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Purpose To investigate the efficacy and safety of immune checkpoint inhibitors in the treatment of gastric cancer patients with different hepatitis B virus (HBV) infection statuses. Patients and methods The clinical data of 89 gastric cancer patients treated at our centre were retrospectively analysed. The patients were divided into chronic hepatitis B (CHB)-infected patients (13 patients), resolved hepatitis B (RHB)-infected patients (49 patients), and HBV-uninfected (HBV-) patients (27 patients) according to their HBV infection status. The efficacy and safety of antitumour treatment in patients in the three groups were analysed. Results During anti-programmed death (ligand) 1 (PD-(L)1) therapy, no significant differences in the overall response rate (69.2% vs. 53.1% vs. 51.9%; P  = 0.536) or disease control rate (92.3% vs. 79.6% vs. 81.5%; P  = 0.567) were observed among the three groups. Progression-free survival benefited more from anti-PD-(L)1 antibody therapy in CHB patients than in HBV- patients (Not reached vs. 7 months; P  = 0.024; hazard ratio (HR) = 0.38(95%CI 0.17–0.88)) and RHB patients (Not reached vs. 6 months; P  = 0.001; HR = 0.34(95%CI 0.17–0.65)). Overall survival was also better in CHB patients than in HBV- patients (Not reached vs. 15 months; P  = 0.014; HR = 0.31(95%CI 0.12–0.79)) and RHB patients (Not reached vs. 16 months; P  = 0.005; HR = 0.32(95%CI 0.14–0.71)). Conclusion Anti-PD-(L)1 immunotherapy may be safe and effective in gastric cancer patients with HBV infection. CHB patients are more likely to have lasting benefits than are HBV- patients and RHB patients. This may be attributed to alterations in the immune microenvironment in patients, and future studies should further explore the relevant mechanisms involved. CHB patients may have a more inflamed immune microenvironment, leading to enhanced ICI efficacy.

Background Gut microbes has become one of the research hotspots in animal ecology, playing an important role in monitoring dietary adaptation and health status of host. However, there are few studies on the gut microbiota in the stomach, smallintestine (ileum), and large intestine (cecum, colon, and rectum) of wild boar. Results Alpha diversity and Beta diversity showed there were significant differences in the abundance and distribution of microbes in gastrointestinal tract of wild boar. Firmicutes and Bacteroidetes were the most dominant phyla in stomach, cecum, colon and rectum of wild boar, while Proteobacteria and Firmicutes were the most dominant in ileum. At genus level, there were different leading genera in stomach ( Prevotella and Lactobacillus ), small intestine ( Escherichia-Shigella and Lactobacillus ), and large intestine ( Ruminococcaceae_UCG-005 , Christensenellaceae_R-7_group , and Escherichia-Shigella ). PICRUSt function predictive analysis suggested that there were significant differences in microbial metabolic pathways among five locations of wild boar. Conclusions This study comprehensively revealed the differences in composition of microbial community in gastrointestinal trac of wild boar. Future work links microbes with the metabolites to accurately reveal the health of wild boar.

Wild boars (Sus scrofa) are extremely common in southern China, but little study has been conducted regarding reporting the dietary habits of wild boars using high-throughput sequencing technology, especially in karst areas, due to the difficulty in obtaining stomach contents of wild boars. In our study, the stomach contents of 14 wild boars in southern China were analyzed by DNA metabarcoding. The results showed that there were 153 genera, 93 families, and 48 orders of plant food sources for wild boars. The main plant food component were Cissus, Dioscorea, Quercus, Actinidia, and Houttuynia. The most numerous taxa of animal food sources were Elaphodus, Amynthas, Chonaphe, Rattus, and Tanytarsus. It is noteworthy that Elaphodus cephalophus were detected in most of the stomach samples, accounting for a large portion of animal food sources. The results showed that there were significant differences in the diets of wild boars in different regions; however, no significant differences were noted between male and female wild boars. Our study revealed the dietary preference of wild boars under the special forest conditions in the mountainous area of southwest China, as well as the relationship between the dietary habits of wild boars and their habitats from the perspective of resource utilization, thus providing a key scientific basis for the prevention and control of wild boars, along with resource protection.

Background The tumor immune microenvironment plays a crucial role in the efficacy of various therapeutics. However, their correlation is not yet completely understood in Clear cell renal cell carcinoma (ccRCC). This study aimed to investigate the potential of TREM-1 as a potential novel biomarker for ccRCC. Methods We constructed a ccRCC immune prognostic signature. The clinical characteristics, the status of the tumor microenvironment, and immune infiltration were analyzed through the ESTIMATE and CIBERSORT algorithms for the hub gene, while the Gene Set Enrichment Analysis and PPI analysis were performed to predict the function of the hub gene. Immunohistochemical staining was used to detect the expression of TREM-1 in renal clear cell carcinoma tissues. Results The CIBERSORT and ESTIMATE algorithms revealed that TREM-1 was correlated with the infiltration of 12 types of immune cells. Therefore, it was determined that TREM-1 was involved in numerous classical pathways in the immune response via GSEA analysis. In Immunohistochemical staining, we found that the expression of TREM-1 was significantly upregulated with increasing tumor grade in renal clear cell carcinoma, and elevated TREM-1 expression was associated with poor prognosis. Conclusions The results suggest that TREM-1 may act as an implicit novel prognostic biomarker in ccRCC that could be utilized to facilitate immunotherapeutic strategy.

Although CD19-specific chimeric antigen receptor (CAR) T cells are curative for patients with relapsed or refractory large B-cell lymphoma (R/R LBCL), disease relapse with tumor antigen-positive remains a challenge. Cytokine/chemokine-expressing CAR-T cells could overcome a suppressive milieu, but the clinical safety and efficacy of this CAR-T therapy remain unclear. Here we report the preclinical development of CD19-specific CAR-T cells capable of expressing interleukin (IL)-7 and chemokine (C-C motif) ligand (CCL)-19 upon CD19 engagement (referred to as 7 × 19 CAR-T cells) and results from a phase 1 and expansion phase trial of 7 × 19 CAR-T cell therapy in patients with R/R LBCL (NCT03258047). In dose-escalation phase, there were no dose-limiting toxicities observed. 39 patients with R/R LBCL received 7 × 19 CAR-T with doses ranged from 0.5 × 10 6 –4.0 × 10 6 cells per kg body weight. Grade 3 cytokine release syndrome occurred in 5 (12.8%) patients and ≥ grade 3 neurotoxicity in 4 (10.3%) patients. The overall response rate at 3 months post-single infusion was 79.5% (complete remission, 56.4%; partial response, 23.1%). With a median follow-up of 32 months, the median progression-free survival was 13 months, and median overall survival was not reached, with an estimated rate of 53.8% (95% CI, 40.3% to 72.0%) at two years. Together, these long-term follow-up data from the multicenter clinical study suggest that 7 × 19 CAR-T cells can induce durable responses with a median overall survival of greater than 2 years, and have a manageable safety profile in patients with R/R LBCL.

Though several anti-PD-1/PD-L1 antibodies approved for monotherapy in microsatellite instability-high or mismatch repair-deficient unresectable/metastatic solid tumors, novel immunotherapy with better anti-tumor activity is needed in clinic. In this single-arm, multicenter, pivotal, phase II study, patients received iparomlimab (a novel humanized anti-PD-1 mAb, 200 mg or 3 mg/kg for patients with body weight < 40 kg, IV, Q3W) until disease progression, intolerable toxicities, withdrawal of consent, death, or up to 2 years. The primary endpoint was objective response rate (ORR) assessed by independent radiological review committee (IRRC). Totally, 120 patients were enrolled, of whom 60 patients failed from prior standard therapy, were enrolled in the full analysis set (FAS). As of Jan 20, 2024, the confirmed ORR per IRRC in FAS were 50.0% (30/60; 95% CI 36.8–63.2%) patients, including 4 (6.7%) complete response (CR) and 26 (43.3%) partial response (PR). In colorectal cancer (CRC) patients in FAS, the ORR reached 57.9% (22/38; 95% CI 40.8–73.7%) per IRRC, with 3 (7.9%) CR and 19 (50.0%) PR. Furtherly, the ORRs in liver metastatic or non-liver metastatic CRC patients were 52.9% (9/17, 95% CI 27.8–77.0%) vs 61.9% (13/21, 95% CI 38.4%–81.9%). The incidence of TRAE was 90.8% (any grade) and 20.8% (grade ≥ 3). Immune-related adverse events occurred in 33.3% (any grade) and 5.0% (grade ≥ 3) of patients. No iparomlimab-related death occurred. Iparomlimab presented encouraging antitumor activity with durable response and tolerable safety profile. Trial registration ClinicalTrials.gov Identifier: NCT04326829.

The study aimed to investigate the reason of HCT116 cell resistance to MEK inhibitor, and the combination treatment effects of MEK inhibitor AZD6244 and JAK2/STAT3 inhibitor AG490 on colon cancer in vitro and in vivo, including cell viability, apoptosis, and explore the partial mechanisms focused on AZD6244 promoted the activation of JAK2-STAT3 pathways. In vitro, we examined the HCT116 cell viability by CCK8, cell apoptosis by flow cytometry; Western blot measured p-ERK, p-JAK2, p-STAT3 and STAT3 expression. In vivo, nude mice were subcutaneously injected by HCT116 cells. The tumor volume and weight were detected. HCT116 cell resistance to MEK inhibitor AZD6244, which inhibited the activation of ERK and promoted the activation of JAK2-STAT3 signaling. The combination treatment of AZD6244 and AG490 significantly inhibited cell viability and induced cell apoptosis, and completely inhibited the activation of ERK and JAK2-STAT3 signaling. Combination treatment of AZD6244 and AG490 had a stronger effect than that of AZD6244 as a monotherapy in vitro and in vivo. The treatment of AZD6244 on K-Ras mutations HCT116 cells promoted the activation of JAK2/STAT3 signaling. JAK2/STAT3 inhibitor AG490 synergistically increases effects of AZD6244 on colon cancer in vitro and in vivo. Collectively, these results provide a rationale for combining inhibitors of the JAK/STAT pathway and MEK inhibitors to reduce the potential impact of drug resistance.

To investigate the hyaluronic acid (HA) modified, doxorubicin (DOX) and gallic acid (GA) co-delivered lipid-polymeric hybrid nano-system for leukemia therapy. We produced a kind of lipid-polymer hybrid nanoparticle (LPHN) with a core-shell structure in which DOX and GA were co-loaded. In vitro and in vivo leukemia therapeutic effects of the HA modified, DOX and GA co-delivered LPHNs (HA-DOX/GA-LPHNs) were evaluated in DOX resistant human HL-60 promyelocytic leukemia cells (HL-60/ADR cells), DOX resistant human K562 chronic myeloid leukemia cells (K562/ADR cells), and HL-60/ADR cells bearing mouse model. The sizes and zeta potentials of HA modified LPHNs were about 160 nm and -40 mV. HA-DOX/GA-LPHNs showed the most prominent cytotoxicity and the best synergistic effect was obtained when DOX/GA ratio was 2/1. In vivo studies revealed that HA-DOX/GA-LPHNs inhibited tumor growth from 956 mm to 213 mm , with an inhibition rate of 77.7%. In summary, the study showed that HA-DOX/GA-LPHNs can be applied as a promising leukemia therapy system.

Though several anti-PD-1/PD-L1 antibodies approved for monotherapy in microsatellite instability-high or mismatch repair-deficient unresectable/metastatic solid tumors, novel immunotherapy with better anti-tumor activity is needed in clinic. In this single-arm, multicenter, pivotal, phase II study, patients received iparomlimab (a novel humanized anti-PD-1 mAb, 200 mg or 3 mg/kg for patients with body weight < 40 kg, IV, Q3W) until disease progression, intolerable toxicities, withdrawal of consent, death, or up to 2 years. The primary endpoint was objective response rate (ORR) assessed by independent radiological review committee (IRRC). Totally, 120 patients were enrolled, of whom 60 patients failed from prior standard therapy, were enrolled in the full analysis set (FAS). As of Jan 20, 2024, the confirmed ORR per IRRC in FAS were 50.0% (30/60; 95% CI 36.8-63.2%) patients, including 4 (6.7%) complete response (CR) and 26 (43.3%) partial response (PR). In colorectal cancer (CRC) patients in FAS, the ORR reached 57.9% (22/38; 95% CI 40.8-73.7%) per IRRC, with 3 (7.9%) CR and 19 (50.0%) PR. Furtherly, the ORRs in liver metastatic or non-liver metastatic CRC patients were 52.9% (9/17, 95% CI 27.8-77.0%) vs 61.9% (13/21, 95% CI 38.4%-81.9%). The incidence of TRAE was 90.8% (any grade) and 20.8% (grade [greater than or equal to] 3). Immune-related adverse events occurred in 33.3% (any grade) and 5.0% (grade [greater than or equal to] 3) of patients. No iparomlimab-related death occurred. Iparomlimab presented encouraging antitumor activity with durable response and tolerable safety profile.

BackgroundIn patients with untreated CD20-positive diffuse large B-cell lymphoma (DLBCL), a phase 3 trial was carried out to evaluate the efficacy and safety of zuberitamab plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone; Hi-CHOP) versus rituximab plus CHOP (R-CHOP) treatment regimens.MethodsIn a 2:1 ratio, eligible patients were assigned randomly to receive treatment of six cycles of either 375 mg/m2 zuberitamab or rituximab together with conventional CHOP chemotherapy. The objective response rate (ORR) at C6D50 served as the primary endpoint, and a non-inferiority margin of 10% was established. The secondary endpoints included the complete response (CR) rate at C6D50, duration of response (DOR), progression-free survival (PFS) and event-free survival (EFS) judged by blinded-independent review committee (BIRC), overall survival (OS) and safety outcomes.ResultsOf the 487 randomized patients, 423 patients including 287 in the Hi-CHOP and 136 in the R-CHOP groups completed the C6D50 assessment. For the full analysis set (FAS) and per-protocol set (PPS), BIRC-assessed ORR at C6D50 for the Hi-CHOP and R-CHOP groups were 83.5% versus 81.4% and 95.3% versus 93.7%, respectively. The non-inferiority was confirmed as the lower limit of the two-sided 95% CI for the intergroup differences of −5.2% and −3.3%; both were >−10% in the FAS and PPS. The BIRC-assessed CR rate of Hi-CHOP was significantly higher in PPS (85.7% vs 77.3%, p=0.038), but comparable in FAS (75.2% vs 67.9%, p=0.092). After a median follow-up of 29.6 months, patients in the Hi-CHOP group had a slight advantage with regard to the DOR (HR 0.74, p=0.173), PFS (HR 0.67, p=0.057), EFS (HR 0.90, p=0.517) and OS (HR 0.60, p=0.059). Patients with the germinal-center B cell-like subtype who received Hi-CHOP exhibited statistically significant improvements in ORR (p=0.034) and CR rate (p=0.038) at C6D50, EFS (p=0.046) and OS (p=0.014). Treatment-emergent adverse event occurrence rates were comparable across groups (all p>0.05). Infusion-related responses occurred more often in the Hi-CHOP group (32.1% vs 19.9%, p=0.006), all of grade 1–3 severity.ConclusionsZuberitamab (375 mg/m2) plus CHOP was non-inferior to R-CHOP regarding ORR but exhibited a higher CR rate and was well tolerated in CD20-positive, previously untreated Chinese patients with DLBCL.Trial registration numberChinese Clinical Trial Registry, ChiCTR2000040602, retrospectively registered.