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(A) WB analysis of HER2 expression after exposure of the indicated SCLC cells to CDDP at IC10 and IC50 concentrations for the indicated times. (B) WB analysis of HER2 expression after exposure of SBC-3 and SBC-5 cells to ETP and CPT-11 at their IC50 concentrations. All experiments were repeated at least three times with similar results. ETP: etoposide, CPT-11: irinotecan.

WB analysis for downstream intracellular signaling of HER2 after exposure to CDDP (IC50 concentration), trastuzumab (1 μg/ml), and CDDP plus trastuzumab.

The primer sequences for qRT-PCR analysis

Small cell lung cancer (SCLC) accounts for 15% of all lung cancer cases and is a highly lethal disease. For the last several decades, the standard treatment for SCLC has been deadlocked, and new therapeutic strategies are urgently needed. HER2 is a member of the HER family and has been reported to be overexpressed in 30% of SCLC cases with poor prognosis. However, the clinical relevance of HER2-targeted therapy for SCLC remains unclear. Here, we first identify that cytotoxic drugs induce significant HER2 overexpression through microRNA-125a (miR-125a) and miR-125b downregulation, which in turn act as a novel therapeutic target for trastuzumab-mediated cellular cytotoxicity in SCLC. In this study, we showed that treatment of the HER2-positive SCLC cells, SBC-3 and SBC-5, with cytotoxic drugs induced a significant upregulation of HER2. Cisplatin (CDDP) treatment of SCLC cells resulted in a significant downregulation of miR-125a and miR-125b. We confirmed that miR-125a and miR-125b bound to the 3′-untranslated regions of HER2 mRNA, and that downregulation of miR-125a and miR-125b resulted in upregulation of HER2 in SCLC cells, suggesting a relationship between cytotoxic drug exposure and miR-125/HER2 dysregulation. Furthermore, using a calcein assay, we demonstrated a significantly enhanced cytotoxic effect of CDDP and trastuzumab that was mediated via antibody-dependent cellular cytotoxicity. Finally, we clearly demonstrated the enhanced antitumor effect of these agents in an orthotopic lung cancer model in vivo. Our results offer a novel therapeutic strategy for HER2-positive SCLCs by using trastuzumab combined with cytotoxic drugs. Mol Cancer Ther; 14(6); 1414–23. ©2015 AACR.

From the viewpoint of self-medication, it is valuable to develop patient-friendly scored tablets that possess dividing uniformity. In this context, we attempted to optimize the preparation conditions for a tablet with a unique shape, such as a concavely curved scored tablet (CCST). Employing a design of experiment and a response surface method incorporating a thin-plate spline interpolation, and a bootstrap resampling technique, the optimal preparation conditions for CCST were successfully developed. To make it possible to scaleup the optimal solution estimated on a trial-scale, a Bayesian estimation was applied. Credible ranges of critical responses in large-scale manufacturing were estimated as a posterior probability from the trial-scale experiment as a prior probability. In terms of the large-scale manufacturing, the possibility of solving the scaleup problem was suggested using Bayesian estimation. Furthermore, a simulation study using a finite element method revealed that strong tensile stresses generated along the tip of the score line in CCST when an outer force was applied to the back surface of CCST. An advantage in dividing uniformity is indicated by the unique shape of CCST.

Introduction The Public Health Center (PHC)—known as hokenjo in Japan—assume a crucial role in disease control. Coronavirus disease 2019 (COVID-19) is one of many designated infectious diseases monitored by the agency. During the present pandemic, patients who suspected COVID-19 were instructed to call the Coronavirus Consultation Center in the PHC prior to visiting the hospital. The aim of this study was to elucidate the differences in polymerase chain reaction (PCR) positivity between PHC referrals and direct walk-in patients. Methods The present was a single-center, retrospective cohort study conducted at the Tokyo Metropolitan Hospital from March to September, 2020. Patients who received a PCR test for SARS-CoV-2 were included and categorized into the PHC referral or direct walk-in groups. The outcomes included the total number of patients undergoing PCR tests and the percentage of PCR positivity in each group. Results We identified 1680 patients (781 PHC referred and 899 direct walk-in groups). The percentage of PCR positivity did not significantly differ between the PHC referral and direct walk-in groups during the first wave (30.5% vs. 29.2%; p = 0.78). PCR positivity was significantly higher in the PHC referral group than the direct walk-in group during the second wave (30.1% vs. 23.1%; p = 0.051) and entire study period (30.2% vs. 24.7%; p = 0.011). Conclusions Despite health authority recommendations, the number of direct walk-in patients were higher than PHC referral patients. The percentage of PCR positivity was significantly higher in the PHC referral group than in the direct walk-in group.

Summary Background In the LYM-3002 study, the efficacy and safety of frontline bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were compared in transplant-ineligible patients with untreated, newly diagnosed, mantle cell lymphoma. We report the final overall survival and safety outcomes for patients in the long-term follow-up phase after the primary progression-free-survival endpoint was met. Methods LYM-3002 was a randomised, open-label, phase 3 study done at 128 clinical centres in 28 countries in Asia, Europe, North America, and South America. Adult patients with confirmed stage II–IV previously untreated mantle cell lymphoma, Eastern Cooperative Oncology Group performance status score of 2 or less, who were ineligible for bone marrow transplantation, were randomly assigned (1:1) to receive six or eight 21-day cycles of VR-CAP (intravenous rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and bortezomib 1·3 mg/m2, plus oral prednisone 100 mg/m2) or R-CHOP (intravenous vincristine 1·4 mg/m2 [2 mg maximum], rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, and doxorubicin 50 mg/m2, plus oral prednisone 100 mg/m2). Randomisation was done according to a computer-generated randomisation schedule prepared by the sponsor; permuted blocks central randomisation was used (block size of 4), and was stratified by International Prognostic Index score and disease stage at diagnosis. The primary endpoint of this final analysis was overall survival, which was analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov , number NCT00722137 , and is closed to new participants with follow-up completed. Findings Between May 22, 2008, and Dec 5, 2011, 487 patients were enrolled and randomly assigned. 268 patients (140 in the VR-CAP group and 128 in the R-CHOP group) were included in the follow-up analysis, which included patients with data available after the primary analysis clinical cutoff date of Dec 2, 2013. After median follow-up of 82·0 months (IQR 74·1–94·2), median overall survival was significantly longer in the VR-CAP group than in the R-CHOP group (90·7 months [95% CI 71·4 to not estimable] vs 55·7 months [47·2 to 68·9]; hazard ratio 0·66 [95% CI 0·51–0·85]; p=0·001). Three new adverse events were reported since the primary analysis cutoff (one each of grade 4 lung adenocarcinoma and grade 4 gastric cancer in the VR-CAP group, and one case of grade 2 pneumonia in the R-CHOP group). 103 (42%) of 243 patients in the VR-CAP group, and 138 (57%) of 244 in the R-CHOP group died; the most common cause of death was progressive disease. Interpretations Compared with R-CHOP, VR-CAP was associated with significantly longer survival, and had a manageable and expected safety profile. Our results support further assessment of VR-CAP in patients with previously untreated mantle cell lymphoma. Funding Janssen Research & Development.

Studies that have evaluated the prognostic value of body mass index (BMI) in patients with diffuse large B-cell lymphoma have recently been reported. However, the impact of BMI on survival outcomes remains controversial. We retrospectively analyzed the data of 406 diffuse large B-cell lymphoma patients treated with R-CHOP or R-CHOP-like regimens. The number (%) of patients that were categorized into 1 of 4 groups according to BMI were underweight (

Central nervous system (CNS) relapse in patients with diffuse large B cell lymphoma (DLBCL) is an uncommon event, and the outcome of patients with CNS relapse is poor. However, no reliable prediction models for CNS relapse have been developed. We retrospectively analyzed consecutive de novo DLBCL patients referred to our department between September 2004 and August 2015 and treated with R-CHOP or R-CHOP-like regimens. Of 413 patients analyzed in this study, a total of 27 patients (6.5 %) eventually developed CNS relapse. The 5-year probability of CNS relapse was 8.4 %. The median time from diagnosis of DLBCL to CNS relapse was 15 months, and the median survival after CNS relapse was 7 months. In univariate analysis, the risk factors significantly associated with CNS relapse were Ann Arbor stage 3 or 4, albumin level3.2 mg/L, number of extranodal sites1, and involvement of retroperitoneal lymph node. We developed a new prognostic model consisting of these four factors. The 5-year probability of CNS relapse was significantly higher in patients with at least three of these four factors than in those with two or fewer factors (26.4 vs. 3.0 %, P 0.001). Using this model, we evaluated the incidence and the risk factors of CNS relapse in DLBCL patients. The new risk model consisting of the four factors demonstrated good risk stratification for CNS relapse, and could help to identify high-risk patients for whom CNS prophylaxis is warranted.

Various types of circulating tumor cell (CTC) detection systems have recently been developed that show a high CTC detection rate. However, it is a big challenge to find a system that can provide better prognostic value than CellSearch in head-to-head comparison. We have developed a novel semi-automated CTC enumeration system (fluidic cell microarray chip system, FCMC) that captures CTC independently of tumor-specific markers or physical properties. Here, we compared the CTC detection sensitivity and the prognostic value of FCMC with CellSearch in breast cancer patients. FCMC was validated in preclinical studies using spike-in samples and in blood samples from 20 healthy donors and 22 breast cancer patients in this study. Using spike-in samples, a statistically higher detection rate (p = 0.010) of MDA-MB-231 cells and an equivalent detection rate (p = 0.497) of MCF-7 cells were obtained with FCMC in comparison with CellSearch. The number of CTC detected in samples from patients that was above a threshold value as determined from healthy donors was evaluated. The CTC number detected using FCMC was significantly higher than that using CellSearch (p = 0.00037). CTC numbers obtained using either FCMC or CellSearch had prognostic value, as assessed by progression free survival. The hazard ratio between CTC + and CTC − was 4.229 in CellSearch (95% CI, 1.31 to 13.66; p = 0.01591); in contrast, it was 11.31 in FCMC (95% CI, 2.245 to 57.0; p = 0.000244). CTC detected using FCMC, like the CTC detected using CellSearch, have the potential to be a strong prognostic factor for cancer patients.

Previous reports have evaluated the prognostic value of serum beta-2 microglobulin (B2MG) level in patients with non-Hodgkin lymphoma. However, its role in predicting clinical outcome of patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era has not been extensively investigated. Here, we evaluated the prognostic value of B2MG and proposed a new prognostic model including B2MG for patients with DLBCL. A total of 274 patients with newly diagnosed de novo DLBCL were retrospectively analyzed. We defined the best cutoff value as 3.2 mg/L by using a receiver operating characteristic curve. Patients with a B2MG level ≥3.2 mg/L had significantly lower overall survival (OS) and progression-free survival than those with a B2MG level

Methods for the enumeration and molecular characterization of circulating tumor cells (CTC) have been actively investigated. However, such methods are still technically challenging. We have developed a novel epithelial cell adhesion molecule independent CTC enumeration system integrated with a sorting system using a microfluidics chip. We compared the number of CTC detected using our system with those detected using the CellSearch system in 46 patients with various cancers. We also evaluated epidermal growth factor receptor (EGFR) and PIK3CA mutations of captured CTC in a study of 4 lung cancer and 4 breast cancer patients. The percentage of samples with detected CTC was significantly higher with our system (65.2%) than with CellSearch (28.3%). The number of detected CTC per patient using our system was statistically higher than that using CellSearch (median 5, 0; P = 0.000172, Wilcoxon test). In the mutation analysis study, the number of detected CTC per patient was low (median for lung, 4.5; median for breast, 5.5); however, it was easy to detect EGFR and PIK3CA mutations in the CTC of 2 lung and 1 breast cancer patient, respectively, using a commercially available kit. Our system is more sensitive than CellSearch in CTC enumeration of various cancers and is also capable of detecting EGFR and PIK3CA mutations in the CTC of lung and breast cancer patients, respectively.

Background Clinical efficacy of second- and later-line chemotherapy for patients with thymic carcinoma previously treated with chemotherapy remains uncertain; limited data are available about this carcinoma because of its rarity. The aim of this study was to investigate effective chemotherapy for patients with thymic carcinoma previously treated with chemotherapy using a retrospective analysis of responses and times to event. Patients and Methods We conducted a retrospective review of the medical records of 23 advanced thymic carcinoma patients previously treated with palliative-intent chemotherapy between 1980 and 2014 in our institution. Clinical demographic characteristics, agents, response, and time to treatment failure for each treatment line and overall survival were reviewed. Factors expected to be associated with survival rates were analyzed. Differences in survival were assessed using Kaplan–Meier analysis and univariate and multivariate Cox proportional hazards regression analyses. Results The study included 13 men (56.5%) and 10 women (43.5%). The median age at diagnosis was 58.5 years. The most common histological subtypes were squamous cell carcinoma (16 patients [69.6%]), followed by neuroendocrine carcinoma (4 patients [17.4%]). The objective response rates of first-, second-, third-, and fourth-line chemotherapy were 60.9%, 39.1%, 23.1%, and 25.0%, respectively. The median survival time was 18.8 months (95% confidence interval, 7.5-40.9 months). Uni- and multivariate analyses of all assessed variables failed to identify any statistically significant indicators of overall survival. Conclusion Patients with thymic carcinoma previously treated with palliative-intent chemotherapy might respond to second- or later-lines of cytotoxic chemotherapy.

No standard therapy for peripheral T-cell lymphomas (PTCLs) has been established, and treatment outcomes are poor. Upfront stem cell transplantation has been investigated in several studies, some of which have reported promising outcomes. However, some patients maintain long-term remission after chemotherapy alone. It is thus important to predict sensitivity to first-line chemotherapy to optimize treatment strategies. In the present study, we retrospectively analyzed time to treatment failure (TTF) of first-line chemotherapy in 59 patients with PTCLs. On multivariate analysis for TTF, elevated lactate dehydrogenase level, hypoalbuminemia, and high neutrophil-to-lymphocyte ratio were significant prognostic factors. Using these three factors, we also developed a new model that effectively distinguished patient outcomes. The TTF rate at 1 year from diagnosis was 71.4% in patients with score 0 (0 factor), 31.8% with score 1 (1 factor) and 4.5% with score 2 (2–3 factors) (P

Background Heterogenous clinical or biological features are characteristic of thymic carcinoma. Well-defined clinical entities remain unclear because of rarity. The aim of this study was to clarify disease profiles, outcomes, and prognostic factors for survival among patients diagnosed with thymic carcinoma. Patients and methods A retrospective review was conducted of the medical records of 68 thymic carcinoma patients among 187 patients diagnosed with thymic epithelial tumors between 1980 and 2013 in our institution. Clinical demographics, histology, overall survival, and factors expected to predict survival were analyzed. Differences in survival were assessed using Kaplan–Meier analysis and uni- and multivariate Cox proportional hazards regression analyses. Results The study included 38 males (55.9%) and 30 females (44.1%). The median age at diagnosis was 63.5 years. The most common subtypes of thymic carcinoma were squamous cell carcinoma (69.1%), neuroendocrine carcinoma (16.2%), and mucoepidermoid carcinoma (5.9%). Masaoka-Koga staging of the 68 patients demonstrated no patients (0%) in Stage I, 3 (4.3%) in Stage II, 14 (20.6%) in Stage III, 12 (17.6%) in Stage IVa, and 39 (57.4%) in Stage IVb. The median survival time for all stages was 36.4 months (95% confidence interval 23.7–56.4); those for stages II, III, IVa, and IVb were: not reached, 65.8, 24.6, and 27.3 months, respectively. The difference by Masaoka-Koga staging was significant ( p =0.04). Overall survival rates at 1-, 5-, and 10-year were 76.3%, 36.0%, and 6.2%, respectively. By univariate analyses, the only favorable prognostic factor for overall survival was surgical intervention ( p =0.03), and, for Stage IVb, lymphatic metastasis without distant metastasis. However, clinically interesting variants did not differ significantly for predicting survival. Conclusion Surgical intervention results in better survival of thymic carcinoma, even in Stage IVb. The survival value of administration of curative-intent radiotherapy, or of identification of "resectability" in Stage IVb patients must continue to be discussed.

Positron emission tomography–computed tomography (PET–CT) is performed as the standard method for response assessment of diffuse large B cell lymphoma (DLBCL) patients. However, a substantial proportion of patients experience relapse even if they have achieved complete response (CR) defined by PET–CT. We validated the prognostic value of CR by PET–CT and applied the National Comprehensive Cancer Network-International Prognostic Index (NCCN–IPI) and cell of origin (COO) to patients with CR by PET–CT to evaluate their additional predictive ability for survival outcomes. We retrospectively analyzed DLBCL patients who were treated with R-CHOP or an R-CHOP-like regimen and who achieved CR by PET–CT or CT only. A total of 185 patients were analyzed: 114 patients achieved CR by PET–CT and 71 patients by CT only. Patients with CR by PET–CT had significantly better overall survival (OS) than those with CR by CT (5-year OS, 87.5 vs. 62.4%, P = 0.003). Patients with high risk according to the NCCN–IPI had a dismal outcome despite achieving CR by PET–CT (5-year OS, 61.8%). In contrast, low-, low-intermediate-, and high-intermediate-risk patients had excellent outcomes (5-year OS, 100, 89.7, and 93.5%, respectively). Among patients with CR by PET–CT, patients with germinal center B cell (GCB) DLBCL (n = 40) had significantly better survival than those with non-GCB DLBCL (n = 57) (5-year OS, 96.9 vs. 75.5%, P = 0.039). We demonstrated that CR by PET–CT was a better predictor of survival outcomes than CR by CT only. The NCCN–IPI and COO subtypes could identify a subpopulation of poor-risk patients among those who achieved CR by PET–CT.

Diffuse large B-cell lymphoma (DLBCL) is the most common subgroup of non-Hodgkin lymphoma.[1] The survival outcome of older patients with DLBCL has improved dramatically with addition of rituximab ...

The Japan Clinical Oncology Group conducted two multicenter phase II trials in 200 patients with advanced Hodgkin lymphoma (HL) in the 1990s. Among 181 patients whose histopathological specimens were available and reviewed by 6 hematopathologists, 167 (92.3%) were diagnosed with HL. Five-year overall survival (OS) among these 167 patients was 88.3%, including 89.2% among nodular sclerosis and 82.2% among mixed cellularity cases. International prognostic score was not closely associated with OS. Seven unfavorable prognostic factors for OS on univariate analysis were male, B symptoms, clinical stage of III or IV, elevated serum LDH, elevated alkaline phosphatase, elevated beta2-microglobulin, and pathological subtype (mixed cellularity and lymphocyte depletion). On multivariate analysis, male [HR 3.30 (95% CI 1.15-9.52, p = 0.027)] and elevated serum LDH [HR 2.41 (95% CI 1.07-5.43, p = 0.034)] were independent factors for OS. Based on these prognostic factors, the 5-year OS was 95.7% in the low-risk group (no adverse factor), 87.9% in the intermediate-risk group (1 adverse factor) and 73.3% in the high-risk group (2 adverse factors). This simple prognostic model for HL warrants further validation studies.

Although most of the time drying operation aims at controlling the mean batch behavior, the quality of the final product is often related to the individual behavior of the supplied materials in a batch. The mean batch models provide limited information for quality evaluation studies. Since the initial physical and thermal properties of rice powder in a batch influence the final condition of product dried with a pneumatic dryer, a Monte Carlo simulation with initial random parameters is useful to investigate the individual behavior of rice particle during pneumatic drying. In this study, we analyzed the influence of initial moisture content and particle diameter of rice powder on the conditions of the final product in pneumatic drying process. Samples of initial moisture content and particle diameter distributions were generated by means of the covariance decomposition algorithm and Monte Carlo simulations with 5000 runs based on momentum, energy and mass balances between drying air and rice particles were performed to obtain the profiles of the response variables, rice powder temperature, moisture content and particle diameter, in a pneumatic dryer. The developed pneumatic conveying drying (PCD) model could describe the complex behavior of rice particles in a batch.

Diffuse large B-cell lymphoma (DLBCL) is the most common subgroup of non-Hodgkin lymphoma.[1] The International Prognostic Index (IPI) was developed more than 20 years ago based on the clinical dat...

Previous reports have evaluated the prognostic value of serum beta-2 microglobulin (B2MG) level in patients with non-Hodgkin lymphoma. However, its role in predicting clinical outcome of patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era has not been extensively investigated. Here, we evaluated the prognostic value of B2MG and proposed a new prognostic model including B2MG for patients with DLBCL. A total of 274 patients with newly diagnosed de novo DLBCL were retrospectively analyzed. We defined the best cutoff value as 3.2 mg/L by using a receiver operating characteristic curve. Patients with a B2MG level ≥3.2 mg/L had significantly lower overall survival (OS) and progression-free survival than those with a B2MG level3.2 mg/L (3-year OS, 50.9% vs. 89.4%, p 0.001; 3-year progression-free survival, 45.3% vs. 79.7%, p 0.001). Multivariate analysis showed that B2MG, age, performance status, and Ann Arbor stage were independent prognostic factors for OS. We developed a new prognostic model consisting of these four significant factors. We stratified patients into four-risk groups: low (L, 0 factor), low-intermediate (LI, 1-2 factors), high-intermediate (HI, 3 factors), high (H, 4 factors). This new prognostic model showed better risk discrimination compared with the National Comprehensive Cancer Network-International Prognostic Index (5-year OS: 100% and 23.4% vs. 100% and 27.1%, in L and H risk groups, respectively). Our study suggested that B2MG level is a significant prognostic factor in patients with DLBCL. A new prognostic index composed of age, performance status, stage, and B2MG could stratify the outcomes of patients with DLBCL effectively and appears to be a valuable risk model for these patients. Copyright © 2016 John WileySons, Ltd.

We are developing device-level neural networks using poly-Si TFTs. We succeeded in dramatically reducing the number of transistors in neurons and synapses to integrate a lot of devices, and we also succeeded in actually checking the operation of learning of logics. In this presentation, for the purpose of improvement of learning efficiency, we changed the synapse TFTs from the SD structure to the LDD structure. As a result, we succeeded in improving the learning efficiency by a 5×5 neural network.

We report here the effectiveness of chemoradiotherapy for a patient with local recurrence followed by curable gastrectomy. A 57-year-old man presented with a history of total gastrectomy with distal pancreatectomy and splenectomy, D2 lymphadenectomy, and Roux-en-Y reconstruction for advanced gastric cancer arising from the cardia. Esophageal intramural metastasis and lymph node metastasis around the right recurrent nerve were detected by chest-abdominal computed tomography and gastrointestinal endoscopy 27 months after the initial gastrectomy. Stable disease was achieved following 7 courses of chemotherapy using S-1 plus CDDP. Concurrent chemoradiotherapy including administration of S-1 and radiation of total 50 Gy (2 Gy/25 Fr) was selected for local tumor control. The patient was not able to eat solid food because of esophageal stenosis from regrowth of intramural metastasis of the esophagus 60 months after the chemotherapy. A WallFlex™ Duodenal Stent was placed to improve the dysphagia 67 months after chemotherapy. The patient died from recurrence of gastric cancer 69 months after completion of the initial chemotherapy and 2 months after the stent insertion.

A practical method for the preparation of TAK-603 , an antirheumatic drug, has been developed. As a result of optimizing the Friedel–Crafts reaction in the presence of SnCl4/POCl3, 2-aminobenzophenone skeleton, the key intermediate of TAK-603 , was formed with good yield. The selective substitution reaction of 1,2,4-triazole was accomplished using 4-amino-1,2,4-triazole and deamination.

Small cell lung cancer (SCLC) accounts for 15% of all lung cancer cases and is a highly lethal disease. For the last several decades, the standard treatment for SCLC has been deadlocked, and new therapeutic strategies are urgently needed. HER2 is a member of the HER family and has been reported to be overexpressed in 30% of SCLC cases with poor prognosis. However, the clinical relevance of HER2-targeted therapy for SCLC remains unclear. Here, we first identify that cytotoxic drugs induce significant HER2 overexpression through microRNA-125a (miR-125a) and miR-125b downregulation, which in turn act as a novel therapeutic target for trastuzumab-mediated cellular cytotoxicity in SCLC. In this study, we showed that treatment of the HER2-positive SCLC cells, SBC-3 and SBC-5, with cytotoxic drugs induced a significant upregulation of HER2. Cisplatin (CDDP) treatment of SCLC cells resulted in a significant downregulation of miR-125a and miR-125b. We confirmed that miR-125a and miR-125b bound to the 3′-untranslated regions of HER2 mRNA, and that downregulation of miR-125a and miR-125b resulted in upregulation of HER2 in SCLC cells, suggesting a relationship between cytotoxic drug exposure and miR-125/HER2 dysregulation. Furthermore, using a calcein assay, we demonstrated a significantly enhanced cytotoxic effect of CDDP and trastuzumab that was mediated via antibody-dependent cellular cytotoxicity. Finally, we clearly demonstrated the enhanced antitumor effect of these agents in an orthotopic lung cancer model in vivo. Our results offer a novel therapeutic strategy for HER2-positive SCLCs by using trastuzumab combined with cytotoxic drugs. Mol Cancer Ther; 14(6); 1414–23. ©2015 AACR.

We have evaluated photoconductivities in diode connections using n-ch, p-ch, and pin-ch poly-Si TFTs for photosensor application. It is found that the photoconductivities increase as the illuminance increases for all the TFTs, but they do not change so much as the applied voltage changes. Moreover, the photoconductivities are: p-ch TFT

BACKGROUND The clinical significance of proteinuria has not been fully understood among patients who are affected with non-Hodgkin lymphoma (NHL). METHODS A 1-year prospective cohort study was conducted to ascertain the association between proteinuria and mortality in 46 hospitalized NHL patients. Proteinuria was defined as persistent dipstick test >= 1+, and the urinary protein creatinine ratio (UPCR),as a quantitative index of protein excretion, was measured simultaneously. A multivariable linear regression model was constructed to determine factors associated with UPCR. Statistical associations between proteinuria and time to mortality were analyzed using the Kaplan-Meier method and multivariable proportional hazards regression analysis, adjusted for covariates including disease severity, renal function, and serum interleukin-6(IL-6) concentration. RESULTS The prevalence of proteinuria was 15.2% in the NHL patients. UPCR was significantly associated with the serum IL-6 level (standardized beta = 0.360, p = 0.0440). The cumulative mortality was significantly higher in proteinuric patients than in non-proteinuric patients, with a graded relationship between the severity of UPCR and mortality. The mortality risk increased with increasing UPCR grade: the hazard ratio (95% confidence interval) was 4.90 (1.29 - 32.3) for UPCR 30 - 300 mg/gand 17.8 (2.84 - 150) for UPCR > 300 mg/g, respectively, when UPCR < 30 mg/g was set as the reference. CONCLUSIONS Proteinuria is a simple sign of coexisting systemic inflammation due to NHL and a harbinger of a poor prognosis.

We have evaluated an artificial retina using thin-film devices driven by wireless power supply. It is found that the illumination profile can be correctly detected as the output voltage profile even if it is driven using unstable wireless power supply. Particularly in this presentation, we confirm correct working of pattern recognition.

食品のマイクロ波加熱過程における殺菌・抑菌効果を動的に予測するためのソフトウェアを開発した.本ソフトは3次元熱移動と菌体の滅菌速度式を基礎としている.基礎方程式を数値解析法により解き,鶏胸肉のマイクロ波加熱過程におけるSalmonella sp.およびListeria innocuaの生存曲線を動的に予測した.ソフトウェアのプログラム開発はVisual Basic言語(Microsoft Co.)により行い,直方体の大きさ・加熱条件に関する情報を入力することで殺菌完了時間,冷点温度を計算して,これらの結果を表示する仕組みとなっている.本研究は,コンピュータ計算による食品の熱殺菌評価を行う上での指針となるものであり,食品のマイクロ波加熱殺菌装置設計支援ツール開発の一助となる成果である.

Hickman catheters are useful for vascular access after bone marrow transportation because they can handle large volume and allow for easy transfusions and blood drawing through wide double lumens making it easier to case for patients under sterile conditions in a clean room. However, the safety of Hickman catheters as compared to Silastic catheters in marrow transplants has never been discussed. We therefore retrospectively reviewed the complications of two catheters in 71 allogeneic bone marrow transplant recipients between September 1986 and August 1994. The complication and infection rates of Hickman catheters were 0.21 and 0.09 per 100 device-life days, and rate of temperature >38° during leukocytopenia (

We report multidisciplinary treatment of 3 patients with lymph node recurrence after curative gastrectomy. Case 1: A 71- year-old woman had a history of distal gastrectomy with D2 lymphadenectomy for the treatment of advanced gastric cancer. Para-aortic lymph node metastasis was observed 36 months after surgery. Complete response( CR) was achieved after concurrent chemoradiotherapy with S-1 plus radiation. Case 2: A 51-year-old man had a history of total gastrectomy with D2 lymphadenectomy for the treatment of advanced gastric cancer. Right cervical lymph node metastasis was observed 48 months after surgery. CR was achieved after concurrent chemoradiotherapy with S-1 plus radiation. Case 3: A 68-year-old man had a history of distal gastrectomy with D2 lymphadenectomy followed by neoadjuvant chemotherapy for the treatment of advanced gastric cancer. CR was achieved after sequential treatment with irinotecan( CPT-11) plus cisplatin( CDDP), radiation, and 5-fluorouraci(l 5-FU) plus Leucovorin therapy for lymph node recurrence near the head of the pancreas. These cases suggest that the combination of systemic chemotherapy and local radiation therapy might be effective for the treatment of lymph node recurrence in patients with gastric cancer.

No current circulating tumor cell (CTC) enumeration system provides better prognostic value than CellSearch. We have developed a novel semi-automated CTC enumeration system (fluidic cell microarray chip system, FCMC) that captures CTC independently of tumor-specific markers or physical properties. This system was validated in preclinical studies and in blood samples from 20 healthy donors and 22 breast cancer patients in this study. Using spike-in samples, a statistically higher detection rate (p = 0.010) of MDA-MB-231 cells and an equivalent detection rate (p = 0.497) of MCF-7 cells were obtained with FCMC in comparison with CellSearch. The number of CTC detected in samples from patients that was above a threshold value as determined from healthy donors was evaluated. The CTC number detected using FCMC was significantly higher than that using CellSearch (p = 0.00037). CTC numbers obtained using either FCMC or CellSearch had prognostic value, as assessed by time-to-treatment-failure. The hazard ratio between CTC+ and CTC- was 4.043 in CellSearch (95% CI, 1.248 to 13.10; p = 0.01985); in contrast, it was 10.97 in FCMC (95% CI, 2.18 to 55.21; p = 0.003662). CTC detected using FCMC have the potential to be a better prognostic factor than CTC detected using CellSearch. Citation Format: Takeshi Sawada, Jungo Araki, Toshinari Yamashita, Manami Masubuchi, Tsuneko Chiyoda, Mayu Yunokawa, Kumiko Hoshi, Shoichi Tao, Shohei Yamamura, Shouki Yatsushiro, Kaori Abe, Masatoshi Kataoka, Tatsu Shimoyama, Yoshiharu Maeda, Katsumasa Kuroi, Kenji Tamura, Tsuneo Sawazumi, Hironobu Minami, Yoshihiko Suda, Fumiaki Koizumi. Prognostic impact of CTC detected using a novel fluidic cell microarray chip CTC detection system in patients with breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 500.

A 74-year-old female, who had been treated at the out-patient-clinic after total gastrectomy for a gastric cancer 8 years before, was admitted to the hospital with a suspicion of ileus, because left upper abdominal pain developed without any inductions. A chest X-ray film taken 3 days after admission showed abnormal gas shadow with air fluid level (niveau) in the left pleural cavity. Colonography revealed an obstruction of the colon at the splenic curvature and intestinal juice like fluid was discharged from left thoracic drainage. A diagnosis of perforation of the colon strangulated to diaphlagmatic herniation was made. Under thoraco-laparotomy, the herniaiton was recognized in the site of Foramen Bochdalek, so direct closure of the hernia opening and resection of the necrotic colon were carried out. There was no hernia sac, and the size of opening 1.2cm in diameter was the smallest in the literature reported previously.