SOX Group Research Articles

Microenvironment modulation of Fe single atoms in porous g-C3N4 by introducing −SOx groups for enhanced photo-Fenton reactions

Heterogeneous photo-Fenton reactions based on hydrogen peroxide (H2O2) activation exhibit great potential in the treatment of organic wastewater. For developing efficient photo-Fenton catalysts, a fundamental investigation into the specific catalytic sites and the reaction mechanism is highly desired. Herein, a novel photo-Fenton catalyst (Fe1/CN-SOx) was constructed by synchronously anchoring Fe single atoms (SAs) and oxidized sulfur (−SOx) groups into porous graphitic carbon nitride (g-C3N4). The presence of trace −SOx groups altered the local configuration of g-C3N4 and optimized the coordination microenvironment of Fe SAs, thereby modulating the electronic structures of catalytic sites in favor of H2O2 activation. The cooperation between Fe SAs and the neighboring C atoms bonded with −SOx (C-SOx) enhanced the adsorption and cleavage of H2O2. The photoinduced charge carriers further accelerated Fe2+/Fe3+ redox cycles and hydroxyl radical (•OH) production, achieving an efficient photo-Fenton synergistic catalysis for continuous degradation of organic contaminants. The Fe1/CN-SOx catalyst also exhibited excellent anti-interference performance in diverse aquatic systems and good long-term stability, indicating its great potential for applications in water treatment. This study provides an in-depth insight into the optimal fabrication of single-atom active sites by modulating the local structures of support materials, aiming to enhance photo-Fenton reactions.

A retrospective study of adjuvant albumin-bound paclitaxel plus S-1 after D2 gastrectomy versus oxaliplatin plus S-1 in gastric cancer

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.

Biological functions and therapeutic potential of SRY related high mobility group box 5 in human cancer.

Cancer is a heavy human burden worldwide, with high morbidity and mortality. Identification of novel cancer diagnostic and prognostic biomarkers is important for developing cancer treatment strategies and reducing mortality. Transcription factors, including SRY associated high mobility group box (SOX) proteins, are thought to be involved in the regulation of specific biological processes. There is growing evidence that SOX transcription factors play an important role in cancer progression, including tumorigenesis, changes in the tumor microenvironment, and metastasis. SOX5 is a member of SOX Group D of Sox family. SOX5 is expressed in various tissues of human body and participates in various physiological and pathological processes and various cellular processes. However, the abnormal expression of SOX5 is associated with cancer of various systems, and the abnormal expression of SOX5 acts as a tumor promoter to promote cancer cell viability, proliferation, invasion, migration and EMT through multiple mechanisms. In addition, the expression pattern of SOX5 is closely related to cancer type, stage and adverse clinical outcome. Therefore, SOX5 is considered as a potential biomarker for cancer diagnosis and prognosis. In this review, the expression of SOX5 in various human cancers, the mechanism of action and potential clinical significance of SOX5 in tumor, and the therapeutic significance of Sox5 targeting in cancer were reviewed. In order to provide a new theoretical basis for cancer clinical molecular diagnosis, molecular targeted therapy and scientific research.

A Retrospective Analysis of the Lauren Classification in the Choice of XELOX or SOX as an Adjuvant Chemotherapy for Gastric Cancer.

We aim to retrospectively explore the guiding value of the Lauren classification for patients who have undergone D2 gastrectomy to choose oxaliplatin plus capecitabine (XELOX) or oxaliplatin plus S-1 (SOX) as a further systemic treatment after the operation. We collected data of 406 patients with stage III gastric cancer(GC)after radical D2 resection and regularly received XELOX or SOX adjuvant treatment after surgery and followed them for at least five years. According to the Lauren classification, we separated patients out into intestinal type (IT) GC together with non-intestinal type(NIT) GC. According to the chemotherapy regimen, we separated patients into the SOX group together with the XELOX group. Among non-intestinal type patients, the 3-year DFS rates in the SOX group and the XELOX group were 72.5%, respectively; 54.5% (P=0.037); The 5-year OS rates were 66.8% and 51.8% respectively (P=0.038), both of which were statistically significant. The patients of non-intestinal type GC may benefit from the SOX regimen. Differences were counted without being statistically significant with intestinal-type GC in the SOX or XELOX groups.

Perioperative chemotherapy with docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) for the treatment of locally advanced gastric or gastro-esophageal junction adenocarcinoma (MATCH): an open-label, randomized, phase 2 clinical trial

BackgroundIt remains unclear whether addition of docetaxel to the combination of a platinum and fluoropyrimidine could provide more clinical benefits than doublet chemotherapies in the perioperative treatment for locally advanced gastric/gastro-esophageal junction (LAG/GEJ) cancer in Asia. In this randomized, phase 2 study, we assessed the efficacy and safety of perioperative docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) in LAG/GEJ adenocarcinoma patients.MethodsPatients with cT3–4 Nany M0 G/GEJ adenocarcinoma were randomized (1:1) to receive 4 cycles of preoperative DOS or SOX followed by D2 gastrectomy and another 4 cycles of postoperative chemotherapy. The primary endpoint was major pathological response (MPR).ResultsFrom Aug, 2015 to Dec, 2019,154 patients were enrolled and 147 patients included in final analysis, with a median age of 60 (26–73) years. DOS resulted in significantly higher MPR (25.4 vs. 11.8%, P = 0.04). R0 resection rate, the 3-year PFS and 3-year OS rates were 78.9 vs. 61.8% (P = 0.02), 52.3 vs. 35% (HR 0.667, 95% CI: 0.432–1.029, Log rank P = 0.07) and 57.5 vs. 49.2% (HR 0.685, 95% CI: 0.429–1.095, Log rank P = 0.11) in the DOS and SOX groups, respectively. Patients who acquired MPR experienced significantly better survival. DOS had similar tolerance to SOX.ConclusionsPerioperative DOS improved MPR significantly and tended to produce longer PFS compared to SOX in LAG/GEJ cancer in Asia, and might be considered as a preferred option for perioperative chemotherapy and worth further investigation.

GjSOX9 Cloning, Expression, and Comparison with gjSOXs Family Members in Gekko japonicus.

SOX9 plays a crucial role in the male reproductive system, brain, and kidneys. In this study, we firstly analyzed the complete cDNA sequence and expression patterns for SOX9 from Gekko japonicus SOX9 (gjSOX9), carried out bioinformatic analyses of physiochemical properties, structure, and phylogenetic evolution, and compared these with other members of the gjSOX family. The results indicate that gjSOX9 cDNA comprises 1895 bp with a 1482 bp ORF encoding 494aa. gjSOX9 was not only expressed in various adult tissues but also exhibited a special spatiotemporal expression pattern in gonad tissues. gjSOX9 was predicted to be a hydrophilic nucleoprotein with a characteristic HMG-Box harboring a newly identified unique sequence, "YKYQPRRR", only present in SOXE members. Among the 20 SOX9 orthologs, gjSOX9 shares the closest genetic relationships with Eublepharis macularius SOX9, Sphacrodactylus townsendi SOX9, and Hemicordylus capensis SOX9. gjSOX9 and gjSOX10 possessed identical physicochemical properties and subcellular locations and were tightly clustered with gjSOX8 in the SOXE group. Sixteen gjSOX family members were divided into six groups: SOXB, C, D, E, F, and H with gjSOX8, 9, and 10 in SOXE among 150 SOX homologs. Collectively, the available data in this study not only facilitate a deep exploration of the functions and molecular regulation mechanisms of the gjSOX9 and gjSOX families in G. japonicus but also contribute to basic research regarding the origin and evolution of SOX9 homologs or even sex-determination mode in reptiles.

Serum basic fibroblast growth factor and interleukin-1β predict the effect of first-line chemotherapy in patients with advanced gastric cancer.

The incidence and mortality rates of gastric cancer in China are the second-highest in the world, and most patients with gastric cancer lose their chance of surgery by the time of their diagnosis. To explore the predictive potential of serum basic fibroblast growth factor and interleukin-1β levels for the effect of first-line chemotherapy in patients with advanced gastric cancer. From the gastric cancer patients admitted to our hospital from May 2019 to April 2023, 84 patients were selected and randomly and equally assigned to the experimental or control group. The FLOT group received the FLOT chemotherapy regimen (composed of oxaliplatin + calcium folinate + fluorouracil + paclitaxel), while the SOX group received the SOX chemotherapy regimen (composed of oxaliplatin + tiga capsules). The clinical efficacy, tumor marker levels, adverse reactions, and survival rates of the two groups were compared 7 days after the end of the relevant treatments. The target effective rate of the FLOT group was 54.76%, which was much higher than that of the SOX group (33.33%; P < 0.05). After treatment, both the groups demonstrated lower levels of cancer antigen (CEA), carbohydrate antigen 199 (CA199), and peptide tissue antigen (TPS). For several patients before treatment (P < 0.05). Third and fourth grades. In terms of adverse reactions, the level of white blood cells in both the groups was lower. Moreover, the incidence of hand-foot skin reactions in these two study groups was lower (P < 0.05), while those of peripheral neuritis, vomiting, diarrhea, and abnormal liver function were significant (P < 0.05). No statistically significant difference was noted between the two groups (P < 0.05). The 1-year survival rate was higher in the FLOT group (P < 0.05). The FLOT regimen was effective in reducing the serum CEA, CA199, and TPS levels as well as in improving the 1-year survival rate of patients with good tolerability, making it worthy of clinical promotion and application.

Apatinib combined with SOX regimen for conversion therapy in advanced gastric cancer patients: a retrospective cohort study

BackgroundRecently, many studies have shown that the progress of conversion therapy can provide surgical opportunities for patients with advanced gastric cancer (GC) and bring survival benefits. However, the results of the current study show that the regimen used in conversion therapy is still controversial. Apatinib, as the standard third-line treatment for GC, has an inconclusive status in conversion therapy.MethodsThis study retrospectively analyzed GC patients admitted to Zhejiang Provincial People’s Hospital from June 2016 to November 2019. All patients were pathologically diagnosed, had unresectable factors, and received SOX regimen with or without apatinib as conversion therapy.ResultsA total of 50 patients were enrolled in the study. Altogether 33 patients (66%) received conversion surgery and 17 patients (34%) received conversion therapy without surgery. The median progression-free survival (PFS) between surgery group and non-surgery group were 21.0 versus 4.0 months (p < 0.0001), and the median overall survival (OS) were 29.0 versus 14.0 months (p < 0.0001). In conversion surgery group, 16 patients (16/33) were treated with SOX plus apatinib, and the R0 resection rate was 81.3%; 17 patients (17/33) were treated with SOX regimen along, and the R0 resection rate was 41.2% (p = 0.032). The PFS in the SOX combined with apatinib group was significantly longer than that of SOX group (25.5 versus 16 months, p = 0.045), and the median OS were 34.0 versus 23.0 months (p = 0.048). The addition of apatinib did not increase the incidence of serious adverse reactions throughout the preoperative therapy period.ConclusionsPatients with advanced inoperable gastric cancer could benefit probably from conversion chemotherapy and subsequence conversion surgery. Apatinib-targeted therapy combined with SOX chemotherapy may be a safe and feasible option for conversion therapy.

Efficacy and safety evaluation of PSOX, DOF and SOX regimens as neoadjuvant chemotherapy for advanced gastric cancer.

Aim: To explore the efficacy and safety ofpaclitaxel+oxaliplatin+S-1(PSOX), docetaxel+oxaliplatin+fluorouracil (DOF) and oxaliplatin+S-1 (SOX) regimens as neoadjuvant chemotherapy for advanced gastric cancer (GC). Methods: A retrospective analysis was usedin 306 patients with GC who underwent neoadjuvant chemotherapy, consisting of 102 from thePSOX group, 100 from theDOF groupand 104 from theSOX group. Results: The total effective rates and disease control rates for the PSOX, DOF and SOX groups were 31.4, 18and 16.3%and 96.1, 94and 92.3%, respectively. The highest total effective rate and disease control rate were found in the PSOX groups. Moreover, no difference among the PSOX, DOF and SOX groups on the incidence of adverse events was observed(p>0.05). Conclusion: The PSOX regimen is an alternative neoadjuvant chemotherapy regimen for GC patients.

The validity of neoadjuvant chemotherapy with paclitaxel plus S-1 is not inferior to that of SOX regimen for locally advanced gastric cancer: an observational study

BackgroundPaclitaxel plus S-1(PTXS) has shown definite efficacy for advanced gastric cancer. However, the efficacy and safety of this regimen in neoadjuvant setting for locally advanced gastric cancer (LAGC) are unclear. This study aimed to compare the efficacy of neoadjuvant chemotherapy (NAC) PTXS and oxaliplatin plus S-1 (SOX) regime for patients with LAGC.MethodsA total of 103 patients with LAGC (cT3/4NanyM0/x) who were treated with three cycles of neoadjuvant SOX regimen (n = 77) or PTXS regimen (n = 26) between 2011 and 2017 were enrolled in this study. NAC-related clinical response, pathological response, postoperative complication, and overall survival were analyzed between the groups.ResultsThe baseline data did not differ significantly between both groups. After NAC, the disease control rate of the SOX group (94.8%) was comparable with that of the PTXS group (92.3%) (p = 0.641). Twenty-three cases (29.9%) in the SOX group and 10 cases (38.5%) in the PTX group got the descending stage with no statistical difference (p = 0.417). No significant differences were observed in the overall pathological response rate and the overall postoperative complication rate between the two groups (p > 0.05). There were also no differences between groups in terms of 5-year overall and disease-free survival (p > 0.05).ConclusionsThe validity of NAC PTXS was not inferior to that of SOX regimen for locally advanced gastric cancer in terms of treatment response and overall survival. PTXS regimen could be expected to be ideal neoadjuvant chemotherapy for patients with LAGC and should be adopted for the test arm of a large randomized controlled trial.

Molecular Evolution and Inheritance Pattern of Sox Gene Family among Bovidae.

Sox genes are an evolutionarily conserved family of transcription factors that play important roles in cellular differentiation and numerous complex developmental processes. In vertebrates, Sox proteins are required for cell fate decisions, morphogenesis, and the control of self-renewal in embryonic and adult stem cells. The Sox gene family has been well-studied in multiple species including humans but there has been scanty or no research into Bovidae. In this study, we conducted a detailed evolutionary analysis of this gene family in Bovidae, including their physicochemical properties, biological functions, and patterns of inheritance. We performed a genome-wide cataloguing procedure to explore the Sox gene family using multiple bioinformatics tools. Our analysis revealed a significant inheritance pattern including conserved motifs that are critical to the ability of Sox proteins to interact with the regulatory regions of target genes and orchestrate multiple developmental and physiological processes. Importantly, we report an important conserved motif, EFDQYL/ELDQYL, found in the SoxE and SoxF groups but not in other Sox groups. Further analysis revealed that this motif sequence accounts for the binding and transactivation potential of Sox proteins. The degree of protein–protein interaction showed significant interactions among Sox genes and related genes implicated in embryonic development and the regulation of cell differentiation. We conclude that the Sox gene family uniquely evolved in Bovidae, with a few exhibiting important motifs that drive several developmental and physiological processes.

Carbon doped with binary heteroatoms (N,X–C, where X = P, B, or S) derived from polypyrrole for enhanced electromagnetic wave absorption at microwave frequencies

Dual heteroatom-doped carbon materials show great promise as electromagnetic wave absorbers. However, synthesizing carbons containing multiple heteroatoms at controlled heteroatom doping levels has provided challenges to date. Herein, we report a simple method for manufacturing dual heteroatom doped carbons (N,X–C, where X = P, B, or S) by direct carbonization of polypyrrole synthesized in the presence of H3PO4, H3BO3, or H2SO4, respectively. The heteroatom content of the N,X–C products could be precisely tuned by varying amounts of acid dopant used in the polypyrrole synthesis. The N,X–C materials showed excellent electromagnetic wave absorption properties, especially N,S1–C (prepared using equimolar amounts of pyrrole and H2SO4) which offered a wide absorption bandwidth up to 6.6 GHz (11.38–18 GHz), and a RLmin of −32.3 dB (14.2 GHz) at 2.5 mm at a filler loading of 9.0 wt%. The outstanding electromagnetic wave absorption performance of N,S1–C was attributed to the presence of N dopant species, defects, C–S, and C–SOx groups, which optimized dipole polarization and conduction loss in the dielectric loss leading to excellent impedance matching.

SOXE group transcription factors regulates the expression of FoxG1 during inner ear development

The transcription factor FOXG1 plays an important role in inner ear development; however, the cis-regulatory mechanisms controlling the inner-ear-specific expression of FOXG1 are poorly understood. In this study, we aimed to identify the element that specifically regulates FoxG1 expression in the otic vesicle, which develops into the inner ear, through comparative genome analysis between vertebrate species and chromatin immunoprecipitation. The cis-regulatory element (E2) identified showed high evolutionary conservation among vertebrates in the genomic DNA of FoxG1 spanning approximately 3 Mbp. We identified core sequences important for the activity of the otic-vesicle-specific enhancer through in vitro and in vivo reporter assays for various E2 enhancer mutants and determined the consensus sequence for SOX DNA binding. In addition, SoxE, a subfamily of the Sox family, was simultaneously expressed in the otic vesicles of developing embryos and showed a similar protein expression pattern as that of FoxG1. Furthermore, SOXE transcription factors induced specific transcriptional activity through the FoxG1 Otic enhancer (E2b). These findings suggest that the interaction between the otic enhancer of FoxG1 and SOXE transcription factor, in which the otic expression of FoxG1 is evolutionarily well-conserved, is important during early development of the inner ear, a sensory organ important for survival in nature.

Perioperative chemotherapy with docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) for locally advanced gastric or gastro-esophageal junction adenocarcinoma (MATCH): An open-label, randomized, phase 2 study.

4031 Background: The optimal perioperative chemotherapy of locally advanced gastric or gastro-esophageal junction (G/GEJ) cancer has not been established in Asia, though FLOT was considered as standard therapy in Europe. Therefore, we aimed to assess efficacy and safety of DOS versus SOX as perioperative treatment in patients with locally advanced G/GEJ cancer in this study. Methods: This was a single center, open-label, randomized, phase 2 study. Eligible pts were aged ≥18 years with histologically diagnosed HER2 negative cT3-4 Nany M0 G/GEJ (Siewert II/III type) adenocarcinoma. Pts were randomized (1:1) to receive either 4 preoperative and 4 postoperative cycles of DOS (docetaxel 60mg/m2 D1, oxaliplatin 100mg/m2 D1, S-1 40-60mg bid D1-14 depending on body surface area (BSA), Q3W) or SOX (oxaliplatin 130mg/m2 D1, S-1 40-60mg bid D1-14 depending on BSA, Q3W). Pts underwent D2 gastrectomy after preoperative treatment. The primary endpoint was major pathological response (MPR) analyzed in the modified intention to treat (mITT) population according to Becker TRG criteria. Secondary endpoints included the 3-year progression free survival (PFS), the 3-year overall survival (OS), pathological complete response, R0 resection rate and safety. Results: From Aug, 2015, to Dec, 2019, 154 pts were enrolled, 7 pts withdrew consent, 147 pts were included as mITT population (DOS 71; SOX 76). 80.3% and 67.1% of the pts in the DOS and SOX groups accepted surgery respectively. More pts achieved MPR (25.4% vs. 11.8%, p = 0.035) and R0 resection (78.9% vs. 61.8%, p = 0.024) in the DOS group than the SOX group. With a median follow-up of 42.4 months, the 3-year PFS and the 3-year OS were 52.3% vs. 35% (p = 0.065, HR 0.667, 95%CI 0.432-1.029) and 57.5% vs. 49.2% (p = 0.114, HR 0.685, 95%CI 0.429-1.095) in the DOS and SOX groups, respectively. Pts who acquired MPR had a significant longer survival than non-MPR pts. The 3-year PFS were 89.4% vs. 38.6% (p &lt; 0.001, HR 0.076, 95%CI 0.018-0.314). The 3-year OS were 100% vs. 50.1% (p = 0.008, HR 0.024, 95%CI 0.002-0.371). 56.1% and 60.8% of the pts completed at least 6 cycles of the perioperative chemotherapy in the DOS and SOX groups, respectively (p = 0.625). The most common grade ≥3 TRAEs included neutropenia (8.5% vs.10.5%), leucopenia (1.4% vs. 5.3%), thrombocytopenia (1.4% vs 15.8%, p = 0.002), anemia (1.4% vs. 3.9%) and diarrhea (1.4% vs. 2.6%). The incidence of grade 1-2 thrombocytopenia was also significant lower in the DOS group (15.5% vs. 31.6%, p = 0.022). No treatment-related deaths occurred. Conclusions: Perioperative DOS improved MPR significantly and tended to have better PFS compared with SOX in locally advanced G/GEJ cancer, might be regarded as a prefered option of perioperative chemotherapy. Clinical trial information: NCT02725424.

A multicenter randomized phase III study of albumin-bound paclitaxel combined with S-1 (AS) versus oxaliplatin combined with S-1 (SOX) for first-line treatment of advanced gastric cancer (GAPSO study).

282 Background: Albumin-bound paclitaxel has been proven to be an active agent in advanced gastric cancer, and was approved by PMDA Japan for use as a second-line treatment of advanced gastric cancer. The aim of this study was to evaluated the efficacy and safety of AS and SOX in the first-line treatment of advanced gastric cancer. Methods: Patients diagnosed with unresectable locally advanced, recurrent or metastatic human epidermal growth factor receptor type 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma were randomized (1:1) to either AS group (albumin-bound paclitaxel 260mg/m2 d1 or 130mg/m2 d1, 8; S-1 40 mg [BSA &lt; 1.25 m2], 50 mg [1.25 ≤ BSA &lt; 1.50 m2] and 60 mg [BSA ≥1.50 m2] b.i.d. d1-14, every 3wks) or SOX group (oxaliplatin 130mg/m2 d1; S-1 40 mg [BSA &lt; 1.25 m2], 50 mg [1.25 ≤ BSA &lt; 1.50 m2] and 60 mg [BSA ≥1.50 m2] b.i.d. d1-14, every 3wks). Primary endpoint was progression-free survival (PFS), secondary endpoints included overall survival (OS), objective response rate (ORR) and safety. Results: Between March 2019 and March 2021, 96 patients were enrolled and 85 patients (AS group, n = 43; SOX group, n = 42) who received at least one dose of study drug and had at least one postbaseline efficacy evaluation were included in the final analysis. 34 (79.0%) patients in the AS group and 35 (83.3%) in the SOX group had discontinued treatment. Of these 85 patients, 78.8% had two or more organs involved, 61.2% had peritoneal dissemination, and more than 1/4 had massive ascites. Patient demographics and disease characteristics were generally balanced between arms. With median follow-up 15.4 months (95% CI, 8.8-21.9), the median PFS of AS group vs. SOX group was 9.2 vs.5.1 months (HR = 0.58 [95% CI 0.36-0.96], p = 0.034); and the median OS was 14.4 vs. 15.4 months (HR = 0.73 [95%CI 0.40-1.34], p = 0.375). Tumor response was assessable in 33 patients according to RECIST V1.1 in both cohorts, the ORR and DCR were similar in AS vs. SOX arm (ORR: 54.5% vs. 51.5%, P = 0.805; DCR: 78.8% vs. 78.8%, P = 1.000). The main grade 3 or worse treatment-related adverse events were neutropenia (30.2% vs 23.8%), Leucopenia (11.6% vs 11.9%) and peripheral sensory neuropathy (4.7% vs 7.1%) in AS and SOX group. The study was planned to be adjusted, due to the widespread use of immunotherapy in first-line treatment of gastric cancer. Conclusions: The results of this study indicated that in previously untreated patients with unresectable locally advanced, recurrent or metastatic HER2-negative gastric or GEJ adenocarcinoma, AS achieved better PFS than SOX, with an inadequate power. The toxicities were controllable and consistent with previously reported. Clinical trial information: NCT03801668.

Safety and Efficacy of Camrelizumab in Combination With Nab-Paclitaxel Plus S-1 for the Treatment of Gastric Cancer With Serosal Invasion

ObjectiveTo investigate the safety and efficacy of camrelizumab in combination with nab-paclitaxel plus S-1 for the treatment of gastric cancer with serosal invasion.MethodTwo hundred patients with gastric cancer with serosal invasion who received neoadjuvant therapy from January 2012 to December 2020 were retrospectively analyzed. According to the different neoadjuvant therapy regimens, the patients were divided into the following three groups: the SOX group (S-1 + oxaliplatin) (72 patients), SAP group (S-1 + nab-paclitaxel) (95 patients) and C-SAP group (camrelizumab + S-1 + nab-paclitaxel) (33 patients).ResultThe pathological response (TRG 1a/1b) in the C-SAP group (39.4%) was not significantly different from that in the SAP group (26.3%) and was significantly higher than that in the SOX group (18.1%). The rate of ypT0 in the C-SAP group (24.2%) was higher than that in the SAP group (6.3%) and the SOX group (5.6%). The rate of ypN0 in the C-SAP group (66.7%) was also higher than that in the SAP group (38.9%) and the SOX group (36.1%). The rate of pCR in the C-SAP group (21.2%) was higher than that in the SAP group (5.3%) and the SOX group (2.8%). The use of an anti-PD-1 monoclonal antibody was an independent protective factor for TRG grade (1a/1b). The use of camrelizumab did not increase postoperative complications or the adverse effects of neoadjuvant therapy.ConclusionCamrelizumab combined with nab-paclitaxel plus S-1 could significantly improve the rate of tumor regression grade (TRG 1a/1b) and the rate of pCR in gastric cancer with serosal invasion.

Nab-paclitaxel plus S-1 versus oxaliplatin plus S-1 as first-line treatment in advanced gastric cancer: results of a multicenter, randomized, phase III trial (GAPSO study).

Background:This study aimed to investigate the superiority of nab-paclitaxel plus S-1 (AS) over oxaliplatin plus S-1 (SOX) in patients with advanced gastric cancer (AGC).Methods:In this multicenter, randomized, phase III superiority trial, eligible patients with unresectable, locally advanced gastric adenocarcinoma were recruited and randomly assigned (1:1) to receive AS (nab-paclitaxel 260 mg/m2 on day 1 or 130 mg/m2 on days 1 and 8; oral S-1 40–60 mg twice daily for 14 days) or SOX (130 mg/m2 oxaliplatin on day 1; oral S-1 40–60 mg twice daily for 14 days) every 3 weeks for up to six cycles. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival, objective response rate, and safety.Results:Owing to slow enrolment, an unplanned interim analysis was performed, resulting in the early termination of the study on 31 December 2021 (data cutoff). Between March 2019 and March 2021, 97 patients (AS, n = 48; SOX, n = 49) were treated and evaluated for efficacy and safety of AS and SOX. As of the data cutoff, the median follow-up was 23.13 months [95% confidence interval (CI), 13.39–32.87]. The median PFS was 9.03 months (95% CI, 6.50–11.56) in the AS group and 5.07 months (95% CI, 4.33–5.81) in the SOX group, demonstrating a better PFS tendency following AS treatment than SOX treatment (hazard ratio = 0.59; 95% CI, 0.37–0.94; p = 0.03). The most common grade 3 or worse adverse events were anemia, neutropenia, and leukopenia in both groups, with a higher incidence of thrombocytopenia in the SOX group.Conclusion:Although this study was terminated early, the results demonstrated a better PFS tendency in patients with AGC who were treated with AS than in those treated with SOX, with controllable toxicities.Trial registration:Clinical Trials.gov identifiers: NCT03801668. Registered January 11, 2019.

SoxE group transcription factor Sox8 promotes astrocytic differentiation of neural stem/precursor cells downstream of Nfia.

The brain consists of three major cell types: neurons and two glial cell types (astrocytes and oligodendrocytes). Although they are generated from common multipotent neural stem/precursor cells (NS/PCs), embryonic NS/PCs cannot generate all of the cell types at the beginning of brain development. NS/PCs first undergo extensive self‐renewal to expand their pools, and then acquire the potential to produce neurons, followed by glial cells. Astrocytes are the most frequently found cell type in the central nervous system (CNS), and play important roles in brain development and functions. Although it has been shown that nuclear factor IA (Nfia) is a pivotal transcription factor for conferring gliogenic potential on neurogenic NS/PCs by sequestering DNA methyltransferase 1 (Dnmt1) from astrocyte‐specific genes, direct targets of Nfia that participate in astrocytic differentiation have yet to be completely identified. Here we show that SRY‐box transcription factor 8 (Sox8) is a direct target gene of Nfia at the initiation of the gliogenic phase. We found that expression of Sox8 augmented leukemia inhibitory factor (LIF)‐induced astrocytic differentiation, while Sox8 knockdown inhibited Nfia‐enhanced astrocytic differentiation of NS/PCs. In contrast to Nfia, Sox8 did not induce DNA demethylation of an astrocyte‐specific marker gene, glial fibrillary acidic protein (Gfap), but instead associated with LIF downstream transcription factor STAT3 through transcriptional coactivator p300, explaining how Sox8 expression further facilitated LIF‐induced Gfap expression. Taken together, these results suggest that Sox8 is a crucial Nfia downstream transcription factor for the astrocytic differentiation of NS/PCs in the developing brain.

Neoadjuvant FLOT versus SOX phase II randomized clinical trial for patients with locally advanced gastric cancer

Neoadjuvant chemotherapy with docetaxel, oxaliplatin, fluorouracil, and leucovorin (FLOT regimen) has shown promising results in terms of pathological response and survival rate in patients with locally advanced resectable gastric cancer (LAGC). However, tegafur gimeracil oteracil potassium capsule (S-1) plus oxaliplatin (SOX regimen) is the preferred chemotherapy regimen in Eastern countries. Here, we conduct an open label, two-arm, phase II randomized interventional clinical trial (Dragon III; ClinicalTrials.gov: NCT03636893) to evaluate the safety and efficacy of both regimens. Patients with LAGC are randomly assigned to receive either 4 cycles of the neoadjuvant FLOT regimen (40 patients) or 3 cycles of the SOX regimen (34 patients) before gastrectomy. The primary endpoint is the comparison of complete (TRG1a) or subtotal (TRG1b) tumor regression grading in the primary tumor. There are no significant differences in adverse effects or postoperative morbidity and mortality between the two groups. No significant differences in the proportion of tumor regression grading between the FLOT group and the SOX group are found. Complete or subtotal TRG is 20.0% in the FLOT group versus 32.4% in the SOX group. Therefore, our study does not find statistically significant differences between neoadjuvant FLOT and SOX regimens for the primary outcomes reported here in locally advanced gastric cancer.

Comparison of Docetaxel + Oxaliplatin + S-1 vs Oxalipatin + S-1 as Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: A Propensity Score Matched Analysis.

BackgroundWhat is the optimal neoadjuvant chemotherapy (NAC) regimen for locally advanced gastric cancer (LAGC) remains debatable. The objective of this study was to compare the efficacy of docetaxel+oxaliplatin+S-1 (DOS) vs oxaliplatin+S-1 (SOX) as NAC for LAGC.MethodsData of 248 LAGC patients who received either DOS or SOX as NAC in our hospital between January 2010 and January 2018 were reviewed retrospectively. Propensity score matched (PSM) analysis was applied to minimize the selection bias in both groups. Prognostic factors were screened by univariate and multivariate Cox regression analyses.ResultsOf the 248 LAGC patients included, 180 patients were subjected to the PSM analysis. Patients in DOS group showed a better tumor response to NAC, higher radical resection rate and R0 resection rate than those in SOX group. The overall survival (OS) rate in DOS group was better than that in SOX group, although the overall incidence of Grade 3/4 NAC-related toxicity in DOS group was higher, as represented by leukopenia and neutropenia. Multivariate analysis revealed that the NAC regimen, cTNM stage and the R0 resection rate were independent prognostic factors. In addition, patients with TLND less than 16 population showed a worse OS rate. Subgroup analysis indicated that patients benefited from the addition of docetaxel regardless of the clinical T stage, but those with high clinical N stages (N2-3) did not.ConclusionDOS is a safe and feasible NAC regimen for LAGC, which is worth popularizing in clinical practice.