Medical Oncology最新文献

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by a lack of hormones receptors and the HER2 receptor, making it unresponsive to targeted therapy. Triterpenoids such as betulinic acid (BA) and oleanolic acid (OA) have anticancer effects by inducing apoptosis in TNBC cells. CD81 is a tetraspanin that affects the growth and metastasis of cancer cells. To examine the effect of BA and OA on the viability of TNBC cell line (MDA-MB 231) by analyzing the CD81 expression, intracellular ROS, and apoptosis. The MDA-MB 231 cells was cultured and treated by BA and OA. The viability cell was evaluated by the CCK8 assay. This study analyzed the binding of BA and OA with CD81 using molecular docking and evaluated CD81 expression, intracellular ROS, and apoptosis by flow cytometry. The result showed that BA and OA inhibited viability of MDA-MB-231 cells. BA and OA bind to CD81 in silico, with binding affinities of 9.0 kcal/mol for BA and 7.2 kcal/mol for OA. Flow cytometry results revealed that BA can downregulate CD81 expression. BA and OA also increased intracellular ROS levels and induced apoptosis. These findings suggest that BA and OA, especially BA, can modulate CD81 expression and promote apoptosis in TNBC cells through the generation of ROS, thereby offering a potential therapeutic strategy for the treatment of TNBC.

Melanoma has a low incidence, accounting for less than 5% of skin cancers; however, it is the most lethal cancer, primarily because of its high potential for metastasis and resistance to different treatments. Natural products can sensitize melanoma to chemotherapy and overcome drug resistance. Previous studies have reported Cedrus atlantica extract has various pharmacological benefits such as anti-inflammatory, antioxidant, antibacterial, and analgesic properties. This study aimed to explore the effects of C. atlantica extract (CAt) against melanoma in vitro and in vivo. The effects of CAt on B16F10 cell viability, proliferation, migration, invasion, and apoptosis were detected using MTT, colony formation, wound-healing, Boyden chamber, and TUNEL assays. Semi-quantitative RT-PCR and western blotting were used to measure mRNA and protein expression, respectively. Results revealed that CAt selectively decreased the viability of B16F10 cells and inhibited colony formation in a dose-dependent manner. CAt reduces cell migration and invasion by regulating epithelial-mesenchymal transition-associated proteins (Snail, E-cadherin, and vimentin). Moreover, CAt enhanced the Bax/Bcl-2 ratio and the expression of cleaved-caspase-9, caspase-3, and PARP1, resulting in the activation of mitochondria-mediated apoptosis. In an in vivo study, CAt significantly inhibited tumor growth and prolonged the lifespan of mice at a well-tolerated dose. Importantly, the combination of CAt and 5-fluorouracil (5-FU) exhibited synergistic growth suppression and attenuated the development of 5-FU resistance. Overall, the findings suggest that CAt holds promise as a potential drug or adjuvant to improve melanoma treatment.

Doxorubicin (DOX) chemotherapy for breast cancer is an effective treatment option, but it also has disadvantages. Exosomes (EXOs) have safely and successfully transported DOX and reduced its adverse effects; however, its use is still being explored. In this study, a co-culture system of malignant and non-malignant breast cells was used to generate an in vitro model reflecting the in vivo cellular microenvironment, and the effects of this treatment were investigated by examining inflammatory genes. Extracellular matrices (EXOs) were extracted from mesenchymal stem cells derived from human adipose tissue by ultracentrifugation. Later, Western blotting, dynamic light scattering (DLS) and transmission electron microscopy methods were used to examine the properties of the EXO. DOX was encapsulated in the EXOs by sonication and the loading rate was measured by spectrophotometry. In the current study, a co-culture system was used to investigate the cytotoxic effects of free DOX and DOX encapsulated in EXOs (EXO-DOX) on various breast cell lines, including MCF-7, MCF-10A, MDA-MB-231, and A-MSC. Additionally, the expression levels of inflammatory cytokines (IL-1β, IL-6, IL-10, and TNF-α) were examined. Methylthiazolyldiphenyl-tetrazolium bromide assay demonstrated that free DOX showed the highest cytotoxicity against MCF-10A cells, followed by MCF-7 cells. Conversely, EXO-DOX indicated a greater effect on MCF-7 cells and had a lower IC₅₀ compared to MDA-MB-231 cells. Free DOX significantly downregulated the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), particularly in MCF-7 and MCF-10A cells, while concurrently upregulating IL-10 expression. EXO-DOX induced a more significant alteration in cytokine expression than the control and free DOX treatment groups. The co-culture system revealed a synergistic effect of free DOX on cancer cells while simultaneously mitigating the toxic effects of DOX on normal cells. This study suggests that EXO-DOX has promising potential as a targeted drug delivery system that could potentially improve therapeutic efficacy and minimize off-target toxicity.

The integration of pharmaceutical and medical device companies with clinical practice is under scrutiny due to financial incentives that may influence oncology care. The Physician Payments Sunshine Act mandates transparency in these financial relationships. This study examines the trends in non-research payments to oncology specialists between 2017 and 2023, analyzing amounts, reasons, and variations by subspecialty and region. We conducted a retrospective analysis of the Centers for Medicare and Medicaid Services Open Payments database, focusing on U.S.-based hematology, medical oncology, and hematology-oncology specialists. Payments were categorized by amount, purpose, and payment type, with temporal and geographic comparisons. Data analysis was conducted in Rstudio (version 2022.07.0) with Kruskal-Wallis, Mann-Whitney U, and Chi-square tests to assess statistical significance across specialties, regions, and payment periods. Between 2017 and 2023, 2,158,140 payments totaling $601,567,196.10 were made to 19,585 U.S.-based hematology, medical oncology, and hematology-oncology specialists. Hematology-oncology received the highest total payment amount ($393,169,915.10) and transaction count (1,700,202), while hematology had the highest median payment ($23.05) compared to hematology-oncology ($18.12) and medical oncology ($19.5). Payment patterns demonstrated seasonal peaks, particularly in Q1 and Q4, and increased markedly during major oncology conferences (ASCO, ASH). Analysis by geographic region revealed that the South consistently received the highest total payments, peaking at $36.8 million in 2023, while the Northeast had the highest median payment values, reaching $22.87 in 2023. The COVID-19 pandemic corresponded with lasting shifts in payment patterns, with median payment values rising significantly during the pandemic period and remaining elevated post-COVID across all specialties. Additionally, the distribution of payments by type revealed that direct cash payments and consulting fees were the most prominent, with hematology-oncology showing the greatest reliance on high-value cash transactions, while stock payments featured prominently in hematology. Sensitivity analyses confirmed these patterns as robust, with minimal variance observed when excluding extreme values, further validating consistent trends across specialties, regions, and periods. This study reveals specialty- and region-specific variations in oncology-related payments, with significant increases during key conferences and the COVID-19 pandemic. These findings underscore the importance of continued transparency and scrutiny in industry-oncology financial interactions to mitigate potential conflicts of interest in oncology care.

The current study investigates the anticancer activity of protein derived from yeast against breast cancer. Yeast-derived proteins illustrate potential as an anticancer agent through mechanisms, such as immune system stimulation via beta-glucans, cytotoxic effects, and modulation of gut microbiota by probiotic strains. The antioxidant activity of yeast-derived proteins can aid in anticancer activity by neutralizing free radicals, thereby reducing oxidative stress and preventing damage to cellular DNA. Employing a comprehensive methodology encompassing yeast isolation, antioxidant screening, molecular characterization, bioactive protein purification, and MTT assay, the research provides crucial insights into the anticancer attributes of the protein extracted from the yeast. The findings reveal significant antioxidant activity that reduces reactive oxygen species (ROS) levels, which are implicated in cancer development. The MTT assay on MCF-7 breast cancer cell lines, characterized by estrogen receptor and progesterone receptor positivity and HER-2 negativity, determined an IC₅₀ value of 54.89 µg/ml, indicating a dose-dependent decrease in cytotoxic effects. These results suggest that the protein derived from Trichosporon asahii VITSTB1 exhibits promising anti-breast cancer properties. Further research is necessary to elucidate the underlying mechanisms, assess efficacy and safety profiles, explore synergies with existing therapies, and conduct animal model studies. Advancing this line of inquiry will significantly contribute to biomedical research and industrial innovation.

Esophageal cancer (EC) is one of the most common malignant tumors worldwide. Exosomes are a type of extracellular vesicles produced by eukaryotic cells and present in all body fluids. Recent studies have revealed that exosomes can be used as a tool for cell signaling and have great potential in cancer diagnosis and treatment strategies. This article reviews the research progress of exosomes in EC in recent years, mainly including the mechanism of action, diagnostic markers, therapeutic targets, and drug carriers. The challenges faced are discussed to provide guidelines for further research in future.

AXL has ubiquitous expression in multiple cancers, and is strongly linked to both tumor progression, metastasis, and poor prognosis, as well as anti-tumor immune response suppression and induction of tumor resistance to immunotherapy. Therefore, it is a strong target for cancer intervention. Despite the wide application of AXL inhibitors in clinical trials, the role of AXL in the tumor immune microenvironment (TIME) remains undetermined. Herein, we established cell lines with stable AXL knockdown or overexpression using lentiviral infection. Subsequently, we co-cultured the cells with healthy human blood-derived CD33 + PBMCs. After two days of culture, we evaluated the differentiation of PBMCs into MDSCs. Additionally, the culture supernatants were collected from both the co-culture system and the individual cultures of each cell group to measure the concentrations of IL-6 and GM-CSF. Additionally, we subcutaneously administered nasopharyngeal carcinoma (NPC) cells into mice, and evaluated the association between AXL content and MDSC recruitment in the resulting tumors. We demonstrated that AXL is a critical modulator of MDSC differentiation and accumulation in NPC. It modulates IL-6, GM-CSF, and Toll-like receptor contents to achieve the aforementioned actions. Herein, we revealed a strong and direct link between AXL, cytokines in TIME, and MDSC differentiation and accumulation. Our work highlights novel approaches to optimizing existing immunotherapeutic interventions.

The combined effect of cardiovascular risk factors on breast cancer in women is unknown. The relationship between genetic risk combined with cardiovascular health (CVH) levels and breast cancer has not been confirmed. This study aims to explore the relationship between CVH level based on life's essential 8 (LE8) score and breast cancer risk in women with different menopausal statuses and to estimate further the effect of CVH level combined with genetic susceptibility on breast cancer risk. A total of 118,911 women from UK Biobank were included in the study, including 22,676 premenopausal women and 96,235 postmenopausal women. The association between the CVH level and the risk of breast cancer in women with different menopausal statuses was assessed using the Cox proportional hazards regression models, with the healthiest CVH group as the reference. In addition, risk ratios (HRs) and 95% confidence intervals (95% CIs) for the joint effect of the CVH level and polygenic risk score (PRS) were calculated using the PRS from the UK Biobank. During a mean follow-up period of 13.8 years, we observed 733 cases and 3,645 cases of breast cancer in premenopausal and postmenopausal women, respectively. In premenopausal women, the risk of breast cancer was significantly increased in the intermediate CVH group (HR, 1.28; 95%CI 1.08-1.52) and the low CVH group (HR, 1.44; 95%CI 1.13-1.85). In postmenopausal women, the risk of incidence was also significantly increased in the intermediate CVH group (HR, 1.20; 95%CI 1.07-1.32) and the low CVH group (HR, 1.34; 95%CI 1.17-1.54). In the joint effect analysis, the risk of breast cancer for women in the low CVH group and the high genetic risk group was highest in both premenopausal (HR, 8.26; 95%CI 4.44-15.35) and postmenopausal (HR, 8.10; 95%CI 5.50-11.93) women. Women with lower LE8 scores and higher genetic susceptibility have the higher risk of breast cancer. This suggests that women with lower levels of CVH and higher genetic susceptibility have an increased risk of breast cancer under different menopausal statuses.

Breast cancer is a major health problem, accounting for one third of all cancers in women. There is no definitive treatment for breast cancer and its incidence is increasing worldwide every year. Furthermore, breast cancer stem cells cause resistance to radiation and chemotherapy. Telomerase is an enzyme that protects telomeres and is activated in 90% of cancer cells, and telomerase activation is a hallmark of cancer. In this review, we examine telomerase activation in breast cancer and breast cancer stem cells and the therapeutic effects of telomerase inhibition in these cells. In this review, we aim to highlight the importance and impact of telomerase inhibition in the treatment of breast cancer and the lack of studies specifically in breast cancer stem cells.

Cytotoxic T lymphocyte antigen 4 (CTLA-4), in conjunction with PD-1 and CD28, plays a pivotal role in the modulation of T-cell activation. Specifically, CTLA-4 exerts its influence by impeding the generation of IL-2 and the proliferation of T cells. CTLA-4, being a receptor with a high affinity, engages in competitive binding with CD28 for the interaction with primary T-cell activator molecules, specifically CD80 and CD86. The appropriate functioning of T-cell activation is contingent upon maintaining a precise equilibrium between CTLA-4 and CD28. Consequently, any disruption in the expression of CTLA-4 significantly enhances the risk for a range of severe ailments, such as cancer, infectious diseases, allergies, and notably autoimmune diseases. The significance of epigenetic regulation of CTLA-4, particularly through non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), has considerable weight within this particular framework. To date, there have been associations shown between various abnormalities in the expression of ncRNAs that regulate CTLA-4 and clinicopathological characteristics. Nevertheless, it is evident that there is a lack of a comprehensive investigation. Hence, the present work was undertaken to summarize the existing research on the epigenetic control of CTLA-4, with a primary emphasis on elucidating the regulatory procedures, biological processes, and clinical applications in human diseases. The objective of this review is to acquire a thorough comprehension of the relationship between RNA/lncRNA/miRNA/mRNA (CTLA-4) and its role in the progression of diverse human disorders.