A pH-triggered N-oxide polyzwitterionic nano-drug loaded system for the anti-tumor immunity activation research.

Triple negative breast cancer (TNBC) has the characteristics of low immune cell infiltration, high expression of tumor programmed death ligand 1 (PD-L1), and abundant cancer stem cells. Systemic toxicity of traditional chemotherapy drugs due to poor drug selectivity, and chemotherapy failure due to tumor drug resistance and other problems, so it is particularly important to find new cancer treatment strategies for TNBC with limited treatment options. Both the anti-tumor natural drugs curcumin and ginsenoside Rg3 can exert anti-tumor effects by inducing immunogenic cell death (ICD) of tumor cells, reducing PD-L1 expression, and reducing cancer stem cells. However, they have the disadvantages of poor water solubility, low bioavailability, and weak anti-tumor effect of single agents. We used vinyl ether bonds to link curcumin (Cur) with N-O type zwitterionic polymers and at the same time encapsulated ginsenoside Rg3 to obtain hyperbranched zwitterionic drug-loaded micelles OPDEA-PGED-5HA@Cur@Rg3 (PPH@CR) with pH response. In vitro cell experiments and in vivo animal experiments have proved that PPH@CR could not only promote the maturation of dendritic cells (DCs) and increase the CD4+ T cells and CD8+ T cells by inducing ICD in tumor cells but also reduce the expression of PD-L1 in tumor tissues, and reduce cancer stem cells and showed better anti-tumor effects and good biological safety compared with free double drugs, which is a promising cancer treatment strategy.

Switching from eltrombopag to hetrombopag in patients with primary immune thrombocytopenia: a post-hoc analysis of a multicenter, randomized phase III trial.

While studies have explored the feasibility of switching between various thrombopoietin receptor agonists in treating immune thrombocytopenia (ITP), data on the switching from eltrombopag to hetrombopag remains scarce. This post-hoc analysis of a phase III hetrombopag trial aimed to assess the outcomes of ITP patients who switched from eltrombopag to hetrombopag. In the original phase III trial, patients initially randomized to the placebo group were switched to eltrombopag. Those who completed this 14-week eltrombopag were eligible to switch to a 24-week hetrombopag. Treatment response, defined as a platelet count of ≥ 50 × 109/L, and safety were evaluated before and after the switch. Sixty-three patients who completed the 14-week eltrombopag and switched to hetrombopag were included in this post-hoc analysis. Response rates before and after the switch were 66.7% and 88.9%, respectively. Among those with pre-switching platelet counts below 30 × 109/L, eight out of 12 patients (66.7%) responded, while eight out of nine patients (88.9%) with pre-switching platelet counts between 30 × 109/L and 50 × 109/L responded post-switching. Treatment-related adverse events were observed in 50.8% of patients during eltrombopag treatment and 38.1% during hetrombopag treatment. No severe adverse events were noted during hetrombopag treatment. Switching from eltrombopag to hetrombopag in ITP management appears to be effective and well-tolerated. Notably, hetrombopag yielded high response rates, even among patients who had previously shown limited response to eltrombopag. However, these observations need to be confirmed in future trials.

Finotonlimab with chemotherapy in recurrent or metastatic head and neck cancer: a randomized phase 3 trial.

Immunotherapy combined with chemotherapy regimen has been shown to be effective in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, due to the small number of patients, its efficacy remains controversial in Asian populations, particularly in mainland China. Here a randomized, double-blind phase 3 trial evaluated the efficacy and safety of finotonlimab (SCT-I10A), a programmed cell death 1 (PD-1) monoclonal antibody, combined with cisplatin plus 5-fluorouracil (C5F) for the first-line treatment of R/M HNSCC. Eligible patients (n = 370) were randomly 2:1 assigned to receive finotonlimab plus C5F (n = 247) or placebo plus C5F (n = 123). The primary endpoint was overall survival (OS). In the finotonlimab plus C5F group, OS was 14.1 months (95% confidence interval (CI) 11.1-16.4), compared with 10.5 months (95% CI 8.1-11.8) in the placebo plus C5F group. The hazard ratio was 0.73 (95% CI 0.57-0.95, P = 0.0165), meeting the predefined superiority criteria for the primary endpoint. Finotonlimab plus C5F showed significant OS superiority compared with C5F alone and acceptable safety profile with R/M HNSCC, supporting its use as a first-line treatment option for R/M HNSCC. These results validate the efficacy and safety of the combination of finotonlimab and C5F in Asian patients with R/M HNSCC. ClinicalTrials.gov identifier: NCT04146402 .

BeEAM vs. BEAM: evaluating conditioning regimens for autologous stem cell transplantation in patients with relapsed or refractory DLBCL.

PURPOSE: To evaluate whether BeEAM is an alternative to BEAM for autologous stem cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). METHODS: Data of 60 patients with relapsed or refractory DLBCL who underwent ASCT from January 2018 to June 2023 in our center, including 30 patients in the BeEAM group and 30 patients in the BEAM group, were retrospectively analyzed. The time to hematopoietic reconstitution, treatment-related adverse events, number of hospitalization days, hospitalization cost, and survival benefit were compared between the two groups. RESULTS: The clinical characteristics of the patients did not significantly differ between the two groups. The median number of reinfused CD34 + cells was 5.06 × 106/kg and 5.17 × 106/kg in the BeEAM and BEAM groups, respectively, which did not significantly different (p = 0.8829). In the BeEAM and BEAM groups, the median time to neutrophil implantation was 10.2 and 10.27 days, respectively (p = 0.8253), and the median time to platelet implantation was 13.23 and 12.87 days, respectively (p = 0.7671). In the BeEAM and BEAM groups, the median hospitalization duration was 30.37 and 30.57 days, respectively (p = 0.9060), and the median hospitalization cost was RMB 83,425 and RMB 96,235, respectively (p = 0.0560). The hospitalization cost was lower in the BeEAM group. The most common hematologic adverse events were grade ≥ 3 neutropenia and thrombocytopenia, whose incidences were similar in the two groups. The most common non-hematologic adverse events were ≤ grade 2 and the incidences of these events did not significantly differ between the two groups. Median overall survival was not reached in either group, with predicted 5-year overall survival of 72.5% and 60% in the BeEAM and BEAM groups, respectively (p = 0.5872). Five-year progression-free survival was 25% and 20% in the BeEAM and BEAM groups, respectively (p = 0.6804). CONCLUSION: As a conditioning regimen for relapsed or refractory DLBCL, BeEAM has a desirable safety profile and is well tolerated, and its hematopoietic reconstitution time, number of hospitalization days, and survival benefit are not inferior to those of BEAM. BeEAM has a lower hospitalization cost and is an alternative to BEAM.

Assessment of prolonged proteasome inhibition through ixazomib-based oral regimen on newly diagnosed and first-relapsed multiple myeloma: A real-world Chinese cohort study.

OBJECTIVE: To evaluate the effectiveness, safety, and convenience of in-class transition (iCT) from intravenous bortezomib-based induction to ixazomib-based oral regimens. METHODS: This retrospective real-world study was conducted in 16 Chinese hospitals between October 2017 and April 2023 and analyzed newly diagnosed (NDMM) and first-line relapsed multiple myeloma (FRMM) patients who attained at least a partial response from bortezomib-based induction therapy, followed by an ixazomib-based oral regimen for 2 year or until disease progression or intolerable toxicity. RESULTS: The study enrolled 199 patients, median age: 63 years old, male 55.4%, 53% as high risk (HR), and 47% as standard risk. Cytogenetic risk stratification by metaphase fluorescence in situ hybridization (M-FISH), based on the Mayo Clinic risk stratification system. The median duration of total PI therapy was 11 months, with ixazomib-based treatment spanning 6 months. At the 20-month median follow-up, 53% of patients remained on therapy. The 24-month PFS rate was 84.3% from the initiation of bortezomib-based induction and 83.4% from the start of ixazomib-based treatment. Overall response rate (ORR) was 100% post-bortezomib induction and 90% following 6 cycles of the ixazomib-based regimen. Based on the Sankey diagrams, 89.51% of patients maintained or improved their disease response after 2 cycles of iCT, 6 cycles (90.14%), and 12 cycles (80%). The HR level of Mayo was found to be a significant independent factor in a worse remission (hazard ratio (HR) 2.55; p = 0.033). Ixazomib's safety profile aligned with previous clinical trial data, with 49% of patients experiencing at least one AE of any grade. The most common AEs included peripheral neuropathy, nausea and vomiting, diarrhea, thrombocytopenia, and granulocytopenia. CONCLUSION: In the real-world Chinese MM population, NDMM and FRMM patients responded favorably to PI-based continuous therapy, demonstrating substantial response rates. The ixazomib-based iCT allows for sustained PI-based treatment, offering promising efficacy and tolerable AEs.

Applying machine learning algorithms to develop a survival prediction model for lung adenocarcinoma based on genes related to fatty acid metabolism.

Background: The progression of lung adenocarcinoma (LUAD) may be related to abnormal fatty acid metabolism (FAM). The present study investigated the relationship between FAM-related genes and LUAD prognosis. Methods: LUAD samples from The Cancer Genome Atlas were collected. The scores of FAM-associated pathways from the Kyoto Encyclopedia of Genes and Genomes website were calculated using the single sample gene set enrichment analysis. ConsensusClusterPlus and cumulative distribution function were used to classify molecular subtypes for LUAD. Key genes were obtained using limma package, Cox regression analysis, and six machine learning algorithms (GBM, LASSO, XGBoost, SVM, random forest, and decision trees), and a RiskScore model was established. According to the RiskScore model and clinical features, a nomogram was developed and evaluated for its prediction performance using a calibration curve. Differences in immune abnormalities among patients with different subtypes and RiskScores were analyzed by the Estimation of STromal and Immune cells in MAlignant Tumours using Expression data, CIBERSORT, and single sample gene set enrichment analysis. Patients' drug sensitivity was predicted by the pRRophetic package in R language. Results: LUAD samples had lower scores of FAM-related pathways. Three molecular subtypes (C1, C2, and C3) were defined. Analysis on differential prognosis showed that the C1 subtype had the most favorable prognosis, followed by the C2 subtype, and the C3 subtype had the worst prognosis. The C3 subtype had lower immune infiltration. A total of 12 key genes (SLC2A1, PKP2, FAM83A, TCN1, MS4A1, CLIC6, UBE2S, RRM2, CDC45, IGF2BP1, ANGPTL4, and CD109) were screened and used to develop a RiskScore model. Survival chance of patients in the high-RiskScore group was significantly lower. The low-RiskScore group showed higher immune score and higher expression of most immune checkpoint genes. Patients with a high RiskScore were more likely to benefit from the six anticancer drugs we screened in this study. Conclusion: We developed a RiskScore model using FAM-related genes to help predict LUAD prognosis and develop new targeted drugs.

Stromal cells in the tumor microenvironment: accomplices of tumor progression?

The tumor microenvironment (TME) is made up of cells and extracellular matrix (non-cellular component), and cellular components include cancer cells and non-malignant cells such as immune cells and stromal cells. These three types of cells establish complex signals in the body and further influence tumor genesis, development, metastasis and participate in resistance to anti-tumor therapy. It has attracted scholars to study immune cells in TME due to the significant efficacy of immune checkpoint inhibitors (ICI) and chimeric antigen receptor T (CAR-T) in solid tumors and hematologic tumors. After more than 10 years of efforts, the role of immune cells in TME and the strategy of treating tumors based on immune cells have developed rapidly. Moreover, ICI have been recommended by guidelines as first- or second-line treatment strategies in a variety of tumors. At the same time, stromal cells is another major class of cellular components in TME, which also play a very important role in tumor metabolism, growth, metastasis, immune evasion and treatment resistance. Stromal cells can be recruited from neighboring non-cancerous host stromal cells and can also be formed by transdifferentiation from stromal cells to stromal cells or from tumor cells to stromal cells. Moreover, they participate in tumor genesis, development and drug resistance by secreting various factors and exosomes, participating in tumor angiogenesis and tumor metabolism, regulating the immune response in TME and extracellular matrix. However, with the deepening understanding of stromal cells, people found that stromal cells not only have the effect of promoting tumor but also can inhibit tumor in some cases. In this review, we will introduce the origin of stromal cells in TME as well as the role and specific mechanism of stromal cells in tumorigenesis and tumor development and strategies for treatment of tumors based on stromal cells. We will focus on tumor-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), tumor-associated adipocytes (CAAs), tumor endothelial cells (TECs) and pericytes (PCs) in stromal cells.

Case report: long-term sustained remission in a case of metastatic colon cancer with high microsatellite instability and KRAS exon 2 p.G12D mutation treated with fruquintinib after local radiotherapy: a case report and literature review.

To demonstrate the efficacy of fruquintinib administration after local radiotherapy in a patient with metastatic colon cancer with high microsatellite instability and the KRAS exon 2 p. G12D mutation. The patient was administered four cycles of pembrolizumab intravenous infusion and achieved stable disease as the best outcome. He was then underwent follow-up concurrent radiochemical therapy (local DT4600cGy/23f/32d radiotherapy, and S-1 to increase sensitivity to radiotherapy), but this had little efficacy. Following this, he was administered fruquintinib and achieved sustained partial remission. At the time of last follow-up, the patient was in continuous remission for 30 months. Administration of fruquintinib after local radiotherapy may be an effective treatment for specific populations with metastatic colorectal cancer.

Prognostic value of long noncoding RNA LINC00924 in lung adenocarcinoma and its regulatory effect on tumor progression.

PURPOSE: Long non-coding RNAs (lncRNAs) have been used in the study of tumor biomarkers in recent years. However, the prognostic role of lncRNA LINC00924 (LINC00924) in lung adenocarcinoma (LUAD) has not yet been concluded. Therefore, this study investigates the prognostic value of LINC00924 in LUAD and its regulatory effect on tumor progression. PATIENTS AND METHODS: The LUAD tissues and adjacent normal tissues of 128 subjects were extracted, and the expressions of LINC00924 and miR-196a-5p in tissues and cells were detected by RT-qPCR. The prognostic value of LINC00924 in LUAD patients was obtained by Kaplan-Meier analysis and multivariate Cox regression test. The cell counting kit-8 (CCK-8) and Transwell assay were used to detect the effect of overexpression LINC00924 on LUAD cells. RESULTS: In LUAD tissues and cells, LINC00924 expression was down-regulated and miR-196a-5p expression was up-regulated compared with the normal control group. High expression of LINC00924 inhibited the proliferation level, migration ability and invasion situation of LUAD cells, which was more conducive to the survival and prognosis of LUAD patients. Bioinformatics studies indicated that overexpression of LINC00924 inhibited the development of LUAD by targeting miR-196a-5p, while miR-196a-5p mimic effectively weakened the inhibition. CONCLUSION: LINC00924 sponges of miR-196a-5p may be considered as a potential prognostic biomarker for LUAD.

Immune-related adverse events as independent prognostic factors for camrelizumab in patients with esophageal squamous cell carcinoma: a retrospective cohort study.

Background: While programmed cell death protein 1 (PD-1) blockade has demonstrated varying effectiveness in treating advanced esophageal squamous cell carcinoma (ESCC), no validated prognostic factors have been identified. Immune-related adverse events (irAEs) have been shown to predict immunotherapy outcomes in multiple cancers, but their relationship with ESCC remains unclear. This study aims to evaluate the prognostic value of irAEs in patients with advanced ESCC treated with camrelizumab. Methods: We conducted a retrospective chart review of patients with recurrent or metastatic ESCC who were treated with single-agent camrelizumab at the Department of Oncology and Hematology in China-Japan Union Hospital of Jilin University between 2019 and 2022. The study's primary endpoint was objective response rate (ORR), while secondary endpoints included disease control rate (DCR), overall survival (OS), and safety. We used the chi-squared test and odds ratio (OR) to evaluate any relationships between the occurrence of irAEs and ORR. Prognostic factors for OS were identified through survival analysis using the Kaplan-Meier method and multivariate Cox regression. Results: The study included 136 patients with a median age of 60 years, of whom 81.6% were male and 89.7% received platinum-based chemotherapy as their first-line therapy. Among these patients, 128 irAEs were observed in 81 patients (59.6%). Patients who experienced irAEs achieved a significantly better ORR [39.5% vs. 14.5%; OR =3.84; 95% confidence interval (CI): 1.60-9.18; P=0.003] and longer OS [13.5 vs. 5.6 months; adjusted hazard ratio (HR) =0.56, 95% CI: 0.41-0.76; P=0.0013] than those who did not experience irAEs. Multivariate analysis identified the presence of irAEs as an independent prognostic factor for OS (HR =0.57, 95% CI: 0.42-0.77; P=0.0002). Conclusions: The presence of irAEs in ESCC patients treated with anti-PD-1 therapy (camrelizumab) may serve as a clinical prognostic factor, indicating improved therapeutic effectiveness. These findings suggest that irAEs could be used as a potential marker to predict outcomes in this patient population.

Metastatic germ cell tumor showing a durable response to the anti-PD-1 antibody toripalimab.

The outcome for patients with recurrent and metastatic germ cell tumors can be dismal, and novel salvage therapies are required for these patients. Here we describe a case of metastatic germ cell tumor in which 30% of cells were positive for PD-L1. This tumor achieved a durable response to toripalimab, a monoclonal anti-PD-1 antibody. Follow-up for 36 months post-treatment confirmed no disease progression. Continuous remission was maintained even when treatment was interrupted after 18 months because of an immune-related adverse event (allergic rhinitis). Thus, toripalimab may be an alternative choice for salvage therapy in patients with recurrent and metastatic germ cell tumors.

Rescue treatment for recurrent and metastatic germ cell tumors is limited. Immune checkpoint inhibitors have shown certain efficacy and safety in the treatment of a variety of tumors. Here we describe a case of metastatic germ cell tumor in which 30% of cells were positive for PD-L1. This tumor achieved a durable response to toripalimab, a monoclonal anti-PD-1 antibody. Follow-up for 36 months post-treatment confirmed no disease progression. We not only report the first use of toripalimab for the treatment of a metastatic germ cell tumor but also describe a patient with the longest sustained remission with an anti-PD-1 antibody to date.

Therapeutic strategies for gastric cancer targeting immune cells: Future directions.

Gastric cancer (GC) is a malignancy with a high incidence and mortality, and the emergence of immunotherapy has brought survival benefits to GC patients. Compared with traditional therapy, immunotherapy has the advantages of durable response, long-term survival benefits, and lower toxicity. Therefore, targeted immune cells are the most promising therapeutic strategy in the field of oncology. In this review, we introduce the role and significance of each immune cell in the tumor microenvironment of GC and summarize the current landscape of immunotherapy in GC, which includes immune checkpoint inhibitors, adoptive cell therapy (ACT), dendritic cell (DC) vaccines, reduction of M2 tumor-associated macrophages (M2 TAMs), N2 tumor-associated neutrophils (N2 TANs), myeloid-derived suppressor cells (MDSCs), effector regulatory T cells (eTregs), and regulatory B cells (Bregs) in the tumor microenvironment and reprogram TAMs and TANs into tumor killer cells. The most widely used immunotherapy strategies are the immune checkpoint inhibitor programmed cell death 1/programmed death-ligand 1 (PD-1/PD-L1) antibody, cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibody, and chimeric antigen receptor T (CAR-T) in ACT, and these therapeutic strategies have significant anti-tumor efficacy in solid tumors and hematological tumors. Targeting other immune cells provides a new direction for the immunotherapy of GC despite the relatively weak clinical data, which have been confirmed to restore or enhance anti-tumor immune function in preclinical studies and some treatment strategies have entered the clinical trial stage, and it is expected that more and more effective immune cell-based therapeutic methods will be developed and applied.

Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer: The ASTRUM-005 Randomized Clinical Trial.

Importance: Programmed cell death ligand 1 inhibitors combined with chemotherapy has changed the approach to first-line treatment in patients with extensive-stage small cell lung cancer (SCLC). It remained unknown whether adding a programmed cell death 1 (PD-1) inhibitor to chemotherapy provided similar or better benefits in patients with extensive-stage SCLC, which would add evidence on the efficacy of checkpoint inhibitors in the treatment of extensive-stage SCLC. Objective: To evaluate the efficacy and adverse event profile of the PD-1 inhibitor serplulimab plus chemotherapy compared with placebo plus chemotherapy as first-line treatment in patients with extensive-stage SCLC. Design, Setting, and Participants: This international, double-blind, phase 3 randomized clinical trial (ASTRUM-005) enrolled patients at 114 hospital sites in 6 countries between September 12, 2019, and April 27, 2021. Of 894 patients who were screened, 585 with extensive-stage SCLC who had not previously received systemic therapy were randomized. Patients were followed up through October 22, 2021. Interventions: Patients were randomized 2:1 to receive either 4.5 mg/kg of serplulimab (n = 389) or placebo (n = 196) intravenously every 3 weeks. All patients received intravenous carboplatin and etoposide every 3 weeks for up to 12 weeks. Main Outcomes and Measures: The primary outcome was overall survival (prespecified significance threshold at the interim analysis, 2-sided P < .012). There were 13 secondary outcomes, including progression-free survival and adverse events. Results: Among the 585 patients who were randomized (mean age, 61.1 [SD, 8.67] years; 104 [17.8%] women), 246 (42.1%) completed the trial and 465 (79.5%) discontinued study treatment. All patients received study treatment and were included in the primary analyses. As of the data cutoff (October 22, 2021) for this interim analysis, the median duration of follow-up was 12.3 months (range, 0.2-24.8 months). The median overall survival was significantly longer in the serplulimab group (15.4 months [95% CI, 13.3 months-not evaluable]) than in the placebo group (10.9 months [95% CI, 10.0-14.3 months]) (hazard ratio, 0.63 [95% CI, 0.49-0.82]; P < .001). The median progression-free survival (assessed by an independent radiology review committee) also was longer in the serplulimab group (5.7 months [95% CI, 5.5-6.9 months]) than in the placebo group (4.3 months [95% CI, 4.2-4.5 months]) (hazard ratio, 0.48 [95% CI, 0.38-0.59]). Treatment-related adverse events that were grade 3 or higher occurred in 129 patients (33.2%) in the serplulimab group and in 54 patients (27.6%) in the placebo group. Conclusions and Relevance: Among patients with previously untreated extensive-stage SCLC, serplulimab plus chemotherapy significantly improved overall survival compared with chemotherapy alone, supporting the use of serplulimab plus chemotherapy as the first-line treatment for this patient population. Trial Registration: ClinicalTrials.gov Identifier: NCT04063163.

Efficacy and Safety of Limertinib (ASK120067) in Patients With Locally Advanced or Metastatic EGFR Thr790Met-Mutated NSCLC: A Multicenter, Single-Arm, Phase 2b Study.

INTRODUCTION: Limertinib (ASK120067) is a newly developed third-generation EGFR tyrosine kinase inhibitor targeting both sensitizing EGFR and EGFR Thr790Met (T790M) mutations. This study aimed to evaluate the efficacy and safety of limertinib in patients with locally advanced or metastatic EGFR T790M-mutated NSCLC. METHODS: This is a single-arm, open-label, phase 2b study conducted at 62 hospitals across the People's Republic of China. Patients with locally advanced or metastatic NSCLC with centrally confirmed EGFR T790M mutations in tumor tissue or blood plasma who progressed after first- or second-generation EGFR tyrosine kinase inhibitors or with primary EGFR T790M mutations were enrolled. Patients received limertinib 160 mg orally twice daily until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) assessed by independent review committee per the Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included disease control rate, progression-free survival (PFS), duration of response (DoR), overall survival, and safety. Safety was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. RESULTS: From July 16, 2019, to March 10, 2021, a total of 301 patients were enrolled and started the treatment of limertinib. All patients entered the full analysis set and safety set. By the data cutoff date on September 9, 2021, 76 (25.2%) remained on treatment. The median follow-up time was 10.4 months (range: 0.3-26.3). On the basis of full analysis set, the independent review committee-assessed ORR was 68.8% (95% confidence interval [CI]: 63.2%-74.0%) and disease control rate was 92.4% (95% CI: 88.8%-95.1%). The median PFS was 11.0 months (95% CI: 9.7-12.4), median DoR was 11.1 months (95% CI: 9.6-13.8), and median OS was not reached (95% CI 19.7 months-not evaluable). Objective responses were achieved across all prespecified subgroups. For 99 patients (32.9%) with central nervous system (CNS) metastases, the ORR was 64.6% (95% CI: 54.4%-74.0%), median PFS was 9.7 months (95% CI: 5.9-11.6), and median DoR was 9.6 months (95% CI: 8.1-15.2). For 41 patients who had assessable CNS lesion, the confirmed CNS-ORR was 56.1% (95% CI: 39.7%-71.5%) and median CNS-PFS was 10.6 months (95% CI: 5.6-not evaluable). In safety set, 289 patients (96.0%) experienced at least one treatment-related adverse event (TRAE), with the most common being diarrhea (81.7%), anemia (32.6%), rash (29.9%), and anorexia (28.2%). Grade ≥3 TRAEs occurred in 104 patients (34.6%), with the most common including diarrhea (13.0%), hypokalemia (4.3%), anemia (4.0%), and rash (3.3%). TRAEs leading to dose interruption and dose discontinuation occurred in 24.6% and 2% of patients, respectively. No TRAE leading to death occurred. CONCLUSIONS: Limertinib (ASK120067) was found to have promising efficacy and an acceptable safety profile for the treatment of patients with locally advanced or metastatic EGFR T790M-mutated NSCLC. CLINICAL TRIAL INFORMATION: NCT03502850.

Dose tapering to withdrawal stage and long-term efficacy and safety of hetrombopag for the treatment of immune thrombocytopenia: Results from an open-label extension study.

BACKGROUND: The efficacy of hetrombopag in Chinese patients with immune thrombocytopenia (ITP) has been demonstrated in a randomized, double-blind, placebo-controlled, multicenter, phase III trial (NCT03222843). OBJECTIVE: This study aimed to report comprehensive data on a ≤6-week dose tapering to withdrawal (Stage 3) and an additional 24-week long-term extension period (Stage 4) in this phase III trial. PATIENTS/METHODS: Patients who fulfilled the screening criteria were eligible to enter Stage 3 or 4. During Stage 3, hetrombopag was gradually tapered to withdrawal. During Stage 4, hetrombopag treatment was initiated at 2.5, 3.75, 5, or 7.5 mg once daily. The efficacy endpoints during Stage 3 or 4 and the safety profile during the entire treatment period were reported. RESULTS: Among 194 patients who entered Stage 3, 171 (88.1%) relapsed. The median time to the first relapse since the start of Stage 3 was 15.0 days (95% CI, 14.0-16.0). In Stage 4, 144 (42.5%) patients responded at ≥75% of their assessments and 254 (74.9%) patients achieved platelet count ≥30 × 109 /L at least once, which was at least twice their baseline platelet count in the hetrombopag group (n = 339). The most common adverse events were upper respiratory tract infection (53.1%), thrombocytopenia (27.1%), and urinary tract infection (21.2%) in the hetrombopag group. CONCLUSION: The majority of patients who experienced dose tapering to withdrawal experienced a relapse. Long-term treatment with hetrombopag was effective in increasing and maintaining platelet count within the desired range in Chinese adults with ITP. Hetrombopag was well tolerated.

Detection and clinical significance of serum EPO levels in patients with haematological tumours.

This experiment aimed to detect serum erythropoietin (EPO) levels in patients with haematological tumours and to investigate its clinical significance. For this purpose, 110 patients with haematological tumours admitted to our hospital between January 2019 and December 2020 were selected as the study population according to the inclusion and exclusion criteria, and they were included in the case group, and the clinical data of the patients were retrospectively analysed. 90 cases of people without hematological tumors who underwent physical examination during the same period were also included as a control group. The serum EPO levels of the two study groups were compared, and the clinical diagnostic value of EPO was analysed using the subject operating characteristic curve (ROC). Results indicated that of the 110 patients, 56 were leukaemia patients, 24 were multiple myeloma patients and 30 were malignant lymphoma patients. The differences in gender, age, disease history, alcohol consumption and smoking history between the two groups were not significant (P>0.05), while the EPO levels in the control group were significantly lower than those in the case group, with a statistical significant difference of P<0.05. The EPO levels in patients with leukaemia, multiple myeloma and malignant lymphoma were (165.43± 20.46) mU/mL, ( 28.14± 4.51) mU/mL and (86.25±10.33) mU/mL significantly higher than the control group, with a significant difference of P<0.05. Using the absence of haematological tumours as a control, the analysis yielded an area under the ROC curve of 0.995 for EPO diagnosis in patients with leukaemia, a 95% confidence interval of 0.987 to 1.000, a sensitivity of 97.80%, with a sensitivity of 98.2 %; the area under the ROC curve for patients with multiple myeloma was 0.910, with a 95% confidence interval of 0.818 to 1.000, with a sensitivity of 98.90% and specificity of 87.50%; the area under the ROC curve for patients with malignant lymphoma was 0.992, with a 95% confidence interval of 0.978 to 1.000, with a sensitivity of 96.70% and specificity of 96.70%. In conclusion, the serum EPO levels of patients with haematological tumours are significantly higher than those of the normal population, and the detection of serum EPO levels is valuable for the diagnosis of clinical haematological tumours.

Prognostic value of microRNA-4521 in non-small cell lung cancer and its regulatory effect on tumor progression.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a malignant tumor with the highest mortality rate in our country. It has been found in many studies that microRNA-4521 (miR-4521) is abnormally expressed and plays a role in clear cell renal cell carcinoma and other cancers. OBJECTIVE: The purpose of this study was to explore the relationship between miR-4521 expression and clinical prognosis, as well as its influence on cell biological behavior. METHODS: The expression differences of miR-4521 in NSCLC tissues and cells were examined by qRT-PCR technology. Kaplan-Meier survival analysis and Cox regression analysis were used to analyze the clinical information and survival status of patients to explore the relationship. Using the vitro cell MTT assay, Transwell assay, and western-blot analysis, the effects of miR-4521 on cell proliferation, migration, and invasion were analyzed. RESULTS: The expression of miR-4521 in NSCLC tissues and cells was significantly downregulated. miR-4521 can be used as an independent prognostic factor. The survival rate of the miR-4521 low expression group was lower, which was significantly related to poor prognosis. In addition, the low expression of miR-4521 significantly promoted cell proliferation, migration, and invasion with highly expressed related protein levels. FOXM1 might be a direct target of miR-4521. CONCLUSION: The results of this study showed that the low expression of miR-4521 indicated the poor prognosis of NSCLC and promoted cell proliferation, migration, and invasion by targeting FOXM1.

Retraction of "Icariin Alleviates Bisphenol A Induced Disruption of Intestinal Epithelial Barrier by Maintaining Redox Homeostasis In Vivo and In Vitro".

[This retracts the article DOI: 10.1021/acsomega.0c02364.].

Diagnostic and prognostic value of microRNA-2355-3p and contribution to the progression in lung adenocarcinoma.

The aim of this study was to delve into the clinical significance and biological function of miR-2355-3p in LUAD. Tissues and blood samples from 116 LUAD patients and blood samples of 90 healthy volunteers were collected. The relative expression of miR-2355-3p was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The receiver operating curve (ROC) was plotted for diagnostic value estimation. Kaplan-Meier survival curves were constructed, and multivariate survival analyses were performed for prognostic value estimation. A luciferase reporter assay was carried out to confirm the interaction of miR-2355-3p and ZCCHC14. The CCK-8 and transwell assays were conducted to explore the function of miR-2355-3p on LUAD cells. Rescue experiments were performed to verify the interaction. miR-2355-3p showed an upregulated expression in the samples of LUAD patients. For diagnostic value estimation, the AUC was 0.905 with a sensitivity was 84.5% and specificity of 83.3%. For the estimation of prognostic value, the P-value of log-rank test on K-M curves was 0.002 and 0.006 for overall survival and progression survival, respectively. Based on multivariate Cox regression analysis, miR-2355-3p was a powerful prognostic tool with a P-value of 0.027. ZCCHC14 has binding sites with miR-2355-3p, an expression level, and luciferase activity negatively correlated with miR-2355-3p expression. Knockdown of miR-2355-3p inhibited proliferation, migration, and invasion of LUAD cells, but ZCCHC14 can rescue this inhibition. miR-2355-3p has the potential to be a diagnostic marker and prognostic marker for LUAD. Inhibition of miR-2355-3p in LUAD cells can suppress the progression of LUAD at least partly by direct targeting ZCCHC14.