Results of Proton Beam Therapy without Concurrent Chemotherapy for Patients with Unresectable Stage III Non-small Cell Lung Cancer

Introduction:This study was performed retrospectively to evaluate the outcome of patients with stage III non-small cell lung cancer (NSCLC) after proton beam therapy (PBT) alone.Methods:The subjects were 57 patients with histologically confirmed NSCLC (stage IIIA/IIIB: 24/33) who received PBT without concurrent chemotherapy. The cohort included 32 cases of squamous cell carcinoma, 18 adenocarcinoma, and 7 non-small cell carcinoma. Lymph node metastases were N0 7, N1 5, N2 30, and N3 15. Planned total doses ranged from 50 to 84.5 GyE (median, 74 GyE).Results:Planned treatment was completed in 51 patients (89%). At the time of analysis, 20 patients were alive, and the median follow-up periods were 16.2 months for all patients and 22.2 months for survivors. The median overall survival period was 21.3 months (95% confidence interval: 14.2–28.4 months), and the 1- and 2-year overall survival rates were 65.5% (52.9–78.0%) and 39.4% (25.3–53.5%), respectively. Disease progression occurred in 38 patients, and the 1- and 2-year progression-free survival rates were 36.2% (23.1–49.4%) and 24.9% (12.7–37.2%), respectively. Local recurrence was observed in 13 patients, and the 1- and 2-year local control rates were 79.1% (66.8–91.3%) and 64.1% (47.5–80.7%), respectively. Grade ≥3 lung toxicity was seen in six patients, esophageal toxicity occurred at grade ⩽2, and there was no cardiac toxicity.Conclusion:The prognosis of patients with unresectable stage III NSCLC is poor without chemotherapy. Our data suggest that high-dose PBT is beneficial and tolerable for these patients

Hypoxia promotes the phenotypic change of aldehyde dehydrogenase activity of breast cancer stem cells

Stable breast cancer cell (BCC) lines are valuable tools for the identification of breast cancer stem cell (BCSC) phenotypes that develop in response to several stimuli as well as for studying the basic mechanisms associated with the initiation and maintenance of BCSCs. However, the characteristics of individual, BCC-derived BCSCs varies and these cells show distinct phenotypes depending on the different BCSC markers used for their isolation. Aldehyde dehydrogenase (ALDH) activity is just such a recognized biomarker of BCSCs with a CD44+/CD24− phenotype. We isolated BCSCs with high ALDH activity (CD44+/CD24−/Aldefluorpos) from a primary culture of human breast cancer tissue and observed that the cells had stem cell properties compared to BCSCs with no ALDH activity (CD44+/CD24−/Aldefluorneg). Moreover, we found Aldefluorpos BCSCs had a greater hypoxic response and subsequent induction of HIF-1α expression compared to the Aldefluorneg BCSCs. We also found that knocking down HIF-1α, but not HIF-2α, in Aldefluorpos BCSCs led to a significant reduction of the stem cell properties through a decrease in the mRNA levels of genes associated with the epithelial-mesenchymal transition. Indeed, HIF-1α overexpression in Aldefluorneg BCSCs led to Slug and Snail mRNA increase and the associated repression of E-cadherin and increase in Vimentin. Of note, prolonged hypoxic stimulation promoted the phenotypic changes of Aldefluorneg BCSCs including ALDH activity, tumorigenesis and metastasis, suggesting that hypoxia in the tumor environment may influence BCSC fate and breast cancer clinical outcomes

特発性血小板減少性紫斑病に対する経尿道的尿管砕石術および体外衝撃波砕石術

特発性血小板減少性紫斑病(ITP)は, 抗血小板抗体により血小板減少を来たす自己免疫性疾患である。血小板減少による出血性素因は, 各種治療を困難にする。今回われわれは, 本疾患2症例に対し, ガンマグロブリン大量療法を行った後, 経尿道的尿管砕石術(TUL)および体外衝撃波砕石術(ESWL)が施行可能であったので報告する。症例1は52歳, 女性, 症例2は65歳, 女性, 静脈性腎盂造影にて左尿管結石症および両側尿管結石症と診断された。ガンマグロブリン大量療法と血小板輸血により血小板数は増加し, TULおよびESWLを合併症なく施行可能であった。ITPに対するガンマグロブリン大量療法後のESWL施行例は, 本報告が初めてである。ガンマグロブリン大量療法は, ITP症例において外科的治療を施行するにあたり, 十分な血小板数を得られる有効な方法であると考えられた。(著者抄録)Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease defined by a low platelet count secondary to accelerated platelet destruction by anti-platelet antibodies. The resulting bleeding diathesis can present a therapeutic dilemma. We have treated two cases of ITP in which ureteral stones were successfully extracted by transurethral ureterolithotripsy (TUL) and extracorporeal shock wave lithotripsy (ESWL) after high-dose gamma-globulin therapy. The first case was in a 52-year-old woman and the second case was in a 65-year-old woman. Intravenous pyelography revealed a left ureteral stone in the first case and bilateral ureteral stones in the second case. High-dose gamma-globulin therapy and platelet transfusion elevated their platelet counts to safe levels; TUL and ESWL were then performed successfully with no bleeding complications. This is the first case report of ITP being treated by ESWL after high-dose gamma-globulin therapy. High-dose gamma-globulin therapy effectively provides adequate platelet counts for surgical treatment in patients with ITP

Differences in Expression of Toll-Like Receptors and Their Reactivities in Dendritic Cells in BALB/c and C57BL/6 Mice

We have previously reported that differences in early production of interleukin 12 (IL-12) by dendritic cells (DC) underlies the difference between the susceptibilities to Listeria monocytogenes of C57BL/6 and BALB/c mice. To elucidate mechanisms for the different abilities of DC to produce cytokine in C57BL/6 and BALB/c mice, we examined Toll-like receptor (TLR) expression by DC and their responses in vitro to known microbial ligands for TLRs. We found that DC isolated from the spleens of naive C57BL/6 mice preferentially expressed TLR9 mRNA, whereas DC from naive BALB/c mice strongly expressed TLR2, -4, -5, and -6 mRNAs. C57BL/6 DC produced a higher level of IL-12p40 in response to the ligands for TLR4 (lipopolysaccharide), TLR2 (lipoprotein), and TLR9 (CpG), whereas BALB/c DC responded to these ligands by producing a larger amount of monocyte chemoattractant protein 1. C57BL/6 DC expressed higher levels of CD40 and Stat4 than BALB/c DC did, suggesting that naive C57BL/6 mice contained more-mature subsets of DC than naive BALB/c mice. Differences in reactivities of DC to microbial molecules through TLRs may be associated with susceptibility and resistance to Listeria infection in BALB/c and C57BL/6 mice

Optically controlled magnetic-field etching onthe nano-scale

Open access articleInternational audienceElectric and magnetic fields play an important role in both chemical and physical reactions. However, since the coupling efficiency between magnetic fields and electrons is low in comparison with that between electric fields and electrons in the visible wavelength region, the magnetic field is negligible in photo-induced reactions. Here, we performed photo-etching of ZrO2 nano-stripe structures, and identified an etching-property polarisation dependence. Specifically, the etching rate and etched profiles depend on the structure width.To evaluate this polarisation-dependent etching, we performed numerical calculations using a finite-difference time-domain method. Remarkably, the numerical results revealed that the polarisation-dependent etching properties were determined by the magnetic field distributions, rather than the electric field distributions. As nano-scale structures induce a localised magnetic field, the discovery of this etching dependence on the magnetic field is expected to introduce a new perspective on advanced nano-scale structure fabricatio

Nanogravure douce induite par la composante magnétique du champ lumineux

posterNational audienc

Development of Gentle Slope Light Guide Structure in a 3.4 μm Pixel Pitch Global Shutter CMOS Image Sensor with Multiple Accumulation Shutter Technology

CMOS image sensors (CISs) with global shutter (GS) function are strongly required in order to avoid image degradation. However, CISs with GS function have generally been inferior to the rolling shutter (RS) CIS in performance, because they have more components. This problem is remarkable in small pixel pitch. The newly developed 3.4 µm pitch GS CIS solves this problem by using multiple accumulation shutter technology and the gentle slope light guide structure. As a result, the developed GS pixel achieves 1.8 e− temporal noise and 16,200 e− full well capacity with charge domain memory in 120 fps operation. The sensitivity and parasitic light sensitivity are 28,000 e−/lx·s and −89 dB, respectively. Moreover, the incident light angle dependence of sensitivity and parasitic light sensitivity are improved by the gentle slope light guide structure