Cancer Phenotype Diagnosis and Drug Efficacy within Japanese Health Care

An overview on targeted personalized medicine is given describing the developments in Japan of lung cancer patients. These new targeted therapies with novel personalized medicine drugs require new implementations, in order to follow and monitor drug efficacy and outcome. Examples from IRESSA (Gefitinib) and TARCEVA (Erlotinib) treatments used in medication of lung cancer patients are presented. Lung cancer is one of the most common causes of cancer mortality in the world. The importance of both the quantification of disease progression, where diagnostic-related biomarkers are being implemented, in addition to the actual measurement of disease-specific mechanisms relating to pathway signalling activation of disease-progressive protein targets is summarised. An outline is also presented, describing changes and adaptations in Japan, meeting the rising costs and challenges. Today, urgent implementation of programs to address these needs has led to a rebuilding of the entire approach of medical evaluation and clinical care

Reorganization of Corticospinal Projections after Prominent Recovery of Finger Dexterity from Partial Spinal Cord Injury in Macaque Monkeys

We investigated morphologic changes in the corticospinal tract (CST) to understand the mechanism underlying recovery of hand function after lesion of the CST at the C4/C5 border in seven macaque monkeys. All monkeys exhibited prominent recovery of precision grip success ratio within a few months. The trajectories and terminals of CST from the contralesional (n = 4) and ipsilesional (n = 3) hand area of primary motor cortex (M1) were investigated at 5–29 months after the injury using an anterograde neural tracer, biotinylated dextran amine (BDA). Reorganization of the CST was assessed by counting the number of BDA-labeled axons and bouton-like swellings in the gray and white matters. Rostral to the lesion (at C3), the number of axon collaterals of the descending axons from both contralesional and ipsilesional M1 entering the ipsilesional and contralesional gray matter, respectively, were increased. Caudal to the lesion (at C8), axons originating from the contralesional M1, descending in the preserved gray matter around the lesion, and terminating in ipsilesional Laminae VI/VII and IX were observed. In addition, axons and terminals from the ipsilesional M1 increased in the ipsilesional Lamina IX after recrossing the midline, which were not observed in intact monkeys. Conversely, axons originating from the ipsilesional M1 and directed toward the contralesional Lamina VII decreased. These results suggest that multiple reorganizations of the corticospinal projections to spinal segments both rostral and caudal to the lesion originating from bilateral M1 underlie a prominent recovery in long-term after spinal cord injury

Midterm surgical results of total cavopulmonary connection: clinical advantages of the extracardiac conduit method

AbstractObjectiveWe evaluated the midterm surgical outcomes of intra-atrial lateral tunnel and extracardiac conduit total cavopulmonary connection to clarify the clinical superiority.MethodsPatients (n = 167) underwent total cavopulmonary connection (88 with lateral tunnel and 79 with extracardiac conduit) from November 1991 to March 1999. Survival, incidence of reoperation and late complications, exercise tolerance, hemodynamic variables, and plasma concentration of natriuretic peptide type A were compared. In the lateral tunnel group, time-related change in lateral tunnel size was investigated for its relationship to postoperative arrhythmias.ResultsThe 8-year survival was 93.2% in the lateral tunnel group and 94.9% in the extracardiac conduit group. Seven reoperations were performed in the lateral tunnel group but none in the extracardiac conduit group. Supraventricular arrhythmias developed in 14 patients (15.9%) in the lateral tunnel group and in 4 patients (5.1%) in the extracardiac conduit group (P = .003). Freedom from cardiac-related events was 72.5% in the lateral tunnel group and 89.8% in the extracardiac conduit group at 8 years (P = .0098). Hemodynamic variables and exercise tolerance were similar in both groups but plasma natriuretic peptide type A concentration, a parameter of atrial wall tension, was higher in the lateral tunnel group. In the lateral tunnel group, intra-atrial tunnel size increased by 19.4% during the 44.2-month interval and the percent increase in tunnel size was an independent predictor of supraventricular arrhythmias.ConclusionsThe midterm survival, hemodynamic variables, and exercise tolerance were similar and satisfactory in both lateral tunnel and extracardiac conduit groups; however, the incidence of cardiac-related events was significantly less frequent in the extracardiac conduit group. In the lateral tunnel group, careful observation is required to monitor the relationship of the dilating tendency of the intra-atrial tunnel and the development of late complications

Cancer cell immunity-related protein co-expression networks are associated with early-stage solid-predominant lung adenocarcinoma

BackgroundSolid-predominant lung adenocarcinoma (SPA), which is one of the high-risk subtypes with poor prognosis and unsatisfactory response to chemotherapy and targeted therapy in lung adenocarcinoma, remains molecular profile unclarified. Weighted correlation network analysis (WGCNA) was used for data mining, especially for studying biological networks based on pairwise correlations between variables. This study aimed to identify disease-related protein co-expression networks associated with early-stage SPA.MethodsWe assessed cancerous cells laser-microdissected from formalin-fixed paraffin-embedded (FFPE) tissues of a SPA group (n = 5), referencing a low-risk subtype, a lepidic predominant subtype group (LPA) (n = 4), and another high-risk subtype, micropapillary predominant subtype (MPA) group (n = 3) and performed mass spectrometry-based proteomic analysis. Disease-related co-expression networks associated with the SPA subtype were identified by WGCNA and their upstream regulators and causal networks were predicted by Ingenuity Pathway Analysis.ResultsAmong the forty WGCNA network modules identified, two network modules were found to be associated significantly with the SPA subtype. Canonical enriched pathways were highly associated with cellular growth, proliferation, and immune response. Upregulated HLA class I molecules HLA-G and HLA-B implicated high mutation burden and T cell activation in the SPA subtype. Upstream analysis implicated the involvement of highly activated oncogenic regulators, MYC, MLXIPL, MYCN, the redox master regulator NFE2L2, and the highly inhibited LARP1, leading to oncogenic IRES-dependent translation, and also regulators of the adaptive immune response, including highly activated IFNG, TCRD, CD3-TCR, CD8A, CD8B, CD3, CD80/CD86, and highly inhibited LILRB2. Interestingly, the immune checkpoint molecule HLA-G, which is the counterpart of LILRB2, was highly expressed characteristically in the SPA subtype and might be associated with antitumor immunity.ConclusionOur findings provide a disease molecular profile based on protein co-expression networks identified for the high-risk solid predominant adenocarcinoma, which will help develop future therapeutic strategies

Compressed Amplatzer Vascular Plug II Embolization of the Left Subclavian Artery for Thoracic Endovascular Aortic Repair is Efficient and Safety Method Comparable to Conventional Coil Embolization

[Background] Left subclavian artery (LSA) embolization is occasionally required to prevent type II endoleak in the thoracic endovascular aortic repair (TEVAR) procedure. This is a retrospective study comparing compressed Amplatzer Vascular Plug II embolization (CAE) and conventional coil embolization (CCE) in preventing retrograde flow into the aneurysmal sac through the LSA after TEVAR. [Methods] We retrospectively reviewed the records of patients who underwent CAE or CCE of the LSA during TEVAR from June 2013 to March 2016 in our hospital. The efficacy, safety and cost of each method were compared between two groups. [Results] Thirty patients underwent LSA embolization during TEVAR. Six CCEs in 6 patients were performed from June 2013 to November 2013, while twenty-four CAEs in 24 patients were performed from December 2013 to March 2016. Technical success was achieved in all patients in both groups. No embolization-related complications or type II endoleaks from LSA were recorded during the follow-up period in all patients. In both groups, all embolic materials were detected in the proximal portion of the LSA from the LSA orifice to the vertebral artery origin and no vertebral artery occlusions were detected. The mean compression ratio of AVP II was 58 ± 5.9% of predicted length of standard procedure. In the CAE group, one AVP II was sufficient to achieve complete LSA occlusion in all patients. On the other hand, multiple coils (10.2 ± 2.7) were used in the CCE group (P < .01), resulting in a significantly lower cost incurred in the CAE group (CAE: 129,000 JPY vs. CCE: 639,600 ± 140,060 JPY; P < .01). [Conclusion] The CAE is a useful and cost-effective procedure for TEVAR-related LSA embolization