Gefitinib and erlotinib, which are epidermal growth factor receptor- (EGFR-) specific tyrosine kinase inhibitors (TKIs), are widely used as molecularly targeted drugs for non-small-cell lung cancer (NSCLC). Currently, the search for EGFR gene mutations is becoming essential for the treatment of NSCLC since these have been identified as predictive factors for drug sensitivity. On the other hand, in almost all patients responsive to EGFR-TKIs, acquired resistance is a major clinical problem. Mechanisms of acquired resistance reported in the past few years include secondary mutation of the EGFR gene, amplification of the MET gene, and overexpression of HGF; novel pharmaceutical agents are currently being developed to overcome resistance. This review focuses on these mechanisms of acquired resistance to EGFR-TKIs and discusses how they can be overcome.

Our data demonstrated that SIRT6 expression in NSCLC could be a useful prognostic marker and that SIRT6 might represent a novel target gene for predicting sensitivity of chemotherapy in lung adenocarcinoma.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. To improve the prognosis of patients with NSCLCs, new and validated therapeutic targets are critically needed. In this study, we focused on F-box and WD repeat domain containing-7 (FBXW7), an E3 ubiquitin ligase, that regulates the degradation of MCL1, Myc, cyclin E, and TOP2A. Importantly, loss of FBXW7 was associated with increased sensitivity of tumors to a class I-specific histone deacetylase (HDAC) inhibitor, MS-275. Immunohistochemical analysis revealed increased expression of FBXW7 targets, MCL1 and TOP2A, in NSCLC tumors with low expression of FBXW7. Moreover, clinical specimens exhibiting low FBXW7 expression presented with more progressive cancer and significantly shorter cancer-specific survival than patients with high FBXW7 expression. Mechanistic study of NSCLC cell lines with silenced FBXW7 revealed enhanced MS-275 sensitivity and taxol resistance. Interestingly, taxol resistance was eliminated by MS-275 treatment, suggesting the potential of HDAC inhibitors for the treatment of aggressive taxol-resistant NSCLCs that lack FBXW7.

Endometriosis is a relatively common disorder in women of reproductive age; however, appendiceal endometriosis is rare. Thus, a definitive diagnosis is likely to be established only by histology of the appendix. We report a case of endometriosis of the appendix in a 42-year-old woman who presented with symptoms of acute appendicitis. We treated the patient by performing laparoscopic appendectomy, which resulted in a good outcome.

No abstract

Video-assisted thoracic surgery (VATS) has been enthusiastically used as a less-invasive diagnostic or therapeutic surgical procedure in recent years. VATS results in considerably less postoperative pain than traditional thoracotomy incisions. The current trend is to reduce the number of ports and minimize the length of incisions to further reduce postoperative pain, chest wall paresthesia, and length of hospitalization. Although several accounts of reduced port surgery, such as single-incision laparoscopic surgery (SILS), have been reported, there are few descriptions of single-incision thoracoscopic surgery (SITS) using a thin puncture device for a variety of diseases. Herein, we describe a minimally invasive SITS technique using a thin puncture device.

Meningiomas are common neoplasms arising from the central nervous system meninges. On the other hand, primary ectopic meningiomas are extremely rare and usually limited to the head and neck region or to the paravertebral soft tissues. Their occurrence in the mediastinum is even rarer. Until now, only 4 cases of primary mediastinal meningioma have been reported in the literature searched on Medline. Because of its rarity and intriguing pathogenesis, we report here a case of primary mediastinal meningioma that was treated by surgical resection. The clinical features, treatment, pathological findings, and prognosis are analyzed, and the literature on ectopic meningioma is reviewed.

Podoplanin, a small type I integral membrane mucin-type sialoglycoprotein, serves as a useful marker for diagnosing malignant pleural mesothelioma (MPM); however, the physiological function of podoplanin in mesothelioma cells is not known. To elucidate the role of podoplanin in the pathogenesis of MPM, we generated two mesothelioma cell lines (PODO1 and PODO2) that stably express high levels of podoplanin. Although PODO1 cells proliferated to the same extent in culture or in nude mice, the survival rate of the mice was significantly reduced compared with that of the controls. We demonstrated that PODO1 and PODO2 cells had increased invasive ability in in vitro assays and induced upregulation of matrix metalloproteinase-1. PODO1 and PODO2 cultures could not be induced to undergo apoptosis when starved or treated with cis-diamminedichloroplatinum(II) (CDDP) compared with the controls. Moreover, silencing of podoplanin expression using RNA interference restored the ability of CDDP to induce apoptosis. Consistent with their growth properties, we detected constitutive activation of extracellular signal-regulated kinase in PODO1 and PODO2 cultures. These findings suggest that constitutive expression of podoplanin contributes to the invasive growth properties of mesothelioma cells and their resistance to apoptosis. Moreover, our data suggest that podoplanin or components of its signaling pathway, or both, may serve as important targets for developing novel treatments for MPM.