An Intratracheal Instillation Bioassay System for Detection of Lung Toxicity Due to Fine Particles in F344 Rats

It is an urgent priority to establish in vivo bioassays for detection of hazards related to fine particles, which can be inhaled into deep lung tissue by humans. In order to establish an appropriate bioassay for detection of lung damage after particle inhalation, several experiments were performed in rats using quartz as a typical lung toxic particle. The results of pilot experiments suggest that Days 1 and 28 after intratracheal instillation of 2 mg of fine test particles in vehicle are most appropriate for detection of acute and subacute inflammatory changes, respectively. Furthermore, the BrdU incorporation on Day 1 and the iNOS level on Day 28 proved to be suitable end-point markers for this purpose. An examination of the toxicity of a series of particles was performed with the developed bioassay. Although some materials, including nanoparticles, demonstrated toxicity that was too strong for sensitive assessment, a ranking order could be clarified. The bioassay thus appears suitable for rapid hazard identification with a possible ranking of the toxicity of various particles at single concentrations

Positive Therapeutic Response to Bevacizumab Plus Paclitaxel in a Patient with Advanced, Life-Threatening Breast Cancer and Carcinomatous Lymphangitis:a Subsequent Treatment Change to Hormone Therapy

We present a case of advanced, life-threatening breast cancer with carcinomatous lymphangitis treatedwith bevacizumab plus paclitaxel. A positive therapeutic response was achieved and the treatment was subsequentlychanged to hormone therapy.The patient was a 53-year-old postmenopausal woman with a non-contributory medical history. She presentedto a nearby hospital with chief complaints of continued exertional dyspnea and coughing since March2012. Physical findings included a palpable mass in the left breast, and the patient was referred and presentedto our hospital in May. Examinations at our hospital revealed left-sided breast cancer (estrogen receptorpositive, progesterone receptor positive, and no amplification of the human epidermal growth factorreceptor 2 by FISH). The patient had bone metastasis and carcinomatous lymphangitis (cT2N3cM1-stageIV). The condition was life threatening, and administration of bevacizumab plus weekly paclitaxel was initiatedwith the expectation of a high response rate. Coughing and dyspnea resolved two weeks later. CTscans were taken in August after the completion of 3 cycles and showed improvement in carcinomatouslymphangitis. No major side effects were observed due to bevacizumab plus weekly paclitaxel. When theCT scans were taken in December after the completion of 6 cycles, the primary lesion and lymph node metastaseswere reduced in size. In the lung field, there was no thickening of the interlobular septa or subpleuralinterstitium, and the findings of carcinomatous lymphangitis were improved. Thus, bevacizumab plus paclitaxelwere discontinued and the treatment was changed to oral letrozole (2.5 mg/day). The patient hasbeen followed up with no recurrence as of March 2013

A Case of Inflammatory Pseudotumor of the Breast after Augmentation Mammoplasty

Inflammatory pseudotumor is a benign reactive lesion which forms due to diverse tissue responses of inflammatory cells and mesenchymal cells. It can occur in various organs of the body but rarely in the breast. We report a case of inflammatory pseudotumor of the breast after augmentation mammoplasty. The patient was a 78-year-old woman who noticed a mass in her right breast in July 2012. She had a history of augmentation mammoplasty at age 24 years. She was referred to our hospital for thorough examination. A 3-cm immovable induration was palpated in the upper lesion of the right breast. Ultrasound examination revealed a hypoechoic mass at the same site. The mass was 2.9×1.7 cm with irregular, ill-defined borders. Mammography revealed some areas of elevated density with coarse, lucent-centered calcifications in bilateral breasts but no clear findings of malignancy. Core needle biopsy of this site revealed marked fibrous hyperplasia and proliferation of fibroblast-like spindle cells. Infiltration of neutrophils and plasma cells was observed in the stroma. There were spindle cells with no atypia and scarce mitotic figures. Thus, the patient was diagnosed with inflammatory pseudotumor. The patient received only follow-up observation without surgical resection as per the patient\u27s wishes. There has not been any change as of May 2013

Gender-dependent effects of gonadectomy on lung carcinogenesis by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in female and male A/J mice

The present study was conducted to investigate the effects of gonadectomy on lung carcinogenesis in female and male mice, and to determine an association between sex hormone and lung carcinogenesis. Female and male A/J mice were divided into gonadectomized and unoperated control groups and all animals were treated intraperitoneally with 1 or 2 injections of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) at the dose of 2 mg/mouse. The mice were sacrificed 18 or 56 weeks after surgery. Serum levels of estradiol in females and testosterone in males were confirmed to be decreased by gonadectomy. Lung white nodules were detected in all mice of all groups. In the control groups of 18- and 56-week studies, the multiplicities of lung nodules in females were significantly greater than in males. In males in the 56-week study, the multiplicity of macroscopical lung nodules, bronchiolo-alveolar hyperplasias, adenomas and tumors (adenomas and adenocarcinomas) showed significant increase with castration. In females in the 18-week study, the multiplicity of adenomas decreased significantly by ovariectomy. Based on the results of the present study, female A/J mice were confirmed to be more susceptible to NNK-induced lung carcinogenesis than males. Furthermore, it was suggested that the process is inhibited by testosterone and accelerated by estradiol. These findings indicate the possibility that sex hormones play important roles in determining sex differences in lung carcinogenesis in the A/J mice initiated by NNK