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.

Irinotecan plus temozolomide in relapsed Ewing sarcoma: an integrated analysis of retrospective studies.

BACKGROUND: The prognosis of patients with relapsed Ewing sarcoma is poor. In this study, we aimed to pooled-analyze the efficacy and safety of the combination of irinotecan and temozolomide in treating patients with relapsed Ewing sarcoma. METHODS: PubMed, Cochrane CENTRAL, Web of Science, and EMBASE were systematically searched on September 27, 2021. The primary outcomes were rates of objective response and disease control, and the secondary outcomes were toxicities. RESULTS: Six retrospective studies with 184 patients were enrolled in the analysis. The median age ranged from 14 to 21. The integrated rates were 44% (95% confidence interval [CI] 31-58) for objective response and 66% (55-77) for disease control. Grade 3-4 neutropenia, thrombocytopenia, and diarrhea occurred in 8% (3-16), 7% (3-11), and 8% (5-10) of chemotherapeutic cycles, respectively. 18% (7-32) and 6% (2-11) of patients suffered grade 3-4 neutropenia and thrombocytopenia after irinotecan plus temozolomide treatment. CONCLUSION: Irinotecan plus temozolomide combination chemotherapy showed antitumor activity and an acceptable safety profile in patients with relapsed Ewing sarcoma. More future prospective studies are needed to confirm the retrospective results.

The efficacy and safety of cemiplimab in locally advanced or metastatic cutaneous squamous cell carcinoma: A comparative analysis of retrospective studies versus prospective studies.

Cemiplimab has been widely recommended by international guidelines to treat patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC). In this study, we conducted a comparative analysis to integrate the efficacy and safety data in the published prospective and retrospective studies for better understanding the application of cemiplimab. The online databases (PubMed, Cochrane CENTRAL, Web of Science, and EMBASE) were searched to find out eligible studies from inception to November 4, 2021. The "R" software and the "meta" package were used to synthesize the objective response rates (ORRs), disease control rates (DCRs), and the incidences of treatment-related adverse events (TRAEs). Overall, three retrospective studies with 398 patients and three prospective studies with 219 patients were enrolled. The pooled ORR and DCR were 53% (95% confidence interval [CI] 46-59) and 70% (95% CI 57-82) for retrospective studies versus 45% (95% CI 39-52) and 68% (95% CI 56-79) for prospective studies. In regard of toxicities, prospective studies reported much higher incidences of any grade (99% vs. 47%) and grade 3-4 TRAEs (43% vs. 15%) against retrospective studies. The most reported TRAE was fatigue, followed by diarrhea and pruritus. In addition, nine treatment-related deaths (four in retrospective studies vs. five in prospective studies) were documented. In both retrospective and prospective clinical practices, cemiplimab could be an effective regimen for locally advanced or metastatic CSCC patients, but toxicities during the treatment deserve further attention.

A pooled analysis of adding olanzapine to guideline-recommended antiemetic therapy for breast cancer patients treated with an anthracycline and cyclophosphamide in prospective and retrospective studies.

PURPOSE: As an antipsychotic agent that targets multiple neurotransmitter receptors, olanzapine has been added to antiemetic therapies. For better understanding the application of olanzapine in antiemetic strategies for breast cancer patients who suffered anthracycline plus cyclophosphamide-induced nausea and vomiting, we comprehensively reviewed the antiemetic researches related to olanzapine and pooled-analyzed the results to confirm the efficacy and safety of olanzapine in breast cancer. METHODS: PubMed, Web of Science, EMBASE, and Cochrane CENTRAL databases were searched from inception through Sep 15, 2021. Both prospective and retrospective studies were eligible. The primary outcomes were complete response (defined as no vomiting and no use of rescue medications) and no nausea rate, and the secondary outcome was treatment-related adverse events. RESULTS: Four studies with 466 breast cancer patients were identified in the pooled analysis. In the acute period (0-24 h), the olanzapine group had significantly higher rates of complete response (71.3% vs 48.1%, odds ratio [OR]: 2.66, 95% confidence interval [CI] 1.39-5.11, p = 0.003) and no nausea (70.0% vs 43.0%, OR: 3.55, 95% CI 1.76-7.18, p = 0.04) than the placebo group, while in the delayed period, the olanzapine group was also superior to the placebo group in terms of the complete response (82.5% vs 63.3%, OR: 3.81, 95% CI 1.58-9.15, p = 0.003) and no nausea (66.3% vs 51.9%, OR: 2.08, 95% CI 1.03-4.21, p = 0.04) rates. During the overall period in prospective studies, the proportions of complete response (50.0% vs 34.2%, OR: 1.93, p = 0.04) and no nausea (51.3% vs 25.3%, OR: 3.40, p = 0.0006) in the olanzapine group were higher than those in the placebo group. CONCLUSION: Highly emetogenic chemotherapy breast patients could benefit from olanzapine-contained antiemetic therapy. Furthermore, since the cost is low, olanzapine is worth further clinical application and promotion.

The efficacy and safety of induction chemotherapy combined with concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in nasopharyngeal carcinoma patients: a systematic review and meta-analysis.

BACKGROUND: Induction chemotherapy (IC) combined with concurrent chemoradiotherapy (CCRT) has been recommended as the first-line therapy for locoregional nasopharyngeal carcinoma (NPC). Due to the different chemotherapeutic drugs used in the IC and CCRT, the results remain controversial. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library databases were systematically retrieved to search potentially eligible clinical trials up to Sep 11, 2019. Eligible studies were registered and prospective randomized controlled clinical trials. RESULTS: From 526 records, nine articles including seven randomized controlled clinical trials were eligible, with a total of 2311 locoregional advanced NPC patients. IC + CCRT had significantly lower risks of death (3-year hazard ratio [HR]: 0.70, 95% confidence interval [CI] 0.55-0.89, p = 0.003; 5-year HR: 0.77, 95% CI 0.62-0.94, p = 0.01), disease progression (3-year HR: 0.67, 95% CI 0.55-0.80, p < 0.001; 5-year HR: 0.70, 95% CI 0.58-0.83, p < 0.0001), distant metastasis (3-year HR: 0.58, 95% CI 0.45-0.74, p < 0.0001; 5-year HR: 0.69, 95% CI 0.55-0.87, p = 0.001) and locoregional relapse (3-year HR: 0.69, 95% CI 0.50-0.95, p = 0.02; 5-year HR: 0.66, 95% CI 0.51-0.86, p = 0.002) than CCRT. Compared with CCRT, IC + CCRT showed higher relative risks of grade 3 or more neutropenia, thrombocytopenia, nausea, vomiting and hepatotoxicity throughout the course of treatment, and higher relative risks of grade ≥ 3 thrombocytopenia and vomiting during CCRT. CONCLUSION: IC combined with CCRT significantly improved the survival in locoregional advanced NPC patients. Moreover, toxicities were well tolerated during IC and CCRT. Further clinical trials are warranted to confirm the optimal induction chemotherapeutic regimen in the future.

Comparative Toxicities of Neoadjuvant Chemotherapy With or Without Bevacizumab in HER2-Negative Breast Cancer Patients: A Meta-analysis.

Background: The addition of bevacizumab to neoadjuvant chemotherapy improves the pathological complete response rate of human epidermal growth factor 2 (HER2)-negative breast cancer patients. However, the characteristics of adverse events associated with the use of bevacizumab should receive more attention from clinicians. Objective: This meta-analysis aimed to detect the adverse events of adding bevacizumab to neoadjuvant chemotherapy compared with neoadjuvant chemotherapy alone in HER2-negative breast cancer patients. Methods: PubMed, Cochrane Library, Web of Science, and EMBASE databases were systematically accessed to find eligible studies from January 1, 2000, to October 20, 2019. Reference lists were searched for additional studies. Pooled risk ratios for adverse events of bevacizumab were meta-analyzed. Results: Overall, 6 of 829 initially identified studies met the inclusion criteria, with 4681 patients randomized (2321 in the bevacizumab plus neoadjuvant chemotherapy group and 2360 in the neoadjuvant chemotherapy group). The incidence of grade ≥3 hypertension, left-ventricular dysfunction, mucositis, febrile neutropenia, infection, pain, hand-foot syndrome, hemorrhage, and neutropenia significantly increased in patients treated with bevacizumab plus neoadjuvant chemotherapy. However, adding bevacizumab to neoadjuvant chemotherapy was not associated with increasing the incidences of grade ≥3 proteinuria, dyspnea, heart failure, peripheral neurotoxicity, thrombosis, thrombocytopenia, fatigue, leucopenia, vomiting, nausea, and diarrhea. Conclusion and Relevance: Adding bevacizumab to neoadjuvant chemotherapy to treat HER2-negative breast cancer patients increased adverse events. However, most adverse events are clinically manageable. Patients, therefore, need to be monitored carefully for hypertension, left-ventricular dysfunction, mucositis, febrile neutropenia, infection, pain, hand-foot syndrome, hemorrhage, and neutropenia when treated with bevacizumab and neoadjuvant chemotherapy simultaneously.

Tumor-Derived Exosomal Long Noncoding RNAs as Promising Diagnostic Biomarkers for Prostate Cancer.

BACKGROUND/AIMS: Exosomal circulating long non-coding RNAs (lncRNAs) in blood are emerging as clinically useful and non-invasive biomarkers for tumor diagnosis. However, normal cells can also secrete exosomes, so it is a prerequisite to obtain tumor-derived exosomes for better understanding of their diagnostic impacts in cancer. In this study, a dual-antibody-functionalized immunoaffinity system was established to isolate exosomes and investigate their lncRNAs expression pattern and clinical significance in prostate cancer (PCa). METHODS: A commercially available kit was used to isolate total exosomes, which were then purified by a dual-antibody-functionalized immunoaffinity system. RT-qPCR was performed to detect the expression of exosomal lncRNAs. Receiver operating characteristic (ROC) curves were plotted to assess the diagnostic value. RESULTS: Expression levels of two lncRNAs in tumor-derived exosomes were significantly higher than those in total exosomes. The levels of SAP30L-AS1 were upregulated in benign prostatic hyperplasia (BPH), and SChLAP1 levels were significantly higher in PCa than in BPH and healthy individuals. The area under the ROC curve indicated that SAP30L-AS1 and SChLAP1 had adequate diagnostic value to distinguish PCa from controls. Two lncRNAs separately combined with prostate specific antigen (PSA) possessed a moderate ability for discrimination. SAP30L-AS1 expression level was related to PSA values and tumor invasion. SChLAP1 expression was significantly higher in patients with higher Gleason scores, and was also effective in differentiating between BPH and PCa when the concentration of PSA was in the gray zone. CONCLUSION: The isolation of tumor-derived exosomes by dual-antibody-functionalized immunoaffinity systems and detection of their lncRNAs in plasma may lead to the identification of suitable biomarkers, with potential diagnostic utility.

Fast native-SAD phasing for routine macromolecular structure determination.

We describe a data collection method that uses a single crystal to solve X-ray structures by native SAD (single-wavelength anomalous diffraction). We solved the structures of 11 real-life examples, including a human membrane protein, a protein-DNA complex and a 266-kDa multiprotein-ligand complex, using this method. The data collection strategy is suitable for routine structure determination and can be implemented at most macromolecular crystallography synchrotron beamlines.

Inhibition of Sonic Hedgehog Signaling Pathway by Thiazole Antibiotic Thiostrepton Attenuates the CD44+/CD24-Stem-Like Population and Sphere-Forming Capacity in Triple-Negative Breast Cancer.

BACKGROUND/AIM: Triple-negative breast cancer (TNBC) represents a particular clinical challenge because these cancers do not respond to endocrine therapy or other available targeted agents. The lack of effective agents and obvious targets are major challenges in treating TNBC. In this study we explored the cytostatic effect of thiazole ring containing antibiotic drug thiostrepton on TNBC cell lines and investigated the molecular mechanism. METHODS: Cell viability was measured by MTT assay. Cell surface marker was monitored by FCM. Western blot was applied to assess the protein expression levels of target genes. RESULTS: We found that thiostrepton remarkably suppressed the CD44+/CD24- stem-like population and sphere forming capacity of TNBC cell lines. Notably, we showed for the first time that thiostrepton exerted its pharmacological action by targeting sonic hedgehog (SHH) signaling pathway. Thiostrepton repressed SHH ligand expression and reduced Gli-1 nuclear localization in TNBC cell line. Furthermore, the downstream target of SHH signaling undergone dose-dependent, rapid, and sustained loss of mRNA transcript level after thiostrepton treatment. Finally, we showed that SHH ligand was essential for maintaining CD44+/CD24- stem-like population in TNBC cell line. CONCLUSION: We conclude that thiostrepton suppresses the CD44+/CD24- stem-like population through inhibition of SHH signaling pathway. Our results give a new insight into the mechanism of thiostrepton anti-tumor activity and suggest thiostrepton as a promising agent that targets hedgehog signaling pathway in TNBC.

SAD phasing: History, current impact and future opportunities.

Single wavelength anomalous diffraction (SAD) can trace its beginnings to the early 1950s. Researchers at the time recognized that SAD offers some unique features that might be advantageous for crystallographic phasing, despite the fact that at that time recording accurate SAD data was problematic. In this review we will follow the trail from those early days, highlighting key advances in the field and interpreting them in terms on how they stimulated continued phasing development that produced the theoretical foundation for the routine macromolecular structure determination by SAD today. The technological advances over the past three decades in both hardware and software, which played a significant role in making SAD phasing a 'first choice method', will also be described.

Crystal structure of Cry51Aa1: A potential novel insecticidal aerolysin-type ß-pore-forming toxin from Bacillus thuringiensis.

The structures of several Bacillus thuringiensis (Bt) insecticidal crystal proteins have been determined by crystallographic methods and a close relationship has been explicated between specific toxicities and conserved three-dimensional architectures. In this study, as a representative of the coleopteran- and hemipteran-specific Cry51A group, the complete structure of Cry51Aa1 protoxin has been determined by X-ray crystallography at 1.65 Å resolution. This is the first report of a coleopteran-active Bt insecticidal toxin with high structural similarity to the aerolysin-type ß-pore forming toxins (ß-PFTs). Moreover, study of featured residues and structural elements reveal their possible roles in receptor binding and pore formation events. This study provides new insights into the action of aerolysin-type ß-PFTs from a structural perspective, and could be useful for the control of coleopteran and hemipteran insect pests in agricultures.

Spatial structure of the novel light-sensitive photoprotein berovin from the ctenophore Beroe abyssicola in the Ca(2+)-loaded apoprotein conformation state.

The bright bioluminescence of ctenophores, found in oceans worldwide, is determined by Ca(2+)-regulated photoproteins, functionally identical to and sharing many properties of hydromedusan photoproteins. In contrast, however, the ctenophore photoproteins are extremely sensitive to UV and visible light over the range of their absorption spectrum. The spatial structure of a novel light-sensitive photoprotein from the ctenophore Beroe abyssicola in its apoform bound with three calcium ions is determined at 2.0Å. We demonstrate that the apoberovin is a slightly asymmetrical compact globular protein formed by two domains with a cavity in the center, which exactly retains the fold architecture characteristic of hydromedusan photoproteins despite their low amino acid sequence identity. However, the structural alignment of these two photoprotein classes clearly shows that despite the high similarity of shape and geometry of their coelenterazine-binding cavities, their interiors differ drastically. The key residues appearing to be crucial for stabilizing the 2-hydroperoxycoelenterazine and for formation of the emitter in hydromedusan photoproteins, are replaced in berovin by amino acid residues having completely different side chain properties. Evidently, these replacements must be responsible for the distinct properties of ctenophore photoproteins such as sensitivity to light or the fact that the formation of active photoprotein from apophotoprotein, coelenterazine, and oxygen is more effective at alkaline pH.

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.

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.

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.

High-resolution crystal structure of the catalytic domain of human dual-specificity phosphatase 26.

Dual-specificity phosphatases (DUSPs) play an important role in regulating cellular signalling pathways governing cell growth, differentiation and apoptosis. Human DUSP26 inhibits the apoptosis of cancer cells by dephosphorylating substrates such as p38 and p53. High-resolution crystal structures of the DUSP26 catalytic domain (DUSP26-C) and its C152S mutant [DUSP26-C (C152S)] have been determined at 1.67 and 2.20 Å resolution, respectively. The structure of DUSP26-C showed a novel type of domain-swapped dimer formed by extensive crossover of the C-terminal α7 helix. Taken together with the results of a phosphatase-activity assay, structural comparison with other DUSPs revealed that DUSP26-C adopts a catalytically inactive conformation of the protein tyrosine phosphate-binding loop which significantly deviates from that of canonical DUSP structures. In particular, a noticeable difference exists between DUSP26-C and the active forms of other DUSPs at the hinge region of a swapped C-terminal domain. Additionally, two significant gaps were identified between the catalytic core and its surrounding loops in DUSP26-C, which can be exploited as additional binding sites for allosteric enzyme regulation. The high-resolution structure of DUSP26-C may thus provide structural insights into the rational design of DUSP26-targeted anticancer drugs.

The efficacy of adebrelimab compared with durvalumab and atezolizumab in untreated extensive-stage small-cell lung cancer: a survival analysis of reconstructed patient-level data.

Background: Adebrelimab showed excellent efficacy in the first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, whether adebrelimab is superior to durvalumab and atezolizumab remains unclear. Therefore, we, in this study, aimed to compare the survival data of adebrelimab (CAPSTONE-1 trial) with durvalumab (CASPIAN trial) and atezolizumab (IMpower133 trial) in the first-line setting of ES-SCLC patients. Methods: Online databases, including PubMed, Embase, Web of Science, and Cochrane CENTRAL, were systematically searched on December 2, 2022. The metaSurvival and IPDfromKM methods were used to analyze the summary survival curves and the reconstructed patient-level data. The main endpoints were median overall survival (OS) and progression-free survival (PFS). Results: In this analysis, survival data in the CASPIAN, IMpower133, and CAPSTONE-1 trials were collected from five published studies. The pooled median OS and PFS were 14.0 months (95% CI 11.2-16.6) and 5.6 months (95% CI 4.7-6.7) when ES-SCLC patients received chemotherapy (etoposide and cisplatin/carboplatin) and anti-PD-L1 therapy. Based on the reconstructed patient-level data, adebrelimab significantly prolonged survival outcomes against atezolizumab (OS: Hazard ratio [HR]0.76, 95% CI 0.60-0.95; PFS: HR 0.67, 95% CI 0.54-0.83) and durvalumab (OS: HR 0.75, 95% CI 0.60-0.92). Conclusion: For previously untreated ES-SCLC patients, longer survival time might be benefited from adding adebrelimab to etoposide-platinum chemotherapy. In future studies, further real-world evidence or head-to-head clinical trials are warranted to confirm the differences between the PD-L1 inhibitors.

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.

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.