Strategy For Cancer Treatment Research Articles

Cu0-based nanoparticles boost anti-tumor efficacy via synergy of cuproptosis and ferroptosis enhanced by cuproptosis-induced glutathione synthesis disorder

Apoptotic resistance of tumor often leads to poor efficacy from mono-therapy based on apoptosis. Cuproptosis, a new type of non-apoptotic cell death related to mitochondrial dysfunction, can alter metabolism and enhance ferroptosis, providing a promising strategy for effective synergistic cancer treatment. In this work, Cu0-based nanoparticles (denoted as HA-ZCu) were successfully developed to improve anti-tumor efficacy by combining cuproptosis with enhanced ferroptosis, which was achieved by cuproptosis-induced glutathione synthesis disorder. In vitro studies revealed that HA-ZCu effectively induced cuproptosis and ferroptosis in HepG2 cells. Moreover, HA-ZCu induced mitochondrial dysfunction and decreased intracellular adenosine triphosphate (ATP), glutamate, and glutathione, demonstrating the effective synergy. In vivo studies further approved the synergistic therapeutic efficacy of HA-ZCu, where the inhibition rate of tumor growth reached 83.2%. This work represents the first example of enhanced anti-tumor efficacy via cuproptosis and ferroptosis synergy through cuproptosis-induced glutathione synthesis disorder.

289. OUTCOME OF CONVERSION SURGERY FOR ESOPHAGEAL CANCER WITH SYNCHRONOUS ABDOMINAL PARAAORTIC LYMPH NODE METASTASIS

Abstract Background and Purpose Stage IVb esophageal cancer with distant metastasis has a poor prognosis with a 5-year survival rate of approximately 10%. Among distant metastases, the treatment strategy for esophageal cancer with metastasis to the #16 para-aortic lymph node has not been defined, and the significance of surgical resection is not clear. Methods Using the database of Osaka University and related institutions, we selected 41 cases of thoracic esophageal cancer with simultaneous #16 metastasis that underwent surgical resection between 2005 and 2021, and examined treatment outcomes. Results Patient background was median age 64 (43-76) years, gender M/F = 32/9, and primary site of occupancy Ut/Mt/Lt = 1/17/23. Tumor progression was cT factor T1/T2/T3/T4 =0/6/25/10, cN factor N0/N1/N2/N3 =0/13/19/9. Chemotherapy was administered as initial therapy in 38 patients, and CRT was administered in 3. Primary esophageal resection was performed in all 41 patients, and metastases were resected in 36 patients (88%). 38 patients (93%) were eligible for R0 resection. Pathologically, pT0-2/T3-4=22(54%)/19(46%), pN0/1/2-3 8(20%)/6(15%)/27(66%), and pN2 or higher were common. The 3-/5-year survival rate for all patients was 22.8%/19.0%. In all cases, pN0-1 had significantly better survival than pN2-3 (p=0.0252). Conclusion Conversion surgery for esophageal cancer with simultaneous #16 metastasis had a relatively good outcome, suggesting that the pN factor may be a prognostic factor.

Patient-derived organoids and mini-PDX for predicting METN375S-mutated lung cancer patient clinical therapeutic response

Lung cancer as a molecularly and histologically high heterogonous disease, there is an urgent need to predict lung cancer patients' responses to anti-cancer treatment, and patient-derived organoids (PDOs) have been recognized as a valuable platform for preclinical drug screening. In this study, we successfully established 26 PDO lines from various subtypes of lung cancers including benign tumor, adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, large-cell carcinoma, and small-cell carcinoma. These PDOs were shown to retain the major genomic and histological characteristics of primary tumors and remain stable during long-term culture. With the help of targeted genomic sequencing, we found that lung cancer that harbors METN375S mutation is selectively sensitive to afatinib, and a combination of afatinib and gemcitabine induced synthetic lethality in PDO and mini-PDX models. In summary, our findings demonstrate the potential of PDO in predicting lung cancer drug response, and reveal a promising strategy for METN375S mutant lung cancer treatment.

Anti-cancer effects of benzimidazole derivative BNZ-111 on paclitaxel-resistant ovarian cancer

ObjectiveOvarian cancer, a leading cause of cancer-related deaths in women, remains a formidable challenge, especially in the context of platinum-resistant disease. This study investigated the potential of the benzimidazole derivative BNZ-111 as a novel treatment strategy for platinum-resistant ovarian cancer. MethodsThe human EOC cell lines A2780, HeyA8, SKOV3ip1, A2780-CP20, HeyA8-MDR, and SKOV3-TR were treated with BNZ-111, and cell proliferation, apoptosis, and cell cycle were assessed. ResultsIt demonstrated strong cytotoxicity in both chemo-sensitive and chemo-resistant epithelial ovarian cancer cell lines, inducing apoptosis and G2/M cell cycle arrest. In vivo experiments using orthotopic and patient-derived xenograft models showed significant tumor growth inhibition without apparent toxicity to vital organs. Unlike paclitaxel, BNZ-111 proved effective in paclitaxel-resistant cells, potentially by bypassing interaction with MDR1 and modulating β-3 tubulin expression to suppress microtubule dynamics. ConclusionBNZ-111, with favorable drug-like properties, holds promise as a therapeutic option for platinum-resistant ovarian cancer, addressing a critical clinical need in gynecologic oncology.

Modelling Incidence and Mortality Cancer Parameters with Respect to GLOBOCAN 2020Age Standardized World Estimates

In this paper, an empirical model with the critical number of incidences and deaths for female cancers as adjustable parameters has been developed using life expectancy data from GLOBOCAN world estimates on cancer types. The model was developed based on the cumulative risk and exponential correlation techniques such that the significance of the adjustable parameters ascertains the strength of this research in two ways. First, it indicates indicates the rapid increase in female cancer morbidity with increase in the number of male cancer cases, regardless of incidence or mortality. Second, it suggests that female cancer cases may approach a virtual limiting value as male cancer cases reach extremely high levels. This projection aligns with the global population trends, indicating a proportional increase in cancer cases each year. Additionally, the cumulative risk of cancer incidences of each sex has been modelled separately against the global cumulative risk of cancer incidences of both sexes which revealed regions that have passed their inflection point and those that are yet to reach the inflection point. There was a curvature change, which indicates an inflection point coinciding with the South-Eastern Region and indicating that for the regions beyond the inflection point, the increase of the cumulative risk of cancer incidences of females against that of males is more accentuated compared with the regions before the inflection point. However, when the cumulative risk of cancer mortality of each sex is modelled separately against the global cumulative risk of cancer mortality of both sexes shows a non-linear dependence and the increase is more accentuated for males than for females. This finding indicates that cumulative risk is influenced by factors beyond the male-female population ratio. This study advances cancer studies as it provides a nuanced understanding of gender-specific cancer trends, crucial for developing targeted cancer prevention and treatment strategies. By elucidating the dynamics of cancer incidences and mortalities across different regions and sexes, the findings can inform public health policies and resource allocation to combat cancer more effectively on a global scale.

Psychosocial Adaptation in Lung Cancer Patients: a Literature Review

ABSTRACT Lung cancer is one type of cancer with the highest mortality rate, this is often due to delays in diagnosis and the impact of prognosis which can affect the psychosocial adaptation of lung cancer patients. Analyze psychosocial adaptation problems in lung cancer patients, their impacts, and treatment strategies. Systematic review used the PRISMA protocol and JBI scoring tool to determine eligible articles. Five electronic databases were used (Pubmed; Science Direct and Google Scholar. Inclusion criteria included research on lung cancer published in English in the last ten years (2014-2024). The results showed that 20 articles met the inclusion criteria. The results of the review show several common problems experienced by lung cancer patients, including depression, anxiety, social isolation, stigmatization, mental health problems, and difficulties in adaptation. The impact is a decrease in emotional well-being, a reduction in quality of life, an increase in physical symptoms, and a worsening of the disease prognosis. Several prevention strategies include providing multidisciplinary therapy through supportive and palliative care, improving the quality of psychosocial health services, cognitive behavioral therapy, social support therapy, psycho-education, increasing social support, spiritual treatment, increasing healthy behavior, and using confrontation and stress coping. Psychosocial problems experienced by lung cancer patients are often complex and can include various aspects. Several common issues experienced by lung cancer patients are related to psychosocial problems. The impact of psychosocial problems can worsen the prognosis of lung cancer so several treatment efforts are needed to overcome psychosocial problems in lung cancer patients. Keywords: Adaptation, Lung Cancer, Literature Review, Psychosocial

Ferroptosis-induced Cardiotoxicity and Antitumor Drugs.

The induction of regulated cell death ferroptosis in tumors is emerging as an intriguing strategy for cancer treatment. Numerous antitumor drugs (e.g., doxorubicin, etoposide, tyrosine kinase inhibitors, trastuzumab, arsenic trioxide, 5-fluorouracil) induce ferroptosis. Although this mechanism of action is interesting for fighting tumors, the clinical use of drugs that induce ferroptosis is hampered by cardiotoxicity. Besides in cancer cells, ferroptosis induced by chemotherapeutics can occur in cardiomyocytes, and this feature represents an important drawback of antitumor therapy. This inconvenience has been tackled by developing less or no cardiotoxic antitumor drugs or by discovering cardioprotective agents (e.g., berberine, propofol, fisetin, salidroside, melatonin, epigallocatechin-3gallate, resveratrol) to use in combination with conventional chemotherapeutics. This review briefly summarizes the molecular mechanisms of Fer and describes the Fer-dependent mechanisms responsible for cardiac toxicity developed by cancer-suffering patients following the administration of some chemotherapeutics. Additionally, the pharmacological strategies very recently proposed for potentially preventing this inconvenience are considered.

TSPAN1 overexpression as an indicator of poor prognosis in estrogen receptor-positive breast cancer.

Tetraspanin 1 (TSPAN1) is a newly discovered protein of the tetrameric protein family encoded by the TSPAN1 gene localized in the 1p34 chromosome region. TSPAN1 has been shown to be associated with various malignancies. In this study, we aimed to investigate the prognostic significance of TSPAN1 in breast cancer. Estrogen receptor-positive (ER+) breast cancer is the largest breast cancer subgroup, and ER-targeted therapies have significantly prolonged survival and improved symptoms in advanced breast cancer. TSPAN1 overexpression was found to be associated with a poor prognosis in ER+ breast cancer. We analyzed the expression of TSPAN1 in breast cancer tissues and cell lines using western blotting and quantitative reverse transcription polymerase chain reaction (RT-qPCR). TSPAN1 expression was higher in breast cancer cells as compared with normal breast tissue. There was a significant association between a high TSPAN1 level and a low survival rate. Inhibition of TSPAN1 significantly reduced the proliferation and invasion of BT474 cells both in vitro and in vivo. The downregulation of TSPAN1 in breast cancer cells significantly reduced the levels of p-mitogen-activated protein kinase 1 (MEK1) (S298) and p-extracellular signal-regulating kinase (ERK) 1/2. TSPAN1 modulates downstream extracellular matrix (ECM) receptor signaling cascades and promotes cellular proliferation and invasion in breast cancer. TSPAN1 inhibition may be a potential new treatment strategy for breast cancer.

PATTERN OF HER-2 EXPRESSION WITH SPECIAL REFERENCE TO LOW HER-2 EXPRESSION IN IHC SAMPLES OF BREAST CANCER PATIENTS AT TERTIARY CANCER HOSPITAL HCG AHMEDABAD

Background: Breast cancer is the 2nd most common cancer worldwide and number one cancer in women. As per American Society of Clinical Oncology 2018 guidelines, HER2 classification is binary HER2 positive and HER2 negative. DESTINY-Breast04 trial (2022), the FDA expanded the approval of the HER2 antibody-drug conjugate (T-Dxd) from metastatic breast cancer patients with HER2 protein over-expression/amplification, to also include metastatic patients with HER2 IHC 1+ or 2+ & ISH negative results. This clinical trial adopted a new terminology, HER2 Low, which successfully prolonged both progression-free survival (PFS) and overall survival (OS). Material and Method: A descriptive and retrospective analysis was performed, including all patients diagnosed with Invasive breast cancer in HCG cancer Centre, Ahmedabad- Triesta Laboratory between 1st July 2022 to 31st June 2023. Total of 395 patients of both genders were studied. All those individuals who were diagnosed with Invasive breast carcinoma according to WHO and CAP guideline by H&E, IHC and FISH test were included in our study and those with missing data were excluded from our study. Result: This was a descriptive and retrospective study where 395 cases were diagnosed as breast cancer. HER2 low pattern was found commonly in 4th and 6th decades of life. In our study, out of 395 cases, 34.9% (n = 138) were HER2-negative, 39.5% (n = 156) were HER2-low, and 25.6% (n = 101) were HER2-positive. Among 156 HER2-low cases, 15.4% (24/156) cases were hormone negative, and 84.6% (132/156) cases were hormone positive. Conclusion: We observed that approximately 40 % of the cases were recategorized to be HER2 low which were classified HER2 negative according to old guidelines. Approximately 84% cases of HER2 low group were hormone positive. With the development of novel ADCs and other targeted agents, the treatment strategies for HER2-low breast cancer are expanding, and hence detecting low expression levels of HER2 is important.

Enhancing Breast Cancer Survival Prognosis Through Omic and Non-Omic Data Integration

Background and ObjectiveCancer, the second leading cause of death globally, claimed 685,000 lives among 2.3 million women affected by breast cancer in 2020. Cancer prognosis plays a pivotal role in tailoring treatments and assessing efficacy, emphasizing the need for a comprehensive understanding. The goal is to develop predictive model capable of accurately predicting patient outcomes and guiding personalized treatment strategies, thereby advancing precision medicine in breast cancer care. MethodsThis project addresses limitations in current cancer prognosis models by integrating omics and non-omics data. While existing models often neglect crucial omics data like DNA methylation and miRNA, the method utilizes the TCGA dataset to incorporate these data types along with others. Employing mRMR feature selection and CNN models for each type of data for feature extraction, features are stacked and a Random Forest classifier is employed for final prognosis. ResultThe proposed method is applied to the dataset to predict whether the patient is a long-time or a short-time survivor. This strategy showcases excellent performance, with an AUC value of 0.873, precision at 0.881, and sensitivity reaching 0.943. With an accuracy rate of 0.861, signaling an improvement of 11.96% compared to prior studies. ConclusionIn conclusion, integrating diverse data with advanced machine learning holds promise for improving breast cancer prognosis. Addressing model limitations and leveraging comprehensive datasets can enhance accuracy, paving the way for better patient care. Further refinement offers potential for significant advancements in cancer prognosis and treatment strategies.

A manganese-doped layered double hydroxide loaded with lactate oxidase and DNA repair inhibitors for synergistically enhanced tumor immunotherapy

Tumor immunotherapy has gained more and more attention in tumor treatment. However, the accumulation of lactic acid in tumor tissue inhibits the response of immune cells to form an immunosuppressive microenvironment (ISME). To reverse the ISME, an acid-responsive nanoplatform (termed as MLLN@HA) is reported for synergistically enhanced tumor immunotherapy. MLLN@HA is constructed by the co-loading of lactate oxidase (LOX) and DNA repair inhibitor (NU7441) in a manganese-doped layered double hydroxide (Mn-LDH), and then modified with hyaluronic acid (HA) for tumor-targeted delivery. After endocytosis by tumor cells, MLLN@HA decomposes and releases LOX, NU7441 and Mn2+ ions in the acidic tumor microenvironment. The released LOX catalyzes the conversion of lactic acid into hydrogen peroxide (H2O2), which not only alleviates the ISME, but also provides reactants for the Mn2+-mediated Fenton-like reaction to enhance chemodynamic therapy (CDT). Released NU7441 prevents CDT-induced DNA damage from being repaired, thereby increasing double-stranded DNA (dsDNA) fragments within tumor cells. Importantly, the released Mn2+ ions enhance the sensitivity of cyclic GMP-AMP synthase (cGAS) to dsDNA fragments, and activate the stimulator of interferon genes (STING) to induce an anti-tumor immune response. Such an orchestrated immune-boosting strategy ultimately achieves effective tumor growth inhibition and prevents tumor lung metastasis. Statement of significanceTo improve the efficacy of tumor immunotherapy, an innovative acid-responsive MLLN@HA nanoplatform was developed for synergistically enhanced tumor immunotherapy. The MLLN@HA actively targets to tumor cells through the interaction of HA with CD44, and then degrades to release LOX, NU7441 and Mn2+ ions in the acidic tumor microenvironment. The released LOX generates H2O2 for the Mn2+-mediated Fenton reaction and reverses the ISME by consuming lactate. NU7441 prevents DNA damage repair, leading to an increased concentration of free DNA fragments, while Mn2+ ions activate the cGAS-STING pathway, enhancing the systemic anti-tumor immune response. The orchestrated immune-boosting nanoplatform effectively inhibits tumor growth and lung metastasis, presenting a promising strategy for cancer treatment.

Short-term and three-year long-term outcomes of laparoscopic surgery versus open surgery for obstructive colorectal cancer following self-expandable metallic stent placement: a meta-analysis.

A bridge to surgery (BTS) after self-expandable metallic stent (SEMS) placement is a widely recognized treatment strategy for obstructive colorectal cancer. However, there is still a lack of evidence for the efficacy and safety of laparoscopic surgery following SEMS placement. The aim of this systematic review and meta-analysis was to compare the short-term and long-term outcomes of laparoscopic surgery with those of open surgery following SEMS placement in patients with obstructive colorectal cancer. An electronic literature search through to December 2022 was performed to identify studies comparing short-term and long-term outcomes between laparoscopic and open surgery following SEMS placement for obstructive colorectal cancer. The main outcome measures were postoperative complication rates and mortality. Secondary outcome measures were the 3-year recurrence-free survival (RFS) and 3-year overall survival (OS) rates. The meta-analysis was performed using fixed-effect or random-effects methods to calculate odds ratios (ORs) with 95% confidence intervals (95% CIs). The meta-analysis included 15 studies and 883 patients, of whom 467 (52.9%) underwent laparoscopic surgery and 416 (47.1%) underwent open surgery following SEMS placement. The postoperative complication rate was significantly lower in the laparoscopic surgery group than in the open surgery group (OR 0.47, 95% CI 0.32-0.67, P < 0.001). There was no significant difference in the 3-year RFS rate or 3-year OS rate between the laparoscopic and open surgery groups (3-year RFS, OR 0.78, 95% CI 0.50-1.24, P = 0.30; 3-year OS, OR 0.68, 95% CI 0.41-1.12, P = 0.13). This meta-analysis found that the short-term outcome was better in patients who underwent laparoscopic surgery following SEMS placement than in those who underwent open surgery. Furthermore, there was no significant difference in long-term outcomes between the two groups. Laparoscopic surgery following SEMS placement may be a safe and effective treatment option for obstructive colorectal cancer.

Treatment Strategies for BCG Unresponsive Non-muscle Invasive Bladder Cancer

Treatment Strategies for BCG Unresponsive Non-muscle Invasive Bladder Cancer

Single-cell RNA Sequencing Analysis Reveals Cancer-associated Fibroblast Signature for Prediction of Clinical Outcomes and Immunotherapy in Gastric Cancer.

Gastric cancer (GC) is a significant worldwide health concern and is a leading cause of cancer-related mortality. Immunotherapy has arisen as a promising strategy to stimulate the patient's immune system in combating cancer cells. Nevertheless, the effectiveness of immunotherapy in individuals with gastric cancer (GC) is not yet optimal. Thus, it is crucial to discover biomarkers capable appof predicting the advantages of immunotherapy for tailored treatment. The tumor microenvironment (TME) and its constituents, including cancer-associated fibroblasts (CAFs), exert a substantial influence on immune responses and treatment outcomes. In this investigation, we utilized single-cell RNA sequencing to profile CAFs in GC and established a scoring method, referred to as the CAF score (CAFS), for the prediction of patient prognosis and response to immunotherapy. Through our analysis, we successfully identified distinct subgroups within CAFs based on CAF score (CAFS), namely CAFS-high and CAFS-low subgroups. Notably, we noted that individuals within the CAFS-high subgroup experienced a lessF favorable prognosis and displayed diminished responsiveness to immunotherapy in contrast to the CAFS low subgroup. Furthermore, we analyzed the mutation and immune characteristics of these subgroups, identifying differentially mutated genes and immune cell compositions. We established that CAFS could forecast treatment advantages in patients with gastric cancer, both for chemotherapy and immunotherapy. Its efficacy was additionally confirmed in contrast to other biomarkers, including Tumor Immune Dysfunction and Exclusion (TIDE) and Immunophenotypic Score (IPS). These findings emphasize the clinical relevance and potential utility of CAFS in guiding personalized treatment strategies for gastric cancer.

A Narrative Review: Repurposing Metformin as a Potential Therapeutic Agent for Oral Cancer.

Oral cancer, particularly oral squamous cell carcinoma (OSCC), is a significant global health challenge because of its high incidence and limited treatment options. Major risk factors, including tobacco use, alcohol consumption, and specific microbiota, contribute to the disease's prevalence. Recently, a compelling association between diabetes mellitus (DM) and oral cancer has been identified, with metformin, a widely used antidiabetic drug, emerging as a potential therapeutic agent across various cancers, including OSCC. This review explores both preclinical and clinical studies to understand the mechanisms by which metformin may exert its anticancer effects, such as inhibiting cancer cell proliferation, inducing apoptosis, and enhancing the efficacy of existing treatments. Preclinical studies demonstrate that metformin modulates crucial metabolic pathways, reduces inflammation, and impacts cellular proliferation, thereby potentially lowering cancer risk and improving patient outcomes. Additionally, metformin's ability to reverse epithelial-to-mesenchymal transition (EMT), regulate the LIN28/let-7 axis, and its therapeutic role in head and neck squamous cell carcinoma (HNSCC) are examined through experimental models. In clinical contexts, metformin shows promise in enhancing therapeutic outcomes and reducing recurrence rates, although challenges such as drug interactions, complex dosing regimens, and risks such as vitamin B12 deficiency remain. Future research should focus on optimizing metformin's application, investigating its synergistic effects with other therapies, and conducting rigorous clinical trials to validate its efficacy in OSCC treatment. This dual exploration underscores metformin's potential to play a transformative role in both diabetes management and cancer care, potentially revolutionizing oral cancer treatment strategies.

Personalized Dendritic-cell-based Vaccines Targeting Cancer Neoantigens.

Cancer immunotherapy activates the host immune system against tumor cells and has the potential to lead to the development of innovative strategies for cancer treatment. Neoantigens are non-self-antigens produced by genetic mutations in tumor cells that induce a strong immune response against tumor cells without central immune tolerance. Along with advances in neoantigen analysis technology, the development of vaccines focusing on neoantigens is being accelerated. Whereas there are various platforms for neoantigen vaccines, combined immuno-therapies are being developed simultaneously with the clinical application of synthetic long peptides and mRNA and dendritic-cell (DC)-based vaccines. Personalized DC-based vaccines not only can load various antigens including neoantigens, but also have the potential to elicit a strong immune response in T cells as antigen-presenting cells. In this review, we describe the properties of neoantigens and the basic characteristics of DCs. We also discuss the clinical applications of neoantigen vaccines, focusing on personalized DC-based vaccines, as well as future research and development directions and challenges.

A Bioinformatics Investigation of Hub Genes Involved in Treg Migration and Its Synergistic Effects, Using Immune Checkpoint Inhibitors for Immunotherapies.

This study aimed to identify hub genes involved in regulatory T cell (Treg) function and migration, offering insights into potential therapeutic targets for cancer immunotherapy. We performed a comprehensive bioinformatics analysis using three gene expression microarray datasets from the GEO database. Differentially expressed genes (DEGs) were identified to pathway enrichment analysis to explore their functional roles and potential pathways. A protein-protein interaction network was constructed to identify hub genes critical for Treg activity. We further evaluated the co-expression of these hub genes with immune checkpoint proteins (PD-1, PD-L1, CTLA4) and assessed their prognostic significance. Through this comprehensive analysis, we identified CCR8 as a key player in Treg migration and explored its potential synergistic effects with ICIs. Our findings suggest that CCR8-targeted therapies could enhance cancer immunotherapy outcomes, with breast invasive carcinoma (BRCA) emerging as a promising indication for combination therapy. This study highlights the potential of CCR8 as a biomarker and therapeutic target, contributing to the development of targeted cancer treatment strategies.

Iturin A and Gramicidin A inhibit proliferation, trigger apoptosis, and regulate inflammation in breast cancer cells

Biosurfactants with antibiotic, antiviral, anti-tumor, and immunomodulatory properties appear to have potential in cancer treatment due to their lack of known toxicities compared with conventional chemotherapy. However, there are few studies on the use of biosurfactants for the treatment of breast cancer. In this study, to develop a new strategy for breast cancer treatment, we evaluated the anti-proliferative, anti-inflammatory, anti-tumor, and apoptotic effects of two different biosurfactants (Iturin A and Gramicidin A) from bacillus in both single and binary combination on two breast cancer cell lines (MDA-MB-231 and MCF-7, which is estrogen receptor-negative and positive, respectively). First, the anti-proliferative effects of Iturin A and Gramicidin A, both single and in combination, were explored by MTT assay. Then, the effects of Iturin A and Gramicidin A on inflammatory factors were evaluated using the ELISA method. Apoptosis was assessed using Annexin V-PE/7-AAD and Giemsa staining methods. RT-qPCR analysis was used to evaluate the expressions of several cytokines with anti-tumor and apoptotic properties and the apoptotic BAX and BCL2 genes. Biosurfactants showed anti-proliferative and anti-tumor properties by decreasing the viability of MDA-MB-231 and MCF-7 cells depending on concentration and time (p < 0.05-p<0.01). Biosurfactants induced apoptosis by stimulating apoptotic cell death (p < 0.05-p<0.001) and by increasing BAX and decreasing BCL2 gene expression levels (p < 0.05-p<0.001) in breast cancer cells. Biosurfactants also regulated the expressions of extracellular and intracellular cytokines (IL-2, IL-6, IL-12, IL12RB2, TGFβ, TNFα, VEGF) and chemokines (IL-8, CCL2, CXCL10) in breast cancer cells (p < 0.05-p<0.01). Both single and binary combination applications of Iturin A and Gramicidin A biosurfactants, may potentially treat breast cancer patients, and the in vitro results presented here warrant further in vivo studies.

Multi-Sensitive Au NCs/5-FU@Carr-LA Composite Hydrogels for Targeted Multimodal Anti-Tumor Therapy.

Multifunctional targeted drug delivery systems have been explored as a novel cancer treatment strategy to overcome limitations of traditional chemotherapy. The combination of photodynamic therapy and chemotherapy has been shown to enhance efficacy, but the phototoxicity of traditional photosensitizers is a challenge. In this study, we prepared a multi-sensitive composite hydrogel containing gold nanoclusters (Au NCs) and the temperature-sensitive antitumor drug 5-fluorourac il (5-FU) using carboxymethyl cellulose (Carr) as a dual-functional template. Au NCs were synthesized using sodium borohydride as a reducing agent and potassium as a promoter. The resulting Au NCs were embedded in the Carr hydrogel, which was then conjugated with lactobionic acid (LA) as a targeting ligand. The resulting Au NCs/5-FU@Carr-LA composite hydrogel was used for synergistic photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy. Au NCs/5-FU@Carr-LA releases the drug faster at pH 5.0 due to the acid sensitivity of the Carr polymer chain. In addition, at 50 °C, the release rate of Au NCs/5-FU@Carr-LA is 78.2%, indicating that the higher temperature generated by the photothermal effect is conducive to the degradation of Carr polymer chains. The Carr hydrogel stabilized the Au NCs and acted as a matrix for drug loading, and the LA ligand facilitated targeted delivery to tumor cells. The composite hydrogel exhibited excellent biocompatibility and synergistic antitumor efficacy, as demonstrated by in vitro and in vivo experiments. In addition, the hydrogel had thermal imaging capabilities, making it a promising multifunctional platform for targeted cancer therapy.

Camrelizumab plus apatinib in patients with advanced or recurrent endometrial cancer after failure of at least one prior systemic therapy (CAP 04): a single-arm phase II trial

BackgroundThe combination of anti-programmed death 1 (PD-1) inhibitors and tyrosine kinase inhibitors is an effective treatment strategy in endometrial cancer. We aimed to explore the efficacy and safety of camrelizumab plus apatinib as an alternative therapeutic option in patients with previously treated endometrial cancer.MethodsThis single-arm Simon’s two-stage phase II trial was conducted at the Fudan University Shanghai Cancer Center. Patients with advanced or recurrent endometrial cancer who had failed at least one prior systemic therapy were screened for potential participation. Eligible patients were treated with intravenous camrelizumab (200 mg d1 q2w) and oral apatinib (250 mg qd) every 4 weeks. The primary end point was the objective response rate (ORR) per RECIST v1.1 in the intention-to-treat principle.ResultsBetween January 20, 2020, and October 14, 2022, 36 patients (29 with microsatellite stability/mismatch repair proficient [MSS/pMMR] tumors; two with microsatellite instability-high/mismatch repair deficient [MSI-H/dMMR] tumors) were enrolled and treated. The confirmed ORR was 44.4% (95% CI: 27.9, 61.9) and the disease control rate was 91.7% (95% CI: 77.5, 98.2). The median duration of response was 9.3 (95% CI: 4.3, not reached) months, the median progression-free survival was 6.2 (95% CI: 5.3, 11.1) months, and the median overall survival was 21.0 (95% CI: 13.4, not reached) months during a median follow-up of 14.2 (interquartile range: 10.3, 27.6) months. Treatment-related adverse events of grade 3 or 4 occurred in 20 (55.6%) patients, with the most common being increased γ-glutamyl transferase (27.8%), alanine aminotransferase (16.7%) and aspartate aminotransferase (13.9%), and hypertension (11.1%). No treatment-related death occurred.ConclusionsCamrelizumab plus apatinib showed promising antitumor activity with manageable toxicity in patients with advanced or recurrent endometrial cancer who had failed at least one prior systemic therapy. The findings of this study support further investigation of camrelizumab plus apatinib as an alternative therapeutic option, especially for patients with MSS/pMMR tumors.Trial registrationThis trial was retrospectively registered with ChiCTR.org.cn, number ChiCTR2000031932.