A Phase II Study of Denileukin Diftitox in Patients with Advanced Treatment Refractory Breast Cancer.

: Regulatory T cells (Treg) suppress immunity in the tumor microenvironment, are linked to poor prognosis across breast cancer subtypes, and suppress the cytolytic function of cytotoxic CD8+ T cells. Denileukin diftitox, a diphtheria toxin (DT)/IL-2 fusion protein, targets and depletes Tregs. This Phase II study aimed to assess the safety of denileukin diftitox and its effect on Tregs and tumor growth in patients with advanced breast cancer.

Phase II Open-Label Trial of Brentuximab Vedotin with Pembrolizumab in PD-1-Pretreated Metastatic Non-Small Cell Lung Cancer and Metastatic Cutaneous Melanoma.

Purpose: Brentuximab vedotin (BV) is hypothesized to selectively deplete T regulatory cells that express CD30 and resensitize tumors to anti-PD-1 therapy. This study evaluated responses to BV + pembrolizumab after PD-1 therapy and explored corresponding biomarkers.

Patients And Methods: A total of 55 patients with metastatic non-small cell lung cancer and 58 patients with metastatic cutaneous melanoma received ≥1 dose of BV + pembrolizumab.

Association of hypoalbuminemia with hospitalization and mortality in hemodialysis patients with COVID-19.

Introduction: Hypoalbuminemia is associated with poor nutritional status and inflammatory response in infectious diseases. It is commonly observed in COVID-19 patients. The aim of this study is to assess the association of serum albumin with hospitalization and mortality in dialysis patients with COVID-19.

Toll-Like Receptor 4 Agonist Injection With Concurrent Radiotherapy in Patients With Metastatic Soft Tissue Sarcoma: A Phase 1 Nonrandomized Controlled Trial.

Importance: Metastatic soft tissue sarcomas (STSs) have limited systemic therapy options, and immunomodulation has not yet meaningfully improved outcomes. Intratumoral (IT) injection of the toll-like receptor 4 (TLR4) agonist glycopyranosyl lipid A in stable-emulsion formulation (GLA-SE) has been studied as immunotherapy in other contexts.

Objective: To evaluate the safety, efficacy, and immunomodulatory effects of IT GLA-SE with concurrent radiotherapy in patients with metastatic STS with injectable lesions.

Inetetamab, a novel anti-HER2 monoclonal antibody, exhibits potent synergistic anticancer effects with cisplatin by inducing pyroptosis in lung adenocarcinoma.

Cisplatin is a first-line chemotherapy drug for lung adenocarcinoma (LUAD). However, its therapeutic efficacy is limited because of serious side effects and acquired drug resistance. Targeting HER2 has been proven to be a viable therapeutic strategy against LUAD.

Apatinib plus etoposide in pretreated patients with advanced triple-negative breast cancer: a phase II trial.

Background: Treatment options for pretreated triple-negative breast cancer (TNBC) are limited. This study aimed to evaluate the efficacy and safety of apatinib, an antiangiogenic agent, in combination of etoposide for pretreated patients with advanced TNBC.

Methods: In this single-arm phase II trial, patients with advanced TNBC who failed to at least one line of chemotherapy were enrolled.

Pathogenesis-related protein-4 (PR-4) gene family in Qingke (Hordeum vulgare L. var. nudum): genome-wide identification, structural analysis and expression profile under stresses.

Background: Pathogenesis-related (PR) proteins are active participants of plant defense against biotic and abiotic stresses. The PR-4 family features a Barwin domain at the C-terminus, which endows the host plant with disease resistance. However, comprehensive analysis of PR-4 genes is still lacking in Qingke (Hordeum vulgare L.

Comparative physiological and transcriptomic analysis of sesame cultivars with different tolerance responses to heat stress.

Unlabelled: High temperature is the main factor affecting plant growth and can cause plant growth inhibition and yield reduction. Here, seedlings of two contrasting sesame varieties, i.e.

Phase 1/2 study of intratumoral G100 (TLR4 agonist) with or without pembrolizumab in follicular lymphoma.

Intratumoral injection of G100, a toll-like receptor 4 (TLR4) agonist, was shown pre-clinically to stimulate anti-tumor immune responses and tumor regression. This open-label, multicenter, phase 1/2 trial evaluated the safety, tolerability, and preliminary efficacy of intratumoral G100 injections following localized low-dose radiation in patients with follicular lymphoma (ClinicalTrials.gov #NCT02501473).

Phase II Randomized Study of CMB305 and Atezolizumab Compared With Atezolizumab Alone in Soft-Tissue Sarcomas Expressing NY-ESO-1.

Purpose: CMB305 is a heterologous prime-boost vaccination regimen created to prime NY-ESO-1-specific CD8 T-cell populations and then activate the immune response with a potent TLR-4 agonist. This open-label randomized phase II trial was designed to investigate the efficacy and safety of adding the CMB305 regimen to atezolizumab (anti-programmed death ligand-1 therapy) in comparison with atezolizumab alone in patients with synovial sarcoma or myxoid liposarcoma.

Patients And Methods: Patients with locally advanced, relapsed, or metastatic synovial sarcoma or myxoid liposarcoma (any grade) were randomly assigned to receive CMB305 with atezolizumab (experimental arm) or atezolizumab alone (control arm).

Association of Rotavirus Vaccines With Reduction in Rotavirus Gastroenteritis in Children Younger Than 5 Years: A Systematic Review and Meta-analysis of Randomized Clinical Trials and Observational Studies.

Importance: Rotavirus vaccines have been introduced worldwide, and the clinical association of different rotavirus vaccines with reduction in rotavirus gastroenteritis (RVGE) after introduction are noteworthy.

Objective: To evaluate the comparative benefit, risk, and immunogenicity of different rotavirus vaccines by synthesizing randomized clinical trials (RCTs) and observational studies.

Data Sources: Relevant studies published in 4 databases: Embase, PubMed, the Cochrane Library, and Web of Science were searched until July 1, 2020, using search terms including "rotavirus" and "vaccin*.

A Phase 1b Study Evaluating the Safety, Tolerability, and Immunogenicity of CMB305, a Lentiviral-Based Prime-Boost Vaccine Regimen, in Patients with Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1.

Preclinical data suggest that a "prime-boost" vaccine regimen using a target-expressing lentiviral vector for priming, followed by a recombinant protein boost, may be effective against cancer; however, this strategy has not been evaluated in a clinical setting. CMB305 is a prime-boost vaccine designed to induce a broad anti-NY-ESO-1 immune response. It is composed of LV305, which is an NY-ESO-1 expressing lentiviral vector, and G305, a recombinant adjuvanted NY-ESO-1 protein.

Too Insecure to Be a Leader: The Role of Attachment in Leadership Emergence.

The antecedents of leadership emergence have received increasing attention over the past decades. Extant work has found that traits that involve with other members in social relations can help employees emerge as leaders. However, attachment has been ignored, even though it can provide a distinct relational perspective to .

Targeting 14-3-3ζ Overcomes Resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in Lung Adenocarcinoma via BMP2/Smad/ID1 Signaling.

The 14-3-3ζ protein, which acts as a putative oncoprotein, has been found to promote the proliferation, metastasis, and chemoresistance of cancer cells in several cancers including lung adenocarcinoma (LUAD); however, its significance in epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance remains unknown. The Cancer Genome Atlas (TCGA) database was used to determine 14-3-3ζ expression in pancancer and LUAD. 14-3-3ζ and ID1 expression was then examined in clinical LUAD samples by immunohistochemistry (IHC).

Leader Humor and Employee Job Crafting: The Role of Employee-Perceived Organizational Support and Work Engagement.

Research on the outcomes of leader humor has mainly focused on attitudinal or in-role behaviors, while proactive change-oriented behaviors have been neglected. Addressing these issues is important for scholars and practitioners to better understand how leader humor enables subordinates to behave proactively. By integrating the resource accumulation perspective and the motivational process of the Job Demands-Resources (JD-R) model, we frame leader humor as a socioemotional resource that can help employees to create other forms of resources, such as job resources (i.

Toll-Like Receptor 4 Expression on Lymphoma Cells Is Critical for Therapeutic Activity of Intratumoral Therapy With Synthetic TLR4 Agonist Glucopyranosyl Lipid A.

Intratumoral (IT) injections of Glucopyranosyl lipid A (G100), a synthetic toll-like receptor 4 (TLR4) agonist formulated in a stable emulsion, resulted in T-cell inflammation of the tumor microenvironment (TME) and complete cure of 60% of mice with large established A20 lymphomas. Strong abscopal effects on un-injected lesions were observed in a bilateral tumor model and surviving mice resisted a secondary tumor challenge. Depletion of CD8 T-cells, but not CD4 or NK cells, abrogated the anti-tumor effect.

Identification and Validation of the Immune Subtypes of Lung Adenocarcinoma: Implications for Immunotherapy.

Lung adenocarcinoma (LUAD) is a devastating disease with poor patient survival. Cancer immunotherapy has revolutionized the treatment of LUAD, but only a limited number of patients effectively respond to this treatment. Thus, the work to elucidate the LUAD immune heterogeneity could be crucial in developing new immunotherapeutic strategies with better efficacy.

USP22 promotes development of lung adenocarcinoma through ubiquitination and immunosuppression.

Ubiquitin-specific protease 22 (USP22) expresses highly in lung adenocarcinoma (LUAD), which are associated with poor overall survival (OS). Microarray processing was performed to determine gene expression profiling, in which it was found that knocking down USP22 resulted in abnormal expression of a large number of genes. Differentially expressed genes (DEGs)-based protein-protein interaction (PPI) network was organized into 9 functional modules.

Targeting the IL-1β/EHD1/TUBB3 axis overcomes resistance to EGFR-TKI in NSCLC.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) significantly prolong the survival time of non-small-cell lung cancer (NSCLC) patients with EGFR-activating mutations, but resistance develops universally. Activation of the phosphatidyl inositol-3 kinase (PI3K)/AKT signaling pathway and phenotypic alterations in epithelial-mesenchymal transition (EMT) are both mechanisms of acquired resistance to EGFR-TKIs. However, the mechanisms underlying this resistance remain unclear.

Association Between Rotavirus Vaccination and Risk of Intussusception Among Neonates and Infants: A Systematic Review and Meta-analysis.

Importance: The conclusions from the multiple randomized clinical trials exploring the relationship between development of intussusception and rotavirus vaccination among neonates and infants have been controversial.

Objective: To evaluate the association between rotavirus vaccination and risk of intussusception.

Data Sources: For this systematic review and meta-analysis, PubMed, Web of Science, Cochrane library, and Embase databases were searched from January 1, 1999, through December 31, 2018, using no language restrictions.

First-in-Class, First-in-Human Study Evaluating LV305, a Dendritic-Cell Tropic Lentiviral Vector, in Sarcoma and Other Solid Tumors Expressing NY-ESO-1.

Purpose: LV305 is a modified, third-generation, nonreplicating, integration-deficient lentivirus-based vector designed to selectively transduce dendritic cells . LV305 induces expression of the New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) cancer testis antigen in dendritic cells, promoting immune responses against NY-ESO-1-expressing tumors. This phase I study evaluated the safety, immunogenicity, and preliminary efficacy of LV305 in patients with sarcoma or other solid tumors.

Tumor-associated antigens identified early in mouse mammary tumor development can be effective vaccine targets.

Breast cancer vaccines composed of antigens identified by serological analysis of cDNA expression libraries (SEREX) induce antigen specific immune responses in patients but have had disappointing clinical benefits. While many attempts to modify the adjuvants and vaccine method have been tried, one issue not addressed was whether the SEREX tumor-associated antigens identified from late stages of disease were ideal targets. We questioned in the transgenic TgMMTV-neu mouse model whether the antigen repertoire is distinct between early and late stage breast cancer and whether the antigens identified via SEREX from transgenic mice with early or late stage tumors would elicit differential anti-tumor effects to address this question.