Safe pneumonectomy for locally advanced lung cancer after induction therapy.

Purpose: To assess the safety and long-term outcomes of pneumonectomy after IT (IT-Pn) versus upfront pneumonectomy without IT (U-Pn) for locally advanced non-small-cell lung cancer (NSCLC).

Methods: We reviewed the clinical records of 69 patients who underwent pneumonectomy as U-Pn (n = 30) or IT-Pn (n = 39) between 2000 and 2019 at our institution, RESULTS: U-Pn included patients with pathological N0 (n = 13), N1 (n = 11) and N2 (n = 6). Among the patients treated with IT-Pn, 18 had pathological N0 (including 7 with complete responses), 5 had N1, 14 had N2, and 2 had N3.

Knockdown of RRM1 with Adenoviral shRNA Vectors to Inhibit Tumor Cell Viability and Increase Chemotherapeutic Sensitivity to Gemcitabine in Bladder Cancer Cells.

RRM1-an important DNA replication/repair enzyme-is the primary molecular gemcitabine (GEM) target. High RRM1-expression associates with gemcitabine-resistance in various cancers and RRM1 inhibition may provide novel cancer treatment approaches. Our study elucidates how RRM1 inhibition affects cancer cell proliferation and influences gemcitabine-resistant bladder cancer cells.

Overexpression of Antiapoptotic MCL-1 Predicts Worse Overall Survival of Patients With Non-small Cell Lung Cancer.

Background/aim: Myeloid cell leukemia-1 (MCL-1) is a member of the B-cell lymphoma-2 (Bcl-2) family of proteins, which regulate the intrinsic (mitochondrial) apoptotic cascade. MCL-1 inhibits apoptosis, which may be associated with resistance to cancer therapy. Therefore, in this study, the clinical role of MCL-1 in non-small cell lung cancer (NSCLC) was explored.

Inhibition of Cell-surface Molecular GPR87 With GPR87-suppressing Adenoviral Vector Disturb Tumor Proliferation in Lung Cancer Cells.

Background/aim: GPR87 is a member of the cell surface molecular G protein-coupled receptors (GPCR) family and suggested to contribute to the viability of human tumor cells. Its tumor-specific expression and cell surface location make it a potential molecule for targeted therapy. In the present study, we aimed to examine the effect of silencing GPR87 expression and explore the possibility of establishing gene therapy against GPR87-overexpressing lung cancer.

Virtual reality and augmented reality applications and simulation in vascular access management with three-dimensional visualization.

Obtaining adequate and precise anatomical information is mandatory to prevent vascular access-related complications in dialysis patients. For this purpose, we underwent Doppler ultrasound, vascular access angiogram, and plain computer-assisted tomography scan of the arm with vascular access. With the use of computer graphics software, the anatomical structure of the vascular access can be visualized three dimensionally which is shared among the staffs for precise and better recognition.

Candidate biomarkers predictive of anthracycline and taxane efficacy against breast cancer.

Background: Since breast cancer shows diversity in clinical behaviors, a standard therapy does not always lead to favorable outcomes.

Materials And Methods: The expression statuses of candidate markers, including topoisomerase-II alpha (TOP2A), beta-tubulin (B-tub), and tissue inhibitor of metalloprotease-1 (TIMP-1), were immunohistochemically evaluated in 70 breast cancer tissues from 68 patients with advanced breast cancers receiving chemotherapy.

Results: The response rates to anthracycline and taxane were 70.

Customized Adjuvant Chemotherapy Based on Biomarker Examination May Improve Survival of Patients Completely Resected for Non-small-cell Lung Cancer.

Aim: Adjuvant platinum-based chemotherapy is recommended for patients with completely resected stage II (N1) or III (N2) non-small cell lung cancer (NSCLC). However, the optimal chemotherapy regimen is difficult to predict for individual patients. Our previous prospective study on individualized treatment according to biomarker status, such as excision repair cross-complementing 1 (ERCC1), class III β-tubulin (tubulin), thymidylate synthase (TYMS) and ribonucleotide reductase M1 (RRM1), achieved encouraging results in patients with advanced NSCLC.

Vimentin Regulates Invasiveness and Is a Poor Prognostic Marker in Non-small Cell Lung Cancer.

Background: Lung cancer cells often express vimentin. However, the function of vimentin in lung cancer cells has not been fully evaluated.

Materials And Methods: We evaluated the association between vimentin expression in resected non-small cell lung cancer (NSCLC) specimens and prognosis.

G Protein-Coupled Receptor 87 (GPR87) Promotes Cell Proliferation in Human Bladder Cancer Cells.

G protein-coupled receptor 87 (GPR87) is a newly deorphanized member of the cell surface molecule G protein-coupled receptor family. GPR signaling was shown to play a role in promotion of cell growth and survival, metastasis, and drug resistance. The overexpression of GPR87 has also been reported in many malignant tumors including bladder cancer.

Potent effect of adenoviral vector expressing short hairpin RNA targeting ribonucleotide reductase large subunit M1 on cell viability and chemotherapeutic sensitivity to gemcitabine in non-small cell lung cancer cells.

Background: Ribonucleotide reductase large subunit (RRM1) is the main enzyme responsible for synthesis of the deoxyribonucleotides used during DNA synthesis. It is also a cellular target for gemcitabine (GEM). Overexpression of RRM1 is reportedly associated with resistance to GEM and the poor prognosis for many types of malignant tumours.

Overexpression of G protein-coupled receptor 87 correlates with poorer tumor differentiation and higher tumor proliferation in non-small-cell lung cancer.

G protein-coupled receptor 87 (GPR87) is a newly deorphanized member of the transmembrane G protein-coupled receptor family. Recently, GPR87 was suggested to contribute to the viability of human tumor cells and overexpression of GPR87 mRNA was detected in a number of malignant tumors, including lung cancer. We performed a retrospective study of GPR87 expression in association with clinical characteristics and biological markers in non-small-cell lung cancer (NSCLC).

Chemotherapy followed by surgery on the basis of biomarker examination for patients with advanced non-small cell lung cancer.

Background/aim: We have previously reported that low expression of excision repair cross-complementing-1 (ERCC1), class III β-tubulin (tubulin), thymidylate synthase (TYMS) and ribonucleotide reductase-M1 (RRM1) is indicative of a favorable prognosis in patients with c-N2,3 non-small cell lung cancer (NSCLC) treated with surgery after induction chemoradiotherapy. In the present study, we prospectively explored the tailor-made treatment menu for induction chemotherapy according to the status of biomarkers, and evaluated the biomarker status pre- and post-chemotherapy.

Patients And Methods: Twenty-five patients with pathologically-proven NSCLC who were not appropriate candidates for initial surgery were enrolled (October 2010 to June 2012, stage IIIA/B/IV1a/1b;14/5/2/4 respectively).

Engineering a well-ordered, functional protein-gold nanoparticle assembly.

The study of interactions between proteins and nanoparticles is important to advancing applications of nanoparticles in biology, medicine, and materials science. Here, we report the encapsulation of a 5-nm diameter gold nanoparticle (AuNP) by thermophilic ferritin (tF), achieved in nearly quantitative yield under mild conditions that preserved the secondary structure, ferroxidase activity, and thermal stability of the native, 4-helix bundle protein subunits. Chromatography-based assays determined that stable protein assembly around AuNPs occurred on long time scales (~48h) and was reversible.

Expression and role of GPR87 in urothelial carcinoma of the bladder.

The orphan GPR87 has recently been matched with its ligand LPA, which is a lipid mediator with multiple physiological functions, including cancer cell proliferation. This study aimed to clarify the role of GPR87 in urothelial carcinoma of the bladder. GPR87 expression was assessed in seven human bladder cancer cell lines.

Biomarkers as prognostic factors for cN2 or 3 non-small cell lung cancer treated by induction chemoradiotherapy and surgery.

Background: We have reported promising results of surgery after induction chemoradiotherapy (carboplatin-taxane, 50 Gy radiation) for cN2,3 non-small cell lung cancer (NSCLC). In order to understand the underlying mechanism, expression of excision repair cross-complementing 1 (ERCC1), class III β-tubulin (tubulin), thymidylate synthase (TYMS), and ribonucleotide reductase M1 (RRM1) were investigated.

Patients And Methods: Immunohistochemistry was performed in 45 patients with cN2,3 NSCLC, but only in twelve pathologically-complete response cases to evaluate intratumoral expression of these biomarkers.

Production of cloned pigs expressing human thrombomodulin in endothelial cells.

For long-term xenograft survival, coagulation control is one of the remaining critical issues. Our attention has been directed toward human thrombomodulin (hTM), because it is expected to exhibit the following beneficial effects on coagulation control and cytoprotection: (i) to solve the problem of molecular incompatibility in protein C activation; (ii) to exert a role as a physiological regulator, only when thrombin is formed; (iii) to suppress direct prothrombinase activity; and (iv) to have anti-inflammatory properties. hTM gene was transfected into pig (Landrace/Yorkshire) fibroblasts using pCAGGS expression vector and pPGK-puro vector.

Wnt3 gene expression promotes tumor progression in non-small cell lung cancer.

The Wnt gene family encodes the multi-functional signaling glycoproteins regulating various normal and pathological processes including tumorigenesis. We investigated the clinical significance of the Wnt3 gene expression in relation to its target genes, c-Myc and survivin, in patients with non-small cell lung cancer (NSCLC). One hundred and twenty-eight patients who underwent resection of NSCLC were analyzed.

Adenoviral vector expressing short hairpin RNA targeting Wnt2B has an effective antitumour activity against Wnt2B2-overexpressing tumours.

Background: The Wnt family encodes multi-functional signalling glycoproteins regulating various normal and pathological processes including tumourigenesis. Wnt2B overexpression is thought to affect tumour progression through the activation of the canonical Wnt pathway.

Method: Experimental studies were conducted using a Wnt2B-inhibiting vector to establish gene therapy against Wnt2B2-overexpressing tumours.

[Prognosis of surgically treated large cell neuroendocrine carcinoma].

Large cell neuroendocrine carcinoma (LCNEC) is a relatively rare tumor in malignant lung neoplasms. The prognosis of LCNEC is poor and there is no consensus on the treatment for LCNEC. We report our retrospective assessment of 11 patients of LCNEC from 1999 to 2008.

Combined therapy with a thymidylate synthase-inhibiting vector and S-1 has effective antitumor activity against 5-FU-resistant tumors.

High levels of intratumoral thymidylate synthase (TS) expression are associated with resistance to 5-fluorourcil (5-FU). In order to establish a new treatment method for 5-FU-resistant tumors, the efficacy of gene therapy was investigated using an adenoviral vector expressing short hairpin RNA (shRNA) targeting TS. A replication-deficient recombinant adenoviral vector expressing shRNA targeting TS was constructed under the control of the human U6 promoter (Ad-shTS).

Intratumoral Wnt1 expression affects survivin gene expression in non-small cell lung cancer.

Survivin, a member of the inhibitor of apoptosis protein family, affects tumorigenesis. Recently, survivin is reported to be a target of the canonical Wnt pathway, which activates the transcription of various tumor-associated target genes. One hundred and twenty-two non-small cell lung cancers (NSCLCs) were investigated to evaluate survivin gene expression in relation to the expression of Wnt1 (a novel member of the canonical Wnt pathway) and Wnt5a (a novel member of the non-canonical Wnt pathway).

Expression of ERCC1 and class III β-tubulin is associated with the survival of resected stage III non-small cell lung cancer patients treated with induction chemoradiotherapy using carboplatin-taxane.

Several molecules have been proven to be associated with responsiveness to chemotherapy. A clinical study on the expression of excision repair cross-complementing (ERCC)-1 and class III β-tubulin was conducted in advanced stage non-small cell lung cancer (NSCLC) patients. We investigated 34 resected stage III NSCLC patients treated with induction chemoradiotherapy using carboplatin-taxane.

The clinical significance of the tumor cell D2-40 immunoreactivity in non-small cell lung cancer.

Background: A monoclonal antibody D2-40 has been widely used for tumor lymphangiogenesis and lymphatic vessel invasion (LVI) in human cancers. However, the clinical significance of the tumor cell D2-40 immunoreactivity has not been clearly understood.

Patients And Methods: We evaluated the tumor cell D2-40 immunoreactivity in non-small cell lung cancer (NSCLC).

Successful cross-breeding of cloned pigs expressing endo-beta-galactosidase C and human decay accelerating factor.

Background: For successful organ xenotransplantation, genetically engineered pigs have been actively produced. Our attention has focused on (i) reduction of alphaGal expression by its digestion enzyme, endo-beta-galactosidase C (EndoGalC), and (ii) inhibition of complement activation by human decay accelerating factor (hDAF). Cell sorting and nuclear transfer enabled the effective production of cloned pigs expressing transgene at high levels.