DAB2 + macrophages support FAP + fibroblasts in shaping tumor barrier and inducing poor clinical outcomes in liver cancer.

Background: Cancer-associated fibroblasts (CAFs) are the key components of the immune barrier in liver cancer. Therefore, gaining a deeper understanding of the heterogeneity and intercellular communication of CAFs holds utmost importance in boosting immunotherapy effectiveness and improving clinical outcomes. Methods: A comprehensive analysis by combing single-cell, bulk, and spatial transcriptome profiling with multiplexed immunofluorescence was conducted to unravel the complexities of CAFs in liver cancer. Results: Through an integrated approach involving 235 liver cancer scRNA-seq samples encompassing over 1.2 million cells, we found that CAFs were particularly increased in hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). FAP + fibroblasts were identified as the dominant subtype of CAFs, and which were mainly involved in extracellular matrix organization and angiogenesis. These CAFs were enriched in the tumor boundary of HCC, but diffusely scattered within ICC. The DAB2 + and SPP1 + tumor-associated macrophages (TAMs) reinforce the function of FAP + CAFs through signals such as TGF-ß, PDGF, and ADM. Notably, the interaction between DAB2 + TAMs and FAP + CAFs promoted the formation of immune barrier and correlated with poorer patient survival, non-response to immunotherapy in HCC. High FAP and DAB2 immunohistochemical scores predicted shorter survival and higher serum AFP concentration in a local clinical cohort of 90 HCC patients. Furthermore, this communication pattern might be applicable to other solid malignancies as well. Conclusions: The interaction between DAB2 + TAMs and FAP + CAFs appears crucial in shaping the immune barrier. Strategies aimed at disrupting this communication or inhibiting the functions of FAP + CAFs could potentially enhance immunotherapy effectiveness and improve clinical outcomes.

Identification of glycosyltransferases mediating 2-O-arabinopyranosyl and 2-O-galactosyl substitutions of glucuronosyl side chains of xylan.

Xylan is one of the major hemicelluloses in plant cell walls and its xylosyl backbone is often decorated at O-2 with glucuronic acid (GlcA) and/or methylglucuronic acid (MeGlcA) residues. The GlcA/MeGlcA side chains may be further substituted with 2-O-arabinopyranose (Arap) or 2-O-galactopyranose (Gal) residues in some plant species, but the enzymes responsible for these substitutions remain unknown. During our endeavor to investigate the enzymatic activities of Arabidopsis MUR3-clade members of the GT47 glycosyltransferase family, we found that one of them was able to transfer Arap from UDP-Arap onto O-2 of GlcA side chains of xylan, and thus it was named xylan 2-O-arabinopyranosyltransferase 1 (AtXAPT1). The function of AtXAPT1 was verified in planta by its T-DNA knockout mutation showing a loss of the Arap substitution on xylan GlcA side chains. Further biochemical characterization of XAPT close homologs from other plant species demonstrated that while the poplar ones had the same catalytic activity as AtXAPT1, those from Eucalyptus, lemon-scented gum, sea apple, 'Ohi'a lehua, duckweed and purple yam were capable of catalyzing both 2-O-Arap and 2-O-Gal substitutions of xylan GlcA side chains albeit with differential activities. Sequential reactions with XAPTs and glucuronoxylan methyltransferase 3 (GXM3) showed that XAPTs acted poorly on MeGlcA side chains, whereas GXM3 could efficiently methylate arabinosylated or galactosylated GlcA side chains of xylan. Furthermore, molecular docking and site-directed mutagenesis analyses of Eucalyptus XAPT1 revealed critical roles of several amino acid residues at the putative active site in its activity. Together, these findings establish that XAPTs residing in the MUR3 clade of family GT47 are responsible for 2-O-arabinopyranosylation and 2-O-galactosylation of GlcA side chains of xylan.

The efficacy and safety of antiangiogenesis tyrosine kinase inhibitors in patients with advanced anaplastic thyroid cancer: A meta-analysis of prospective studies.

BACKGROUND: The poor prognosis of anaplastic thyroid cancer (ATC) patients is associated with limited effective therapeutic strategies. Multiple antiangiogenesis tyrosine kinase inhibitors (TKIs) have been applied in later-line treatment of ATC; however, the results reported in clinical trials were controversial. In this study, we reconstructed the patient-level data to pooled-analyze the survival data, responses, and adverse events. METHODS: Online databases (PubMed, Web of Science, Embase, and Cochrane CENTRAL) were searched on September 03, 2023. R software combined with the "metaSurvival" and "meta" packages were used to reconstruct the survival curves and summarize the response rates. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were survival rate, objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events. RESULTS: Six prospective clinical trials involving 140 ATC patients were enrolled. Four types of TKIs (imatinib, pazopanib, sorafenib, and lenvatinib) were included. When advanced ATC patients were treated with the TKIs, the median OS was 4.8 months and the median PFS was 2.6 months. The pooled ORR and DCR were 9% and 53%. Hypertension, decreased appetite, rash, and lymphopenia were the most common grade ≥ 3 treatment-related adverse events. CONCLUSION: Mono-anitangiogenesis TKI therapy showed limited improvements in treating advanced ATC patients. Combining antiangiogenesis TKI therapy with chemotherapy, radiotherapy, or immunotherapy could be the direction of future studies.

Plant Cell Wall Polysaccharide O-Acetyltransferases.

Plant cell walls are largely composed of polysaccharide polymers, including cellulose, hemicelluloses (xyloglucan, xylan, mannan, and mixed-linkage ß-1,3/1,4-glucan), and pectins. Among these cell wall polysaccharides, xyloglucan, xylan, mannan, and pectins are often O-acetylated, and polysaccharide O-acetylation plays important roles in cell wall assembly and disease resistance. Genetic and biochemical analyses have implicated the involvement of three groups of proteins in plant cell wall polysaccharide O-acetylation: trichome birefringence-like (TBL)/domain of unknown function 231 (DUF231), reduced wall acetylation (RWA), and altered xyloglucan 9 (AXY9). Although the exact roles of RWAs and AXY9 are yet to be identified, members of the TBL/DUF231 family have been found to be O-acetyltransferases responsible for the O-acetylation of xyloglucan, xylan, mannan, and pectins. Here, we provide a comprehensive overview of the occurrence of O-acetylated cell wall polysaccharides, the biochemical properties, structural features, and evolution of cell wall polysaccharide O-acetyltransferases, and the potential biotechnological applications of manipulations of cell wall polysaccharide acetylation. Further in-depth studies of the biochemical mechanisms of cell wall polysaccharide O-acetylation will not only enrich our understanding of cell wall biology, but also have important implications in engineering plants with increased disease resistance and reduced recalcitrance for biofuel production.

Emerging chemotherapy-based treatments in anaplastic thyroid cancer: an updated analysis of prospective studies.

Background: For patients with anaplastic thyroid cancer (ATC) without mutational driver genes, chemotherapy is suggested to be the first-line treatment option. However, the benefits of chemotherapy in treating ATC are limited. In this analysis, we collected the prospective data reported since 2010 to analyze the emerging chemotherapy-based treatments in ATC comprehensively. Methods: For this updated analysis, we searched PubMed (MEDLINE), Web of Science, Embase, and Cochrane CENTRAL databases from 1 January 2010 to 7 February 2024 for prospective clinical studies that contained chemotherapy-based treatments. This analysis was done to pool overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), disease control rates (DCRs), and grade 3 or worse treatment-related adverse events (TRAEs). Results: Six prospective clinical trials with 232 patients were included. Chemotherapy was commonly combined with targeted therapy or radiotherapy. The pooled median OS was 6.0 months (95% CI 4.1-9.7), and the median PFS was 3.2 months (95% CI 1.9-6.0) in patients with ATC who received chemotherapy-based strategies. The integrated ORR and DCR were 21% (95% CI 15%-27%) and 64% (95% CI 55%-72%), respectively. Regarding the grade 3 or worse TRAE, the pooled incidence was 68% (95% CI 47%-86%). Conclusion: Although the emerging chemotherapy-based treatments showed antitumor activity in patients with ATC, these strategies failed to prolong the survival time substantially. More practical, safe, and novel therapeutic regimens for patients with ATC warrant further investigations.

Infrared Interlayer Excitons in Twist-Free MoTe2/MoS2 Heterobilayers.

Excitonic devices based on interlayer excitons in van der Waals heterobilayers are a promising platform for advancing photoelectric interconnection telecommunications. However, the absence of exciton emission in the crucial telecom C-band has constrained their practical applications. Here, this limitation is addressed by reporting exciton emission at 0.8 eV (1550 nm) in a chemically vapor-deposited, strictly aligned MoTe2/MoS2 heterobilayer, resulting from the direct bandgap transitions of interlayer excitons as identified by momentum-space imaging of their electrons and holes. The decay mechanisms dominated by direct radiative recombination ensure constant emission quantum yields, a basic demand for efficient excitonic devices. The atomically sharp interface enables the resolution of two narrowly-splitter transitions induced by spin-orbit coupling, further distinguished through the distinct Landé g-factors as the fingerprint of spin configurations. By electrical control, the double transitions coupling into opposite circularly-polarized photon modes, preserve or reverse the helicities of the incident light with a degree of polarization up to 90%. The Stark effect tuning extends the emission energy range by over 150 meV (270 nm), covering the telecom C-band. The findings provide a material platform for studying the excitonic complexes and significantly boost the application prospects of excitonic devices in silicon photonics and all-optical telecommunications.

Iron accumulation in ovarian microenvironment damages the local redox balance and oocyte quality in aging mice.

Accumulating oxidative damage is a primary driver of ovarian reserve decline along with aging. However, the mechanism behind the imbalance in reactive oxygen species (ROS) is not yet fully understood. Here we investigated changes in iron metabolism and its relationship with ROS disorder in aging ovaries of mice. We found increased iron content in aging ovaries and oocytes, along with abnormal expression of iron metabolic proteins, including heme oxygenase 1 (HO-1), ferritin heavy chain (FTH), ferritin light chain (FTL), mitochondrial ferritin (FTMT), divalent metal transporter 1 (DMT1), ferroportin1(FPN1), iron regulatory proteins (IRP1 and IRP2) and transferrin receptor 1 (TFR1). Notably, aging oocytes exhibited enhanced ferritinophagy and mitophagy, and consistently, there was an increase in cytosolic Fe2+, elevated lipid peroxidation, mitochondrial dysfunction, and augmented lysosome activity. Additionally, the ovarian expression of p53, p21, p16 and microtubule-associated protein tau (Tau) were also found to be upregulated. These alterations could be phenocopied with in vitro Fe2+ administration in oocytes from 2-month-old mice but were alleviated by deferoxamine (DFO). In vivo application of DFO improved ovarian iron metabolism and redox status in 12-month-old mice, and corrected the alterations in cytosolic Fe2+, ferritinophagy and mitophagy, as well as related degenerative changes in oocytes. Thereby in the whole, DFO delayed the decline in ovarian reserve and significantly increased the number of superovulated oocytes with reduced fragmentation and aneuploidy. Together, our findings suggest that aging-related disturbance in ovarian iron homeostasis contributes to excessive ROS production and that iron chelation may improve ovarian redox status, and efficiently delay the decline in ovarian reserve and oocyte quality in aging mice. These data propose a novel intervention strategy for preserving the ovarian reserve function in elderly women.

A rice GT61 glycosyltransferase possesses dual activities mediating 2-O-xylosyl and 2-O-arabinosyl substitutions of xylan.

MAIN CONCLUSION: A member of the rice GT61 clade B is capable of transferring both 2-O-xylosyl and 2-O-arabinosyl residues onto xylan and another member specifically catalyses addition of 2-O-xylosyl residue onto xylan. Grass xylan is substituted predominantly with 3-O-arabinofuranose (Araf) as well as with some minor side chains, such as 2-O-Araf and 2-O-(methyl)glucuronic acid [(Me)GlcA]. 3-O-Arabinosylation of grass xylan has been shown to be catalysed by grass-expanded clade A members of the glycosyltransferase family 61. However, glycosyltransferases mediating 2-O-arabinosylation of grass xylan remain elusive. Here, we performed biochemical studies of two rice GT61 clade B members and found that one of them was capable of transferring both xylosyl (Xyl) and Araf residues from UDP-Xyl and UDP-Araf, respectively, onto xylooligomer acceptors, whereas the other specifically catalysed Xyl transfer onto xylooligomers, indicating that the former is a xylan xylosyl/arabinosyl transferase (named OsXXAT1 herein) and the latter is a xylan xylosyltransferase (named OsXYXT2). Structural analysis of the OsXXAT1- and OsXYXT2-catalysed reaction products revealed that the Xyl and Araf residues were transferred onto O-2 positions of xylooligomers. Furthermore, we demonstrated that OsXXAT1 and OsXYXT2 were able to substitute acetylated xylooligomers, but only OsXXAT1 could xylosylate GlcA-substituted xylooligomers. OsXXAT1 and OsXYXT2 were predicted to adopt a GT-B fold structure and molecular docking revealed candidate amino acid residues at the predicted active site involved in binding of the nucleotide sugar donor and the xylohexaose acceptor substrates. Together, our results establish that OsXXAT1 is a xylan 2-O-xylosyl/2-O-arabinosyl transferase and OsXYXT2 is a xylan 2-O-xylosyltransferase, which expands our knowledge of roles of the GT61 family in grass xylan synthesis.

PLD1 promotes spindle assembly and migration through regulating autophagy in mouse oocyte meiosis.

PLD1 has been implicated in cytoskeletal reorganization and vesicle trafficking in somatic cells; however, its function remains unclear in oocyte meiosis. Herein, we found PLD1 stably expresses in mouse oocytes meiosis, with direct interaction with spindle, RAB11A+ vesicles and macroautophagic/autophagic vacuoles. The genetic or chemical inhibition of PLD1 disturbed MTOC clustering, spindle assembly and its cortical migration, also decreased PtdIns(4,5)P2, phosphorylated CFL1 (p-CFL1 [Ser3]) and ACTR2, and their local distribution on MTOC, spindle and vesicles. Furthermore in PLD1-suppressed oocytes, vesicle size was significantly reduced while F-actin density was dramatically increased in the cytoplasm, the asymmetric distribution of autophagic vacuoles was broken and the whole autophagic process was substantially enhanced, as illustrated with characteristic changes in autophagosomes, autolysosome formation and levels of ATG5, BECN1, LC3-II, SQSTM1 and UB. Exogenous administration of PtdIns(4,5)P2 or overexpression of CFL1 hyperphosphorylation mutant (CFL1S3E) could significantly improve polar MTOC focusing and spindle structure in PLD1-depleted oocytes, whereas overexpression of ACTR2 could rescue not only MTOC clustering, and spindle assembly but also its asymmetric positioning. Interestingly, autophagy activation induced similar defects in spindle structure and positioning; instead, its inhibition alleviated the alterations in PLD1-depleted oocytes, and this was highly attributed to the restored levels of PtdIns(4,5)P2, ACTR2 and p-CFL1 (Ser3). Together, PLD1 promotes spindle assembly and migration in oocyte meiosis, by maintaining rational levels of ACTR2, PtdIns(4,5)P2 and p-CFL1 (Ser3) in a manner of modulating autophagy flux. This study for the first time introduces a unique perspective on autophagic activity and function in oocyte meiotic development.Abbreviations: ACTR2/ARP2: actin related protein 2; ACTR3/ARP3: actin related protein 3; ATG5: autophagy related 5; Baf-A1: bafilomycin A1; BFA: brefeldin A; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GOLGA2/GM130: golgin A2; GV: germinal vesicle; GVBD: germinal vesicle breakdown; IVM: in vitro maturation; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MI: metaphase of meiosis I; MII: metaphase of meiosis II; MO: morpholino; MTOC: microtubule-organizing center; MTOR: mechanistic target of rapamycin kinase; PB1: first polar body; PLA: proximity ligation assay; PLD1: phospholipase D1; PtdIns(4,5)P2/PIP2: phosphatidylinositol 4,5-bisphosphate; RAB11A: RAB11A, member RAS oncogene family; RPS6KB1/S6K1: ribosomal protein S6 kinase B1; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TUBA/α-tubulin: tubulin alpha; TUBG/γ-tubulin: tubulin gamma; UB: ubiquitin; WASL/N-WASP: WASP like actin nucleation promoting factor.

Tyrosine kinase inhibitors in patients with advanced anaplastic thyroid cancer: an effective analysis based on real-world retrospective studies.

Background: Tyrosine kinase inhibitors (TKIs) contribute to the treatment of patients with anaplastic thyroid cancer (ATC). Although prospective clinical studies of TKIs exhibit limited efficacy, whether ATC patients benefit from TKI treatment in real-world clinical practice may enlighten future explorations. Therefore, we conducted this effective analysis based on real-world retrospective studies to illustrate the efficacy of TKI treatment in ATC patients. Methods: We systematically searched the online databases on September 03, 2023. Survival curves were collected and reconstructed to summarize the pooled curves. Responses were analyzed by using the "meta" package. The primary endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Results: 12 studies involving 227 patients were enrolled in the study. Therapeutic strategies included: anlotinib, lenvatinib, dabrafenib plus trametinib, vemurafenib, pembrolizumab plus dabrafenib and trametinib, pembrolizumab plus lenvatinib, pembrolizumab plus trametinib, and sorafenib. The pooled median OS and PFS were 6.37 months (95% CI 4.19-10.33) and 5.50 months (95% CI 2.17-12.03). The integrated ORR and DCR were 32% (95% CI 23%-41%) and 40% (95% CI 12%-74%). Conclusion: In real-world clinical practice, ATC patients could benefit from TKI therapy. In future studies, more basic experiments and clinical explorations are needed to enhance the effects of TKIs in the treatment of patients with ATC.

Safety and efficacy of pyrotinib for HER­2­positive breast cancer in the neoadjuvant setting: A systematic review and meta­analysis.

As a novel tyrosine kinase inhibitor (TKI), pyrotinib can irreversibly block dual pan-ErbB receptors and has been used in the treatment of advanced or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, there are limited data on the use of pyrotinib in early breast cancer. Therefore, the present meta-analysis was conducted to evaluate the safety and efficacy of pyrotinib in the neoadjuvant setting for patients with early-stage or locally advanced HER2-positive breast cancer. Online databases (Pubmed, Web of Science, Embase and Cochrane Library) were comprehensively searched for eligible prospective clinical trials on August 17, 2023. The primary endpoint was the treatment-related adverse events (TRAEs), and the secondary endpoint was pathological complete response (pCR) rate. In total, seven trials with a total enrolment of 407 patients were included. A total of seven studies evaluated pyrotinib in combination with trastuzumab and chemotherapy in the neoadjuvant setting. The median age ranged from 47-50 years. The most common TRAEs were diarrhea [98% of patients; 95% confidence interval (CI): 92-100%], followed by anemia (71%; 95% CI: 55-89%), vomiting (69%; 95% CI: 55-82%), and leucopenia (66%; 95% CI: 35-91%). No treatment-related deaths occurred. The pooled pCR rate was 57% (95% CI: 47-68%). It was concluded that pyrotinib-containing neoadjuvant therapy could be an effective treatment strategy in patients with early-stage or locally advanced HER2-positive breast cancer; however, the management of adverse events should be a key consideration. The management of adverse events should be paid great attention to, during pyrotinib therapy, although pyrotinib-contained neoadjuvant therapy could be an effective treatment for patients with early-stage or locally advanced HER2-positive breast cancer. Head-to-head randomized clinical trials are warranted to further confirm the benefits and risks associated with pyrotinib therapy in patients with breast cancer.

Lenvatinib Versus Atezolizumab Plus Bevacizumab in the First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Meta-Analysis of Real-World Studies.

BACKGROUND: Immunotherapy has revolutionized the treatment of hepatocellular carcinoma (HCC). However, whether adding immunotherapy to antiangiogenic therapy benefits patients with unresectable HCC (uHCC) more in the first-line setting remains controversial. OBJECTIVE: In this analysis, we compared the clinical outcomes of lenvatinib monotherapy with atezolizumab plus bevacizumab combination therapy in advanced uHCC in real-world clinical practice. METHODS: The MEDLINE, Embase, and Cochrane CENTRAL databases were systematically searched on 23 April 2023. The "metaSurvival" and "meta" packages of the R software (version 4.2.2) were used to summarize the survival curves and meta-analyze the survival data. Overall survival (OS) and progression-free survival (PFS) were defined as dual primary endpoints. Secondary endpoints included the objective response rate (ORR) and disease control rate (DCR). RESULTS: Overall, the pooled median OS was 18.4 months in the lenvatinib group versus 18.5 months in the atezolizumab plus bevacizumab group; the pooled median PFS was 6.9 months in the lenvatinib group versus 7.3 months in the atezolizumab plus bevacizumab group. Lenvatinib therapy showed similar OS [hazard ratio (HR): 0.91, 95% confidence interval (CI): 0.55-1.52, p = 0.72] and PFS (HR: 0.79, 95% CI: 0.56-1.12, p = 0.19) compared with atezolizumab plus bevacizumab therapy. In addition, a comparable ORR [odds ratio (OR): 0.89, 95% CI: 0.65-1.20, p = 0.44) was observed between lenvatinib and atezolizumab plus bevacizumab. CONCLUSIONS: Comprehensive analysis suggested that lenvatinib monotherapy exhibited survival outcomes comparable to those of atezolizumab plus bevacizumab combination therapy, which may provide useful insights for clinicians in future clinical practice.

LIM domain only 7 negatively controls nonalcoholic steatohepatitis in the setting of hyperlipidemia.

BACKGROUND AND AIMS: Hyperlipidemia has been extensively recognized as a high-risk factor for NASH; however, clinical susceptibility to NASH is highly heterogeneous. The key controller(s) of NASH susceptibility in patients with hyperlipidemia has not yet been elucidated. Here, we aimed to reveal the key regulators of NASH in patients with hyperlipidemia and to explore its role and underlying mechanisms. APPROACH AND RESULTS: To identify the predominant suppressors of NASH in the setting of hyperlipidemia, we collected liver biopsy samples from patients with hyperlipidemia, with or without NASH, and performed RNA-sequencing analysis. Notably, decreased Lineage specific Interacting Motif domain only 7 (LMO7) expression robustly correlated with the occurrence and severity of NASH. Although overexpression of LMO7 effectively blocked hepatic lipid accumulation and inflammation, LMO7 deficiency in hepatocytes greatly exacerbated diet-induced NASH progression. Mechanistically, lysine 48 (K48)-linked ubiquitin-mediated proteasomal degradation of tripartite motif-containing 47 (TRIM47) and subsequent inactivation of the c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) cascade are required for the protective function of LMO7 in NASH. CONCLUSIONS: These findings provide proof-of-concept evidence supporting LMO7 as a robust suppressor of NASH in the context of hyperlipidemia, indicating that targeting the LMO7-TRIM47 axis is a promising therapeutic strategy for NASH.

Novel-fosfamide monotherapy or in combination with doxorubicin versus doxorubicin alone in patients with advanced soft tissue sarcoma: A pooled analysis of randomized clinical trials.

BACKGROUND: Novel-fosfamides (NFOs) belong to active metabolites of ifosfamide that bypass the generation of toxic byproducts. In this analysis, we aimed to comprehensively assess the benefits and risks of NFO monotherapy or in combination with doxorubicin (DOX) versus single-drug DOX in previously untreated patients with advanced soft-tissue sarcoma (ASTS). METHODS: Online PubMed, Web of Science, Embase, and Cochrane CENTRAL databases were systematically searched on April 26, 2022. Objective response rate and disease control rate were primary outcomes. Overall survival (OS), progression-free survival (PFS), and grade ≥ 3 treatment-related adverse events were secondary outcomes. RESULTS: In all, 3 randomized clinical trials with a total of 1207 ASTS patients were eligible. DOX plus NFO combination therapy showed higher risk ratios of objective response rate (1.50, 95% CI 1.20-1.68, P = .0003) and disease control rate (1.15, 95% CI 1.05-1.27, P = .0030) compared with DOX monotherapy. Nevertheless, NFO-based monotherapy and combination therapy were found no improvements on OS (hazard ratio 0.93, 95% CI 0.52-1.65, P = .8050) and PFS (hazard ratio 0.88, 95% CI 0.54-1.43, P = .6088) against DOX. More incidences of grade 3 or worse anemia, thrombocytopenia, stomatitis, diarrhea, constipation, and febrile neutropenia were observed in NFO-based treatments. CONCLUSION: Adding NFO to DOX as first-line therapy improved the responses in ASTS patients but did not prolong OS and PFS. Grade 3 or worse treatment-related adverse events should be treated with caution during the NFO-based therapies.

An integrated analysis of Sacituzumab govitecan in relapsed or refractory metastatic triple-negative breast cancer.

BACKGROUND: Sacituzumab govitecan (SG) is an antibody-drug conjugate that targets the human trophoblast cell-surface antigen 2 to deliver SN-38 to cancer cells. In this study, we assessed the efficacy and safety of SG in patients with relapsed or refractory metastatic triple-negative breast cancer (RM-TNBC). METHODS: For this integrated analysis, from inception to January 2, 2023, we searched PubMed, Web of Science, Embase, and Cochrane library databases for prospective studies that evaluated SC in RM-TNBC patients. Primary endpoints were survival outcomes and responses. Secondary endpoints were all grade and grade ≥ 3 toxicities. RESULTS: Six hundred potentially relevant records were screened. Our analysis included 3 trials (412 patients). Median overall survival was 12.9 months (95% confidence interval [CI], 11.5-14.4), progression-free survival was 5.7 months (5% CI, 5.1-6.3), and duration of objective response was 7.4 months (5% CI, 5.8-9.0). The objective response rate was 34%, and the disease control rate was 71%. Key grade ≥ 3 toxicities (in over 10% of the patients) included neutropenia (46%), leukopenia (12%), febrile neutropenia (11%), diarrhea (11%), and anemia (10%). Four treatment-related deaths were reported. CONCLUSION: SG was associated with effectiveness in patients with RM-TNBC. Myelosuppression and diarrhea were the primary treatment-related adverse events.

Bibliometric analysis of the association between drinking water pollution and bladder cancer.

Background: Bladder cancer has become an increasingly intractable health problem worldwide. Long-term drinking water pollution is known to promote its occurrence. This study aimed to analyze the research status, hot spots, and future trends of drinking water pollution and bladder cancer through extensive bibliometric examination to provide reference data for better prevention and management of bladder cancer. Methods: The Scopus database developed by Elsevier was browsed for articles that met the predefined criteria using the search terms related to drinking water and bladder cancer. Included articles were further evaluated by year of publication, subject category, institution, article type, source journal, authors, co-authorship networks, and text mining of titles by R software packages tm, ggplot2 and VOSviewer software. Results: In total, 687 articles were selected after a comprehensive literature search by the Scopus database, including 491 research articles, 98 review articles, 26 conference papers, 23 letters and 49 other documents. The total number of articles published showed an upward trend. The United States has the largest number of published articles (345 articles), institutions (7/10) and funding sponsors (top 5). The journal with the most publications was Environmental Health Perspectives, with 46 published. The highest number of citations up to 2330 times for a single article published in 2007 on the journal of Mutation Research. Professor Cantor K.P. was the highest number of publications with 35 articles and Smith A.H. was the most cited author with the number of citations reaching 6987 times overall and 225 times per article. The most frequent keywords excluding the search subject were "arsenic", "chlorination", "trihalomethane", and "disease agents". Conclusion: This study is the first systematic bibliometric study of the literature publications on drinking water pollution and bladder cancer. It offers an overall and intuitive understanding of this topic in the past few years, and points out a clear direction research hotspots and reveals the trends for further in-depth study in future.

Treating radiation­related nasopharyngeal necrosis with endostar in patient with nasopharyngeal carcinoma: A report of two cases and a literature review.

Radiation-related nasopharyngeal necrosis (RRNN) is a rare and often fatal complication in patients with nasopharyngeal carcinoma (NPC). Currently, no standard treatments are recommended for RRNN. The effects of traditional conservative treatments are suboptimal, and surgery for RRNN cannot be performed by inexperienced doctors. In the present study, the use of Endostar in two patients with RRNN was evaluated. Two patients with RRNN were treated at the Department of Oncology, Panyu Central Hospital (Guangzhou, China). Endostar was administrated (15 mg/day from day 1 to day 7, every three weeks) intravenously for four and seven cycles in a male and a female patient, respectively. The effects of Endostar were assessed using magnetic resonance imaging (MRI) and a nasopharyngoscope. The symptoms of RRNN in both patients were relieved after treatment with Endostar. MRI and nasopharyngoscope analysis revealed that necrosis of the nasopharynx was substantially decreased and nasopharyngeal ulcers were healed. Endostar has the potential to be a novel, effective therapy for the treatment of patients with RRNN. However, clinical trials are required to confirm the results of the present study.

The potential crosstalk between tumor and plasma cells and its association with clinical outcome and immunotherapy response in bladder cancer.

BACKGROUND: Although immunotherapy is effective in improving the clinical outcomes of patients with bladder cancer (BC), it is only effective in a small percentage of patients. Intercellular crosstalk in the tumor microenvironment strongly influences patient response to immunotherapy, while the crosstalk patterns of plasma cells (PCs) as endogenous antibody-producing cells remain unknown. Here, we aimed to explore the heterogeneity of PCs and their potential crosstalk patterns with BC tumor cells. METHODS: Crosstalk patterns between PCs and tumor cells were revealed by performing integrated bulk and single-cell RNA sequencing (RNA-seq) and spatial transcriptome data analysis. A risk model was constructed based on ligand/receptor to quantify crosstalk patterns by stepwise regression Cox analysis. RESULTS: Based on cell infiltration scores inferred from bulk RNA-seq data (n = 728), we found that high infiltration of PCs was associated with better overall survival (OS) and response to immunotherapy in BC. Further single-cell transcriptome analysis (n = 8; 41,894 filtered cells) identified two dominant types of PCs, IgG1 and IgA1 PCs. Signal transduction from tumor cells of specific states (stress-like and hypoxia-like tumor cells) to PCs, for example, via the LAMB3/CD44 and ANGPTL4/SDC1 ligand/receptor pairs, was validated by spatial transcriptome analysis and associated with poorer OS as well as nonresponse to immunotherapy. More importantly, a ligand/receptor pair-based risk model was constructed and showed excellent performance in predicting patient survival and immunotherapy response. CONCLUSIONS: PCs are an important component of the tumor microenvironment, and their crosstalk with tumor cells influences clinical outcomes and response to immunotherapies in BC patients.