Treatment Of Cancer Research Articles

CPT1A-mediated MFF succinylation promotes stemness maintenance in ovarian cancer stem cells

Cancer stem cells (CSCs) play crucial roles in cancer progression, immune evasion, drug resistance, and recurrence. Understanding the mechanisms behind CSCs generation and stemness maintenance is vital for early cancer diagnosis and treatment. Here, we unveil that carnitine palmitoyltransferase 1A (CPT1A) is highly expressed in ovarian cancer stem cells (OCSCs) and is essential for maintaining stemness by regulating lipid desaturation. Studies confirmed that CPT1A enhances SREBP1 activation, upregulating SCD1 expression, and promoting lipid desaturation in OCSCs. Mechanistic studies reveal that CPT1A promotes succinylation of mitochondrial fission factor (MFF) through its lysine succinyltransferase (LSTase) activity, crucial for mitochondria-associated membranes formation and SREBP1 activation. Inhibiting CPT1A’s LSTase activity with Glyburide reduces OCSCs’ stemness and enhances cisplatin’s anti-tumor effects against ovarian cancer in vitro and in vivo. Together, our studies highlight the significance of CPT1A’s LSTase activity in maintaining OCSCs’ stemness, offering potential targets and therapeutic strategies for ovarian cancer treatment.

Tongluo Jiedu as an adjuvant therapy for oral cancer

Oral cancer is one of the malignant neoplasms that present major global health challenge. It is the sixth most prevalent type of cancer in the world, with a high incidence and mortality rate. This letter is a review of the study by Yin et al which was published in the World Journal of Clinical Cases (2024). The study evaluated the effect of Tongluo Jiedu as an adjuvant treatment for oral cancer. Over the years, there has been a continuous search for effective and less invasive treatments for oral cancer. This article emphasizes and discusses various therapeutic options currently available, and it highlights that early intervention and multidisciplinary management are crucial for improving outcomes. Traditional Chinese Medicine, particularly Tongluo Jiedu, presents potential complementary approach to conventional oral cancer therapies. Future research on Tongluo Jiedu should be focused on validation of its efficacy and safety through large, well-designed clinical trials, as well as better understanding of the molecular mechanisms involved, and optimization of therapeutic combinations. Additionally, continuous education of health professionals is key to the effective and safe integration of this traditional medicine into clinical practice. Continuous research is essential for optimization of therapeutic strategies and for addressing the challenges presented by this neoplasm.

Anti-proliferative and anti-migratory effects of Urtica dioica agglutinin loaded chitosan nanoparticles with hyaluronic acid coating on the CD44-overexpressing prostate cancer cells

ABSTRACT Urtica dioica agglutinin (UDA), a plant macromolecule with biological properties, shows promise for cancer treatment. Hyaluronic acid (HA), which binds to the CD44 receptor commonly found on cancer cells, can enhance drug delivery. This study investigates the anti-proliferative and anti-migratory potential of UDA encapsulated in chitosan (CS) nanoparticles coated with HA against CD44-overexpressing prostate cancer cells. In vitro tests showed that UDA-CS-HA nanoparticles had more significant cytotoxic effects on PC3 cells at concentrations above 150 µg/mL compared to UDA-CS. They also inhibited wound healing at 100 µg/mL and higher. Higher UDA-CS-HA concentrations correlated with increased CD44 and Nanog expression levels, indicating CD44 pathway activation. These findings suggest that UDA-CS-HA nanoparticles, likely due to their enhanced uptake by CD44 receptors, can function as targeted carriers with combined anti-proliferative and anti-migratory potential against CD44-overexpressing cancers. .

Epidemiology of cancer in older adults: a systematic review of age-related differences in solid malignancies treatment.

We examined the latest epidemiological research on age-related differences in cancer treatment and selected outcomes, among patients with cancer aged 60 and above in comparison to younger patients. Colorectal, pancreatic and lung cancers were studied most often. Most studies were conducted in Europe or the United States of America (USA) within single centers. For unselected patients, older patients receive less treatment, and their survival, regardless of the metric used (cancer-specific survival or overall survival), was poorer than that of middle-aged patients. Age-related differences in treatment and outcomes were more pronounced in patients aged over 80 years. However, among patients selected for treatment, complications, adverse events rates and survival probabilities were comparable between older and younger patients. Treatment differences, especially the omission of therapy, were often smaller for good prognosis cancer types. The likelihood of receiving treatment decreased as age increases, regardless of the cancer types, treatment, countries and setting. More research on treatment in older patients with cancer, especially the frailest and the oldest, is urgently needed as there is still a lack of data to tailor treatment.

Mcl-1 downregulation enhances BCG treatment efficacy in bladder cancer by promoting macrophage polarization

BackgroundBacillus Calmette-Guérin (BCG) is the primary method of postoperative perfusion treatment for bladder cancer. The myeloid cell leukemia gene-1 (Mcl-1) is closely associated with the development of malignant tumors. Previous research by our group has demonstrated that downregulating Mcl-1 using shRNA can enhance the efficacy of BCG treatment in bladder cancer. This study aims to investigate the impact of Mcl-1 downregulation in combination with BCG treatment on bladder cancer, macrophage polarization, and the underlying mechanism of action, with the goal of reducing recurrence and metastasis in bladder cancer.MethodsThe GSE190529 dataset was analyzed to identify differential genes for enrichment analysis. The WGCNA algorithm was then employed to pinpoint gene modules closely associated with the Mcl-1 gene. The overlapping genes between these modules and the differentially expressed genes were subjected to enrichment analysis in GO and KEGG pathways to unveil crucial signaling pathways. In vitro experiments involved the co-culture of Raw264.7 macrophages and MB49 to establish a tumor microenvironment model, while in vivo experiments utilized an MNU-induced rat bladder cancer model. Various methods including Enzyme-Linked Immunosorbent Assay (ELISA), Western blot, immunofluorescence, HE staining, etc. were utilized to assess macrophage polarization and the expression of proteins linked to the ASK1/MKK7/JNK/cJUN signaling pathway.ResultsBioinformatics analysis indicates that the therapeutic mechanism of Mcl-1 in BCG treatment for bladder cancer may be linked to the Mitogen-Activated Protein Kinase (MAPK) signaling pathway. Both in vivo and in vitro experiments have demonstrated that the combination of BCG treatment and Mcl-1shRNA intervention results in elevated expression of M1 markers (TNF-α, CD86, INOS) and reduced expression of M2 markers (IL-10, CD206, Arg-1). Moreover, there was a notable increase in protein levels of P-ASK1, P-MKK7, P-JNK, P-cJUN, and CX43, leading to a significant rise in the apoptosis rate of bladder cancer cells and diminished proliferation, migration, and invasion capabilities. The expression of these markers can be reversed by employing the JNK signaling pathway inhibitor SP600125.ConclusionDown-regulation of Mcl-1 promotes the polarization of macrophages towards the M1 type through activation of the ASK1/MKK7/JNK signaling pathway. This enhances intercellular communication and improves the efficacy of BCG in bladder cancer treatment.Graphical

Docetaxel-loaded pH/ROS dual-responsive nanoparticles for the targeted treatment of gastric cancer

Gastric cancer (GC), characterized by its high incidence and mortality, poses a great threat to public health worldwide. Although various advanced treatments have been developed for GC, the cure rate remains poor. Docetaxel (DTX), a broad-spectrum antitumor drug, has been widely used for the treatment of GC. However, its use in clinical practice is limited by its low water solubility and severe side effects. Our previous work developed a pH/ROS dual-responsive nanoplatform to deliver DTX (DTX/FA-CA-Oxi-αCD NPs) for the targeted treatment of breast cancer. These nanotherapeutics displayed desirable therapeutic effects for breast cancer without obvious adverse effects. On the basis of the treatment potential of DTX/FA-CA-Oxi-αCD NPs, these nanoparticles (NPs) were used for the targeted treatment of GC. In vitro experiments demonstrated that DTX/FA-CA-Oxi-αCD NPs can be efficiently internalized by HGC-27 cells and deeply penetrate tumor spheroids. Moreover, DTX/FA-CA-Oxi-αCD NPs effectively hindered GC cell migration by approximately 60.1% and decreased GC cell invasion. In vivo experiments revealed that DTX/FA-CA-Oxi-αCD NPs obviously accumulated at the tumor site and that the released DTX significantly blocked tumor growth by approximately 79.6%. In conclusion, DTX/FA-CA-Oxi-αCD NPs exhibited promising therapeutic outcomes for GC treatment.

Anxiety and depression in cancer patients and survivors in the context of restrictions in contact and oncological care during the COVID-19 pandemic.

Treatment modifications and contact restrictions were common during the COVID-19 pandemic and can be stressors for mental health. There is a lack of studies assessing pandemic-related risk factors for anxiety and depression of cancer patients and survivors systematically in multifactorial models. A total of 2391 participants, mean age 65.5 years, ≤5 years post-diagnosis of either lung, prostate, breast, colorectal cancer, or leukemia/lymphoma, were recruited in 2021 via the Baden-Württemberg Cancer Registry, Germany. Sociodemographic information, pandemic-related treatment modifications, contact restrictions, and anxiety/depression (Hospital Anxiety and Depression Scale, HADS) were assessed via self-administered questionnaire. Clinical information (diagnosis, stage, and treatment information) was obtained from the cancer registry. Overall, 22% of participants reported oncological care modifications due to COVID-19, mostly in follow-up care and rehabilitation. Modifications of active cancer treatment were reported by 5.8%. Among those, 50.5% had subclinical anxiety and 55.4% subclinical depression (vs. 37.4% and 45.4%, respectively, for unchanged active treatment). Age <60 years, female sex, lung cancer, low income, and contact restrictions to peer support groups or physicians were identified as independent risk factors for anxiety. Risk factors for depression were lung cancer (both sexes), leukemia/lymphoma (females), recurrence or palliative treatment, living alone, low income, and contact restrictions to relatives, physicians, or caregivers. The study demonstrates that changes in active cancer treatment and contact restrictions are associated with impaired mental well-being. The psychological consequences of treatment changes and the importance for cancer patients to maintain regular contact with their physicians should be considered in future responses to threats to public health.

Comprehensive pan-cancer analysis of ENOPH1 in human tumors

BackgroundENOPH1 (Enolase-phosphatase 1), a member of the HAD-like hydrolase superfamily, has been linked to a range of physiological conditions, including neurological disorders. However, its involvement in tumorigenesis remains underexplored. This study is the first to conduct a pan-cancer analysis of ENOPH1, aiming to elucidate its role in multiple cancers through various bioinformatics platforms.MethodsWe conducted a thorough analysis using data from UCSC databases. ENOPH1 expression in tumor and normal tissues was evaluated using R language software. Survival analyses, genetic alterations, and RNA modifications were assessed through the GEPIA2 and cBioPortal platforms. The relationships between ENOPH1 and immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), and homologous recombination deficiency (HRD) were examined using TIMER2 and R software. ENOPH1-related gene enrichment analysis was performed using the STRING and GEPIA2 databases, followed by Gene Ontology (GO) and KEGG pathway enrichment analyses.ResultsENOPH1 expression was significantly upregulated in various cancers, including ACC, BLCA, BRCA, and COAD. High ENOPH1 expression was associated with poor overall survival (OS) in cancers such as KICH, LIHC, BRCA and LUAD. High ENOPH1 expression was associated with poor disease specific survival (DSS) in cancers such as KICH, LIHC, BRCA and MESO. Genetic alterations of ENOPH1, primarily mutations and deep deletions, were identified in UCEC, BLCA, and OV. ENOPH1 showed significant correlations with RNA modifications (m1A, m5C, m6A), immune checkpoints, and immune modulators across multiple cancer types. ENOPH1 was positively correlated with TMB, MSI, and HRD in cancers like BLCA, BRCA, and STAD. Furthermore, enrichment analysis revealed that ENOPH1 interacts with proteins involved in critical pathways such as AMPK, Hippo, and PI3K-AKT, suggesting its role in cancer progression.ConclusionThis pan-cancer analysis reveals ENOPH1’s potential as a prognostic biomarker and its involvement in key signaling pathways across multiple cancers. Our findings provide new insights into the role of ENOPH1 in tumorigenesis and highlight its potential as a therapeutic target in cancer treatment.

Nanoscale strategies: doxorubicin resistance challenges and enhancing cancer therapy with advanced nanotechnological approaches.

Doxorubicin (DOX), an anthracycline, is widely used in cancer treatment by interfering RNA and DNA synthesis. Its broad antitumour spectrum makes it an effective therapy for a wide array of cancers. However, the prevailing drug-resistant cancer has proven to be a significant drawback to the success of the conventional chemotherapy regime and DOX has been identified as a major hurdle. Furthermore, the clinical application of DOX has been limited by rapid breakdown, increased toxicity, and decreased half-time life, highlighting an urgent need for more innovative delivery methods. Although advancements have been made, achieving a complete cure for cancer remains elusive. The development of nanoparticles offers a promising avenue for the precise delivery of DOX into the tumour microenvironment, aiming to increase the drug concentration at the target site while reducing side effects. Despite the good aspects of this technology, the classical nanoparticles struggle with issues such as premature drug leakage, low bioavailability, and insufficient penetration into tumours due to an inadequate enhanced permeability and retention (EPR) effect. Recent advancements have focused on creating stimuli-responsive nanoparticles and employing various chemosensitisers, including natural compounds and nucleic acids, fortifying the efficacy of DOX against resistant cancers. The efforts to refine nanoparticle targeting precision to improve DOX delivery are reviewed. This includes using receptor-mediated endocytosis systems to maximise the internalisation of drugs. The potential benefits and drawbacks of these novel techniques constitute significant areas of ongoing study, pointing to a promising path forward in addressing the challenges posed by drug-resistant cancers.

Racial/Ethnic Differences and Effects of Clinical/Socioeconomic Factors on Time from Diagnosis to Treatment in Pancreatic Cancer

PurposeFive-year survival for pancreatic adenocarcinoma (PDAC) is < 10% but can vary by a patient’s race, socioeconomic status (SES), and the factors related to the neighborhood where a patient lives (nSES) . Prolonged time from diagnosis to first treatment (T2T) is another important disparity indicator. Here, we examined the effect of race, nSES, and patient-level clinical factors on T2T and survival in metastatic PDAC (mPDAC) patients.MethodsPatients with mPDAC treated at an academic cancer center between 2010 and 2018 (n = 334) were evaluated for nSES measures related to racial concentration, neighborhood deprivation, stability, immigration status, and transportation access from the US Census. We assessed and reported the effects of nSES and patient-level variables (age, race, gender, Charlson Comorbidity Index (CCI), etc.) on T2T and survival using univariate and multivariate Cox proportional hazards regression, hazard ratios (HR), confidence intervals (CI).Results82.9% of the patients were White; 17.1% were Black. Median T2T was 26 days with no significant difference in T2T and survival by race. In multivariable models, no nSES variables were significantly associated with T2T. T2T did not significantly impact survival; however, receipt of chemotherapy (HR = 0.14 [95% CI = 0.06, 0.30]) was associated with better survival outcomes.ConclusionAmong patients with mPDAC, T2T was not associated with race/ethnic disparities or survival in a mostly White, high SES population treated at a comprehensive cancer center. Future investigations into pancreatic cancer disparities may be warranted in other hospital settings and in larger, more diverse study samples.

Integrated network pharmacology, molecular docking and experimental validation to investigate the mechanism of tannic acid in nasopharyngeal cancer

Tannic acid (TA) is the primary bioactive component in the gallnut (Galla chinensis) and has exhibited the anticancer effects. However, the mechanism of its anti-cancer activity in nasopharyngeal carcinoma (NPC) remains unclear. This research aims to explore the underlying mechanism of TA in the treatment of nasopharyngeal cancer using network pharmacology, molecular docking and experimental validation. Firstly, the targets of TA and NPC were predicted and collected through databases, and the intersection targets were identified. Subsequently, protein-protein interaction (PPI) network analysis, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes Genomes (KEGG) pathway enrichment analysis, molecular docking and molecular dynamics (MD) simulation were conducted to uncover the potential mechanisms of TA in treatment of NPC. Finally, in vitro experiments were utilized to verify the mechanism of TA with anticancer activity in NPC. The results of network pharmacology revealed 42 intersection targets between NPC-related targets and TA-related targets. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling was identified as the main target pathway of TA against NPC. Additionally, molecular docking and MD simulation confirmed the closely binding affinities of TA with AKT1. Furthermore, the results of in vitro experiments demonstrated that TA exerts anticancer activity against NPC by targeting the PI3K/AKT signaling pathway, leading to the suppression of cell proliferation. TA is a promising therapeutic candidate for NPC through PI3K/AKT signaling pathway. These results provide insights into the clinical application of TA, particularly when considered in combination with other therapeutic modalities.

Neurosurgical management of brain metastases in the elderly: a prospective study on adverse event prevalence and predictors

The management of brain metastases (BM) in geriatric patients poses significant challenges in the context of an aging population and advances in systemic cancer treatment. This study provides insights into the prevalence and nature of adverse events (AEs) following intracranial surgery in patients aged 65 years and older. It highlights the complexities and implications of treating this demographic patient population and identifies risk factors associated with AEs. This prospective study includes patients aged 65 years and older with BM who underwent surgery between January 2022 and December 2023. A detailed assessment of AEs, defined as any complication occurring within the first 30 days post-surgery, was conducted. Potential risk factors for the occurrence of AEs were examined. The study encompassed 104 patients, averaging 70.1 ± 2.8 years, with 102 undergoing surgery. The mean age-adjusted Charlson Comorbidity Index (CCI) score was 8.9 ± 1.2, indicating a significant comorbidity burden, predominantly cardiac conditions. The Karnofsky Performance Scale (KPS) showed substantial improvement post-surgery, increasing from 71.3% ± 7.8 to 75.1% ± 5.0 (p = 0.045). The average hospital stay was 10.6 days. Four non-surgery-related mortalities occurred within the 30-day postoperative period. Surgery-related AEs included wound complications in two patients, with one necessitating surgical revision. Advanced age and comorbidities emerged as significant predictors of AEs. Our findings suggest that neurosurgical intervention for BM in the elderly is a feasible and safe option, demonstrating favorable morbidity and mortality rates. However, careful postoperative monitoring is crucial, especially considering the baseline health status of these patients, which increases their susceptibility to AEs. Standardizing protocols for AE reporting and analysis is essential for improving clinical outcomes and maintaining the quality of healthcare for this patient population.

Mechanistic insights of lenvatinib: enhancing cisplatin sensitivity, inducing apoptosis, and suppressing metastasis in bladder cancer cells through EGFR/ERK/P38/NF-κB signaling inactivation

BackgroundThe persistent activation of the epidermal growth factor receptor (EGFR) leads to the activation of downstream oncogenic kinases and transcription factors, resulting in tumor progression and an increased resistance to cisplatin in bladder cancer (BC) cells. Lenvatinib, an oral multikinase inhibitor, has the potential to offer therapeutic benefits as an adjuvant treatment for BC patients. The investigation into its application in bladder cancer treatment is a valuable endeavor. The primary goal of this study is to confirm the effectiveness and mechanism of lenvatinib in inhibiting the progression of BC and enhancing the anticancer efficacy of cisplatin.MaterialsThree BC cell lines, namely, TSGH-8301, T24, and MB49, along with an MB49-bearing animal model, were utilized in this study.ResultsIn vitro experiments utilizing MTT assays demonstrated that lenvatinib sensitized BC cells to cisplatin, exhibiting a synergistic effect. Flow cytometry indicated apoptotic events and signaling, presenting that lenvatinib effectively induced apoptosis and triggered extrinsic/intrinsic apoptotic pathways. In vivo studies using a mouse model of BC confirmed the antitumor efficacy of lenvatinib, demonstrating significant tumor growth suppression without inducing toxicity in normal tissues. Western blotting analysis and immunohistochemistry stain revealed EGF-phosphorylated EGFR and EGFR-mediated ERK/P38/NF-κB signaling were suppressed by treatment with lenvatinib. In addition, lenvatinib also suppressed anti-apoptotic (MCL1, c-FLIP, and XIAP) and metastasis-related factors (Twist, Snail-1, ZEB-1, ZEB-2, and MMP9) and promoted epithelial markers (E-cadherin) while reducing mesenchymal markers (N-cadherin).ConclusionIn conclusion, the induction of apoptosis and the inhibition of EGFR/ERK/P38/NF-κB signaling are correlated with lenvatinib’s ability to hinder tumor progression and enhance the cytotoxic effects of cisplatin in bladder cancer. These findings underscore the potential of lenvatinib as a therapeutic option for bladder cancer, either as a standalone treatment or in combination with cisplatin.

Nucleolar NOL9 regulated by DNA methylation promotes hepatocellular carcinoma growth through activation of Wnt/β-catenin signaling pathway

Ribosome biogenesis (RiboSis) and ribosomal stress are critical in tumor progression, positioning RiboSis as a promising therapeutic target for cancer treatment and for overcoming drug resistance. In this study, we examined the role of RiboSis in the progression from hepatitis B virus (HBV) infection to HBV-related hepatocellular carcinoma (HCC), focusing specifically on nucleolar protein 9 (NOL9) and its influence on HCC pathogenesis and therapeutic response. Our findings showed that NOL9 was significantly upregulated in HCC tissues, correlating with larger tumor sizes and more advanced pathological grades. High levels of NOL9 expression were associated with unfavorable prognosis in both the TCGA-LIHC and our HCC cohorts. Functional assays indicated that NOL9 regulated HCC cell proliferation and apoptosis; specifically, NOL9 knockdown inhibited cell proliferation and promoted apoptosis, while overexpression enhanced these processes. In vivo studies confirmed that NOL9 depletion reduced tumor growth. Mechanistically, NOL9 expression was regulated by DNA methylation and the transcription factor ZNF384. Our DNA methylation analysis revealed an inverse correlation between NOL9 expression and methylation at specific CpG sites, implicating DNMT1 in its epigenetic regulation. Additionally, NOL9-mediated cell proliferation was dependent on activation of the Wnt/β-catenin signaling pathway. This study highlights the multifaceted role of NOL9 in HCC pathogenesis, underscoring its potential as a diagnostic biomarker and therapeutic target.

Immuno-oncological Challenges and Chemoresistance in Veterinary Medicine: Probiotics as a New Strategic Tool.

Cancer has the highest death rates due to increased immuno-oncological (IO) challenges and chemoresistance caused by gut dysbiosis, whereas administration of probiotics may reverse these responses against anticancer therapies. Recently, immunotherapeutics have extensively been focused for significant advancements in pharmacological drug discovery and clinical outcomes. Mammals have intestinal epithelial cells, mucosal immune cells, and indigenous gut microbiota which may reshape immunotherapeutics efficacy. These include use of T-cell immune checkpoint inhibitors (ICPI), genetically engineered T-cells, tumor vaccines, monoclonal antibodies (mAbs), and anti-B- and T-cell antibodies. Immunotherapeutics for cancer treatment became popular in both veterinary and human health care systems due to their strong inhibitory actions against PD-1 and CTLA-4 to check tumorigenesis. IO issues in animals also need special attention, where caninized mAbs targeting CD-20 and CD-52 have been clinically used in treating canine B-cell and T-cell lymphomas, respectively. Probiotics appeared as strong immunotherapeutics that might be shaping the epigenetics of the organisms specifically in animal breeding practices for desired features, but limited literature regarding the immunomodulatory effects in humans and animals is available. In addition, considering the important role of probiotics in humans and veterinary medicine, a new perspective on the probiotic-mediated modulation of ncRNAs (miRNAs, lncRNAs, circRNAs) is also highlighted and would be a new therapeutic tool. This review provides insight into the cellular processes and pharmacological activities for treating veterinary infectious diseases and covers small drug molecules as ncRNA-modulators in veterinary medicine.

Probiotics: A New Approach for the Prevention and Treatment of Cervical Cancer.

Cervical cancer is closely linked to high-risk human papillomavirus (HR-HPV) infections which could crosstalk with the diversity of microorganisms within the cervicovaginal microbiota (CVM). Conventional treatments can disrupt the host microbial communities, which in turn affect the efficacy and side effects of these interventions, potentially jeopardizing the lives and health of patients. Therefore, there is a need to develop new approaches for the prevention and treatment of cervical cancer, and probiotics have shown significant potential as effective agents against cervical cancer. Studies have demonstrated that probiotics induce anticancer action by inducing apoptosis in tumor cells, inhibiting metastasis, reducing inflammation, enhancing immune functions, and modifying the effect of chemo/radiation therapy. Recent reports showed that probiotics had the ability to restore the CVM, clear HPV infections in cervical epithelial cells, and modulate immune responses. Despite these promising findings, the efficacy and safety of probiotic formulations require further validation through comprehensive research. This review focused on elucidating the mechanism behind the anticancer action and the importance of addressing the challenges associated with the clinical application of probiotics to realize their full potential as a novel and complementary approach in the prevention and treatment of cervical cancer.

Using major histocompatibility complex (MHC) II expression to predict antitumor response to CD4 + lymphocyte depletion

Immunotherapy targeting CD4 + FoxP3 + regulatory T cells (Tregs) through CD4 + lymphocyte depletion is being investigated as cancer treatment. This study examines the efficacy and limitations of CD4 depletion across various cancer models. We examined CD4 depletion in syngeneic mouse tumor models including B16 melanoma, Renca kidney cancer, and Hepa1-6 hepatocellular carcinoma. The study explored the relationship between MHC II expression and tumor growth, immune response, and survival. In mouse models, CD4 depletion suppressed B16 and Renca tumor growth but accelerated Hepa1-6 tumors. Hepa1-6 had high MHC II expression while the other two lines had low MHC II expression. Manipulation of MHC II expression in Hepa1-6 and Renca cell lines confirmed the mechanistic importance of MHC II in generating a CD4-based antitumor immune response. Analysis of the TCGA dataset supports the relevance of this mechanism in patients. In tumors with high MHC II and low MHC I expression, increased CD4 levels correlated with improved survival. CD4 depletion can suppress tumor growth or promote tumor growth, depending on tumor MHC expression status. MHC status may identify tumors where intratumor CD4 may be a better early-response marker than CD8.

Mitoxantrone-Encapsulated ZIF-8 Enhances Chemo-Immunotherapy via Amplified Immunogenic Cell Death.

Chemo-immunotherapy, combining systemic chemotherapeutic drugs and immune checkpoint blockers, is a promising paradigm in cancer treatment. However, challenges such as limited induction of immune responses and systemic immune toxicity have hindered its clinical applications. Here, a zeolite imidazolate framework-8 (ZIF-8) that encapsulates mitoxantrone (MIT), an immune cell death (ICD)-inducing chemotherapeutic agent (MIT@ZIF-8), is synthesized using a one-pot aqueous-phase process. ZIF-8 serves as a dual-functional nanomaterial for chemo-immunotherapy: a carrier to enhance tumor uptake of MIT for improved chemotherapy efficacy, and a pyroptosis inducer to amplify MIT-induced ICD for augmented anti-tumor immune responses. As a result, in vivo administration of MIT@ZIF-8 markedly inhibits tumor growth in both immunologically "hot" colon cancer and immunologically "cold" prostate cancer. Moreover, MIT@ZIF-8 treatment increases the abundance of cytotoxic CD8+ T cells and reduces the amount of immunosuppressive regulatory T cells in tumors, thereby enhancing anti-tumor immunity and sensitizing prostate cancer to anti-CTLA-4 immunotherapy. In summary, MIT@ZIF-8 offers a highly translational approach for chemo-immunotherapy.

Identifying traditional Chinese medicine combinations for breast cancer treatment based on transcriptional regulation and chemical structure

Breast cancer (BC) is a prevalent form of cancer among women. Despite the emergence of numerous therapies over the past few decades, few have achieved the ideal therapeutic effect due to the heterogeneity of BC. Drug combination therapy is seen as a promising approach to cancer treatment. Traditional Chinese medicine (TCM), known for its multicomponent nature, has been validated for its anticancer properties, likely due to the synergy effect of the key components. However, identifying effective component combinations from TCM is challenging due to the vast combination possibilities and limited prior knowledge. This study aims to present a strategy for discovering synergistic compounds based on transcriptional regulation and chemical structure. First, BC-related gene sets were used to screen TCM-derived compound combinations guided by synergistic regulation. Then, machine learning models incorporating chemical structural features were established to identify potential compound combinations. Subsequently, the pair of honokiol and neochlorogenic acid was selected by integrating the results of compound combination screening. Finally, cell experiments were conducted to confirm the synergistic effect of the pair against BC. Overall, this study offers an integrated screening strategy to discover compound combinations of TCM against BC. The tumor cell suppression effect of the honokiol and neochlorogenic acid pair validated the effectiveness of the proposed strategy.

Control Over Kinetic Self-Assembly of Phthalocyanine into Photothermal Nano-Vaccine Enabling Tunable Superlarge Absorption Redshift.

Supramolecular near-infrared (NIR) nanomaterials show great application prospects in cancer photothermal immunotherapy. However, the direct self-assembly of photothermal nanomaterials absorbed in biological transparent window and control over their absorption properties through aggregation behavior remains a grand challenge. Here, the control over superlarge absorption redshift (ranging from 105 nm to 150 nm) of mono-α-substituted carboxy zinc phthalocyanine (αZnPc) through kinetic assembly methodologies is demonstrated, resulting in the fabrication of photothermal nanoagents within tissue-transparent NIR window. Tailoring the solvent polarity allows for the manipulation of kinetic pathways, leading to a variety of self-assembled structures exhibiting distinct αZnPc macrocycle stacking modes that attribute to their different absorption redshift properties. Mechanistic studies of the relationship between solvent polarity and pathway complexity revealed the energy landscape that governs the unique kinetic behavior. The specific stacking mode and conformation conforming to the charge-transfer model within these αZnPc assembled structures have been revealed by theoretical calculations. Crucially, the αZnPc nanostructures show remarkable physiological stability and robust photothermal performances within biological transparent window, efficiently ablating primary tumors and triggering immunogenic cell death. This effect is further augmented by the immunomodulatory effects of thymopentin, exhibiting vaccine-like capabilities in suppressing the growth of distant tumors. This research demonstrates unprecedented levels of control over supramolecular structures and their superlarge red-shifted absorption, providing great opportunities for future design and construction of supramolecular NIR materials with fascinating properties toward cancer treatments.