Le fédéralisme et la Révolution française : pour comprendre le républicanisme français

Federalism and the French Revolution: Towards an understanding of French Republicanism Even today, in the twenty-first century, the tendency towards centralization of power is strong in France. Now, however, at least in Europe with the creation of the EU, the framework of the unitary state itself is in question. Therefore, in such an environment is centralization as can be seen in France still acceptable? In order to answer this question, we shall examine the French people’s understanding of the state through a study of the French Revolution; the cradle of the French nation state. For this research, we will examine the concept of the one and indivisible republic and federalism from both the philosophical and the linguistic points of view. 21世紀を迎えた現在においても、フランスでは中央集権的志向が強い。しかし、現在はヨーロッパ統合の時代であり、少なくともヨーロッパにおいては、単一国家という枠組みは試練を受けようとしている。このような環境において、フランスのような中央集権体制は望ましいのであろうか。この問いに答えるためには、フランス国民国家形成の契機となったフランス革命にまで遡り、フランス人の国家に関する、一にして不可分の共和国の観念と、それに対比されるフェデラリスムについて調査することが、有効であると思われる。本論文はそれらに対し、言語学的研究、思想史的研究を試みるものである

Novel quantitative immunohistochemical analysis for evaluating PD-L1 expression with phosphor-integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitors

IntroductionProgrammed cell death ligand 1 (PD-L1) expression in tumor tissues is measured as a predictor of the therapeutic efficacy of immune checkpoint inhibitors (ICIs) in many cancer types. PD-L1 expression is evaluated by immunohistochemical staining using 3,3´-diaminobenzidine (DAB) chronogenesis (IHC-DAB); however, quantitative and reproducibility issues remain. We focused on a highly sensitive quantitative immunohistochemical method using phosphor-integrated dots (PIDs), which are fluorescent nanoparticles, and evaluated PD-L1 expression between the PID method and conventional DAB method.MethodsIn total, 155 patients with metastatic or recurrent cancer treated with ICIs were enrolled from four university hospitals. Tumor tissue specimens collected before treatment were subjected to immunohistochemical staining with both the PID and conventional DAB methods to evaluate PD-L1 protein expression.ResultsPD-L1 expression assessed using the PID and DAB methods was positively correlated. We quantified PD-L1 expression using the PID method and calculated PD-L1 PID scores. The PID score was significantly higher in the responder group than in the non-responder group. Survival analysis demonstrated that PD-L1 expression evaluated using the IHC-DAB method was not associated with progression-free survival (PFS) or overall survival (OS). Yet, PFS and OS were strikingly prolonged in the high PD-L1 PID score group.ConclusionQuantification of PD-L1 expression as a PID score was more effective in predicting the treatment efficacy and prognosis of patients with cancer treated with ICIs. The quantitative evaluation of PD-L1 expression using the PID method is a novel strategy for protein detection. It is highly significant that the PID method was able to identify a group of patients with a favorable prognosis who could not be identified by the conventional DAB method

AN AWARENESS SURVEY OF SURGEONS INVOLVED IN BREAST CANCER TREATMENT REGARDING THEIR PATIENTS RETURNING TO WORK

Surgeons focus on the period of absence from work during the initial treatment of breast cancer. The aim of this study was to determine surgeons’ perceptions and awareness regarding the necessary period of absence from work during breast cancer treatment. We created a questionnaire for all surgeons involved in breast cancer treatment who are affiliated with the Department of Surgery at the Nagoya University Graduate School of Medicine and its associated facilities. The necessary leave of absence period for each treatment was considered, and the decision regarding whether patients should return to work was examined. The surgeons were instructed to assume that a ‘heavy load worker’ was a nurse or caregiver and that a ‘light load worker’ was a medical office worker. This study included 184 surgeons (response rate: 96.8%). More than half of the surgeons considered that light load workers could return to work within 2 weeks; 89.8% after conservative resection, 71.6% after total mastectomy, 50.3% after axillary dissection. In contrast, more than half of the surgeons considered that heavy load worker should wait returning to work more than 3 weeks; 49.4% after conservative resection, 73.3% after total mastectomy, 85.7% after axillary dissection. For patients treated with chemotherapy, three-quarters of the surgeons indicated that it would be difficult to work while receiving anthracycline regimens. The results suggest that surgeons can predict the approximate period of absence from work for patients who receive an initial treatment of breast cancer

Synaptotagmin 13 Is Highly Expressed in Estrogen Receptor-Positive Breast Cancer

Background: Accumulating evidence indicates tumor-promoting roles of synaptotagmin 13 (SYT13) in several cancers; however, no studies have investigated its expression in breast cancer (BC). This study aimed to clarify the significance of SYT13 in BC. Methods: SYT13 mRNA expression levels were evaluated in BC cell lines. Polymerase chain reaction (PCR) array analysis was conducted to determine the correlation between expression levels of SYT13 and other tumor-associated genes. Then, the association of SYT13 expression levels in the clinical BC specimens with patients’ clinicopathological factors was evaluated. These findings were subsequently validated using The Cancer Genome Atlas (TCGA) database. Results: Among 13 BC cell lines, estrogen receptor (ER)-positive cells showed higher SYT13 mRNA levels than ER-negative cells. PCR array analysis revealed positive correlations between SYT13 and several oncogenes predominantly expressed in ER-positive BC, such as estrogen receptor 1, AKT serine/threonine kinase 1, and cyclin-dependent kinases 4. In 165 patients, ER-positive specimens exhibited higher SYT13 mRNA expression levels than ER-negative specimens. The TCGA database analysis confirmed that patients with ER-positive BC expressed higher SYT13 levels than ER-negative patients. Conclusion: This study suggests that SYT13 is highly expressed in ER-positive BC cells and clinical specimens, and there is a positive association of SYT13 with the ER signaling pathways

Bevacizumab Exacerbates Paclitaxel-Induced Neuropathy: A Retrospective Cohort Study

<div><p>Background</p><p>Bevacizumab (BEV), a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, enhances the antitumor effectiveness of paclitaxel (PTX)-based chemotherapy in many metastatic cancers. A recent study in mice showed that VEGF receptor inhibitors can interfere with the neuroprotective effects of endogenous VEGF, potentially triggering the exacerbation of PTX-induced neuropathy. In clinical trials, exacerbation of neuropathy in patients who received PTX combined with BEV (PTX+BEV) has generally been explained by increased exposure to PTX owing to the extended duration of chemotherapy. We investigated whether the concurrent use of BEV is associated with the exacerbation of PTX-induced neuropathy.</p><p>Methods</p><p>Female patients with breast cancer who had received weekly PTX or PTX+BEV from September 2011 through May 2016 were studied retrospectively. PTX-induced neuropathy was evaluated at the same time points (at the 6^th and 12^th courses of chemotherapy) in both cohorts. A multivariate Cox proportional-hazards model was used to assess the independent effect of BEV on the time to the onset of neuropathy.</p><p>Results</p><p>A total of 107 patients (median age, 55 years; range, 32–83) were studied. Sixty-one patients received PTX as adjuvant chemotherapy, 23 received PTX for metastatic disease, and 23 received PTX+BEV for metastatic disease. Peripheral sensory neuropathy was worse in patients who received PTX+BEV than in those who received PTX alone: at the 6^th course, Grade 0/1/2/3 = 4/13/4/0 vs. 25/42/6/0 (<i>P</i> = 0.095); at the 12^th course, 2/3/11/3 vs. 7/30/23/2 (<i>P</i> = 0.016). At the 12^th course, the incidence of Grade 2 or higher neuropathy was significantly higher in patients treated with PTX+BEV than in those treated with PTX alone (74% vs. 40%; <i>P</i> = 0.017). In multivariate analysis, BEV was significantly associated with an increased risk of neuropathy (HR 2.32, 95% CI 1.21–4.44, <i>P</i> = 0.012).</p><p>Conclusions</p><p>The concurrent use of BEV could worsen PTX-induced neuropathy in patients with breast cancer.</p></div