Hiromi Wada

Kyoto University | Kyodai · Department of Thoracic Surgery

BACKGROUND/AIMS: For lung preservation, one of two types of solutions is commonly employed: Euro-Collins (EC) or low potassium dextran glucose (LPDG). These two solutions have been compared regarding biological, morphometrical and physiological outcomes in many experiments. However, the dynamic mechanics of perfused lung are not well understood bec...

After lung transplantation, early detection of acute allograft rejection is important not only for timely and optimal treatment, but also for the prediction of chronic rejection which is a major cause of late death. Many biological and immunological approaches have been developed to detect acute rejection; however, it is not well known whether lung...

Objectives: This retrospective, multicenter study aimed to determine prognostic factors of completely resected pathologic N2 stage IIIA non-small cell cancer (NSCLC). Methods: From 25 participating hospitals, 496 patients (325 men and 171 women; median age, 65 years) who underwent complete resection without preoperative treatment for pT1-3 N2 M0...

Magnetic entropy change, ΔSM, and the refrigeration capacity, q, of MnFeP1−xSix have been examined. In accordance with the previous report, the compounds with 0.30 ⩽ x ⩽ 0.60 undergo a first-order magnetic transition near room temperature. The Curie temperature is increased linearly from 210 K to 360 K with increasing x from 0.30 to 0.60. The compo...

S-1, an oral fluoropyrimidine, is usually given for 4 weeks (80 mg/m2/day) followed by a 2-week rest. However, compliance with this regimen is unsatisfactory because of adverse events such as leukopenia, anorexia, and nausea. To reduce adverse effects and improve compliance, we studied a "5-day on/2-day off" low-dose regimen of S-1 and evaluated ph...

Sepsis caused by the bacterial contamination of blood products is a major infection risk associated with blood transfusion. Diversion of the initial 25 mL of blood and prestorage leukoreduction were implemented in Japan in 2007 for all donated blood products. We assessed the efficacy of these new collection procedures in preventing bacterial contam...

For lung preservation, one of two types of solutions is commonly employed: Euro-Collins (EC) or low potassium dextran glucose (LPDG). These two solutions have been compared regarding biological, morphometrical and physiological outcomes in many experiments. However, the dynamic mechanics of perfused lung are not well understood because the dynamic...

Overexpression of Her2/ErbB2/Neu in cancer is often correlated with recurrent distant metastasis, although the mechanism still remains largely elusive. We have previously shown that EGFR, when tyrosine-phosphorylated, binds to GEP100/BRAG2 to activate Arf6, which induces cancer invasion and metastasis. We now show that overexpressed Her2 in lung ad...

Distributions of critical current of damaged Bi2223 tape specimens bent by 0.6, 0.8 and 1.0% were investigated analytically with a modelling approach based on the correlation of damage evolution to distribution of critical current. It was revealed that the distribution of critical current is described by three parameter Weibull distribution functio...

Lung cancer is the leading cause of cancer death worldwide, yet there are still no satisfactory protocols available for treating this disease, emphasizing the urgency for more effective therapies. Recent clinical trials have provided encouraging evidence of the benefits of certain forms of immunotherapy. Here, we summarize recent developments in th...

A new oral sustained-release solid-dispersion preparation of cisplatin (cis-diamminedichloroplatinum(II); cisplatin) has been developed for administration to small experimental animals such as mice. This preparation was obtained by formulating cisplatin with the water-insoluble polymer ethylcellulose and with stearic acid in different ratios. In-vi...

The efficiency and usefulness of oral cisplatin using sustained-release cisplatin solid dispersions was studied in tumour-loaded mice.Mice were inoculated intraperitoneally with P815 tumour cells, before treatment with 10 mg kg−1 cisplatin. Cisplatin solid dispersions were suspended in 1% sodium carboxy-methylcellulose and administered according to...

To assess whether early lung cancer prediction might be informed by an mRNA assay for 5-fluorouracil pathway genes in peripheral blood mononuclear cells (PBMNCs), we examined specimens taken from 51 adenocarcinoma patients and 38 controls (including six patients with benign tumors). PBMNCs and tumor-tissue specimens were taken for measurement of th...

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 recombina...

Under applied strain, the damage behavior of bent (Bi,Pb)2Sr2Ca2Cu3O10+δ (Bi2223) composite tape is different from specimen to specimen. Accordingly, the irreversible bending strain and critical current differ among specimens. The present work attempted to reveal the irreversible bending strain distribution and the critical current distribution in...

We have recently reported that perioperative low-dose carbon monoxide (CO) inhalation decreases lung ischemia-reperfusion injury in miniature swine. The aims of this study were to establish a large animal model of pulmonary allograft rejection using polymerase chain reaction-typed major histocompatibility complex (MHC)-inbred CLAWN miniature swine...

Magnetic resonance imaging (MRI) requires a highly homogenous magnetic field zone which usually appears at the center of the MRI magnet coil. If this homogeneous zone is allowed to occur at an off-centered position along the coil axis, quite new applications of MRI may be possible. In order to examine this idea, we fabricate a model magnet consisti...

High-Field MRI provides high resolutions, well-defined chemical shift spectra and large data acquisition rates, and may bring about a paradigm shift in medicine through the in-vivo observation of metabolism. An 11.7 T whole body MRI magnet, for example, should be able to observe metabolic reactions occurring in a human body in addition to producing...

e17512 Background: S-1, an oral fluoropyrimidine is usually used as 4-week administration (80mg/m²/day) followed by 2-week rest. However, the compliance of this drug schedule is not satisfactory because of adverse events such as leucopenia, anorexia, and nausea. To improve the compliance with less adverse effect, 5-day on/2-day off low dose of S-1...

Mutations in Kelch-like ECH-associated protein 1 (Keap1) have been reported to protect tumor cells from chemotherapeutic agents. However, their prognostic significance in nonsmall cell lung cancer (NSCLC) is still unclear. In this study, we examined the effect of Keap1 gene mutations on survival and disease-free interval using resected primary NSCL...

UFT and S-1 are oral 5-fluorouracil (5-FU) derivative drugs containing an inhibitor of dihydropyrimidine dehydrogenase (DPD); they are defined as DPD-inhibitory fluoropyrimidine (DIF). Because DPD is the key enzyme of 5-FU degradation, 5-FU is not active in primary lung cancers with high DPD activity, which causes rapid degradation of 5-FU. Thus, t...

We usually use spirometry for the medical follow-up of respiratory mechanics after lung transplantation. However, especially in the first few post-operative weeks, it is easily affected by postoperative pain and the patient's co-operation during forced breathing effort. To avoid missing out on assessing pulmonary function, we perform non-invasive f...

When the critical current of bent Bi2223 composite tape is measured for many specimens, the critical current value is different from specimen to specimen, being distributed from low to high values. We need to characterize the distribution of critical current at various applied strains and also to predict the distribution of irreversible strain for...

Aminopeptidase-N (APN) is a membranebound protein that acts as a zinc-binding protease and participates in extracellular proteolysis. APN plays important roles in tumor progression through promoting invasion and metastasis, prolonging survival of tumor cells, and tumor angiogenesis. We evaluated APN expression in non-small-cell lung cancer patients...

Lung cancer is the leading cause of cancer death in Japan and still requires more effective treatments. The potential of cancer vaccines is promising, although there are no satisfactory protocols available for lung cancer at present. However, encouraging evidence of clinical benefits from cancer vaccines is beginning to accumulate in several lung c...

The Seventh Edition of the Tumor, Node, Metastasis Classification of Malignant Tumors in non-small cell lung cancer (NSCLC) proposes a more detailed classification of primary tumor diameter. Stage IA T1 disease is subdivided into two groups: T1a disease (tumor diameter, < or = 2 cm) and T1b disease (tumor diameter, >2 to < or = 3 cm). Tegafur-uraci...

In Japan, high incidences of interstitial lung disease (ILD) and ILD-related deaths have been reported among gefitinib-treated patients with non-small cell lung cancer (NSCLC). We investigated the efficacy of gefitinib, the incidence of ILD and risk factors for ILD in these patients. We obtained patient data retrospectively using questionnaires sen...

The cell-to-cell junction of endothelial cells (ECs) regulates the fence function of the vascular system. Previously we showed that ECs derived from embryonic stem cells (i.e., EECs) develop to form stable endothelial sheets in monolayer cultures. Immunohistochemical analysis revealed that these EECs formed intercellular junctions with the help of...

Lung cancer is an intractable disease urgently requiring more effective treatment approaches. The potential of immunotherapy in this context remains promising, although presently there are no satisfactory protocols available for lung cancer. However, encouraging evidence of clinical benefits from immunotherapy is beginning to accumulate in several...

The serious shortage of organs for transplantation, especially lungs, has drawn increasing attention to donation after cardiac death and protection of organs against warm ischemic injury. Atrial natriuretic peptide (ANP) activates guanylate cyclase receptors and increases cyclic guanosine monophosphate (cGMP) levels, which decrease in the lung duri...

The authors elucidated particular chemokine receptors that are expressed on lung cancer cells, as well as the clinical significance of the expression of these chemokine receptors in completely resected nonsmall cell lung cancer (NSCLC). The authors examined gene expression of chemokine receptors (CCR1-11, CXCR1-7, XCR1, and CX3CR1) in 11 cell lines...

Synovial sarcoma of the mediastinum is a rare neoplasm that has overlapping histological and immunophenotypic features with other tumors in the differential diagnosis. We describe a case of this disease. The tumor was located at the right side of the pericardium, where an FDG-PET scan showed an uptake. It was resected, a resection which was complic...

Liposarcomas are the most common soft tissue sarcomas in adults, although liposarcomas of the chest are uncommon. We report two cases of giant liposarcoma in the mediastinum and chest wall, respectively. An 82-year-old man presented with a mass in the right upper mediastinum, as seen by computed tomography (CT). He had a past history of subcutaneou...

Experimental studies have revealed that D2-40 is useful in identifying the presence of lymphatic invasion in various malignant neoplasms, but the clinical significance remains unclear. The purpose of this study is to assess the clinical significance of D2-40 status in completely resected non-small cell lung cancer. A total of 215 consecutive patien...

Management of pulmonary metastasis of non-small cell lung cancer (NSCLC) remains controversial. We reviewed our surgical treatment for pulmonary metastasis of NSCLC. Seventy-six patients with pulmonary metastasis of NSCLC underwent pulmonary resections in two institutes during the past 10 years. Eighteen patients with simultaneous same lobe metasta...

The prognosis of patients with malignant pleural effusion (MPE) is poor. An MPE model is necessary for developing new therapeutic strategies. We established a MPE model and investigated the therapeutic effects of the administration of serial doses of docetaxel on intrathoracic disseminated foci using an in vivo image system (IVIS). First, mice with...

Thioredoxin is a ubiquitous protein with anti-oxidative, anti-apoptotic, and anti-inflammatory effects. It was reported [Fukuse T, Hirata T, Yokomise H et al. Attenuation of ischaemia reperfusion injury by human thioredoxin. Thorax 1995; 50: 387-391] that rhTRX protected lungs from ischemia-reperfusion injury as a radical scavenger; however, the me...

Outcome for highly immunogenic lung transplantation remains unsatisfactory despite the development of potent immunosuppressants. The poor outcome may be the result of a lack of minimally invasive methods to detect early rejection. There is emerging clinical evidence that, paradoxically, expression of forkhead box P3 (FOXP3, a specific marker for th...

A lower temperature, namely below 0 degrees C, has been thought to be desirable for organ preservation because of the lower rate of metabolism; however, its benefits are still poorly understood. Supercooling is a non-freezing state of liquid below the freezing point, and the new development of a refrigerator for supercooling has now made it possibl...

We report here a successful case of balloon angioplasty for a stenosis of the pulmonary artery after lung transplantation. A 49-year-old patient with end stage diffuse bronchiectasis with sinusitis underwent bilateral living donor lobar lung transplantation. After treatment of postoperative right pneumothorax, a perfusion lung scan revealed deficie...

Introduction of spinal surgery into lung cancer operations has made extensive operations feasible with an acceptable long-term survival. We report our successful experience of en bloc total vertebrectomy for lung cancer invading the spine. A 49-year-old man was found to have squamous cell carcinoma of the posterior apex of the right lung with an in...

We previously reported a new method of segmentectomy, pulmonary artery-guided segmentectomy as a surgical alternative for small-sized early lung cancer with favorable results, but the follow-up time was too short for definitive conclusion. To examine the efficacy of the segmentectomy, and to determine the appropriate surgical procedure for early lu...

A method to compensate for donor shortages could be donation after cardiac death. In this study, we considered endothelial cell-specific molecules, claudin-5 and VE-cadherin, as possible biomarkers predicting lung injury against warm ischemia. We investigated how the expression of these molecules could change after cardiac arrest in a mouse lung, c...

A modeling study was carried out to provide a description of the critical current distribution of bent multifilamentary Bi2223/Ag/Ag alloy superconducting composite tape samples. In the modeling, the difference between the tensile fracture strain of the Bi2223 filaments along the sample length under no residual strain and residual strain was used a...

To evaluate the prognostic value of folate receptor alpha (FOLR1) and/or reduced folate carrier (RFC1) expression, which are well-characterized folate transporters, in completely resected non-small-cell lung cancer (NSCLC). We quantitatively examined gene expression of FOLR1 and RFC1 in surgical specimens resected from NSCLC patients. A total of 11...

Aurora-A, also known as STK15/BTAK, is a member of the protein serine/threonine kinase family, and experimental studies have revealed that Aurora-A plays critical roles in cell mitosis and in carcinogenesis. However, no clinical studies on Aurora-A expression in non-small-cell lung cancer (NSCLC) have been reported. Thus, the present study was cond...

Pemetrexed, a multi-targeted antifolate (MTA), is a promising agent in the treatment of malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC). With the aim of finding an optimal schedule for the combination therapy of MTA and gemcitabine (GEM), we investigated their interaction against an MPM cell line, 211H, and the NSCLC cel...

Radiofrequency ablation (RFA) is one of the minimally invasive therapeutic modalities for malignant tumors. However, the effects and risks associated with RFA on pulmonary tumors have not yet been well investigated. We pathologically examined the effects of RFA on the healthy pulmonary parenchyma in the inflated and deflated states of swine lungs....

Epidermal growth factor (EGF) receptor (EGFR) signalling is implicated in tumour invasion and metastasis. However, whether there are EGFR signalling pathways specifically used for tumour invasion still remains elusive. Overexpression of Arf6 and its effector, AMAP1, correlates with and is crucial for the invasive phenotypes of different breast canc...

ET-Kyoto solution (ET-K) is an extracellular-type organ preservation solution containing the cytoprotective disaccharide, trehalose. A previous study reported the supplement of dibutyryl cyclic adenosine monophosphate (db-cAMP) in conventional ET-K to attenuate lung ischemia-reperfusion injury. In this study, the efficacy of this modified ET-K for...

We investigated the clinical significance of E2F1 gene expression in relation to its target genes, thymidylate synthase (TS) and Survivin, in case of non-small-cell lung cancer (NSCLC). One hundred twenty-seven cases of resected NSCLC were analyzed. Quantitative reverse transcription-PCR was done to evaluate the gene expression of E2F1, TS, and Sur...

A 54-year-old woman was admitted to our hospital because of an abnormal shadow on chest X-ray. Chest computed tomography (CT) scan and magnetic resonance imaging (MRI) demonstrated an anterior mediastinal tumor. The tumor was resected completely through a median sternotomy. The tumor was dissected successfully from the surrounding vessels in spite...

We experienced 3 cases of viral infections after lung transplantation. Case 1: Fifty-two-year-old male with pulmonary emphysema underwent left single lung transplantation from a cadaveric donor. Three months after transplantation he presented Epstein-Barr virus (EBV) viremia, resulting in multiple lymphadenopathy. Biopsy showed post-transplant lymp...

Thioredoxin-1 (TRX) is a redox-active protein with anti-inflammatory effects. This study investigated the optimal delivery method and the mechanisms of recombinant human TRX (rhTRX) to suppress neutrophil recruitment in a rat bleomycin (BLM)-induced sustained acute lung injury model. In male Wister rats intratracheally administered with 0.125 mg/kg...

The scatter of critical current of bent Bi2223 composite tape was analyzed from a statistical viewpoint. It was revealed that the increase in scatter of the critical current beyond the irreversible bending strain is attributed to the heterogeneous damage evolution. Further modeling analysis, based on the heterogeneous damage evolution, revealed tha...

The mucin-type transmembrane glycoprotein podoplanin (also known as T1alpha, gp38 or Aggrus) is well established as one of the lymphatic-specific markers. Podoplanin was also reported to be associated with tumor-induced platelet aggregation and tumor metastasis. Here, we generated a novel monoclonal antibody (clone; 7B10) that specifically recogniz...

It is now well established that the interaction between "inducer" cells of hemopoietic origin and "organizer" cells of mesenchymal lineage is involved in the organogenesis of lymph node (LN) and Peyer's patch (PP). Organizer cells are defined by the expression of VCAM-1 and ICAM-1 and the production of homeostatic chemokines. However, several studi...

7647 Background: This study evaluates the influence of gender on survival and tumor recurrence in patients with completely resected stage IA and IB adenocarcinoma of the lung based on the analysis of the Japan Lung Cancer Research Group trial, which was a randomized prospective study of adjuvant chemotherapy with uracil-tegaful for stage I pulmonar...

Background. In a case of a endobronchial tumor originating from a main bronchus presenting complete lung atelectasis, it is sometimes difficult to decide the peripheral resection line even with detailed imaging including multidimensional CT scan and MRI. Case. A 20-year-old woman with persistent hemoptysis was referred to our hospital because an oc...

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are reported to be associated with clinical responsiveness of lung cancer to gefitinib, an EGFR tyrosine kinase inhibitor. To elucidate the association between somatic mutations and the pharmacological actions of gefitinib, the chemosensitivity of is...

Tissue inhibitor of metalloproteinase-3 (TIMP-3) inhibits the activity of metalloproteinases that play important roles in development and progression of malignant tumors. We conducted a retrospective study of TIMP-3 expression in resected non-small cell lung cancer (NSCLC). TIMP-3 expression was examined immunohistochemically in primary tumor speci...

Fms-like tyrosine kinase 1 (Flt-1), a receptor for vascular endothelial growth factor (VEGF), have two isoforms: membrane-bound form (mFlt-1) and soluble form. In the present study, we quantitatively evaluated expression level of mFlt-1 mRNA and VEGF mRNA in non-small cell lung cancer, and demonstrated the clinical significance of the ratio of mFlt...

We report a case of malignant melanoma of the lung of unknown origin. Case. A 50-year-old man was admitted to our hospital because of an abnormal shadow on chest roentgenogram and bilateral multiple pulmonary nodules on chest CT. Right upper lobectomy was carried out and the histological diagnosis of the tumor was malignant melanoma. Two nodules of...

In this paper we examined the influence of epidermal growth factor receptor (EGFR) gene mutations on EGFR expression, downstream mediators, and survival in patients with non-small cell lung cancer (NSCLC). We retrospectively analyzed the tumors of 53 patients with completely resected pathological stage I-IIIA NSCLC for the presence of EGFR gene mut...

Mediastinal germ cell tumor (MGCT) is histologically similar to, but is different from that in gonad glands. As to therapy, mature teratoma can be cured by resection alone. But cisplatin-based chemotherapy, often together with resection and radiation, has been playing a primary role in managing malignant MGCT consisting of seminoma and non-seminoma...

Living-donor lobar lung transplantation (LDLLT) has been applied to patients with various end-stage lung diseases. The recurrence of pulmonary lymphangioleiomyomatosis (LAM) after lung transplantation has been rarely reported. Herein, we report a case of recurrent pulmonary LAM after LDLLT. A 24-year-old woman presented with pneumothorax and infilt...

Non-heart-beating donors are expected to ameliorate shortages of donors for organ transplantation. The issue of preventing warm ischemic injury after circulatory arrest must be investigated. In the current study, we investigated whether isoflurane inhalation during warm ischemia could attenuate ischemia reperfusion injury (IRI) of the lung. An isol...

Maspin is a member of the serpin (serine protease inhibitor) superfamily, and its exact function in the development and progression of malignant tumors remains controversial, though some experimental studies have revealed potential tumor-suppressor activities. In addition, there have been only a few clinical studies on maspin expression in malignan...

A 72-year-old man who had been diagnosed with second recurrent lung cancer was referred for consideration of a surgical resection. He had undergone a right upper lobectomy with bronchoplasty for the primary lung cancer and stereotactic radiation therapy for the first recurrent tumor. Owing to the comorbid diseases, video-assisted wedge resection an...

We report two cases of bilateral diffuse bronchiectasis in which early recurrence of the original lung disease occurred after bilateral lung transplantation (LT). Patient 1 underwent cadaveric LT. Recurrent bronchiectasis occurred 4 months later, and he died 6 years after LT. Patient 2 underwent living-related lobar LT, bronchiectasis relapsed 4 mo...

The discovery of vascular endothelial growth factor C (VEGF-C) and VEGF receptor-3 (VEGFR-3) has started to provide an understanding of the molecular mechanisms of lymphangiogenesis. The homeobox gene prox1 has been proven to specify lymphatic endothelial cells (ECs) from blood ECs. We investigated the process of lymphatic EC (LEC) differentiation...

We present a case of pulmonary sclerosing hemangioma with multiple involvements. Pulmonary sclerosing hemangioma is a relatively rare neoplasm. Although it is thought to be benign, cases with lymph node metastasis or multiple pulmonary involvement have been reported in clinical settings. To date, no case has been reported with mortality due to scle...

The sensitivity to 5-fluorouracil (5-FU) has been reported to be associated with target molecule thymidylate synthase (TS), fluoropyrimidine-metabolising enzymes such as orotate phosphoribosyltransferase (OPRT), and dihydropyrimidine dehydrogenase (DPD). We performed an immunohistochemical study on the clinical significance of TS, OPRT, and DPD exp...

It seems inevitable that non-beating-heart donors will be utilized to resolve the shortage of donors for clinical lung transplantation. The control of warm ischemia-reperfusion injury is crucial in manipulating non-beating-heart donors. We hypothesized that nebulization of a beta2-adrenoreceptor agonist, salmeterol xinafoate (SLM), during warm isch...