Stage-Specific Guideline Concordant Treatment Impacts on Survival in Nonsmall Cell Lung Cancer: A Novel Quality Indicator.

Background: Lung cancer in Australia contributes 9% of all new cancer diagnoses and is the leading cause of cancer death and burden. Clinical practice guidelines provide evidence-based treatment recommendations for best practice management. We aimed to determine the extent of delivery of guideline-concordant treatment (GCT) and to identify modifiable variables influencing receipt of GCT and survival.

BRCA1 secondary splice-site mutations drive exon-skipping and PARP inhibitor resistance.

PARP inhibitor (PARPi) therapy has transformed outcomes for patients with homologous recombination DNA repair (HRR) deficient ovarian cancers, for example those with BRCA1 or BRCA2 gene defects. Unfortunately, PARPi resistance is common. Multiple resistance mechanisms have been described, including secondary mutations that restore the HR gene reading frame.

Patterns of care for people with small cell lung cancer in Victoria, 2011-19: a retrospective, population-based registry data study.

Objectives: To report stage-specific patterns of treatment and the influence of management and treatment type on survival rates for people newly diagnosed with small cell lung cancer (SCLC).

Design: Cross-sectional patterns of care study; analysis of data prospectively collected for the Victorian Lung Cancer Registry (VLCR).

Setting, Participants: All people diagnosed with SCLC in Victoria during 1 April 2011 - 18 December 2019.

Targeting homologous recombination deficiency in uterine leiomyosarcoma.

Background: Uterine leiomyosarcoma (uLMS) is a rare and aggressive gynaecological malignancy, with individuals with advanced uLMS having a five-year survival of < 10%. Mutations in the homologous recombination (HR) DNA repair pathway have been observed in ~ 10% of uLMS cases, with reports of some individuals benefiting from poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) therapy, which targets this DNA repair defect. In this report, we screened individuals with uLMS, accrued nationally, for mutations in the HR repair pathway and explored new approaches to therapeutic targeting.

secondary splice-site mutations drive exon-skipping and PARP inhibitor resistance.

splice isoforms Δ11 and Δ11q can contribute to PARP inhibitor (PARPi) resistance by splicing-out the mutation-containing exon, producing truncated, partially-functional proteins. However, the clinical impact and underlying drivers of exon skipping remain undetermined. We analyzed nine ovarian and breast cancer patient derived xenografts (PDX) with exon 11 frameshift mutations for exon skipping and therapy response, including a matched PDX pair derived from a patient pre- and post-chemotherapy/PARPi.

Acquired Promoter Methylation Loss Causes PARP Inhibitor Resistance in High-Grade Serous Ovarian Carcinoma.

In high-grade serous ovarian carcinoma (HGSC), deleterious mutations in DNA repair gene are established drivers of defective homologous recombination and are emerging biomarkers of PARP inhibitor (PARPi) sensitivity. promoter methylation (me) is detected at similar frequencies to mutations, yet its effects on PARPi responses remain unresolved.In this study, three HGSC patient-derived xenograft (PDX) models with methylation at most or all examined CpG sites in the promoter show responses to PARPi.

Monoclonal antibody therapy in cancer: When two is better (and considerably more expensive) than one.

What Is Known And Objective: It is 20 years since the US Food and Drug Administration approved the first successful monoclonal anticancer antibody, trastuzumab. The therapeutic utility of monoclonal antibodies in cancer is often limited by partial clinical responses and the development of tumour resistance. An expanding strategy, to be reviewed here, to overcome the limited response and resistance to monotherapy utilizes concurrent treatment with two synergistic monoclonal antibodies.

The Effect of Undaria pinnatifida Fucoidan on the Pharmacokinetics of Letrozole and Tamoxifen in Patients With Breast Cancer.

Background: Although the use of complementary and alternative medicines is widespread in cancer patients, clinical evidence of their benefits is sparse. Furthermore, while they are often assumed to be safe with regard to concurrent use of anticancer therapies, few studies have been carried out to investigate possible interactions. Fucoidans are a group of sulfated carbohydrates, derived from marine brown algae, which have long been used as dietary supplements due to their reported medicinal properties, including anticancer activity.

Characteristics of cancer diagnoses and staging in South Western Victoria: a rural perspective.

Objective: Australian states and territories have legislation mandating reporting of cancer diagnoses; however, tumour stage at diagnosis, treatment plan and associated outcomes are not routinely recorded in cancer registries for all tumour types. This study describes the Evaluation of Cancer Outcomes study that collects detailed information for patients diagnosed with cancer in south-western Victoria.

Design: Retrospective data collection.

Investigation of herb-drug interactions with ginkgo biloba in women receiving hormonal treatment for early breast cancer.

Women receiving treatment for breast cancer commonly ingest herbal medicines. Little is known about the potential for herb-drug interactions in this population. The aim of this study is to investigate the effect of ginkgo biloba co-administration on the pharmacokinetics of tamoxifen, anastrozole and letrozole.

Differentiation of the virulence potential of Campylobacter jejuni strains by use of gene transcription analysis and a Caco-2 assay.

Campylobacter jejuni is the leading cause of bacterial diarrheal disease in humans, and contaminated poultry and poultry products are recognized as the main vehicle of infection. Despite the significance of C. jejuni as a foodborne pathogen, little is known about its response to stress, and, especially, how its virulence is modulated under such conditions.

Relative gene transcription and pathogenicity of enterohemorrhagic Escherichia coli after long-term adaptation to acid and salt stress.

Relative gene transcription and virulence potential, as measured by a Caco-2 adhesion assay, were investigated for three enterohemorrhagic Escherichia coli (EHEC) strains after long-term adaptation for 24h to acid (BHI pH 5.5) and salt (BHI 4.5% (w/v) NaCl) stress.

Relative transcription of Listeria monocytogenes virulence genes in liver pâtés with varying NaCl content.

Quantitative real time polymerase chain reaction (qRT PCR) was used to compare the relative transcription of prfA, inlA, sigB and clpC for three Listeria monocytogenes strains after incubation in i) a standard liver pâté versus brain heart infusion (BHI) broth and ii) the standard liver pâté versus three liver pâtés with reduced NaCl content of which one also has been supplied with organic acids (Ca-acetate and Ca-lactate). The three strains (EGD-e: reference strain; O57: more NaCl sensitive; 6896: more NaCl tolerant) were selected out of twelve strains based on their growth in BHI broth adjusted to 6%, 8%, 10% (w/v) NaCl. The three strains were spiked into the liver pâtés (10(9) cfu/g) and the BHI (10(9) cfu/ml) and incubated for 48 h at 7 degrees C; all incubation conditions supported growth of the strains.

Survival of Listeria monocytogenes in simulated gastrointestinal system and transcriptional profiling of stress- and adhesion-related genes.

Food ingestion is the major route of exposure to the important human pathogen Listeria monocytogenes. An in vitro gastrointestinal model was used to (1) compare the survival rates of L. monocytogenes strains of serotypes 1/2a, 1/2c, and 4b; and (2) examine the transcription of stress- and adhesion-related genes after exposure to the conditions similar to those encountered in the mouth, stomach, and small intestine.

Gene transcription and virulence potential of Listeria monocytogenes strains after exposure to acidic and NaCl stress.

Gene transcription and virulence potential of two strains of Listeria monocytogenes, EGD-e and 4140, were compared by quantitative real-time polymerase chain reaction and in a Caco-2 in vitro model after exposure to acidic (pH 5.5) and NaCl (4.5% w/v) stress.

beta-Lactamases among extended-spectrum beta-lactamase (ESBL)-resistant Salmonella from poultry, poultry products and human patients in The Netherlands.

Objectives: The purpose of this work was to study the genetic determinants responsible for extended-spectrum beta-lactamase (ESBL) resistance of Salmonella isolated from Dutch poultry, poultry meat and hospitalized humans.

Methods: Thirty-four ESBL-resistant Salmonella isolates from The Netherlands were tested towards 21 antimicrobial agents. PCR and sequencing were used to determine the underlying genetic determinants responsible for the ESBL phenotypes.

Prevalence of beta-lactamases among ampicillin-resistant Escherichia coli and Salmonella isolated from food animals in Denmark.

The genetic background for beta-lactamase-mediated resistance to beta-lactam antibiotics was examined by PCR and sequencing in 160 ampicillin-resistant isolates (109 Escherichia coli and 51 Salmonella) obtained from healthy and diseased food animals in Denmark. Sequencing revealed three different variants of bla (TEM-1), of which bla (TEM-1b) was the most frequently detected (80 E. coli and 47 Salmonella), followed by bla (TEM-1a) (eight E.

Predictors of the accuracy of self-reported height and weight in adolescent female school students.

Objective: The authors investigated predictors of the accuracy of self-reported values of body weight and height in adolescent females.

Method: Self-reported and measured weight and height values were obtained for 683 school students aged 11-18 years. Predictors of accuracy were determined for self-reported weight, height, and body mass index (BMI; based on self-reported values).