Observational study of the efficacy and safety of first-line osimertinib and later treatments for uncommon epidermal growth factor receptor-activating mutation-positive advanced non-small cell lung cancer.

Introduction: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is a first-line therapy for advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR mutations, including both sensitizing and T790M resistance mutations. Its real-world efficacy against uncommon EGFR mutations remains under-researched.

Methods: The REIWA study, a multicentric, prospective, observational study conducted in Japan from September 2018 to August 2020, enrolled patients with advanced or recurrent EGFR mutation-positive NSCLC receiving osimertinib.

Clinical outcomes of patients with EGFR-mutated NSCLC developing interstitial lung disease during first-line osimertinib therapy: a sub-analysis of the Reiwa study.

Introduction: Osimertinib-induced interstitial lung disease in untreated EGFR-mutated, advanced non-small cell lung cancer is being reported at a higher rate in Japan than elsewhere. However, data on the interstitial lung disease incidence during first-line osimertinib therapy and the course of lung cancer treatments administered after interstitial lung disease onset in the real-world setting are scarce.

Materials And Methods: The present study reviewed the data from the Reiwa study, a multicentric, observational study examining the efficacy and safety of first-line osimertinib therapy in the clinical setting.

Outcome of osimertinib-treated patients with epidermal growth factor receptor mutation-positive nonsmall cell lung cancer requiring dose reduction: a secondary analysis of the Reiwa study.

Background: Osimertinib is effective in patients with epidermal growth factor receptor (EGFR) mutation-positive nonsmall cell lung cancer (NSCLC). However, some patients require osimertinib dose reduction because of adverse events. This study assessed the characteristics of osimertinib dose reduction and compared the efficacies of reduced-dose and regular-dose osimertinib.

Real-World Study of EGFR-TKI Rechallenge With Another TKI After First-Line Osimertinib Discontinuation in Patients With EGFR-Mutated Non-Small Cell Lung Cancer: A Subset Analysis of the Reiwa Study.

Introduction: First-line osimertinib is widely used to treat patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancers (NSCLC). In clinical practice, rechallenge therapy with another EGFR-tyrosine kinase inhibitor (TKI) is often performed after first-line TKI discontinuation owing to resistance or toxicity; however, the efficacy and toxicity of EGFR-TKI rechallenge after first-line osimertinib have not been adequately investigated. This study aimed to examine the efficacy and safety of EGFR-TKI rechallenge with another TKI.

Difference in efficacy of osimertinib between patients with EGFR-positive NSCLC with postoperative recurrence and those with de novo unresectable disease: A prospective, observational study.

Background: Although clinical trials of systemic chemotherapy for advanced non-small-cell lung cancer (NSCLC) have included both postoperative recurrence and de novo unresectable cases, postoperative recurrence is reported to have a better efficacy and prognosis. However, there are no efficacy data of first-line osimertinib for postoperative recurrence.

Methods: We conducted a post hoc analysis of a multicenter, prospective, observational study that evaluated the efficacy of first-line osimertinib in patients with epidermal growth factor receptor (EGFR)-positive NSCLC.

Involvement of Mediterranean fever gene mutations in colchicine-responsive enterocolitis: a retrospective cohort study.

Background: The involvement of Mediterranean fever (MEFV) gene mutations in patients with inflammatory bowel disease unclassified (IBDU) remains unclear. This study aimed to determine the clinical characteristics and responsiveness to colchicine in Japanese patients with IBDU carrying MEFV mutations.

Methods: In this retrospective cohort study, we examined MEFV mutations using gene analysis, clinical information, and colchicine responsiveness.

Chemical-induced lung tumor in Tg-rasH2 mice: a novel mouse tumor model to assess immune checkpoint inhibitors combined with a chemotherapy drug.

In subcutaneous tumor models, changes in the tumor microenvironment can lead to differences in therapeutic treatment responses between the subcutaneous and parent tumors. Accordingly, we generated a lung carcinogenesis model that combines genetically modified mice (Tg-rasH2 mice) with two-stage chemical carcinogenesis as an alternative to the subcutaneous tumor model. In this model, Tg-rasH2 mice were treated with 1-ethyl-1-nitrosourea, followed by butylhydroxytoluene.

Effects of administering different vehicles via single intratracheal instillation on responses in the lung and pleural cavity of Crl:CD(SD) rats.

Intratracheal instillation is the introduction of a substance directly into the trachea. Intratracheal instillation has been used to investigate the lung toxicity of several chemicals and requires the suspension or dissolution of test material in a vehicle for even dispersal throughout the lung. Importantly, the toxicities of vehicles used in intratracheal instillation studies are generally considered to be insignificant.

Sonodynamic Therapy With Anticancer Micelles and High-Intensity Focused Ultrasound in Treatment of Canine Cancer.

Sonodynamic therapy (SDT) is a minimally invasive anticancer therapy involving a chemical sonosensitizer and high-intensity focused ultrasound (HIFU). SDT enables the reduction of drug dose and HIFU irradiation power compared to those of conventional monotherapies. In our previous study, mouse models of colon and pancreatic cancer were used to confirm the effectiveness of SDT vs.

Improving computational accuracy in dissipative particle dynamics via a high order symplectic method.

This study was focused on improving the numerical accuracy of the dissipative particle dynamics simulation via modifying its numerical time integration scheme. Despite the integration of the pairwise Langevin part dealt with by most of the previous studies, we paid attention to the improvement of the standard Liouville part. The numerical accuracy was measured by the configurational temperature in this study.

Lung Tumor Induction by 26-week Dermal Application of 1,2-Dichloroethane in CB6F1-Tg rasH2 Mice.

Short-term alternatives to traditional 2-year carcinogenic studies in rodents are being actively pursued. Recently, a 26-week short-term carcinogenicity study using CB6F1-Tg rasH2@Jcl (rasH2) mice has become a worldwide standard for the evaluation of chemical carcinogenesis. However, an acceptable short-term carcinogenic study model for dermally applied products is still lacking.

Synthetic aperture ultrasound imaging with a ring transducer array: preliminary ex vivo results.

Purpose: The conventional medical ultrasound imaging has a low lateral spatial resolution, and the image quality depends on the depth of the imaging location. To overcome these problems, this study presents a synthetic aperture (SA) ultrasound imaging method using a ring transducer array.

Methods: An experimental ring transducer array imaging system was constructed.

Promotion of liver and kidney carcinogenesis by ethyl tertiary-butyl ether (ETBE) in male Wistar rats.

Tumor-promoting effects of ethyl tertiary-butyl ether (ETBE) were investigated in a 2-stage carcinogenesis bioassay with regard to hepatic and renal carcinogenesis in rats. Male 6-week-old Wistar rats were given drinking water containing N-ethyl-N-(2-hydroxyethyl)nitrosamine (EHEN), as an initiator, at a dose of 500 ppm for 2 weeks. Starting one week thereafter, the animals were administered ETBE at dose levels of 0 (control), 100, 300, 500 or 1,000 mg/kg/day by gavage for 19 weeks from week 4 to 22.

Lack of Hepatocarcinogenicity of Combinations of Low Doses of 2-amino-3, 8-dimethylimidazo[4,5- f ]quinoxaline and Diethylnitrosamine in Rats: Indication for the Existence of a Threshold for Genotoxic Carcinogens.

The purposes of the present study were to evaluate the hepatocarcinogenicity of concurrent treatment of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and diethylnitrosamine (DEN) in rats and to determine whether no effect levels of combinations of these two different structural categories of genotoxic hepatocarcinogens exist. Two 16-week rat hepatocarcinogenesis assays were performed using a total of 790 male F344 rats. In experiment 1, we evaluated the effects of concurrent treatment of a subcarcinogenic dose of DEN on rat hepatocarcinogenesis induced by various doses of MeIQx.

Arachidonate-enriched triglyceride oil does not promote tumor development in a rat medium-term multi-organ carcinogenesis model.

The modifying potential on tumor development of arachidonate-enriched triglyceride oil (ARA-oil) containing approximately 40% arachidonic acid was investigated in a medium-term multi-organ carcinogenesis bioassay using male and female F344 rats. The animals were sequentially given five carcinogens with different target sites in the first 4 weeks, and then administered ARA-oil for 24 weeks at dietary levels of 0% (control), 1.25%, 2.

Concordance between Results of Medium-term Liver Carcinogenesis Bioassays and Long-term Findings for Carcinogenic 2-Nitropropane and Non-carcinogenic1-Nitropropane in F344 Rats.

This study was conducted to determine the concordance of results for a pair of structural isomers, 2-nitropropane (2-NP) and 1-nitropropane (1-NP), using the rat medium-term liver carcinogenesis bioassay (Ito test) and previously published long-term carcinogenicity tests. Male F344 rats were given a single intraperitoneal injection of DEN (200 mg/kg b.w.

Medium-term multi-organ carcinogenesis bioassay of ethyl tertiary-butyl ether in rats.

The modifying potential of ethyl tertiary-butyl ether (ETBE) on tumor development was investigated in a medium-term multi-organ carcinogenesis bioassay using male F344 rats. Animals were sequentially given 5 carcinogens with different target sites in the first 4 weeks for multi-organ initiation. After one week they received ETBE by gavage at dose levels of 0 (control), 300 or 1000mg/kg/day until experimental week 28.

Ninety-day oral toxicity study of rhamsan gum, a natural food thickener produced from Sphingomonas ATCC 31961, in Crl:CD(SD)IGS rats.

This study was designed to evaluate and characterize any subchronic toxicity of rhamsan gum, a polysaccharide produced from Sphingomonas strain ATCC 31961, when administered to both sexes of Crl:CD(SD)IGS rats at dietary levels of 0 (control), 0.5, 1.5, and 5.

Carcinogenesis risk assessment of chemicals using medium-term carcinogenesis bioassays.

There is a pressing need for medium term models as alternatives for two year testing of environmental compounds for carcinogenicity and toxicity. Optimally these should be of short duration in vivo, readily performed in the laboratory without the need for specialist equipment, be based on a priori reasoning and scientific principles and use effective surrogates for malignancies. The two models developed in DIMS Institute of Medical Science, the medium-term liver carcinogenesis bioassay and the medium-term multi-organ carcinogenesis bioassay, fulfil these criteria and have the massive advantage of already being used for testing of large numbers of agents.

A 28-day oral toxicity study of fermentation-derived cellulose, produced by Acetobacter aceti subspecies xylinum, in F344 rats.

This study was designed to evaluate any adverse effect of fermentation-derived cellulose, produced by Acetobacter aceti subspecies xylinum, when administered to both sexes of F344 rats at dietary levels of 0, 1.25, 2.5, and 5.

Lack of adverse effects of whole-body exposure to a mobile telecommunication electromagnetic field on the rat fetus.

Abstract The recent steep increase in the number of users of cellular phones is resulting in marked increase of exposure of humans to radiofrequency electromagnetic fields (EMFs). Children are of particular concern. Our goal was to evaluate potential adverse effects of long-term whole-body exposure to EMFs simulating those from base stations for cellular phone communication.

Involvement of macrophage inflammatory protein 1alpha (MIP1alpha) in promotion of rat lung and mammary carcinogenic activity of nanoscale titanium dioxide particles administered by intra-pulmonary spraying.

Titanium dioxide (TiO(2)) is evaluated by World Health Organization/International Agency for Research on Cancer as a Group 2B carcinogen. The present study was conducted to detect carcinogenic activity of nanoscale TiO(2) administered by a novel intrapulmonary spraying (IPS)-initiation-promotion protocol in the rat lung. Female human c-Ha-ras proto-oncogene transgenic rat (Hras128) transgenic rats were treated first with N-nitrosobis(2-hydroxypropyl)amine (DHPN) in the drinking water and then with TiO(2) (rutile type, mean diameter 20 nm, without coating) by IPS.

A twenty eight-day repeated dose toxicity study of black soybean extract in Sprague-Dawley rats.

This study was designed to evaluate any adverse effect of a hot water extract of black soybeans (Glycine max (L.) Merr.), when administered to both sexes of Crj:CD(SD)IGS rats at dietary levels of 0 (control), 0.

A medium-term, rapid rat bioassay model for the detection of carcinogenic potential of chemicals.

The Ito Liver Model and the Ito Multi-organ Model are used in conjunction and constitute an efficient and rapid bioassay for the identification of both genotoxic and nongenotoxic carcinogenic chemicals. The Ito Liver Model is an 8-week bioassay system that uses the number and size of foci of hepatocytes positive for glutathione S-transferase placental form (GST-P) as the end-point marker. One hundred fifty-nine compounds were tested using the Ito Liver Model: 61 of 66 hepatocarcinogens tested positive, and 10 of 43 nonliver carcinogens were also positive.