Immune checkpoint inhibitors (ICIs) are potent and precise therapies for various cancer types, significantly improving survival rates in patients who respond positively to them. However, only a minority of patients benefit from ICI treatments.

Identifying ICI responders before treatment could greatly conserve medical resources, minimize potential drug side effects, and expedite the search for alternative therapies. Our goal is to introduce a novel deep-learning method to predict ICI treatment responses in cancer patients.

The proposed deep-learning framework leverages graph neural network and biological pathway knowledge. We trained and tested our method using ICI-treated patients' data from several clinical trials covering melanoma, gastric cancer, and bladder cancer.

Our results demonstrate that this predictive model outperforms current state-of-the-art methods and tumor microenvironment-based predictors. Additionally, the model quantifies the importance of pathways, pathway interactions, and genes in its predictions. A web server for IRnet has been developed and deployed, providing broad accessibility to users at https://irnet.missouri.edu.

IRnet is a competitive tool for predicting patient responses to immunotherapy, specifically ICIs. Its interpretability also offers valuable insights into the mechanisms underlying ICI treatments.

The tumor microenvironment (TME) plays a crucial role in the occurrence and progression of gastric cancer. Yet, we still don't understand how immune and stromal components of TMEs are modulated. In this study, we applied the ESTIMATE algorithm to calculate the number of immune and stromal components in 410 STAD cases in the Cancer Genome Atlas (TCGA) database. COX regression analysis and protein-protein interaction (PPI) network construction were used to analyze differentially expressed genes (DEGs). Then, P-selectin (SELP) was identified as a predictor by cross-analysis of univariate COX and PPI. After verifying the clinical significance of SELP for study, we performed an immune infiltration analysis and identified 54 immunomodulators associated with SELP through public data. Immunomodulation associated with gastric cancer prognosis was then confirmed by LASSO regression, and the previous results were further validated with single-cell data. Finally, we verified that SELP can promote EMT on gastric cancer cells. In conclusion, we validated that SELP may affect the biological phenotype of gastric cancer with the immune microenvironment alteration of gastric cancer.

Osteosarcoma, an aggressive bone malignancy predominantly affecting children and adolescents, is characterized by a poor prognosis and high mortality rates. The development of reliable prognostic tools is critical for advancing personalized treatment strategies. However, identifying robust gene signatures to predict osteosarcoma outcomes remains a significant challenge. In this study, we analyzed gene expression data from 138 osteosarcoma samples across two multicenter cohorts and identified 14 consensus prognosis-associated genes via univariate Cox regression analysis. Using 66 combinations of 10 machine learning (ML) algorithms, we developed a machine learning-derived prognostic signature (MLDPS) optimized by the average C-index across TARGET, GSE21257, and merged cohorts. The MLDPS effectively stratified osteosarcoma patients into high- and low-risk score groups, achieving strong predictive performance for 1-, 3-, and 5-year overall survival (AUC range: 0.852 - 0.963). The MLDPS, comprising seven genes (CTNNBIP1, CORT, DLX2, TERT, BBS4, SLC7A1, NKX2-3), exhibited superior predictive accuracy compared to 10 established gene signatures. The findings of the MLDPS carry significant clinical implications for osteosarcoma treatment. Patients with a high-risk score demonstrated worse prognosis, increased metastasis risk, reduced immune infiltrations, and greater sensitivity to immunotherapy. Conversely, low-risk patients exhibited prolonged survival and distinct drug sensitivities. These findings underscore the potential of MLDPS to guide risk stratification, inform personalized therapeutic strategies, and improve clinical management in osteosarcoma.

Anesthesia and perioperative management significantly influence long-term outcomes in patients with early and intermediate stage cancer. Midazolam, a commonly used benzodiazepine anesthetic, has shown potential anti-tumor effects. This study aimed to explore the anti-tumor properties of midazolam in non-small cell lung cancer (NSCLC). The anti-tumor effects of midazolam on A549 and H1650 NSCLC cell lines were assessed using CCK-8 assays, colony-forming assays, and the Annexin V-fluorescein isothiocyanate Apoptosis Detection Kit I. Additionally, Transwell assays were conducted in vitro, and subcutaneous tumor models in nude mice were established to assess the anti-tumor effects in vivo. The interaction within the lncRNA XLOC_010706/miR-520d-5p/STAT3 axis was confirmed through dual-luciferase reporter assays, RT-qPCR, and Western blotting. Midazolam significantly inhibited cell proliferation and invasion while inducing apoptosis in A549 and H1650 cells, both in vitro and in vivo, by promoting autophagy (P<0.05). It also down-regulated the expression of lncRNA XLOC_010706 in the tumor microenvironment (P<0.05). Within the signaling pathway, lncRNA XLOC_010706 functioned as a competing endogenous RNA (ceRNA) targeting miR-520d-5p, with STAT3 identified as a functional target gene for miR-520d-5p in NSCLC. Furthermore, lncRNA XLOC_010706 acted as an oncogene, promoting cell proliferation and invasion while inhibiting apoptosis through the miR-520d-5p/STAT3 axis. Midazolam down-regulates the expression of lncRNA XLOC_010706, which acts as an oncogene in NSCLC. The anti-tumor effects of midazolam occur via the lncRNA XLOC_010706/miR-520d-5p/STAT3 pathway, enhancing autophagy in NSCLC. This indicates that lncRNA XLOC_010706 could serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients.

Liquid biopsy is a laboratory test used to detect and analyze circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and other tumor-derived components, in a blood sample. In the context of breast cancer (BC), liquid biopsies hold significant promise for guiding the use of immune checkpoint inhibitors and immune-based combinations, offering real-time insights into tumor dynamics, treatment response, and resistance mechanisms. This review explores the role of liquid biopsy in BC immunotherapy, focusing on its applications, benefits, issues, and current and future research directions.

Hepatoid adenocarcinoma of the stomach (HAS) is a rare and aggressive malignancy with poor prognosis. HAS is characterized by both adenocarcinoma and hepatocellular carcinoma like differentiation, which often produces alpha-fetoprotein (AFP) and responds poorly to systemic chemotherapy. Herein we report a case of 62-year-old male diagnosed with liver metastatic HAS, who progressed rapidly after first-line cisplatin + fluorouracil chemotherapy combined with pembrolizumab. However, the patient achieved favourable outcome after second-line oxaliplatin + capecitatine chemotherapy combined with pembrolizumab. This case indicated that the chemotherapy regimen might influence the efficacy of immune check-point inhibiors plus chemotherapy.

BackgroundIpilimumab disinhibits immune system activity which results in the elimination of malignant cells. An unintended consequence of ipilimumab therapy is off-target immune-related adverse events (irAEs). It has therefore been proposed that the incidence of irAEs is a manifestation of treatment effectiveness. The objective of this systematic review is to examine the relationship between irAEs and survivability among melanoma patients administered ipilimumab monotherapy.MethodsA comprehensive search was conducted across several databases which yielded a total of 2381 studies. Clinical trials and prospective studies administering ipilimumab monotherapy to melanoma patients were included. Furthermore, there was no restriction placed on publication date. After screening, five studies were included for data extraction. The primary outcome of median overall survival (OS) and the secondary outcome of OS hazard ratio were extracted from the included studies.ResultsBased on qualitative analysis of the included studies, there seemed to be an association between the occurrence of non-lethal irAEs and improved survival outcomes among melanoma patients administered ipilimumab monotherapy. With that being said, the poorer survivability among patients who experienced high-grade irAEs may be the result of subsequent treatment discontinuation. Potential confounders such as corticosteroid use should be accounted for. Finally, landmark analyses may be conducted to account for immortal time bias.ConclusionsThe findings from this systematic review provide evidence suggesting that the incidence of irAEs is a marker of an improved anti-tumor response.

Pembrolizumab has been approved as a first-line treatment for non-small cell lung cancer (NSCLC) patients. However, a percentage of patients discontinue immunotherapy due to immune-related adverse events (irAE). Among these events, immune-related endocrine toxicities (E-irAE) represents the most common form, though their etiology, risk factors, and impact on patient outcomes remain poorly understood.

This retrospective cohort study was conducted across 5 multiple centers to investigate the outcomes of NSCLC patients who received pembrolizumab treatment between October 1, 2019, and September 30, 2023. E-irAE can occur on the thyroid, pituitary, adrenal glands, pancreas, and parathyroid. So thyroid function, adrenocorticotropic hormone, cortisol, sex hormone and glycaemia were measured at baseline and at regular intervals after the initiation of pembrolizumab treatment.

Our study included a total of 380 NSCLC patients treated with pembrolizumab, 114 patients (30.00%) developed E-irAE. Among them, 107 patients (93.86%) developed immune-related thyroid dysfunction (irTD) (5 cases of combined immune-related hypophysitis (IH)), 4 patients (3.51%) only developed IH, and 3 patients (2.63%) developed type 1 diabetes mellitus. IrTD was found to be independently associated only with monocyte-to-lymphocyte ratio (MLR) (odds ratios (OR) = 0.060, 95% CI 0.000-0.375; p = 0.015) and anti-thyroglobulin antibody (TGAb) (OR = 31.898, 95% CI 1.516-671.367; p = 0.026). Kaplan-Meier Survival Analysis showed that the progression-free survival (PFS) was significant longer in stage IV NSCLC patients with irTD than in those who did not (44.72 weeks vs. 27.79 weeks; hazard ratio (HR) = 0.645, 95% CI 0.440-0.946; p = 0.025), particularly in the subgroup of subclinical hypothyroidism (HR = 0.567, 95% CI 0.324-0.994; p = 0.047). We also found that sex (HR = 0.493, 95% CI 0.291-0.834; p = 0.008) was identified as an independent factor associated with better PFS.

E-irAE are recognized as prevalent common irAE with various phenotypic manifestations. Low MLR and positive TGAb at baseline have been identified as risk factors that increase the likelihood of developing irTD. Sex and the occurrence of irTD were independently associated with improved PFS.

In the past decade, there has been a significant advancement in targeted therapy and immunotherapy, leading to the discovery of new drugs and changes in the treatment approach for patients with HER2-positive gastric cancer. Although several drugs are available for treating these patients, there is still no consensus on their selection, and there has been limited direct or indirect comparison among them.

To address this gap, a network meta-analysis was conducted to assess the efficacy and safety of different drugs used in the treatment of HER2-positive gastric cancer.

By searching through databases such as PubMed, Embase, Web of Science, and Cochrane Library, we identified 16 randomized controlled trials that involved a total of 4485 patients and utilized 9 different intervention measures.

Based on the current evidence, compared with chemotherapy alone, the hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS) in gastric cancer patients treated with nivolumab were [hazard ratio (HR): 2.61 95%confidence interval (CI) (1.51, 4.51)] and [hazard ratio (HR): 2.01 95% confidence interval (CI) (1.18, 3.42)], respectively. Compared with chemotherapy alone, the hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS) in gastric cancer patients treated with trastuzumab deruxtecan were [hazard ratio (HR): 1.7 95% confidence interval (CI) (1.13, 2.56)] and [hazard ratio (HR): 2.13 95% confidence interval (CI) (1.42, 3.22)], respectively. It is suggested that nivolumab and trastuzumab deruxtecan can effectively prolong overall survival (OS) and progression-free survival(PFS) in patients with HER2-positive gastric cancer, while also reducing the risk of adverse events to some extent. Therefore, these two regimens, nivolumab and trastuzumab deruxtecan, are considered to be effective and safe options for the treatment of patients with HER2-positive gastric cancer.

In previous studies, trastuzumab-based chemotherapy has been a common treatment for HER2-positive gastric cancer. To a certain extent, our study provides a reliable direction for future treatment options for HER2-positive gastric cancer.

PROSPERO CRD42023420941.

The immune resistance of tumor microenvironment (TME) causes immune checkpoint blockade therapy inefficient to hepatocellular carcinoma (HCC). Emerging strategies of using chemotherapy regimens to reverse the immune resistance provide the promise for promoting the efficiency of immune checkpoint inhibitors. The induction of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) in tumor cells evokes the adaptive immunity and remodels the immunosuppressive TME. In this study, we report that mitoxantrone (MIT, a chemotherapeutic drug) activates the cGAS-STING signaling pathway of HCC cells. We provide an approach to augment the efficacy of MIT using a signal transducer and activator of transcription 3 (STAT3) inhibitor called napabucasin (NAP). We prepare an aminoethyl anisamide (AEAA)-targeted polyethylene glycol (PEG)-modified poly (lactic-co-glycolic acid) (PLGA)-based nanocarrier for co-delivery of MIT and NAP. The resultant co-nanoformulation can elicit the cGAS-STING-based immune responses to reshape the immunoresistant TME in the mice orthotopically grafted with HCC. Consequently, the resultant co-nanoformulation can promote anti-PD-1 antibody for suppressing HCC development, generating long-term survival, and inhibiting tumor recurrence. This study reveals the potential of MIT to activate the cGAS-STING signaling pathway, and confirms the feasibility of nano co-delivery for MIT and NAP on achieving HCC chemo-immunotherapy.

Liver cancer remains a significant global health challenge, characterized by high incidence and mortality rates. Despite advancements in medical treatments, the prognosis for liver cancer patients remains poor, highlighting the urgent need for novel therapeutic approaches. Traditional Chinese medicine (TCM), particularly Calculus bovis (CB), has shown promise in addressing this need due to its multi-target therapeutic mechanisms. CB refers to natural or synthetic gallstones, traditionally sourced from cattle, and used in TCM for their anti-inflammatory, detoxifying, and therapeutic properties. In modern practice, synthetic CB is often utilized to ensure consistent supply and safety. This article aims to discuss the findings of Huang et al, who investigated the anti-liver cancer properties of CB, focusing on its ability to inhibit M2 tumor-associated macrophage (TAM) polarization via modulation of the Wnt/β-catenin pathway. Huang et al employed a comprehensive approach integrating chemical analysis, animal model testing, and advanced bioinformatics. They identified active components of CB using UPLC-Q-TOF-MS, evaluated its anti-neoplastic effects in a nude mouse model, and elucidated the underlying mechanisms through network pharmacology, transcriptomics, and molecular docking studies. The study demonstrated that CB significantly inhibited liver tumor growth in vivo, as evidenced by reduced tumor size and weight in treated mice. Histological analyses confirmed signs of tumor regression. CB was found to modulate the tumor microenvironment by inhibiting the polarization of M2 phenotype-TAMs, as shown by reduced expression of M2 markers and downregulation of mRNA levels of C-C motif chemokine 22, arginase-1, transforming growth factor-beta 2, and interleukin-10. The study further revealed that CB's antineoplastic activity involved the downregulation of Wnt5B and β-catenin and upregulation of Axin2, thus inhibiting the Wnt/β-catenin signaling pathway. These findings highlight the therapeutic potential of CB in liver cancer treatment through its modulation of the Wnt/β-catenin pathway and suppression of M2 phenotype-TAM polarization. This study underscores the value of integrating TCM with modern therapeutic strategies to develop novel effective treatments for liver cancer.

Non-small cell lung cancer (NSCLC) patients often benefit from EGFR inhibitors like gefitinib. However, drug resistance remains a significant challenge in treatment. The unique properties of 1,2,3-triazole, a nitrogen-based compound, hold promise as potential solutions due to its versatile structural attributes and diverse biological effects, including anticancer properties.

Our synthesis process involved the huisgen cycloaddition chemical method, which generated diverse icotinib derivatives. We evaluated the anticancer capabilities of these derivatives against various cancer cell lines, with a specific focus on NSCLC cells that exhibit drug resistance. Additionally, we investigated the binding affinity of selected compounds, including 3l, towards wild-type EGFR using surface plasmon resonance (SPR) experiments.

Notably, icotinib derivatives such as derivative 3l demonstrated significant efficacy against different cancer cell lines, including those resistant to conventional therapies. Compound 3l exhibited potent activity with IC50 values below 10 μM against drug-resistant cells. SPR experiments revealed that 3l exhibited enhanced affinity towards wild-type EGFR compared to icotinib. Our research findings suggest that 3l acts as a compelling antagonist for the protein tyrosine kinase of EGFR (EGFR-PTK).

Icotinib derivative 3l, featuring a 1,2,3-triazole ring, demonstrates potent anticancer effects against drug-resistant NSCLC cells. Its enhanced binding affinity to EGFR and modulation of the EGFR-RAS-RAF-MAPK pathway position 3l as a promising candidate for the future development of anticancer drugs.

Sorafenib is currently the first choice for the treatment of patients with advanced hepatocellular carcinoma, but its therapeutic effect is still limited.

This study aims to examine whether WEE family kinase inhibitors can enhance the anticancer effect of sorafenib.

We analyzed the expression levels of PKMYT1 kinase and WEE1 kinase in HCC, studied the inhibitory effect of PKMYT1 kinase inhibitor RP-6306, WEE1 kinase inhibitor adavosertib combined with sorafenib on the proliferation of HCC cells, and detected the effect of drug combination on CDK1 phosphorylation.

We found that PKMYT1 and WEE1 were upregulated in HCC and were detrimental to patient survival. Cell experiments showed that both RP-6306 and adavosertib (1-100 μM) inhibited the proliferation of HCC cell lines in a dose-dependent manner alone, and the combination of the two drugs had a synergistic effect. In HCC cell lines, sorafenib combined with RP-6306 or adavosertib showed a synergistic antiproliferation effect and less toxicity to normal cells. Sorafenib combined with RP-6306 and adavosertib further inhibited the proliferation of HCC cells and caused complete dephosphorylation of CDK1.

Taken together, our findings provide experimental evidence for the future use of sorafenib in combination with RP-6306 or adavosertib for the treatment of HCC.

Non-small cell lung cancer (NSCLC) represents the leading cause of cancer deaths in the world. We previously found that daidzein, one of the key bioactivators in soy isoflavone, can inhibit NSCLC cell proliferation and migration, while the molecular mechanisms of daidzein in NSCLC remain unclear.

We developed an NSCLC nude mouse model using H1299 cells and treated the mice with daidzein (30 mg/kg/day). Mass spectrometry analysis of tumor tissues from daidzein-treated mice identified 601 differentially expressed proteins (DEPs) compared to the vehicle-treated group. Gene enrichment analysis revealed that these DEPs were primarily associated with immune regulatory functions, including B cell receptor and chemokine pathways, as well as natural killer cell-mediated cytotoxicity. Notably, the NOD-like receptor signaling pathway, which is closely linked to pyroptosis, was significantly enriched.

Further analysis of key pyroptosis-related molecules, such as ASC, CASP1, GSDMD, and IL-1β, revealed differential expression in NSCLC versus normal tissues. High levels of ASC and CASP1 were associated with a favorable prognosis in NSCLC, suggesting that they may be critical effectors of daidzein's action. In NSCLC-bearing mice treated with daidzein, RT-qPCR and Western blot analyses showed elevated mRNA and protein levels of ASC, CASP1, and IL-1β but not GSDMD, which was consistent with the proteomic data.

In summary, this study demonstrated that daidzein inhibits NSCLC growth by inducing pyroptosis. Key pathway modulators ASC, CASP1, and IL-1β were identified as primary targets of daidzein. These findings offer insights into the molecular mechanisms underlying the anti-NSCLC effects of daidzein and could offer dietary recommendations for managing NSCLC.

Circadian rhythm-related genes (CRRGs) play essential roles in cancer occurrence and development. However, the prognostic significance of CRRGs in breast cancer (BC) has not been fully elucidated. Our study aimed to develop a prognostic gene signature based on CRRGs that can accurately and stably predict the prognosis of BC.

The transcriptome data and clinical information for BC patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A consensus unsupervised clustering analysis was carried out to investigate the roles of CRRGs in BC. A CRRGs-related prognostic risk model was established by using logistic least absolute shrinkage and selection operator (LASSO) Cox regression and univariate Cox regression analyses. Kaplan-Meier (KM) curves analysis, time-dependent receptor operation characteristics (ROC) curves analysis, and nomogram were plotted to evaluate the predictive efficacy of the model. The relevance of risk score to the immune cell infiltration, tumor burden mutation (TMB), and therapeutic response was assessed.

A risk model comprising six CRRGs (SLC44A4, SLC16A6, TPRG1, FABP7, GLYATL2, and FDCSP) was constructed and validated, demonstrating an effective predictor for the prognosis of BC. The low-risk group displayed a higher expression of immune checkpoint genes and a lower burden of tumor mutation. Additionally, drug sensitivity analysis demonstrated that the prognostic signature may serve as a potential chemosensitivity predictor.

We established a CRRGs-related risk signature, which is of great value in predicting the prognosis of patients with BC and guiding the treatment for BC.

This study aimed to investigate the role of the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) in unresectable hepatocellular carcinoma (HCC) patients treated with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). The optical cutoff values of the NLR and PNI were determined via time-dependent receiver operating characteristic curve analysis. The associations between overall survival (OS) and various potential risk factors were analyzed. Forty-nine HCC patients were enrolled in this retrospective study. The optimal pretreatment NLR and PNI cutoff values were 2.4 and 41, respectively. The median follow-up was 8 (range 3-36) months. The median OS in the high NLR subgroup was lower than that in the low NLR subgroup (7 vs. 9 months, p < .05). However, the high PNI group had better OS than the low PNI group did (12 vs. 7 months, p < .05). Univariate analysis revealed that tumor distribution (p = .003), PNI < 41 (p = .013), and NLR ≥ 2.4 (p = .010) were associated with unfavorable OS in HCC patients. The multivariate analysis revealed that the PNI (HR = 0.353, 95% CI 0.150-0.831; p = .017) and tumor distribution (HR = 0.336, 95% CI 0.137-0.826; p = .017) were independent indicators of poor prognosis. A pretreatment NLR ≥ 2.4 and PNI < 41 are related to poor survival in unresectable HCC patients receiving TKI and ICI treatment. Moreover, a lower PNI is an independent indicator of poor prognosis when ICIs are combined with TKIs.

Gastric cancer (GC) is a significant global concern, ranking as the fifth most prevalent cancer. Unfortunately, the five-year survival rate is less than 30 %. Additionally, approximately 50 % of patients experience a recurrence or metastasis. As a result, finding new drugs to prevent relapse is of utmost importance.

The inhibitory effect of Dronedarone hydrochloride (DH) on gastric cancer cells was examined using proliferation assays and anchorage-dependent assays. The binding of DH with SRC was detected by molecular docking, pull-down assays, and cellular thermal shift assays (CETSA). DH's inhibition of Src kinase activity was confirmed through in vitro kinase assays. The SRC knockout cells, established using the CRISPR-Cas9 system, were used to verify Src's role in GC cell proliferation. Patient-derived xenograft (PDX) models were employed to elucidate that DH suppressed tumor growth in vivo.

Our research discovered DH inhibited GC cell proliferation in vitro and in vivo. DH bound to the SRC protein to inhibit the SRC/AKT1 signaling pathway in gastric cancer. Additionally, we observed a decrease in the sensitivity of gastric cancer cells to DH upon down-regulation of SRC. Notably, we demonstrated DH's anti-tumor effects were similar to those of Dasatinib, a well-known SRC inhibitor, in GC patient-derived xenograft models.

Our research has revealed that Dronedarone hydrochloride, an FDA-approved drug, is an SRC inhibitor that can suppress the growth of GC cells by blocking the SRC/AKT1 signaling pathway. It provides a scientific basis for use in the clinical treatment of GC.

Immune checkpoint inhibitors (ICIs) have demonstrated their efficacy with a 7.5-year overall survival (OS) close to 50% for advanced stages. The design of clinical trials provides for treatment until progression or toxicity, or for a maximum duration of two years. Prolonged follow-up of responders after treatment cessation shows sustained response and a low risk of relapse in the months following cessation. To date, the optimal duration of anti-PD-1 therapy for metastatic melanoma remains unestablished. The objective of this work was to evaluate the optimal duration of ICI administration.

We emulated target trials using the cloning, weighting and censoring approach. Each emulation trial aimed to compare the effect of discontinuing versus continuing ICIs at a specific timepoint, among patients still under treatment and with disease control at that time. Patients were from MelBase between 2015 and 2021.

435 participants in the MelBase cohort were eligible and were included in the 6-month discontinuation emulated trial. The results showed significantly lower OS when treatment was discontinued, than when treatment was prolonged for at least three months. The 48-month survival difference was 37.8% (95% confidence interval [CI] 19.8-60.5), and the corresponding restricted mean survival time difference was 8.3 months (95% CI: 4.1-12.7). Neither the 12-month nor the 18-month discontinuation emulated trials showed evidence of benefit of either discontinuing or continuing ICIs at either of these timepoints. The 24-month discontinuation emulated trial results were more in favor of discontinuing than continuing treatment at that time point, with an absolute 48-month survival rate that was 10.5% higher (95% CI 4.4-18.1).

These results suggest that a one-year course of immunotherapy is both necessary and sufficient for patients with advanced melanoma. Prolonged treatment beyond 2 years does not appear to be beneficial in terms of survival and could even be detrimental.

This work was supported by a grant from Bristol Myers Squibb, Merck Sharp Dhome, Pierre Fabre, Novartis, Sun Pharm, Regeneron, Sanofi, Nektar, Therapeutics and Oncyte.

During the progression of lung cancer, cancer pain is a common complication. Currently, there are no accurate tools or methods to predict the occurrence of cancer pain in lung cancer. Our study aims to construct a predictive model for lung cancer pain to assist in the early diagnosis of cancer pain and improve prognosis. We retrospectively collected clinical data from 300 lung cancer patients between March 2013 and March 2023. First, we compared the clinical data of the groups with and without cancer pain. Significant factors were further screened using random forest analysis (IncMSE% > 2) to identify those with significant differences. Finally, these factors were incorporated into a multifactorial logistic regression model to develop a predictive model for lung cancer pain. The predictive accuracy and performance of the model were assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) analysis. Our study collected data from 300 lung cancer patients, including 100 in the pain-free group and 200 in the pain group. Subsequently, we conducted univariate analysis on 22 factors and selected statistically significant factors using random forest methods. Ultimately, lymphocytes(LYM) percentage, bone metastasis, tumor necrosis factor alpha (TNFα), and interleukin-6 (IL6) were identified as key factors. These 4 factors were included in a multivariate logistic regression analysis to construct a predictive model for lung cancer pain. The model demonstrated good predictive ability, with an area under the curve (AUC) of 0.852 (95% CI: 0.806-0.899). The calibration curve indicated that the model has good accuracy in predicting the risk of lung cancer pain. DCA further emphasized the model's high accuracy. The model was finally validated using 5-fold cross-validation. We developed a reliable predictive model for cancer pain in lung cancer. This can provide a theoretical basis for future large-sample, multi-center studies and may also assist in the early prevention and intervention of cancer pain in lung cancer.

Immune checkpoint inhibitors (ICIs) are pharmacological agents indicated for recurrent and metastatic head and neck squamous cell carcinoma (HNCSCC). Immune-related adverse events (irAEs) have been reported as predictors of therapeutic response to ICIs. However, previous studies have not adequately addressed the immortal time bias. Therefore, we aimed to investigate the association between the onset of irAEs and oncological outcomes, accounting for immortal time bias. We conducted a retrospective study involving 130 patients with HNSCC who were treated with ICIs. The objective response, progression-free survival (PFS), and overall survival (OS) were assessed using logistic regression analysis, the Kaplan-Meier method, and the Cox proportional hazard (PH) model. The immortal time bias was considered using a landmark analysis and an extended Cox (EC) model. The odds ratios for response and disease control were smaller in the landmark than in the naïve analyses. In the landmark analysis, the 1-year PFS rates were 47.6% and 27.2% for irAE+ and irAE- patients, respectively (p = 0.049), and the 1-year OS rates were 85.7% and 66.5%, respectively (p = 0.006). Regarding PFS, the adjusted HRs for irAEs were 0.49 (95% confidence interval (CI) 0.28-0.85) in the PH analysis and 0.75 (95% CI 0.40-1.40) in the EC analysis. As for OS, the adjusted HRs for irAEs were 0.36 (95% CI 0.19-0.66) in the PH analysis and 0.51 (95% CI 0.27-0.95) in the EC analysis. IrAEs were an independent prognostic factor for OS but not PFS. Without considering the immortal time bias, the association between irAEs and oncologic outcomes in patients with HNSCC treated with ICIs was overestimated. Therefore, the balance between the benefits and risks of ICI therapy must be carefully weighed in clinical settings.

Immune checkpoint inhibitors (ICIs) are currently the first line of tumor immunotherapy for the treatment of a wide range of tumors. However, the main side effect of immune checkpoint inhibitors is that they cause immune-related adverse events (irAEs) in patients. The relationship between the occurrence of immune side effects in patients and efficacy is controversial. The objective of this study was to confirm the relationship between patients who develop thyroid dysfunction after immune checkpoint inhibitors and efficacy.

This study was a retrospective real-world clinical study, and a total of 50 patients with advanced tumors treated with immune checkpoint inhibitors at Anqing People's Hospital from 2020.8 to 2022.5 were retrospectively collected. Among them, 30 patients with hypothyroidism and 20 patients with normal or hyperthyroidism occurred, and the treatment effects and prognostic differences between the two groups were compared.

After PD1 treatment in all patients, there were 10 cases of partial remission(PR), 18 cases of stable disease(SD) and 2 cases of progressive disease(PD) in patients who developed hypothyroidism, with a disease control rate(DCR) of 93.3% and objective remission rate(ORR) of 33.3%. There were 0 complete remission (CR) patient, 3 PR patients, 11 SD patients, 6 PD patients, 70.0% DCR and 15.0% ORR in patients who did not develop hypothyroidism. The DCR and ORR of patients who developed hypothyroidism were better than those of non-hypothyroid patients, and the difference was statistically significant (P < 0.05). Kaplan-Meier survival analysis showed that progression-free survival (PFS) reached 9.2 months (95% CI 7.726-10.779) in patients who developed hypothyroidism and did not hypothyroidism patients have a PFS of 7.3 months (95% CI 5.604-8.505), with a statistically significant difference (P = 0.0341 < 0.05). Further subgroup analysis revealed that among patients who developed hypothyroidism, PFS was 3.3 months (95% CI 0.630-5.440) in patients with cholangiocarcinoma, 6.89 months (95% CI 5.604-8.505) in patients with non-small cell lung cancer, > 12 months in patients with hepatocellular carcinoma, and 11.05 months (95% CI 9.308-12.792) in patients with esophageal cancer months and PFS for patients with gastric cancer was 9.74 months (95% CI 6.979-12.502).

When patients with advanced tumors were treated with immune checkpoint inhibitors, DCR and ORR were higher in patients who developed hypothyroidism, and patients had better PFS. The benefits were greater in patients with gastric, esophageal, and hepatocellular carcinomas.

This study aims to identify key regulators of paraptosis in gastric cancer (GC) and explore their potential in guiding therapeutic strategies, especially in stomach adenocarcinoma (STAD). Genes associated with paraptosis were identified from the references and subjected to Cox regression analysis in the TCGA-STAD cohort. Using machine learning models, LPAR1 consistently ranked highest in feature importance. Multiple sequencing data showed that LPAR1 was significantly overexpressed in cancer-associated fibroblasts (CAFs). LPAR1 expression was significantly higher in normal tissues, and ROC analysis demonstrated its discriminative ability. Copy number alterations and microsatellite instability were significantly associated with LPAR1 expression. High LPAR1 expression correlated with advanced tumor grades and specific cancer immune subtypes, and multivariate analysis confirmed LPAR1 as an independent predictor of poor prognosis. LPAR1 expression was associated with different immune response metrics, including immune effector activation and upregulated chemokine secretion. High LPAR1 expression also correlated with increased sensitivity to compounds, such as BET bromodomain inhibitors I-BET151 and RITA, suggesting LPAR1 as a biomarker for predicting drug activity. FOXP2 showed a strong positive correlation with LPAR1 transcriptional regulation, while increased methylation of LPAR1 promoter regions was negatively correlated with gene expression. Knockdown of LPAR1 affected cell growth in most tumor cell lines, and in vitro experiments demonstrated that LPAR1 influenced extracellular matrix (ECM) contraction and cell viability in the paraptosis of CAFs. These findings suggest that LPAR1 is a critical regulator of paraptosis in GC and a potential biomarker for drug sensitivity and immunotherapy response. This underscores the role of CAFs in mediating tumorigenic effects and suggests that targeting LPAR1 could be a promising strategy for precision medicine in GC.

Retrospective studies suggest that immunosuppressive treatment of immune-related adverse events (irAEs) impairs survival in patients with melanoma who received immune checkpoint inhibitors. Here, we study this association across tumor types using data from six international phase II/III registrational trials.

A post hoc analysis was performed on individual patient data from the anti-programmed cell death-1 (anti-PD-1) + anti-cytotoxic T lymphocyte-associated protein-4 (anti-CTLA-4) treatment arms of six clinical trials (CheckMate-067, -142, -214, -648, -743, and -9LA). Among patients who received systemic immunosuppression for treatment-related adverse events (trAEs), associations of peak and cumulative corticosteroid dose, and use of second-line immunosuppression with overall survival (OS) and progression-free survival (PFS) were assessed using multilevel Cox regression with adjustment for age and sex.

Of the 1,959 patients who received anti-PD-1 + anti-CTLA-4 therapy, 834 patients who were treated with immunosuppression for trAEs were included. Eight hundred and thirty-two patients (100%) received corticosteroids and 81 patients (10%) received second-line immunosuppressants. High corticosteroid peak dose was associated with worse PFS: adjusted hazard ratio (HRadj), 1.15 (95% CI, 1.02 to 1.29) for 1 versus 0.5 mg/kg prednisolone and HRadj, 1.43 (95% CI, 1.05 to 1.96) for 2 versus 0.5 mg/kg. Similar effects were observed for OS: HRadj, 1.21 (95% CI, 1.06 to 1.39) and HRadj, 1.66 (95% CI, 1.17 to 2.37) for 1 and 2 versus 0.5 mg/kg, respectively. Cumulative corticosteroid dose was not associated with survival. HRadj of use of second-line immunosuppression was 1.23 (95% CI, 0.90 to 1.68) for PFS and 1.25 (95% CI, 0.88 to 1.77) for OS.

Higher corticosteroid peak dose for trAEs is associated with worse survival across tumor types, while cumulative dose is not. Too few patients received second-line immunosuppressants to confirm or reject an association with survival. These data argue for a reconsideration of irAE management approaches, starting with lower corticosteroid dose whenever feasible.

This study aims to identify key glycosyltransferases (GTs) in colorectal cancer (CRC) and establish a robust prognostic signature derived from GTs.

Utilizing the AUCell, UCell, singscore, ssgsea, and AddModuleScore algorithms, along with correlation analysis, we redefined genes related to GTs in CRC at the single-cell RNA level. To improve risk model accuracy, univariate Cox and lasso regression were employed to discover a more clinically subset of GTs in CRC. Subsequently, the efficacy of seven machine learning algorithms for CRC prognosis was assessed, focusing on survival outcomes through nested cross-validation. The model was then validated across four independent external cohorts, exploring variations in the tumor microenvironment (TME), response to immunotherapy, mutational profiles, and pathways of each risk group. Importantly, we identified potential therapeutic agents targeting patients categorized into the high-GARS group.

In our research, we classified CRC patients into distinct subgroups, each exhibiting variations in prognosis, clinical characteristics, pathway enrichments, immune infiltration, and immune checkpoint genes expression. Additionally, we established a Glycosyltransferase-Associated Risk Signature (GARS) based on machine learning. GARS surpasses traditional clinicopathological features in both prognostic power and survival prediction accuracy, and it correlates with higher malignancy levels, providing valuable insights into CRC patients. Furthermore, we explored the association between the risk score and the efficacy of immunotherapy.

A prognostic model based on GTs was developed to forecast the response to immunotherapy, offering a novel approach to CRC management.

Immune checkpoint inhibitors (ICIs) carry the risk of immune-related adverse events (irAEs), a significant concern as therapy has transitioned to the adjuvant setting. Balancing therapeutic benefits against potential risks is crucial, necessitating real-world data from an unselected patient population in addition to clinical trial data to ensure optimal clinical decision-making.

This nationwide real-world study assessed irAEs in patients receiving adjuvant anti-PD1 therapy, primarily nivolumab, for resected stage III-IV melanoma between 2018-2022. Data were retrieved from two national databases: the IMMUNOTOX database and the Danish Metastatic Melanoma Database (DAMMED). IrAEs were sub-grouped according to organ systems graded using CTCAE ver. 5.0 ranging from mild toxicities (grade 1-2) to severe (grade 3-4) and fatal (grade 5).

Among 792 included patients, (55 % male, median age 62 years (range 16-88)), 697 patients (88 %) experienced an irAE. Severe irAEs occurred in 116 patients (15 %) and five (0.6 %) died due to toxicity. A landmark analysis showed that patients who experienced at least one irAE before the 1st evaluation at 90 days had an increased progression free survival (PFS) (p = 0.032) and overall survival (OS) (p = 0.0071). Additionally, a seasonal pattern was noted with higher incidence of irAEs during summer.

The prevalence of irAEs in real-world patients is comparable to the observed risk in clinical trials. Patients experiencing irAEs demonstrate a lower risk of melanoma relapse. Further, gender, age and seasonal variation may impact the incidence of irAEs.

There are insufficient data about the optimal treatment for older patients with recurring medium or large hepatocellular carcinoma (HCC). The study intended to assess the effect of transcatheter arterial chemoembolization combined with microwave ablation (TACE-MWA) in an elderly cohort through a retrospective analysis.

From 2011 to 2018, a cohort of individuals (age ≥70 years) with recurrent HCC tumors ranging from 3.1 cm to 7 cm underwent either a combination treatment of TACE and MWA (n = 43) or surgical intervention (n = 33). Using the Inverse Probability of Treatment Weighting (IPTW) technique, factors of disease-free survival (DFS), overall survival (OS), and rates of major adverse events were analyzed, retrospectively.

The group that underwent surgery had a greater history of alcohol use before treatment (P= 0.001), as well as a higher Barcelona Clinic Liver Cancer (BCLC) stage for the primary tumor before treatment (P= 0.014) and a higher primary tumor location before treatment (P= 0.045). The TACE-MWA group had DFS rates of 86.2%, 68.8%, and 60.4% at 1, 3, and 5 years, while the surgery group had rates of 53.0%, 42.2%, and 25.8% at the same time points. In the TACE-MWA treatment group, survival rates at 1 year, 3 years, and 5 years post-treatment were recorded as 93.0%, 80.8%, and 65.7%, respectively, while in the surgery group, they were 62.7%, 46.9%, and 42.6%. In the univariate analysis using IPTW, the type of treatment was found to have a significant correlation with disease progression (hazard ratio [HR] 0.41, 95% CI 0.20-0.86, P=0.017). IPTW multivariate analysis showed that treatment modality (HR, 0.35; 95% CI, 0.17 to 0.79; P= 0.011) was the only significant prognostic factor for OS.

In elderly patients with recurrent 3.1 cm≤ HCC ≤ 7 cm, TACE-WMA was superior to surgery in the respects of DFS and OS.

Describe the demographic data and clinical phenotype of cranial palsy induced by immune checkpoint inhibitors (CNP-ICI).

A systematic literature review of the literature was performed in Pubmed, Web of Science, and Embase, including 68 articles and 136 patients (PROSPERO no. CRD42024517262).

Out of the 1205 articles screened, 68 articles were included after fulfilling the inclusion criteria, for a total of 136 patients. All articles were case reports and case series. In the cohort studied, 52% of patients were treated with anti PD-1/PDL-1 therapies, 14% with anti CTLA-4 therapies, and 34% with a combination of anti CTLA-4 and anti PD-1/PDL-1 therapies. The facial nerve was the most affected cranial nerve, involved in 38% of cases, followed by the optic nerve (35%), the cochleovestibular nerve (12%), and the abducens nerve (10%). The median time from the initial immune checkpoint inhibitor (ICI) injection to the onset CNP-ICI was 10 weeks (IQR 4-20). Magnetic resonance imaging demonstrated contrast enhancement or abnormal signal of the affected nerve in 43% of cases. Cerebrospinal fluid analysis indicated lymphocytic pleocytosis in 59% of cases. At the onset of immune-related adverse events, 89% of patients discontinued immunotherapy, and 92% received treatment for CNP-ICI. Treatment regimens included corticosteroids in 86% of cases, intravenous immunoglobulin in 21%, and plasma exchange in 5.1%. Among the whole population, 33% achieved recovery, 52% showed clinical improvement, 16% remained stable, and 3% experienced worsening of their condition. Rechallenge with immunotherapy was significantly associated with the emergence of new immune-related Adverse Events (irAEs).

ICI therapy may lead to cranial nerve involvement, particularly affecting the facial nerve, typically presenting around 10 weeks after treatment initiation. While corticosteroid therapy often resulted in patient improvement, rechallenging with ICIs were associated with new irAEs.

Lung cancer represents one of the most prevalent malignant neoplasms, commanding an alarming incidence and mortality rate globally. Non-small cell lung cancer (NSCLC), constituting approximately 80 %-90 % of all lung cancer cases, is the predominant pathological manifestation of this disease, with a disconcerting 5-year survival rate scarcely reaching 10 %. Extensive prior investigations have elucidated that the aberrant expression of X-ray repair cross-complementing gene 2 (XRCC2), a critical meiotic gene intricately involved in the DNA damage repair process, is intimately associated with tumorigenesis. Nevertheless, the precise roles and underlying mechanistic pathways of XRCC2 in NSCLC remain largely elusive. In the present study, we discerned an overexpression of XRCC2 within NSCLC patient tissues, particularly in high-grade samples, when juxtaposed with normal tissues. Targeted knockdown of XRCC2 notably impeded the proliferation of NSCLC both in vitro and in vivo. Comprehensive RNA sequencing and flow rescue assays unveiled that XRCC2 augments the proliferation of NSCLC cells through the down-regulation of FOS expression. Moreover, the c-Myc gene was definitively identified as an XRCC2 transcriptional factor by means of chromatin immunoprecipitation (ChIP) and luciferase reporter assays, whereby pharmacological attenuation of c-Myc expression, in conjunction with Doxorubicin, synergistically curtailed NSCLC cell growth both in vitro and in vivo. Collectively, our findings proffer critical insights into the novel c-Myc-XRCC2-FOS axis in promoting both proliferation and resistance to Doxorubicin in NSCLC cells, thereby extending a promising avenue for potential new diagnostic strategies and therapeutic interventions in NSCLC.

Although antibody-drug conjugate (ADC) or immune checkpoint inhibitors (ICIs) alone fosters hope for the treatment of cancer, the effect of single drug treatment is limited and the safety profile of ADC and ICI therapy remains unclear. This meta-analysis aimed to examine the efficacy and safety of the combination of ADC and ICI therapy. This study type is a systematic review and meta-analysis. Literature retrieval was carried out through PubMed, Embase, Cochrane from inception to Jun. 5, 2024. Then, after data extraction, overall response rate (ORR) and adverse effects (AEs) were used to study its efficiency and safety. Publication bias was also calculated through Funnel plot, Begg's Test and Egger's test. Heterogeneity was investigated through subgroup and sensitivity analysis. The research protocol was registered with the PROSPERO (CRD42023375601). A total of 12 eligible clinical studies with 584 patients were included. The pooled ORR was 58% (95%CI 46%, 70%). Subgroup analysis showed an ORR of 77% (95%CI 63%, 91%) in classical Hodgkin lymphoma (cHL) and an ORR of 73% (95%CI 56%, 90%) in non-Hodgkin lymphoma (NHL). The most common AEs was peripheral neuropathy (38.0%). Meanwhile, AEs on skin (13.1-20.0%) and digestive system (9.0-36.0%) was hard be overlooked. ADC + ICI therapy may be recommended in cancer treatment, especially in cHL and NHL. However, strategies to manage toxicities warranted further exploration.

Tumor neoantigens possess specific immunogenicity and personalized therapeutic vaccines based on neoantigens which have shown promising results in some clinical trials, with broad application prospects. However, the field is developing rapidly and there are currently few relevant review articles. Summarizing and analyzing the status of global personalized neoantigen vaccine clinical trials will provide important data for all stakeholders in drug development. Based on the Trialtrove database, a retrospective analysis was conducted using trial quantity as a key indicator for neo-adjuvant and adjuvant therapy anti-PD-1/PD-L1 clinical trials initiated before the end of 2022. The time trend of newly initiated trials was investigated. The sponsor type, host country, treatment mode, combination strategy, tested drugs, and targeted cancer types of these trials were summarized. As of December 2022, a total of 199 trials were included in the analysis. Among these studies, Phase I studies were the most numerous (119, 59.8%), and Phase I studies have been the predominant study type since 2015. Peptide vaccines were the largest neoantigen vaccines type, accounting for 64.8% of all clinical trials. Based on peptide delivery platforms, the proportion of trials was highest for the DC system (32, 16.1%), followed by LNP (11, 5.5%), LPX (11, 5.5%), and viruses (7, 3.5%). Most vaccines were applied in trials as a monotherapy (133/199, 66.8%), meanwhile combining immunotherapeutic drugs was the most common form for combination therapy. In terms of indications, the largest number of trials involved three or more unspecified solid tumors (50/199, 25.1%), followed by non-small cell lung cancer (24/199, 12.1%) and pancreatic cancer (15/199, 7.5%). The clinical development of personalized neoantigen cancer vaccines is still in the early stage. A clear shift in delivery systems from peptides to DC and liposomal platforms, with the largest number of studies in Asia, collectively marks a new era in the field. The adjuvant or maintenance therapy, and the combination treatment with ICIs are becoming the important clinical development orientation. As research on tumor-immune interactions intensifies, the design, development, and application of neoantigen vaccines are bound to develop rapidly, which will bring a new revolution in the future cancer treatment.

The coexistence of esophageal variceal bleeding and superficial esophageal cancer (SEC) is relatively rare in clinical practice. Moreover, there have been few reports of SEC overlying esophageal varices (EVs). Herein, we report our successful use of endoscopic submucosal dissection (ESD), esophageal solitary venous dilatation (ESVD), and endoscopic injection sclerotherapy (EIS) to treat a 75-year-old man who was diagnosed with SEC coexisting with esophageal variceal bleeding.

A 75-year-old man was admitted to the hospital due to black stool for 4 days. The patient had a history of liver cancer, cirrhosis, and portal hypertension. Endoscopic examination revealed esophageal and gastric varicose veins, as well as esophageal carcinoma in situ. We first treated esophageal variceal bleeding by ESVD and EIS. One week later, ESD treatment was done, and the complete resection of early esophageal cancer was successfully completed via endoscopy. There were no postoperative complications, such as bleeding, infection, or perforation.

The sequential treatment of ESVD, EIS, and ESD is an effective method for treating EVs with early esophageal cancer.

Reliable blood-based tests for identifying early-stage breast cancer remain elusive. Employing single-cell transcriptomic sequencing analysis, we illustrate a close correlation between nucleotide metabolism in the breast cancer and activation of regulatory T cells (Tregs) in the tumor microenvironment, which shows distinctions between subtypes of patients with triple-negative breast cancer (TNBC) and non-TNBC, and is likely to impact cancer prognosis through the A2AR-Treg pathway. Combining machine learning with absolute quantitative metabolomics, we have established an effective approach to the early detection of breast cancer, utilizing a four-metabolite panel including inosine and uridine. This metabolomics study, involving 1111 participants, demonstrates high accuracy across the training, test, and independent validation cohorts. Inosine and uridine prove predictive of the response to neoadjuvant chemotherapy (NAC) in patients with TNBC. This study deepens our understanding of nucleotide metabolism in breast cancer development and introduces a promising non-invasive method for early breast cancer detection and predicting NAC response in patients with TNBC.

Increased expression of the B7 family of immune checkpoint proteins hinders tumor elimination by the immune system. Expression levels of the B7-H5 protein were found to be upregulated in clear cell renal cell carcinomas (ccRCC). We here report the molecular, functional, and clinical characterization of B7-H5 from renal cancer cells and metastatic ccRCC tumors. B7-H5 was highly glycosylated and mainly expressed in the cell membrane. Mutagenic studies on B7-H5 identified the residues targeted by N-glycosylation and revealed an impact of B7-H5 glycosylation on protein expression levels and localization. B7-H5 knockdown decreased the cell proliferation and viability of renal cancer cells. We analyzed B7-H5 expression on tumor cells and tumor-infiltrated leukocytes (TILs) in samples from metastatic ccRCC patients and found that B7-H5 expression on TILs correlated with syncronous metastases and poor outcomes. These results provide insights into the molecular properties and clinical impact of B7-H5 and support B7-H5 as a new immunotherapeutic target in metastatic ccRCC.

Zinc finger protein 263 (ZNF263) is frequently upregulated in various tumor types; however, its function and regulatory mechanism in colorectal cancer (CRC) have not yet been elucidated. In this study, the expression of ZNF263 was systematically examined using data from The Cancer Genome Atlas database and samples from patients with CRC. The results indicated that high expression of ZNF263 in CRC tissues is significantly associated with tumor grade, lymph node metastasis and disant metastasis. Additionally, overexpression of ZNF263 significantly promoted the proliferation, invasion, migration, and epithelial-mesenchymal transition of CRC cells, while also increasing signal transducer and activator of transcription 3 (STAT3) expression and mRNA stability. Conversely, knockdown of ZNF263 inhibited the malignant behavior of CRC cells and decreased STAT3 expression and mRNA stability. Further mechanism studies using chromatin immunoprecipitation (CHIP) and luciferase assays verified that ZNF263 directly binds to the STAT3 promoter. Rescue experiments demonstrated that the knockdown or overexpression of STAT3 could significantly reverse the effects of ZNF263 on CRC cells. Additionally, our study found that overexpression of ZNF263 enhanced the resistance of CRC cells to the chemoradiotherapy. In summary, this study not only elucidated the significant role of ZNF263 in CRC but also proposed novel approaches and methodologies for the diagnosis and treatment of this malignancy.

Extracellular vesicles (EVs) are being considered as a potential therapeutic option for ulcerative colitis (UC), and numerous preclinical studies have been conducted on the use of EVs for UC.

A systematic review was conducted to compare the therapeutic effects of mammalian EVs and placebo on UC in animal models, along with a meta-analysis comparing naïve (unmodified) EVs and placebo. The search was performed in four databases (PubMed, Web of Science, Scopus, and EMBASE) up to September 13th, 2023. The primary outcomes included disease activity index (DAI), colonic mucosal damage index (CMDI), and adverse effects (PROSPERO ID: CRD42023458039).

A total of 69 studies were included based on pre-determined criteria, involving 1271 animals. Of these studies, 51 measured DAI scores, with 98 % reporting that EVs could reduce DAI scores. Additionally, 5 studies reported CMDI and all showed that EVs could significantly reduce CMDI. However, only 3 studies assessed adverse effects and none reported any significant adverse effects. The meta-analysis of these studies (40 studies involving 1065 animals) revealed that naïve EVs could significantly decrease the DAI score (SMD = -3.00; 95 % CI: -3.52 to -2.48) and CMDI (SMD = -2.10; 95 % CI: -2.85 to -1.35).

The results indicate that mammalian EVs have demonstrated therapeutic benefits in animal models of UC; however, the safety profile of EVs remains inadequate which highlights the need for further research on safety outcomes.

Aim: This cohort study evaluated the association between immune checkpoint inhibitors (ICIs)-induced immune-related adverse events (irAEs) and mortality as well as ICI discontinuation among older adults with NSCLC.Methods: 2007-2019 Surveillance, Epidemiology and End Results-Medicare linked database was used and survival analysis with time-varying exposure of irAEs was applied to estimate the associations.Results & conclusion: A total of 8,175 individuals were included, with 46.8% of whom developed an irAE. Cox regression models showed the occurrence of any irAEs was associated with increased risk of mortality (HR: 1.73, 95% CI: 1.63-1.82) and treatment discontinuation (HR: 1.87, 95% CI: 1.78-1.97). Some variability was observed in the effect on the two outcomes depending on the type of irAE.

Gastric cancer remains a considerable global health burden, with limited treatment options available for advanced cases, especially for superaged patients. Cadonilimab, a first-in-class bi-specific antibody (BsAb), offer a promising immunotherapy approach by targeting PD-1/CTLA-4 simultaneously. Herein, we present a case report of an 85-year-old patient with HER2-negative advanced gastric cancer who received first-line treatment with cadonilimab combined with chemotherapy, but cadonilimab was discontinued due to the observation of immune-related pneumonitis during treatment. Despite these changes, the patient still exhibited a stable disease condition for a year until now. This case report highlights the potential of cadonilimab in the treatment of superaged patients with advanced gastric cancer, while the efficacy and safety of it need to be further evaluated.

Deep Learning (DL) drives academics to create models for cancer diagnosis using medical image processing because of its innate ability to recognize difficult-to-detect patterns in complex, noisy, and massive data. The use of deep learning algorithms for real-time cancer diagnosis is explored in depth in this work. Real-time medical diagnosis determines the illness or condition that accounts for a patient's symptoms and outward physical manifestations within a predetermined time frame. With a waiting period of anywhere between 5 days and 30 days, there are currently several ways, including screening tests, biopsies, and other prospective methods, that can assist in discovering a problem, particularly cancer. This article conducts a thorough literature review to understand how DL affects the length of this waiting period. In addition, the accuracy and turnaround time of different imaging modalities is evaluated with DL-based cancer diagnosis. Convolutional neural networks are critical for real-time cancer diagnosis, with models achieving up to 99.3% accuracy. The effectiveness and cost of the infrastructure required for real-time image-based medical diagnostics are evaluated. According to the report, generalization problems, data variability, and explainable DL are some of the most significant barriers to using DL in clinical trials. Making DL applicable for cancer diagnosis will be made possible by explainable DL.