Risk Factors for Severe Dysphagia after Concurrent Chemoradiotherapy for Head and Neck Cancers

The aim of this study was to investigate the risk factors for dysphagia induced by chemoradiotherapy for head and neck cancers. Forty-seven patients with head and neck cancers who underwent definitive chemoradiotherapy from December 1998 to March 2006 were reviewed retrospectively. Median age was 63 years (range, 16-81). The locations of the primary lesion were as follows: larynx in 18 patients, oropharynx in 11, nasopharynx in 7, hypopharynx in 7 and others in 4. Clinical stages were as follows: Stage II in 20 and Stages III-IV in 27. Almost all patients underwent platinum-based concomitant chemoradiotherapy. The median cumulative dose of cisplatin was 100 mg/m(2) (range, 80-300) and median radiation dose was 70 Gy (range, 50-70). Severe dysphagia (Grade 3-4) was observed in 22 patients (47%) as an acute toxic event. One patient required tube feeding even at 12-month follow-up. In univariate analysis, clinical stage (III-IV) (P = 0.017), primary site (oro-hypopharynx) (P = 0.041) and radiation portal size (> 11 cm) (P < 0.001) were found to be associated with severe dysphagia. In multivariate analysis, only radiation portal size was found to have a significant relationship with severe dysphagia (P = 0.048). Larger radiation portal field was associated with severe dysphagia induced by chemoradiotherapy.ArticleJAPANESE JOURNAL OF CLINICAL ONCOLOGY. 39(7):413-417 (2009)journal articl

Validation of the Total Dysphagia Risk Score (TDRS) as a predictive measure for acute swallowing dysfunction induced by chemoradiotherapy for head and neck cancers

Background and purpose: Methods for predicting acute swallowing dysfunction in patients with head and neck cancers undergoing definitive chemoradiotherapy have not been established. We investigated the validity of the Total Dysphagia Risk Score (TDRS) as a predictive measure for this morbidity. Materials and methods: Forty-seven patients with head and neck cancers who underwent definitive chemoradiotherapy between December 1998 and March 2006 were reviewed retrospectively. Median age was 63 years (range, 16-81). Almost all patients underwent platinum-based concomitant chemoradiotherapy. Factors of the TDRS were as follows: T-classification, neck irradiation, weight loss, primary tumour site and treatment modality. Patients were classified into three risk groups according to the TDRS. Results: Swallowing dysfunction was observed in 27 patients (57%) as RTOG grade 2 or higher acute morbidity. This classification was significantly associated with grade 2 or higher acute swallowing dysfunction (P = 3) acute swallowing dysfunction was similarly obtained. Conclusion: The TDRS is a useful tool to predict acute swallowing dysfunction induced by chemoradiotherapy for head and neck cancers.ArticleRADIOTHERAPY AND ONCOLOGY. 97(1):132-135 (2010)journal articl

Lzts1 controls both neuronal delamination and outer radial glial-like cell generation during mammalian cerebral development

発生期の大脳で分化細胞と未分化細胞の移動開始をもたらす共通の分子を解明 --「大脳のシワ」形成に貢献する外側放射状グリアはどのように誕生するか--. 京都大学プレスリリース. 2019-07-08.In the developing central nervous system, cell departure from the apical surface is the initial and fundamental step to form the 3D, organized architecture. Both delamination of differentiating cells and repositioning of progenitors to generate outer radial glial cells (oRGs) contribute to mammalian neocortical expansion; however, a comprehensive understanding of their mechanisms is lacking. Here, we demonstrate that Lzts1, a molecule associated with microtubule components, promotes both cell departure events. In neuronally committed cells, Lzts1 functions in apical delamination by altering apical junctional organization. In apical RGs (aRGs), Lzts1 expression is variable, depending on Hes1 expression levels. According to its differential levels, Lzts1 induces diverse RG behaviors: planar division, oblique divisions of aRGs that generate oRGs, and their mitotic somal translocation. Loss-of-function of lzts1 impairs all these cell departure processes. Thus, Lzts1 functions as a master modulator of cellular dynamics, contributing to increasing complexity of the cerebral architecture during evolution

Polycomb repressive complex 1.1 coordinates homeostatic and emergency myelopoiesis

Polycomb repressive complex (PRC) 1 regulates stem cell fate by mediating mono-ubiquitination of histone H2A at lysine 119. While canonical PRC1 is critical for hematopoietic stem and progenitor cell (HSPC) maintenance, the role of non-canonical PRC1 in hematopoiesis remains elusive. PRC1.1, a non-canonical PRC1, consists of PCGF1, RING1B, KDM2B, and BCOR. We recently showed that PRC1.1 insufficiency induced by the loss of PCGF1 or BCOR causes myeloid-biased hematopoiesis and promotes transformation of hematopoietic cells in mice. Here we show that PRC1.1 serves as an epigenetic switch that coordinates homeostatic and emergency hematopoiesis. PRC1.1 maintains balanced output of steady-state hematopoiesis by restricting C/EBPα-dependent precocious myeloid differentiation of HSPCs and the HOXA9- and β-catenin-driven self-renewing network in myeloid progenitors. Upon regeneration, PRC1.1 is transiently inhibited to facilitate formation of granulocyte-macrophage progenitor (GMP) clusters, thereby promoting emergency myelopoiesis. Moreover, constitutive inactivation of PRC1.1 results in unchecked expansion of GMPs and eventual transformation. Collectively, our results define PRC1.1 as a novel critical regulator of emergency myelopoiesis, dysregulation of which leads to myeloid transformation