The tumor suppressor gene TP53 is frequently mutated in human cancers. Abnormality of the TP53 gene is one of the most significant events in lung cancers and plays an important role in the tumorigenesis of lung epithelial cells. Human lung cancers are classified into two major types, small cell lung cancer (SCLC) and nonsmall cell lung cancer (NSCLC). The latter accounts for approximately 80% of all primary lung cancers, and the incidence of NSCLC is increasing yearly. Most clinical studies suggest that NSCLC with TP53 alterations carries a worse prognosis and may be relatively more resistant to chemotherapy and radiation. A deep understanding of the role of TP53 in lung carcinogenesis may lead to a more reasonably targeted clinical approach, which should be exploited to enhance the survival rates of patients with lung cancer. This paper will focus on the role of TP53 in the molecular pathogenesis, epidemiology, and therapeutic strategies of TP53 mutation in NSCLC.

Metabolic response by F-FDG was effective in predicting efficacy and survival at 1 month after nivolumab treatment.

These findings suggest that Cyclin B1 expression could be a significant prognostic parameter in NSCLC. The loss of Wee1 expression may have a potential role in promoting tumor progression and may be a significant prognostic indicator in NSCLC.

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.

In both mice and humans alternate splicing results in isoforms of c-Kit characterized by the presence or the absence of a tetrapeptide sequence, GNNK, in the juxtamembrane region of the extracellular domain. Dramatic differences in the kinetics and magnitude of activation of the intrinsic tyrosine kinase activity of c-Kit between the GNNK؊ and GNNK؉ isoforms has previously been shown. Here we report the analysis of downstream targets of receptor signaling, which revealed that the signaling was differentially regulated in the two splice forms. The kinetics of phosphorylation of Shc, previously demonstrated to be phosphorylated by Src downstream of c-Kit, was stronger and more rapid in the GNNK؊ form, whereas it showed slower kinetics in the GNNK؉ form. Inhibition of Src family kinases with the specific Src family kinase inhibitor SU6656 altered the kinetics of activation of the GNNK؊ form of c-Kit so that it resembled that of the GNNK؉ form. In cells expressing the GNNK؊ form, SCF was rapidly degraded, whereas in cells expressing the GNNK؉ form only showed a very slow rate of degradation of SCF. In the GNNK؉ form the Src inhibitor SU6656 only had a weak effect on degradation, whereas in the GNNK؊ form it dramatically inhibited degradation. In summary, the two splice forms show, despite only a four-amino acid sequence difference, remarkable differences in their signaling capabilities.

No abstract

Video-assisted thoracoscopic surgery (VATS) has gradually been implemented in thoracic surgery, and the VATS approach has now been extended to technically challenging procedures, such as segmentectomy. The definition of VATS segmentectomy is changing over time, and the repertoire of segmentectomy is getting wider with increasing reports on atypical segmentectomy. VATS segmentectomy bears surgical, oncological, and technical advantages; however, there are still areas of controversy, particularly regarding oncological outcomes. The indication of VATS segmentectomy is diverse and is used for treating lung cancer, metastatic lung tumors, or a variety of nonmalignant diseases. It is particularly valuable for the lung-sparing resection of deeply located small nodules or repeated surgery for multiple lung lesions. VATS segmentectomy requires a thorough analysis of segmental anatomy and a tailored preoperative planning with the assessment of surgical margins. Technical challenges include intraoperative navigation, methods to identify and dissect the intersegmental plane, and the prevention of air leakage. This review will discuss the present state of VATS segmentectomy, with a focus on past studies, current indications and techniques, and future view.

ObjectiveThoracic surgeons must be erudite pulmonary vein variation when performing anatomical segmentectomy. We used three-dimensional CT (3DCT) to accumulate variations of the pulmonary veins of the right upper lobe (RUL) and created a simplified RUL vein model.MethodsWe reviewed anatomical variations of the RUL pulmonary veins of 338 patients using 3DCT images, and classified them by position related with bronchus.ResultsOf the “anterior” and “central” RUL veins, all could be classified into 4 types: 2 Anterior with Central types (Iab and Ib), 1 Anterior type, and 1 Central type. The Anterior with Central type was observed in 273 patients (81 %), and was further classified into two types according to the origin of the anterior vein. In the Iab type, the anterior vein originated from V1a to V1b (54 %) whereas, in the Ib type, the anterior vein originated from only V1b (26 %). The Central type, which had no anterior vein, was evident in 23 cases (7 %). These three types could be further divided into three subcategories by reference to the branching pattern of the central vein. The Anterior type, which had no central vein, was evident in 42 cases (12 %), and this type could be further categorized into two types, depending on the branching pattern of the anterior vein.ConclusionWe created a simplified RUL vein model to facilitate anatomical segmentectomy. Our models should find wide application, especially when thoracic surgery requiring anatomical RUL segmentectomy is planned.Electronic supplementary materialThe online version of this article (doi:10.1007/s11748-016-0686-4) contains supplementary material, which is available to authorized users.