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BACKGROUND: Mecapegfilgrastim, a long-acting granulocyte-colony stimulating factor has been approved for reducing the incidence of infection, particularly febrile neutropenia (FN), in China. OBJECTIVE: We conducted a multicenter prospective observational study to examine the safety and effectiveness of mecapegfilgrastim in preventing neutropenia in gastrointestinal patients receiving the chemotherapy, including S-1/capecitabine-based regimens or the fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) regimens. METHOD: Five hundred and sixty-one gastrointestinal patients from 40 sites across China, between May 2019 and November 2021, were included. The administration of mecapegfilgrastim was prescribed at the discretion of local physicians. RESULTS: The most common adverse drug reactions (ADRs) of any grade for all patients was increased white blood cells (2.9%). Grade 3/4 ADRs were observed for anemia (0.2%), decreased white blood cells (0.2%), and decreased neutrophil count (0.2%). Among the 116 patients who received S-1/capecitabine-based chemotherapy throughout all cycles, ADRs of any grade included anemia (1.7%), myalgia (0.9%), and increased alanine aminotransferase (0.9%). No grade 3/4 ADRs were observed. In 414 cycles of patients who underwent S-1/capecitabine-based regimens, only one (0.2%) cycle experienced grade 4 neutropenia. In the FOLFIRINOX, FOLFOXIRI, and FOLFOX chemotherapy regimens, grade 4 neutropenia occurred in one (2.7%) of 37 cycles, four (4.7%) of 85 cycles, and two (1.2%) of 167 cycles, respectively. CONCLUSION: In a real-world setting, mecapegfilgrastim has proven effective in preventing severe neutropenia in gastrointestinal patients following chemotherapy. This includes commonly used moderate or high-risk FN regimens or regimens containing S1/capecitabine, all of which have demonstrated favorable efficacy and safety profiles.
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Protocolos de Quimioterapia Combinada Antineoplásica , Fluorouracilo , Neoplasias Gastrointestinales , Neutropenia , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano , Neoplasias Gastrointestinales/tratamiento farmacológico , Neutropenia/prevención & control , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Adulto , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéutico , Leucovorina/efectos adversos , Irinotecán/uso terapéutico , Irinotecán/efectos adversos , Oxaliplatino/efectos adversos , Oxaliplatino/uso terapéutico , China/epidemiologíaRESUMEN
Background: MET overexpression represents the most MET aberration in advanced non-small-cell lung cancer (NSCLC). However, except MET exon 14 (METex14) skipping mutation was recognized as a clinical biomarker, the role of MET overexpression as a predictive factor to MET inhibitor is not clear. Objectives: The purpose of the pooled analysis is to explore the safety and efficiency of gumarontinib, a highly selective oral MET inhibitor, in drive-gene negative NSCLC patients with MET overexpression. Design and methods: NSCLC patients with MET overexpression [immunohistochemistry (IHC) ⩾3+ as determined by central laboratory] not carrying epidermal growth factor receptor mutation, METex14 skipping mutation or other known drive gene alternations who received Gumarontinib 300 mg QD from two single arm studies were selected and pooled for the analysis. The efficacy [objective response rate (ORR), disease control rate (DCR), duration of response, progression-free survival (PFS) and overall survival (OS)] and safety [treatment emergent adverse event (TEAE), treatment related AE (TRAE) and serious AE (SAE) were assessed. Results: A total of 32 patients with MET overexpression were included in the analysis, including 12 treatment naïve patients who refused or were unsuitable for chemotherapy, and 20 pre-treated patients who received ⩾1 lines of prior systemic anti-tumour therapies. Overall, the ORR was 37.5% [95% confidence interval (CI): 21.1-56.3%], the DCR was 81.3% (95% CI: 63.6-92.8%), median PFS (mPFS) and median OS (mOS) were 6.9 month (95% CI: 3.6-9.7) and 17.0 month (95% CI: 10.3-not evaluable), respectively. The most common AEs were oedema (59.4%), hypoalbuminaemia (40.6%), alanine aminotransferase increased (31.3%). Conclusion: Gumarontinib showed promising antitumour activity in driver-gene negative locally advanced or metastatic NSCLC patients with MET overexpression, which warranted a further clinical trial. Trial registration: ClinicalTrials.gov identifier: NCT03457532; NCT04270591.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorrectales , Irinotecán , Quinazolinas , Sistema de Registros , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Irinotecán/administración & dosificación , Irinotecán/uso terapéutico , Estudios Prospectivos , Masculino , Femenino , Quinazolinas/uso terapéutico , Quinazolinas/administración & dosificación , Persona de Mediana Edad , Anciano , Metástasis de la Neoplasia , Adulto , TiofenosRESUMEN
Adjuvant oxaliplatin plus S-1 (SOX) chemotherapy for gastric cancer (GC) after D2 gastrectomy has been proven effective. There has yet to be a study that evaluates adjuvant nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus S-1. In this single-center, retrospective study, GC patients after D2 gastrectomy received either nab-paclitaxel plus S-1 (AS group) or SOX group were recruited between January 2018 and December 2020 in The First Affiliated Hospital of Zhejiang University. Intravenous nab-paclitaxel 120 mg/m2 or 260 mg/m2 and oxaliplatin 130 mg/m2 were administered as eight 3 week cycle, especially in the AS and SOX group. Patients received S-1 twice daily with a dose of 40 mg/m2 in the two groups on days 1-14 of each cycle. The end points were disease-free survival (DFS) rate at 3 years and adverse events (AEs). There were 56 eligible patients, 28 in the AS group and 35 in the SOX group. The 3 year DFS rate was 78.0% in AS group versus 70.7% in SOX group (p = 0.46). Subgroup analysis showed that the patients with signet-ring positive in the AS group had a prolonged DFS compared with the SOX group (40.0 vs. 13.8 m, p = 0.02). The diffuse-type GC or low differentiation in the AS group was associated with numerically prolonged DFS compared with the SOX group, but the association was not statistically significant (p = 0.27 and p = 0.15 especially). Leukopenia (14.3%) were the most prevalent AEs in the AS group, while thrombocytopenia (28.5%) in the SOX group. Neutropenia (7.1% in AS group) and thrombocytopenia (22.8% in SOX group) were the most common grade 3 or 4 AEs. In this study analyzing past data, a tendency towards a greater 3 year DFS was observed when using AS regimen in signet-ring positive patients. AS group had fewer thrombocytopenia compared to SOX group. More studies should be conducted with larger sample sizes.
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Protocolos de Quimioterapia Combinada Antineoplásica , Combinación de Medicamentos , Gastrectomía , Oxaliplatino , Ácido Oxónico , Neoplasias Gástricas , Tegafur , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/mortalidad , Masculino , Femenino , Tegafur/administración & dosificación , Tegafur/efectos adversos , Tegafur/uso terapéutico , Persona de Mediana Edad , Oxaliplatino/administración & dosificación , Oxaliplatino/uso terapéutico , Estudios Retrospectivos , Gastrectomía/métodos , Ácido Oxónico/administración & dosificación , Ácido Oxónico/efectos adversos , Ácido Oxónico/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anciano , Quimioterapia Adyuvante/métodos , Paclitaxel Unido a Albúmina/administración & dosificación , Paclitaxel Unido a Albúmina/uso terapéutico , Adulto , Supervivencia sin Enfermedad , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Paclitaxel/efectos adversos , Albúminas/administración & dosificaciónRESUMEN
Membrane-based pervaporation (PV) for organic solvent dehydration is of great significance in the chemical and petrochemical industries. In this work, high-aluminum ZSM-5 zeolite membranes were synthesized by a fluoride-assisted secondary growth on α-alumina tubular supports using mordenite framework inverted (MFI) nanoseeds (~110 nm) and a template-free synthesis solution with a low Si/Al ratio of 10. Characterization by XRD, EDX, and SEM revealed that the prepared membrane was a pure-phase ZSM-5 zeolite membrane with a Si/Al ratio of 3.8 and a thickness of 2.8 µm. Subsequently, two categories of PV performance parameters (i.e., flux versus separation factor and permeance versus selectivity) were used to systematically examine the effects of operating conditions on the PV dehydration performance of different organic solvents (methanol, ethanol, n-propanol, and isopropanol), and their PV mechanisms were explored. Employing permeance and selectivity effectively disentangles the influence of operating conditions on PV performance, thereby elucidating the inherent contribution of membranes to separation performance. The results show that the mass transfer during PV dehydration of organic solvents was mainly dominated by the adsorption-diffusion mechanism. Furthermore, the diffusion of highly polar water and methanol molecules within membrane pores had a strong mutual slowing-down effect, resulting in significantly lower permeance than other binary systems. However, the mass transfer process for water/low-polar organic solvent (ethanol, n-propanol, and isopropanol) mixtures was mainly controlled by competitive adsorption caused by affinity differences. In addition, the high-aluminum ZSM-5 zeolite membrane exhibited superior PV dehydration performance for water/isopropanol mixtures.
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Membranas Artificiales , Solventes , Zeolitas , Zeolitas/química , Solventes/química , Agua/química , 2-Propanol/química , Aluminio/química , Etanol/químicaRESUMEN
Treatment with anti-programmed cell death protein 1 (PD-1) therapy and chemotherapy prolongs the survival of patients with unresectable advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. The benefit from anti-PD-1 therapy is enriched in patients with programmed cell death 1 ligand 1 (PD-L1) combined positive score (CPS)-positive or CPS-high tumors compared with patients with PD-L1 CPS-negative or CPS-low tumors. In this phase 1b/2 study, we evaluated the efficacy and safety of cadonilimab, a bispecific antibody targeting PD-1 and cytotoxic T-lymphocyte antigen-4, plus chemotherapy as first-line treatment in patients with human epidermal growth factor receptor 2-negative unresectable advanced or metastatic gastric or GEJ adenocarcinoma. The primary endpoint was the recommended phase 2 dose (RP2D) for phase 1b and the objective response rate for phase 2. Secondary endpoints included disease control rate, duration of response, time to response, progression-free survival, overall survival (OS) and safety. The primary endpoint was met. No dose-limiting toxicities were observed during dose escalation in phase 1b; the recommended phase 2 dose was determined as 6 mg kg-1 every 2 weeks. The objective response rate was 52.1% (95% confidence interval (CI) = 41.6-62.5), consisting of complete and partial responses in 4.3% and 47.9% of patients, respectively. The median duration of response, progression-free survival and OS were 13.73 months (95% CI = 7.79-19.12), 8.18 months (95% CI = 6.67-10.48) and 17.48 months (95% CI = 12.35-26.55), respectively. The median OS in patients with a PD-L1 CPS ≥ 5 was 20.32 months (95% CI = 4.67-not estimable); in patients with a PD-L1 CPS < 1, the median OS reached 17.64 months (95% CI = 11.63-31.70). The most common treatment-related grade 3 or higher adverse events were decreased neutrophil count (19.1%), decreased platelet count (16.0%), anemia (12.8%) and decreased leukocyte count (8.5%). No new safety signal was identified. The current regimen showed promising clinical activity and manageable safety in patients with gastric or GEJ adenocarcinoma regardless of PD-L1 expression. Chinadrugtrials.org.cn registration: CTR20182027.
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Adenocarcinoma , Unión Esofagogástrica , Receptor ErbB-2 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Persona de Mediana Edad , Masculino , Femenino , Unión Esofagogástrica/patología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Anciano , Receptor ErbB-2/metabolismo , Adulto , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Biespecíficos/efectos adversos , Anticuerpos Biespecíficos/administración & dosificación , Antígeno B7-H1/antagonistas & inhibidoresRESUMEN
We present an innovative methodology for the synthesis of MXene membranes through a dual-stage process involving etching and subsequent thermal self-crosslinking. A molar ratio of 1 (Al3+):9 (F-) using HCl/LiF was employed to convert raw Ti3AlC2 (MAX phase) into MXene within 48 h at 40 °C. This procedure predominantly yielded monolayers distinguished by diameters exceeding 500 nm, elevated crystallinity and a high overall yield. Advanced characterization techniques, including FESEM, TEM, HRTEM, AFM, XPS, and FTIR, were utilized. Instrumental analysis confirmed the formation of MXene exhibiting a single-flake morphology with diameters exceeding 500 nm. These monolayers were intact and continuous, with smooth peripheries and a uniform thickness of 2.1 nm. The surfaces were predominantly composed of carbon (C), oxygen (O), and titanium (Ti) atoms, interconnected by chemical bonds such as C-Ti-O, C-Ti-OH, C-C, C-O, and Ti-O. In the subsequent phase, vacuum filtration facilitated the assembly of a self-supporting MXene membrane. Thermal treatment at 170 °C for 30 h resulted in the reinforcement of C-Ti-O bonds within the nanosheets, increasing their prevalence to 43.14 % and 19.47 %, respectively. This thermal regulation reduced the interlayer d-spacing from 4.33 to 3.54 Å, which significantly improved the gas separation efficiency beyond the Knudsen diffusion limit, as demonstrated by the αH2/CF4 value exceeding 23.0.
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Recently, the activation of persulfate (PDS) by non-metallic photocatalysts under visible light has attracted significant interest in applications in environmental remediation. This study presents a pioneering investigation into the combined application of the TpTt-COF and PMS for visible light degradation of organic dyes. Synthesized orange TpTt-COF monomers exhibit exceptional crystallinity, a 2D structure, and notable stability in harsh conditions. The broad visible light absorption around a wavelength of 708 nm. The TpTt-COF emerges as a promising candidate for photocatalytic dye degradation. The study addresses high charge recombination in the TpTt-COF, highlighting the crucial role of its electron donor and acceptor for the PMS activation. Comparative analyses against traditional photocatalytic materials, such as the metal-free carbon-based material g-C3N4 and transition metal-containing TiO2, demonstrate TpTt-COF's superior performance, generating diverse free radicals. In simulated experiments, the TpTt-COF's degradation rate surpasses PMS-combined g-C3N4 by 13.9 times. and 1.6 times higher than the TpTt-COF alone. Remarkably, the TpTt-COF maintains high activity under harsh environments. Investigations into the degradation mechanism and the TpTt-COF's reusability reveal its efficiency and stability. Under visible light, TpTt-COF facilitates efficient electron-hole separation. Combining the TpTt-COF with PMS produces various radicals, ensuring effective separation and a synergistic effect. Radical quenching experiments confirm the pivotal role of O2-· radicals, while ·OH and SO4-· radicals intensify the degradation. After five cycles, TpTt-COF maintains an impressive 83.2% degradation efficiency. This study introduces an efficient photocatalytic system mediated by PMS and valuable insights into governing mechanisms for organic pollutant degradation in water environments.
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Pervaporation (PV), as an energy-efficient mixture separation technology, plays an important role in the chemical industry. In this work, no organic templates were needed to produce high-performance ZSM-5 membranes with an extremely low Si/Al ratio of 3.3 on α-Al2O3 tubular supports using 100 nm nanoseeds. The effects of preparation parameters on the crystalline phase structures, micromorphologies, and PV separation performance of ZSM-5 membranes were comprehensively investigated. The results revealed that the Si/Al ratio of gels significantly affected both the Si/Al ratio and the crystal orientation of the final ZSM-5 membrane. The optimized ZSM-5 membrane with a thickness of 1.8 µm was utilized to dehydrate various organic solvents via PV, and the influence of the operating parameters on PV dehydration performance was evaluated and is described herein. Furthermore, the permeation behaviors of single gases and PV were examined using permeate molecules within a similar size range to reveal the PV mechanism of the ZSM-5 membrane. The results demonstrated that gas permeation followed Knudsen diffusion, while PV permeation was decreased with decreases in the affinity of molecules, revealing an adsorption-diffusion mechanism that dominated PV dehydration through the ZSM-5 membrane. Moreover, the as-synthesized ZSM-5 membrane had good water permselectivity for water/acetone (e.g., total flux = 1.03 kg/(m2 h), α = 307) and for water/isopropanol (e.g., total flux = 1.49 kg/(m2 h), α = 1070) mixtures compared with other membranes reviewed in the literature. The synthesized ZSM-5 membrane also exhibited excellent reproducibility, high stability, and attractive PV separation performance, demonstrating its significant potential application in the PV dehydration of organic solvents.
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Triple-negative breast cancer (TNBC) is widely recognized as the most aggressive form of breast cancer, occurring more frequently in younger patients and characterized by high heterogeneity, early distant metastases and poor prognosis. Multiple treatment options have failed to achieve the expected therapeutic effects due to the lack of clear molecular targets. Based on genomics, transcriptomics and metabolomics, the multi-omics analysis further clarifies TNBC subtyping, which provides a greater understanding of tumour heterogeneity and targeted therapy sensitivity. For instance, the luminal androgen receptor subtype (LAR) exhibits responsiveness to anti-AR therapy, and the basal-like immune-suppressed subtype (BLIS) tends to benefit from poly (ADP-ribose) polymerase inhibitors (PARPis) and anti-angiogenic therapy. The efficacy of multi-dimensional combination therapy holds immense importance in guiding personalized and precision medicine for TNBC. This review offers a systematic overview of recent FuDan TNBC molecular subtyping and its role in the instruction of clinical precision therapy.
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Aim: To evaluate pembrolizumab in patients of Chinese descent with microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) tumors enrolled in KEYNOTE-158 (Cohort L). Methods: Patients with MSI-H/dMMR advanced tumors received pembrolizumab 200 mg IV Q3W. Primary end point was overall response rate (ORR). Secondary end points were duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Results: 24 patients were enrolled (20 were evaluable for efficacy). With median follow-up of 12.4 months, the ORR was 70%. DOR, PFS and OS were all not reached. A total of 19 (79%) patients had a treatment-related adverse event (AE; grade ≥3 in 4 [17%]), and 8 (33%) had an immune-mediated AE (grade ≥3 in (4 [17%]). Conclusion: Pembrolizumab provided meaningful and durable responses with manageable safety. These results are consistent with those reported for the global trial.
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Despite a standardized diagnostic examination, cancer of unknown primary (CUP) is a rare metastatic malignancy with an unidentified tissue of origin (TOO). Patients diagnosed with CUP are typically treated with empiric chemotherapy, although their prognosis is worse than those with metastatic cancer of a known origin. TOO identification of CUP has been employed in precision medicine, and subsequent site-specific therapy is clinically helpful. For example, molecular profiling, including genomic profiling, gene expression profiling, epigenetics and proteins, has facilitated TOO identification. Moreover, machine learning has improved identification accuracy, and non-invasive methods, such as liquid biopsy and image omics, are gaining momentum. However, the heterogeneity in prediction accuracy, sample requirements and technical fundamentals among the various techniques is noteworthy. Accordingly, we systematically reviewed the development and limitations of novel TOO identification methods, compared their pros and cons and assessed their potential clinical usefulness. Our study may help patients shift from empirical to customized care and improve their prognoses.
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Neoplasias Primarias Desconocidas , Medicina de Precisión , Humanos , Neoplasias Primarias Desconocidas/genética , Neoplasias Primarias Desconocidas/terapia , Neoplasias Primarias Desconocidas/patología , Neoplasias Primarias Desconocidas/diagnóstico , Medicina de Precisión/métodos , Perfilación de la Expresión Génica/métodos , Biomarcadores de Tumor/genética , Aprendizaje Automático , Pronóstico , Genómica/métodos , Biopsia Líquida/métodosRESUMEN
BACKGROUND: Penpulimab, a new-generation antiprogrammed cell death-1 immunoglobulin G1 monoclonal antibody, was engineered to optimize receptor occupancy and eliminate fragment crystallizable γ-mediated effector function. In this multicenter, phase 1b/2, multicohort study, the objective was to investigate the efficacy, safety, and immunogenicity of penpulimab in advanced solid tumors. METHODS: Patients who had unresectable, advanced solid tumors were enrolled from six centers and received 200 mg penpulimab on day 1 every 2 weeks for up to 24 months. The primary end point was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors, version criteria 1.1. RESULTS: Between September 2, 2019, and January 1, 2020, 65 patients were enrolled and received penpulimab. At the time of data cutoff (May 11, 2022), the median follow-up was 12.6 months (range, 1.1-28.6 months). The ORR was 12.3 (95% confidence interval [CI], 5.5%-22.8%), with three (4.6%) complete responses and five (7.7%) partial responses. Twelve patients (18.5%) achieved stable disease, resulting in a disease control rate of 30.8% (95% CI, 19.9%-43.4%). The median duration of response was not reached (95% CI, 6.70 months to not estimable). In all cohorts, the median progression-free survival was 1.74 months (95% CI, 1.41-2.69 months), and the median overall survival was 16.59 months (95% CI, 7.82-22.18 months). Grade 3 or greater treatment-related adverse events and immune-related adverse events occurred in 9.2% and 27.7% of patients, respectively. Positive antidrug antibody responses to penpulimab were observed in one patient (1.8%). CONCLUSIONS: Penpulimab showed promising antitumor activity with an acceptable safety profile, offering a potential new treatment approach for solid tumors. These findings supported the evaluation of penpulimab's durable activity and safety, as monotherapy or in combination therapy, in specific malignancies.
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Neoplasias , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/inmunología , Adulto , Anciano de 80 o más Años , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Inmunoglobulina G/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Metástasis de la NeoplasiaRESUMEN
BACKGROUND: The highly heterogeneous, complex pathological histology, and clinical phenotype in bladder cancer (BC) plague the prognostic management of BC to the present day. METHODS: This study was conducted using single-cell sequencing data from the gene expression omnibus (GEO) database (GSE135337). A descending, annotated analysis was performed to identify the cell types contributing to BC aggressiveness. BC cell sequencing data from The Cancer Genome Atlas (TCGA) database were then combined with univariate, least absolute shrinkage and selection operator (LASSO), multivariate COX regression analysis to identify biomarkers of BC prognosis to construct a BC. We identified biomarkers of BC prognosis to construct a prognostic risk guidance system for BC. The feedback of patients in different risk strata to immunotherapy was analyzed. Finally, the regulation of prognostic genes on cancer cell activity was verified in vitro by Western blot and cell counting kit-8 (CCK8) assays. RESULTS: Macrophages specifically expressing CD68 in BC were the cell type with the highest AUCell score, and CD68 was the biomarker of Tumor-associated macrophages (TAMs). CD68 macrophages were potentially the critical cell type in the aggressive BC subtype. Through univariate, LASSO, multivariate COX-based regression analysis. CTSS, GMFG, ANXA5, GSN, SLC2A3, and FTL were authenticated as prognostic biomarkers (p < 0.05) and composed the Risk Score. Patients in the low-risk group showed an excellent survival advantage (p < 0.01) and immunotherapy feedback. Additionally, inhibition of GSN expression decreased EMT activity to inhibit bladder cancer cell viability. CONCLUSION: In conclusion, this study provided feedback on the immune cell types associated with aggressiveness in BC. Importantly, a prognostic management system for BC was created based on the genes involved, providing more insight into the aggressive pathological phenotype as well as the prognosis of BC.
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Neoplasias de la Vejiga Urinaria , Humanos , Pronóstico , Neoplasias de la Vejiga Urinaria/genética , Macrófagos , Bioensayo , BiomarcadoresRESUMEN
In this study, high-performance FAU (NaY type) zeolite membranes were successfully synthesized using small-sized seeds of 50 nm, and their gas separation performance was systematically evaluated. Employing nano-sized NaY seeds and an ultra-dilute reaction solution with a molar composition of 80 Na2O: 1Al2O3: 19 SiO2: 5000H2O, the effects of synthesis temperature, crystallization time, and porous support (α-Al2O3 or mullite) on the formation of FAU membranes were investigated. The results illustrated that further extending the crystallization time or increasing the synthesis temperature led to the formation of a NaP impurity phase on the FAU membrane layer. The most promising FAU membrane with a thickness of 2.7 µm was synthesized on an α-Al2O3 support at 368 K for 8 h and had good reproducibility. The H2 permeance of the membrane was as high as 5.34 × 10-7 mol/(m2 s Pa), and the H2/C3H8 and H2/i-C4H10 selectivities were 183 and 315, respectively. The C3H6/C3H8 selectivity of the membrane was as high as 46, with a remarkably high C3H6 permeance of 1.35 × 10-7 mol/(m2 s Pa). The excellent separation performance of the membrane is mainly attributed to the thin, defect-free membrane layer and the relatively wide pore size (0.74 nm).
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We report a multicenter, phase 2 study evaluating the efficacy of pucotenlimab, an anti-PD-1 antibody, in patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, and potential biomarkers for response. Overall, 100 patients with previously treated, advanced solid tumors centrally confirmed as dMMR or MSI-H received pucotenlimab at 200 mg every 3 weeks. The most common cancer type is colorectal cancer (n = 71). With a median follow-up of 22.5 months, the objective response rate is 49.0% (95% confidence interval 38.86%-59.20%) as assessed by the independent review committee, while the median progression-free survival and overall survival have not been reached. Grade ≥3 treatment-related adverse events were observed in 18 patients. For the biomarker analysis, responders are enriched in patients with mutations in the KMT2D gene. Pucotenlimab is an effective treatment option for previously treated advanced dMMR/MSI-H solid tumors, and the predictive value of KMT2D mutation warrants further research. This study is registered with ClinicalTrials.gov: NCT03704246.
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Neoplasias Colorrectales , Inestabilidad de Microsatélites , Humanos , Reparación de la Incompatibilidad de ADN/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Resultado del TratamientoRESUMEN
Objective: Currently, pre-treatment prediction of patients with pancreatic neuroendocrine tumors with liver metastases (PNELM) receiving surufatinib treatment was unsatisfying. Our objective was to examine the association between radiological characteristics and efficacy/prognosis. Methods: We enrolled patients with liver metastases in the phase III, SANET-p trial (NCT02589821) and obtained contrast-enhanced computed tomography (CECT) images. Qualitative and quantitative parameters including hepatic tumor margins, lesion volumes, enhancement pattern, localization types, and enhancement ratios were evaluated. The progression-free survival (PFS) and hazard ratio (HR) were calculated using Cox's proportional hazard model. Efficacy was analyzed by logistic-regression models. Results: Among 152 patients who had baseline CECT assessments and were included in this analysis, the surufatinib group showed statistically superior efficacy in terms of median PFS compared to placebo across various qualitative and quantitative parameters. In the multivariable analysis of patients receiving surufatinib (N=100), those with higher arterial phase standardized enhancement ratio-peri-lesion (ASER-peri) exhibited longer PFS [HR=0.039; 95% confidence interval (95% CI): 0.003-0.483; P=0.012]. Furthermore, patients with a high enhancement pattern experienced an improvement in the objective response ratio [31.3% vs. 14.7%, odds ratio (OR)=3.488; 95% CI: 1.024-11.875; P=0.046], and well-defined tumor margins were associated with a higher disease control rate (DCR) (89.3% vs. 68.2%, OR=4.535; 95% CI: 1.285-16.011; P=0.019) compared to poorly-defined margins. Conclusions: These pre-treatment radiological features, namely high ASER-peri, high enhancement pattern, and well-defined tumor margins, have the potential to serve as predictive markers of efficacy in patients with PNELM receiving surufatinib.
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BACKGROUND: Notwithstanding that the past decade has witnessed unprecedented medical progress, gastric cancer (GC) remains a leading cause of cancer death, highlighting the need for effective prognostic markers. The Memorial Sloan Kettering Prognostic Score (MPS) has been validated as a valuable prognostic tool for patients with metastatic pancreatic adenocarcinoma (mPDAC). This study aimed to assess the prognostic value of the MPS in advanced GC. METHODS: Data from 367 patients were analyzed in the present study. The MPS for each patient was calculated based on the sum of scores based on the neutrophil-to-lymphocyte ratio and serum albumin levels. Multivariate analyses were performed to identify the independent clinicopathological parameters associated with overall survival (OS). Further subgroup analyses based on clinicopathological features were conducted. RESULTS: Patients with MPS 0 (n = 161), MPS 1 (n = 158), and MPS 2 (n = 48) exhibited significantly different OS, with a median survival duration of 20.7 (95%CI: 12.2-29.2), 14.9 (95%CI: 12.5-17.3), and 12.7 (95%CI: 9.3-16.0) months, respectively (p < 0.001). Significant differences in survival were observed among different groups of patients receiving chemotherapy (18.5 months vs. 14.7 months vs. 11.0 months, p = 0.03) or the subgroup receiving chemotherapy plus immunotherapy as first-line treatment (32.6 months vs. 17.7 months vs. 12.7 months, p = 0.02). The MPS was identified as an independent prognostic factor in multivariate analysis. During subgroup analyses, MPS-low (MPS 0) was consistently associated with a better prognosis than MPS-high (MPS 1 or 2). CONCLUSIONS: MPS is a practical, simple, and useful prognostic tool for patients with advanced GC. Further studies are warranted to validate its prognostic value in advanced GC.
Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Pronóstico , Adenocarcinoma/terapia , Linfocitos/patología , Estudios RetrospectivosRESUMEN
BACKGROUND: Immune checkpoint inhibitors targeting PD-1 or CTLA-4 individually have shown substantial clinical benefits in the treatment of malignancies. We aimed to assess the safety and antitumour activity of cadonilimab monotherapy, a bispecific PD-1/CTLA-4 antibody, in patients with advanced solid tumours. METHODS: This multicentre, open-label, phase 1b/2 trial was conducted across 30 hospitals in China. Patients aged 18 years or older with histologically or cytologically confirmed, unresectable advanced solid tumours, unsuccessful completion of at least one previous systemic therapy, and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible for inclusion. Patients who had previously received anti-PD-1, anti-PD-L1, or anti-CTLA-4 treatment were not eligible for inclusion. In the dose escalation phase of phase 1b, patients received intravenous cadonilimab at 6 mg/kg and 10 mg/kg every 2 weeks. In the dose expansion phase of phase 1b, cadonilimab at 6 mg/kg and a fixed dose of 450âmg were given intravenously every 2 weeks. In phase 2, cadonilimab at 6 mg/kg was administered intravenously every 2 weeks in three cohorts: patients with cervical cancer, oesophageal squamous cell carcinoma, and hepatocellular carcinoma. The primary endpoints were the safety of cadonilimab in phase 1b and objective response rate in phase 2, based on the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The safety analysis was done in all patients who received at least one dose of cadonilimab. Antitumour activity was assessed in the full analysis set for the cervical cancer cohort, and in all patients with measurable disease at baseline and who received at least one dose of cadonilimab in the oesophageal squamous cell carcinoma and hepatocellular carcinoma cohorts. The study is registered on ClinicalTrial.gov, NCT03852251, and closed to new participants; follow-up has been completed. FINDINGS: Between Jan 18, 2019, and Jan 8, 2021, 240 patients (83 [43 male and 40 female] in phase 1b and 157 in phase 2) were enrolled. Phase 2 enrolled 111 female patients with cervical cancer, 22 patients with oesophageal squamous cell carcinoma (15 male and seven female), and 24 patients with hepatocellular carcinoma (17 male and seven female). During dose escalation, no dose-limiting toxicities occurred. Grade 3-4 treatment-related adverse events occurred in 67 (28%) of 240 patients; the most frequent grade 3 or worse treatment-related adverse events were anaemia (seven [3%]), increased lipase (four [2%]), decreased bodyweight (three [1%]), decreased appetite (four [2%]), decreased neutrophil count (three [1%]), and infusion-related reaction (two [1%]). 17 (7%) patients discontinued treatment due to treatment-related adverse events. 54 (23%) of 240 patients reported serious treatment-related adverse events, including five patients who died (one due to myocardial infarction; cause unknown for four). In phase 2, in the cervical cancer cohort, with a median follow-up of 14·6 months (IQR 13·1-17·5), the objective response rate was 32·3% (32 of 99; 95% CI 23·3-42·5). In the oesophageal squamous cell carcinoma cohort, with a median follow-up of 17·9 months (IQR 4·0-15·1), the objective response rate was 18·2% (four of 22; 95% CI 5·2-40·3). In the hepatocellular carcinoma cohort, with a median follow-up of 19·6 months (IQR 8·7-19·8), the objective response rate was 16·7% (four of 24; 95% CI 4·7-37·4). INTERPRETATION: Cadonilimab showed an encouraging tumour response rate, with a manageable safety profile, suggesting the potential of cadonilimab for the treatment of advanced solid tumours. FUNDING: Akeso Biopharma. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
Asunto(s)
Antineoplásicos Inmunológicos , Carcinoma Hepatocelular , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Neoplasias Hepáticas , Neoplasias del Cuello Uterino , Humanos , Masculino , Femenino , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Antígeno CTLA-4 , Receptor de Muerte Celular Programada 1 , Empatía , Anticuerpos Monoclonales Humanizados , Antineoplásicos Inmunológicos/efectos adversos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/inducido químicamente , Neoplasias Hepáticas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Organic polymeric ultrafiltration (UF) membranes have been widely used in protein separation due to their advantages of high flux and simple manufacturing process. However, due to the hydrophobic nature of the polymer, pure polymeric UF membranes need to be modified or hybrid to increase their flux and anti-fouling performance. In this work, tetrabutyl titanate (TBT) and graphene oxide (GO) were simultaneously added to the polyacrylonitrile (PAN) casting solution to prepare a TiO2@GO/PAN hybrid ultrafiltration membrane using a non-solvent induced phase separation (NIPS). During the phase separation process, TBT underwent a sol-gel reaction to generate hydrophilic TiO2 nanoparticles in situ. Some of the generated TiO2 nanoparticles reacted with the GO through a chelation interaction to form TiO2@GO nanocomposites. The resulting TiO2@GO nanocomposites had higher hydrophilicity than the GO. They could selectively segregate towards the membrane surface and pore walls through the solvent and non-solvent exchange during the NIPS, significantly improving the membrane's hydrophilicity. The remaining TiO2 nanoparticles were segregated from the membrane matrix to increase the membrane's porosity. Furthermore, the interaction between the GO and TiO2 also restricted the excessive segregation of the TiO2 nanoparticles and reduced their losing. The resulting TiO2@GO/PAN membrane had a water flux of 1487.6 L·m-2·h-1 and a bovine serum albumin (BSA) rejection rate of 99.5%, which were much higher than those of the currently available UF membranes. It also exhibited excellent anti-protein fouling performance. Therefore, the prepared TiO2@GO/PAN membrane has important practical applications in the field of protein separation.