Incidence of Undifferentiated Pleomorphic Sarcoma (UPS) in the United States.

The classification of undifferentiated pleomorphic sarcoma (UPS) has been evolving with advances in immunohistochemistry and genomic profiling over the past 20 years. There is a lack of current information on UPS incidence. Due to the lack of designated histology codes for UPS in the Surveillance, Epidemiology, and End Results (SEERs) program, we estimated UPS incidence by three different definitions based on clinical opinions using the 2000-2020 data from 22 registries of the SEER program.

The Comparison of Newly Diagnosed Invasive Breast Patient Cohorts in Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative (GENIE-BPC) and Other Real-World Databases.

Background: Oncology databases that integrate genomic and clinical data have become valuable resources for precision medicine. However, the generalizability of these databases has not been comprehensively assessed.

Objectives: To describe the demographics, clinical characteristics, treatments, and overall survival of breast cancer cohorts in GENIE-BPC and three other databases.

Prevalence and prognostic value of PD-L1 expression and tumor mutational burden in persistent, recurrent, or metastatic cervical cancer.

Objective: To evaluate the prevalence and prognostic role of programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB) in patients with non-immunotherapy-treated advanced cervical cancer.

Methods: Clinical data were retrospectively collected from medical records between January 1, 2008, and December 31, 2016, at Asan Medical Center (Korea); archived tumor samples were assessed for PD-L1 expression (combined positive score [CPS] ≥1) and TMB (≥175 mutations/exome). Overall survival (OS) was defined as time from advanced diagnosis or initiation of first-line or second-line systemic therapy until death/last follow-up.

Biomarker Testing Journey Among Patients with Advanced Solid Tumors and Treatment Patterns by Homologous Recombination Repair Status: A Clinico-Genomic Database Study.

Introduction: Defects in the homologous recombination repair (HRR) pathway can include mutations in BRCA1 and BRCA2 (BRCAm) and other HRR genes (HRRm). These mutations are associated with a homologous recombination deficiency (HRD) phenotype. We evaluated testing journey and treatment patterns by BRCAm, HRRm, and HRD status in a real-world dataset.

Association Between Homologous Recombination Repair Biomarkers and Survival in Patients With Solid Tumors.

Purpose: Mutations in and/or (BRCAm), other homologous recombination repair genes (HRRm), and homologous recombination deficiency (HRD) lead to an accumulation of genomic alterations that can drive tumorigenesis. The prognostic impact of these HRR pathway defects on overall survival (OS) in patients not receiving poly (ADP-ribose) polymerase inhibitors (PARPi) or immunotherapy is unclear. We evaluated the association of HRR biomarkers with OS in patients with advanced solid tumors receiving therapy excluding PARPi and immunotherapy.

Evaluation and Comparison of Real-World Databases for Conducting Research in Patients With Colorectal Cancer.

Purpose: Evaluating whether patient populations in clinico-genomic oncology databases are comparable with whom in other databases without genomic component is important.

Methods: Four databases were compared for colorectal cancer (CRC) cases and stage IV CRC cases: American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative (GENIE-BPC), The Cancer Genome Atlas (TCGA), SEER-Medicare, and MarketScan Commercial and Medicare Supplemental claims databases. These databases were also compared with the SEER registry database which serves as national benchmarks.

A comprehensive literature review and meta-analysis of the prevalence of pan-cancer BRCA mutations, homologous recombination repair gene mutations, and homologous recombination deficiencies.

There is significant improvement in the outcomes following treatment with PARP inhibitors among patients with certain tumors that have BRCA mutations (BRCAm), homologous recombination repair (HRR) gene mutations, or homologous recombination deficiency (HRD) positivity. We performed a literature review and meta-analysis to evaluate the prevalence of BRCA1/2m, HRR gene mutations, and HRD positivity across multiple cancers. There were 265 publications on BRCA1/2 mutation prevalence, 189 on HRR gene mutation prevalence, and 7 on HRD positivity prevalence.

A Systematic Review and Meta-Analysis on the Prognostic Value of BRCA Mutations, Homologous Recombination Gene Mutations, and Homologous Recombination Deficiencies in Cancer.

Patients with mutations (m), loss-of-function mutations in other homologous recombination repair (HRRm) genes, or tumors that are homologous recombination deficiency positivity (HRD+) demonstrate a robust response to PARPi therapy. We conducted a systematic literature review and meta-analysis to evaluate the prognostic value of m, HRRm, and HRD+ on overall survival (OS) among those treated by chemotherapy or targeted therapy other than PARPi across tumor types. A total of 135 eligible studies were included.

Association of clinico-genomic characteristics with tumor mutational burden in small cell lung cancer patients.

We evaluated the relationship between clinical and genomic characteristics and tumor mutational burden (TMB) in small cell lung cancer. In a retrospective analysis of small cell lung cancer patients aged ≥18, we assessed treatment patterns and survival in relation to TMB; the association of clinical and genomic characteristics with TMB was determined by multivariate regression. High TMB (TMB-H) was defined as ≥10 mutations/megabase.

Prevalence of High Tumor Mutational Burden and Association With Survival in Patients With Less Common Solid Tumors.

Importance: Tumor mutational burden (TMB) is a potential biomarker associated with response to immune checkpoint inhibitor therapies. The prognostic value associated with TMB in the absence of immunotherapy is uncertain.

Objective: To assess the prevalence of high TMB (TMB-H) and its association with overall survival (OS) among patients not treated with immunotherapy with the same 10 tumor types from the KEYNOTE-158 study.

Chemotherapy treatments, costs of care, and survival for elderly patients diagnosed with cervical cancer: an observational study.

To describe chemotherapy treatments, associated health care use and costs, and survival for women diagnosed with cervical cancer in the United States. This was a retrospective cohort study of patients aged ≥65 years, identified in linked Surveillance, Epidemiology, and End Results (SEER) and Medicare databases. Women with a new primary diagnosis of cervical cancer between January 2007 and December 2013 were followed until December 2014.

Survival, Chemotherapy Treatments, and Health Care Utilization Among Patients with Advanced Small Cell Lung Cancer: An Observational Study.

Introduction: Most cases of small cell lung cancer (SCLC) are diagnosed at an advanced stage. The objective of this study was to investigate patient characteristics, survival, chemotherapy treatments, and health care use after a diagnosis of advanced SCLC in subjects enrolled in a health system network.

Methods: This was a retrospective cohort study of patients aged ≥ 18 years who either were diagnosed with stage III/IV SCLC or who progressed to advanced SCLC during the study period (2005-2015).

Chemotherapy treatments, costs of care, and survival for patients diagnosed with small cell lung cancer: A SEER-Medicare study.

Objectives: The effectiveness and costs of new treatments should be assessed in relation to existing practice. We describe treatments, survival and costs for advanced or metastatic small cell lung cancer (SCLC) patients receiving systemic therapy in the period preceding the introduction of immunotherapies.

Materials And Methods: This was a retrospective cohort study of patients aged ≥65 years, identified using linked Surveillance, Epidemiology, and End Results and Medicare databases.

Treatment patterns, health care resource utilization, and costs in patients with relapsed/refractory Hodgkin lymphoma treated with brentuximab vedotin.

Data are limited on the real-world utilization and costs of brentuximab vedotin (BV) among patients with relapsed/refractory Hodgkin lymphoma (rrHL) in the United States. A total of 219 BV patients identified from the Truven MarketScan databases were followed up for a median of 2.9 years before and 1.

A quantitative and efficient approach to select MIRU-VNTR loci based on accumulation of the percentage differences of strains for discriminating divergent Mycobacterium tuberculosis sublineages.

Although several optimal mycobacterial interspersed repetitive units-variable number tandem repeat (MIRU-VNTR) loci have been suggested for genotyping homogenous Mycobacterium tuberculosis, including the Beijing genotype, a more efficient and convenient selection strategy for identifying optimal VNTR loci is needed. Here 281 M. tuberculosis isolates were analyzed.

Persistently high prevalence of primary resistance and multidrug resistance of tuberculosis in Heilongjiang Province, China.

Background: The spread of multidrug-resistant tuberculosis (MDR-TB) Mycobacterium tuberculosis (M. tuberculosis) strains has been a big challenge to the TB control and prevention in China. Knowledge about patterns of drug resistance in TB high-burden areas of China is crucial to develop appropriate control strategies.

Genetic heterogeneity of pseudoxanthoma elasticum: the Chinese signature profile of ABCC6 and ENPP1 mutations.

Pseudoxanthoma elasticum (PXE), an autosomal recessive disorder characterized by ectopic mineralization, is caused by mutations in the ABCC6 gene. We examined clinically 29 Chinese PXE patients from unrelated families, so far the largest cohort of Asian PXE patients. In a subset of 22 patients, we sequenced ABCC6 and another candidate gene, ENPP1, and conducted pathogenicity analyses for each variant.

Premature termination codon read-through in the ABCC6 gene: potential treatment for pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder manifesting with ectopic connective tissue mineralization, caused by mutations in the ABCC6 gene, with ~35% of all mutations being premature termination mutations. In this study, we investigated the therapeutic potential of the nonsense codon read-through-inducing drug, PTC124, in treating PXE. The ability of this drug to facilitate read-through of nonsense mutations was examined in HEK293 cells transfected with human ABCC6 expression constructs harboring seven different PXE-associated nonsense mutations, and was evaluated by immunofluorescence and In-Cell ELISA.

Type I signal peptidase and protein secretion in Staphylococcus aureus.

Staphylococcus aureus is an important human pathogen whose virulence relies on the secretion of many different proteins. In general, the secretion of most proteins in S. aureus, as well as other bacteria, is dependent on the type I signal peptidase (SPase)-mediated cleavage of the N-terminal signal peptide that targets a protein to the general secretory pathway.

Chemotherapeutic sensitization of leptomycin B resistant lung cancer cells by pretreatment with doxorubicin.

The development of novel targeted therapies has become an important research focus for lung cancer treatment. Our previous study has shown leptomycin B (LMB) significantly inhibited proliferation of lung cancer cells; however, p53 wild type lung cancer cells were resistant to LMB. Therefore, the objective of this study was to develop and evaluate a novel therapeutic strategy to sensitize LMB-resistant lung cancer cells by combining LMB and doxorubicin (DOX).

CRM1-dependent p53 nuclear accumulation in lung lesions of a bitransgenic mouse lung tumor model.

The p53 tumor suppressor gene plays an essential role in tumorigenesis, and the chromosomal region maintenance 1 (CRM1) has been suggested to export p53 protein from the nucleus to the cytoplasm. The objectives of the present study were to evaluate p53 expression and subcellular localization as well as CRM1 expression using immunohistochemistry in our established bitransgenic mouse lung tumor model. In this model, expression of the mutant human Ki-rasG12C allele was regulated in a doxycycline (DOX)-inducible, lung-specific manner.