Application of fused-grid-based CYP-Template systems for genotoxic substances to understand the metabolisms.

Understanding of metabolic processes is a key factor to evaluate biological effects of carcinogen and mutagens. Applicability of fused-grid Template* systems of CYP enzymes (Drug Metab Pharmacokinet 2019, 2020, 2021, and 2022) was tested for three phenomena. (1) Possible causal relationships between CYP-mediated metabolisms of β-naphthoflavone and 3-methylcholanthrene and the high inducibility of CYP enzymes were examined.

Definitive radiotherapy consisting of external beam radiotherapy without central shielding and 3D image-guided brachytherapy for patients with cervical cancer: feasibility for Japanese patients and dose-response analyses for local control in the low-dose range.

Objective: To assess the feasibility of external beam radiotherapy without central shielding in definitive radiotherapy for Japanese patients with cervical cancer.

Methods: We retrospectively analysed the data of cervical cancer patients treated with definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy.

Results: The study included 167 patients (T1 + 2 = 108, T3 + 4 = 59) from eight Japanese institutions.

Hemodynamic Variability During Drainage of Large Volumes of Malignant Ascites in Patients With Cancer.

This study compared the variability in mean arterial pressure (MAP) during drainage of ascites in patients with cancer who underwent drainage of a large (5-10 L) or small (<5 L) volume of ascites. We prospectively enrolled 50 patients scheduled for cell-free and concentrated ascites reinfusion therapy. Equivalence was considered to be established if the 95% confidence interval (95% CI) for the highest variability rate of MAP was within ±20%.

Preliminary results of reduced myocardial blood flow in the subacute phase after radiation therapy for thoracic esophageal cancer: A quantitative analysis with stress dynamic myocardial computed tomography perfusion imaging.

Background And Purpose: Late adverse cardiac events after radiation therapy (RT) for thoracic malignancies are known, but the underlying mechanisms are poorly understood. This study aimed to determine the radiation dose that can cause MBF alterations in the subacute phase after RT for thoracic esophageal cancer using stress dynamic myocardial computed tomography perfusion imaging (CTP).

Materials And Methods: Twenty-five patients with esophageal cancer scheduled for RT were prospectively enrolled.

Formation and evaluation of mechanism-based chemical categories for regulatory read-across assessment of repeated-dose toxicity: A case of hemolytic anemia.

The aim of this study is to define chemical categories that can be applied to regulatory read-across assessments for repeated-dose toxicity, by classifying toxic substances based on their structures and mechanism of actions (MoAs). Hemolytic anemia, which often appears primarily, was examined as an example. An integrated database was constructed by collecting publicly available datasets on repeated-dose toxicity, in which 423 out of a total of 1518 chemicals were identified as capable of inducing hemolytic anemia.

Combined Risk Assessment of Food-derived Coumarin with Approaches.

Hepatotoxicity associated with food-derived coumarin occurs occasionally in humans. We have, herein, assessed the data of existing clinical and nonclinical studies as well as those of models for humans in order to shed more light on this association. The average intakes of food-derived coumarin are estimated to be 1-3 mg/day, while a ten-times higher level is expected in the worst-case scenarios.

Automated preparation of washed platelet concentrates through spinning-membrane filtration.

Background: Washed platelet concentrates (WPC), prepared with an automated system cell processor (ACP), have recently been approved to be manufactured and marketed in Japan. From the perspective of risk management, it is preferable to secure alternative technologies for ACP. Here, we conducted a study to evaluate the quality of WPC prepared using an automated membrane filtration-based system, Lovo.

Intra-arterial chemoradiotherapy for locally advanced buccal mucosal cancer in an elderly patient with multiple comorbidities: A case report.

Background: The management of locally advanced oral cavity squamous cell carcinoma (LA-OCScc) in elderly patients with multiple comorbidities is difficult.

Case: We report the case of an elderly patient with buccal mucosal squamous cell carcinoma as well as chronic renal dysfunction, hepatic cirrhosis, rheumatoid arthritis, and metachronous diffuse large B-cell lymphoma. We performed radiation therapy (a total dose of 70 Gy in 35 fractions) and six cycles of intra-arterial chemotherapy with 40 mg/m cisplatin per week.

Constructing a developmental and reproductive toxicity database of chemicals (DART NIHS DB) for integrated approaches to testing and assessment.

Developmental and reproductive toxicity (DART) is an important endpoint, and databases (DBs) are essential for evaluating the risk of untested substances using alternative methods. We have constructed a reliable and transparent DART DB, which we named DART NIHS DB, using the publicly available datasets of DART studies of industrial chemicals conducted by Japanese government ministries in accordance with the corresponding OECD test guidelines (OECD TG421 and TG422). This DB is unique because its dataset chemicals have little overlap with those of ToxRefDB, which compiles large-scale DART data, and it is reliable because the included datasets were created after reviewing the individual study reports.

Endobronchial brachytherapy combined with surgical procedure for synchronous multiple primary lung cancer: A case report.

The management of synchronous multiple primary lung cancer is a challenge. In this report, we describe our experience in a patient with three synchronous multiple cancers. The first lesion was completely surgically removed, the second lesion received postoperative irradiation, and the third lesion was treated with radiotherapy alone.

Early alteration in apparent diffusion coefficient and tumor volume in cervical cancer treated with chemoradiotherapy or radiotherapy: Incremental prognostic value over pretreatment assessments.

Purpose: Our study aimed to evaluate a prognostic value of early changes in apparent diffusion coefficients (ADC) and tumor volume during treatment in patients with cervical cancer treated with chemoradiotherapy or radiotherapy, and to assess whether the early changes provided an incremental value to pre-treatment ADC and tumor volume in predicting disease recurrences.

Methods And Materials: A total of 103 patients with stage IB-IVA cervical cancer including 76 (74%) patients with stage ≥IIIA who underwent magnetic resonance imaging before and during (25 ± 4.6 days after start) the treatment were enrolled.

Long-term follow-up of intensive chemotherapy followed by reduced-dose and reduced-field irradiation for intracranial germ cell tumor.

OBJECTIVE The authors analyzed the efficacy of intensive chemotherapy followed by reduced-dose and reduced-field irradiation for intracranial germ cell tumors (GCTs) and evaluated the long-term late effects caused by chemoradiotherapy (CRT). METHODS The authors performed a retrospective study. The subjects were 24 patients who received CRT between April 1994 and April 2015.

Initial hazard assessment of benzyl salicylate: In vitro genotoxicity test and combined repeated-dose and reproductive/developmental toxicity screening test in rats.

Benzyl salicylate is used as a fragrance ingredient and an ultraviolet light absorber, but its toxicity is unknown. Therefore, toxicity tests and hazard classification were conducted for screening assessment under the Japanese Chemical Substances Control Law. Benzyl salicylate was found to be non-genotoxic in vitro based on the chromosomal aberration test using Chinese hamster lung cells.

In silico prediction of chromosome damage: comparison of three (Q)SAR models.

Two major endpoints for genotoxicity tests are gene mutation and chromosome damage (CD), which includes clastogenicity and aneugenicity detected by chromosomal aberration (CA) test or micronucleus (MN) test. Many in silico prediction systems for bacterial mutagenicity (i.e.

Initial hazard assessment of 4-benzylphenol, a structural analog of bisphenol F: Genotoxicity tests in vitro and a 28-day repeated-dose toxicity study in rats.

4-Benzylphenol (CAS No. 101-53-1), a structural analog of bisphenol F, has estrogenic activity in vitro and in vivo, as is the case with bisphenol F. 4-Benzylphenol is used in plastics and during organic synthesis.

Endobronchial brachytherapy with curative intent: the impact of reference points setting according to the bronchial diameter.

Endobronchial brachytherapy (EBB) is an effective treatment for endobronchial tumors. However, bronchial toxicity caused by over-irradiation remains problematic. To decrease bronchial toxicity, we developed a source-centralizing applicator for EBB.

A Novel External Carotid Arterial Sheath System for Intra-arterial Infusion Chemotherapy of Head and Neck Cancer.

Purpose: The purpose of this study was to describe a novel system for treating advanced head and neck cancer consisting of an external carotid arterial sheath (ECAS) and a microcatheter to inject drugs retrogradely into multiple feeding arteries through the superficial temporal artery (STA).

Materials And Methods: Four consecutive patients with head and neck cancer that had more than one feeding artery were enrolled in this study. The ECAS was made of polyurethane and surface-coated with heparin resin to prevent thrombus formation, allowing it to remain in place for a prolonged period of time.

The impact of epidermal growth factor receptor mutations on patterns of disease recurrence after chemoradiotherapy for locally advanced non-small cell lung cancer: a literature review and pooled analysis.

The purpose of this review was to evaluate the impact of epidermal growth factor receptor (EGFR) mutation status on disease recurrence in patients treated with chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (NSCLC). A literature search was conducted and a total of three studies were analyzed. There was no significant difference in the objective response rate between the EGFR mutation group and the EGFR wild-type group (odds ratios [OR] 1.

Multimodality Treatment for Patients with Node-Positive Prostate Cancer: the Role of Radiation Therapy.

Prostate cancer is the secondary most frequently diagnosed cancer in the world. Although numerous prospective randomized trial have been conducted to guide the management of patients with localized or locally advanced prostate cancer, few clinical trials targeting node-positive prostate cancer have been reported. Therefore, there are still controversies in the optimal management of node-positive prostate cancer.

Roles of Valproic Acid in Improving Radiation Therapy for Glioblastoma: a Review of Literature Focusing on Clinical Evidence.

Glioblastoma (GBM) is the most common and aggressive type of primary brain neoplasm. The current standard therapy for GBM consists of maximal surgical resection within safe limits, followed by radiation therapy (RT) and chemotherapy with temozolomide. Despite advances in treatment, the prognosis of GBM remains poor.

Radiation-induced organizing pneumonia after stereotactic body radiotherapy for lung tumor.

The aim of this retrospective study was to investigate characteristics of organizing pneumonia (OP) after stereotactic body radiotherapy (SBRT) for lung tumor. Between September 2010 and June 2014, patients who were diagnosed as Stage I lung cancer and treated with SBRT at our institution were included in this study. A total of 78 patients (47 males with a median age of 80 years) were analyzed.

An antioxidant, N,N'-diphenyl-p-phenylenediamine (DPPD), affects labor and delivery in rats: a 28-day repeated dose test and reproduction/developmental toxicity test.

A 28-day repeated dose toxicity test and reproduction/developmental toxicity test for N,N'-diphenyl-p-phenylenediamine (DPPD) were conducted in [Crl:CD(SD)] SPF rats. Male and female rats were dosed with DPPD by gavage for 28 days at 0, 100, 300, or 1000 mg/kg bw/day or for a total of 42-46 days at 0, 8, 50, or 300 mg/kg bw/day. No significant adverse effects were observed in the repeated dose toxicity study up to 1000 mg/kg bw/day in both sexes.

[Toxicity effects of phthalate substitute plasticizers used in toys].

Phthalate esters are widely used as plasticizers in polyvinyl chloride products. Because of human health concerns, regulatory authorities in Japan, US, Europe and other countries control the use of di(2-ethylhexyl) phthalate, diisononyl phthalate, di-n-butyl phthalate, butylbenzyl phthalate, diisodecyl phthalate and di-n-octyl phthalate for the toys that can be put directly in infants' mouths. While these regulatory actions will likely reduce the usage of phthalate esters, there is concern that other plasticizers that have not been sufficiently evaluated for safety will be used more frequently.