential therapeutic targets and biomarkers for early diagnosis and treatment stratification. Identifying reliable lncRNA biomarkers could enable the early detection of patients at risk for developing drug resistance, thereby facilitating personalized treatment strategies to improve patient outcomes and survival rates.