ハイガン タゾウキ テンイ モデル ニヨル テンイ ノ ブンシ キコウ カイメイ ト チリョウ エノ オウヨウ

Lung cancer is a leading cause of malignancy-related death worldwide, and over 90% of deaths from lung cancer can be attributed to metastases. To explore molecular pathogenesis of lung cancer, we recently established multiple-organ metastasis models of human lung cancer cells in SCID mice depleted of NK cells. The pattern of metastasis in our models is similar with that observed in lung cancer patients. Using our models, we have shown that overexpression of cytokines, such as macrophage colony-stimulating factor and interleukin-10, resulted in organ-specific inhibition of metastasis by human lung cancer cell lines, suggesting differential regulation of metastasis by organ microenvironment. We further demonstrated that expression of human cancer cells were heterogenous, and that anti-metastastic effect of MMP inhibitor, a molecular targeted drug, could be organ specific, consistent with the results in recent clinical trials. Further intensive analyses using clinically relevant metastasis models (e.g., multiple-organ metastasis models) are warranted for establishment of novel, effective treatment for lung cancer metastasis

ハイガン ト アクセイ キョウマク チュウヒシュ

Lung cancer is the leading cause of malignancy related death in Japan. Cigarette smoking is the most important preventable risk factor for lung cancer. For smokers who want to quit, nicotine replacement therapy is frequently recommended. The most effective interventions for quitting continue to be a combination of behavioral and pharmacologic approaches. Malignant pleural mesothelioma is closely related to exposure to asbestos, and a rapid increase of the number of MPM patients is estimated to occur from 2010 to 2040. The early detection by the medical check-up is also important for improve the prognosis of patients with lung cancer and malignant pleural mesothelioma

アクセイ キョウマク チュウヒシュ ノ チリョウ : アタラシイ トリクミ オ マジエテ

Malignant pleural mesothelioma（MPM）arises from the mesothelial cells that line the thoracic cavity．MPM grows aggressively with dissemination in the thoracic cavity and frequently produces malignant pleural effusion．Although a surgical resection at an early stage is the only a curative therapeutic modality, the majority of MPM patients are found at an advanced stage．In addition, MPM is refractory to conventional chemotherapy and radiotherapy, and it also has a poor prognosis．Recently, it has been shown that palliative chemotherapy with pemetrexed and cisplatin is beneficial for MPM patients．Development of novel molecular targeted therapy is essential for further improvement of the prognosis of this disease

A case of giant urachal cyst in a neonate

AbstractWe report a case of giant urachal cyst in a neonate presenting characteristic features on fetal ultrasonography. A 28-year-old woman of 21 weeks gestation was referred to our hospital for evaluation of a cystic mass in the lower portion of the fetal abdomen. On fetal ultrasonography, at 23 weeks gestation, the two umbilical arteries in the base of the umbilical cord became separated from each other due to the fetal cyst. On fetal MRI, at 25 weeks gestation, the cyst was depicted as a unilocular serous cyst, independent of the surrounding organs such as the kidney, gallbladder and intestines. The cyst had no communication with the bladder or umbilical cord. A male infant was delivered at term. Although the infant was thriving and remained asymptomatic, an enhanced CT examination 13 days after birth showed the cyst was still present without any decrease in size. The infant underwent surgery to make a definite diagnosis and to prevent future complications. The cyst was excised without any complication and finally diagnosed as a urachal cyst based on morphological and pathological findings

Ligand-triggered resistance to molecular targeted drugs in lung cancer: Roles of hepatocyte growth factor and epidermal growth factor receptor ligands

がん進展制御研究所Recent advances in molecular biology have led to the identification of new molecular targets, such as epidermal growth factor receptor (EGFR) mutations and echinoderm microtubule-associated protein-like 4 (EML4) - anaplastic lymphoma kinase (ALK) fusion gene, in lung cancer. Dramatic response has been achieved with EGFR inhibitors (gefitinib and erlotinib) and an ALK inhibitor (crizotinib) in lung cancer expressing corresponding targets. However, cancer cells acquire resistance to these drugs and cause recurrence. Known major mechanisms for resistance to molecular targeted drugs include gatekeeper mutations in the target gene and activation of bypass survival signal via receptors other than the target receptors. The latter mechanism can involve receptor gene amplification and ligand-triggered receptor activation as well. For example, hepatocyte growth factor (HGF), the ligand of a tyrosine kinase receptor Met, activates Met and the downstream PI3K/Akt pathway and triggers resistance to EGFR inhibitors in EGFR mutant lung cancer cells. Moreover, EGFR ligands activate EGFR and downstream pathways and trigger resistance to crizotinib in EML4-ALK lung cancer cells. These observations indicate that signals from oncogenic drivers (EGFR signaling in EGFR -mutant lung cancer and ALK signaling in EML4-ALK lung cancer) and ligand-triggered bypass signals (HGF-Met and EGFR ligands-EGFR, respectively) must be simultaneously blocked to avoid the resistance. This review focuses specifically on receptor activation by ligand stimulation and discusses novel therapeutic strategies that are under development for overcoming resistance to molecular targeted drugs in lung cancer. © 2012 Japanese Cancer Association

A case of early-stage lung cancer detected by autofluorescence bronchoscopy

A 71-year-old man was referred to our hospital for further examination of abnormal sputum cytology. No abnormal nodular shadows were detected in chest X-ray and chest CT. The location of the tumor was clearly identified as a defect of autofluorescence by autofluorescence bronchoscopy at the bifurcation between the left B1+2 and B3 bronchi, whereas it was quite difficult by conventional bronchoscopy. Trans bronchial biopsy revealed squamous cell carcinoma. Further examinations yielded the diagnosis of early-stage lung cancer. Photodynamic therapy was performed and complete response was confirmed. This case indicates the efficacy of auto fluorescence bronchoscopy for detecting early-stage lung cancer

Flow Characteristics of Gas and Liquid through a Cell Porous Disk

This paper describes applications of cell porous materials. The authors investigated the flow characteristics of a gas-liquid mixture in a rotating porous disk. For theoretical analyses, the gas is assumed to permeate the entire disk surface. A simple one-dimensional model illustrates that the residence time of the liquid is much greater than that of the gas. Violent interaction in small cells is likely to enhance the chemical reaction between gas and liquid. Cell porous materials might also be exploited for chemical reaction purposes

Levels of soluble vascular endothelial growth factor receptor 1 are elevated in the exudative pleural effusions

Purpose : Vascular endothelial growth factor (VEGF) plays a critical role in the production of malignant pleural effusions. In the present study, we examined the levels of soluble VEGF receptor-1 (sVEGFR-1) and angiopoietin-2 (Ang-2), as possible regulators of VEGF activity, in transudative and exudative pleural effusions. Methods : Forty-two patients were included in this study : 4 with transudative pleural effusions due to heart failure (HF), 38 with exudative pleural effusions (lung cancer [LC], 22 ; other malignant diseases [MD], 10 ; tuberculosis [TB], 6) . The levels of VEGF, Ang-2, and sVEGFR-1 in the pleural effusions were measured by an enzyme-linked immunosorbent assay. Results : The levels of VEGF, Ang-2, and sVEGFR-1 in exudative effusions were higher than those in transudative effusions. Interestingly, the levels of VEGF and Ang-2 in bloody effusions were significantly higher than those in non-bloody effusions (p < 0.05), but the level of sVEGFR-1 in bloody effusions was lower than that in non-bloody effusions. The levels of VEGF and Ang-2 were significantly higher in the malignant effusions, compared with effusion from HF and TB (p < 0.05). In addition, sVEGFR-1 was significantly higher in the effusion from LC, MD, and TB compared with effusion from HF (p < 0.05). In the malignant effusions, direct correlations were observed among VEGF, sVEGFR-1, and Ang-2. Conclusions : The sVEGFR-1 levels were elevated in exudative pleural effusions, and were lower in bloody effusions than in non-bloody effusions, thus suggesting the regulatory role of sVEGFR-1 in the exudative pleural effusions

Not just gRASping at flaws: Finding vulnerabilities to develop novel therapies for treating KRAS mutant cancers

がん進展制御研究所Mutations in Kirsten rat-sarcoma (KRAS) are well appreciated to be major drivers of human cancers through dysregulation of multiple growth and survival pathways. Similar to many other non-kinase oncogenes and tumor suppressors, efforts to directly target KRAS pharmaceutically have not yet materialized. As a result, there is broad interest in an alternative approach to develop therapies that induce synthetic lethality in cancers with mutant KRAS, therefore exposing the particular vulnerabilities of these cancers. Fueling these efforts is our increased understanding into the biology driving KRAS mutant cancers, in particular the important pathways that mutant KRAS governs to promote survival. In this mini-review, we summarize the latest approaches to treat KRAS mutant cancers and the rationale behind them. © 2014 The Authors

Resminostat in EGFR-mutated lung cancer

Drug-tolerant cells are mediators of acquired resistance. BIM-intron2 deletion polymorphism (BIM-del) is one of the mechanisms underlying the resistance to epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI)-mediated apoptosis that induces drug tolerance. Here, we investigated whether resminostat, a histone deacetylase inhibitor, circumvents BIM-del-associated apoptosis resistance. The human EGFR-mutated non-small cell lung cancer (NSCLC) cell line PC-9 and its homozygous BIM-del-positive variant (PC-9 BIMi2-/-), established by editing with zinc finger nuclease, were used. In comparison with PC-9 cells, PC-9 BIMi2-/- cells were less sensitive to apoptosis mediated by EGFR-TKIs such as gefitinib and osimertinib. The combined use of resminostat and an EGFR-TKI preferentially induced the expression of the pro-apoptotic BIM transcript containing exon 4 rather than that containing exon 3, increased the level of pro-apoptotic BIM protein (BIMEL), and stimulated apoptosis in vitro. In a subcutaneous tumor model derived from PC-9 BIMi2-/- cells, gefitinib monotherapy decreased tumor size but retained residual lesions, indicative of the presence of tolerant cells in tumors. The combined use of resminostat and gefitinib increased BIMEL protein level and induced apoptosis, subsequently leading to the remarkable shrinkage of tumor. These findings suggest the potential of resminostat to circumvent tolerance to EGFR-TKIs associated with BIM deletion polymorphism