Retrospective Study of Selective Submandibular Neck Dissection versus Radical Neck Dissection for N0 or N1 Necks in Level I Patients with Oral Squamous Cell Carcinoma

Objective. To evaluate the efficacy of selective submandibular neck dissection (SMND) in patients with oral squamous cell carcinoma (OSCC) with or without nodal metastasis. Patients. From a total of 384 patients with untreated OSCC who underwent radical excision, we identified 229 with clinically N0 necks and 68 with clinically N1 necks in level I. Main Outcome Measures. The Kaplan-Meier 5-year regional control and 5-year disease specific survival (DSS) were compared for SMND, radical neck dissection (RND), and modified radical neck dissection (MRND). Results. In clinically node-negative necks, the regional control rates were 85.2% with SMND and 83.3% with MRND (P = 0.89), and 5-year DSS rates were 86.5% and 87.0%, respectively, (P = 0.94). In clinically N1 necks, the regional control rates were 81.3% with SMND and 83.0% with RND (P = 0.72), and the DSS rates were 81.3% and 80.0%, respectively, (P = 0.94). Type of neck dissection was not significantly associated with regional control or DSS on either univariate or multivariate analysis using Cox's proportional hazard model. Conclusions. SMND can be effectively applied in elective and therapeutic management to patients with OSCC that are clinically assessed as N0 or N1 to level I of the neck

FEASIBILITY STUDY ON THE FUSION OF PHITS SIMULATIONS AND THE DLNN ALGORITHM

We have recently have developed an in-situ multiple-channel depth distribution spectrometer (DDS) that can easily acquire on-site measurements of the depth distribution of specific radioactivities of Cs-134 and Cs-137 underground. Despite considerable improvements in the hardware developed for this device, the quantitative method for determining of radioactivities with this DDS device cannot yet achieve satisfactory performance for practical use. For example, this method cannot discriminate each γ-ray spectra of Cs-134 and Cs-137 acquired by the 20 thallium-doped caesium iodine CsI(Tl) scintillation crystal detectors of the DDS device from corresponding depth levels of underground soil. Therefore, we have applied deep learning neural network (DLNN) as a novel radiation measurement technique to discriminate the spectra and to determine the specific radioactivities of Cs-134 and Cs-137. We have developed model soil layers on a virtual space in Monte-Carlo based PHITS simulations and transported γ-ray radiation generated from a particular single soil layer or multiple layers as radiation sources; next, we performed PHITS calculations of those specific radioactivity measurements for each soil layer using DDS device based on machine learning via the DLNN algorithm. In this study, we obtained informative results regarding the feasibility of the proposal innovative radiation measurement method for further practical use in on-site applications

T-box transcription factor Brachyury is associated with prostate cancer progression and aggressiveness

Purpose: Successful therapy of patients with prostate cancer is highly dependent on reliable diagnostic and prognostic biomarkers. Brachyury is considered a negative prognostic factor in colon and lung cancer; however, there are no reports on Brachyury’s expression in prostate cancer. Experimental Design: In this study, we aimed to assess the impact of Brachyury expression in prostate tumorigenesis using a large series of human prostate samples comprising benign tissue, prostate intraepithelial neoplasia (PIN) lesions, localized tumor, and metastatic tissues. The results obtained were compared with what can be inferred from the Oncomine database. In addition, multiple in vitro models of prostate cancer were used to dissect the biologic role of Brachyury in prostate cancer progression. Results: We found that Brachyury is significantly overexpressed in prostate cancer and metastatic tumors when compared with normal tissues, both at protein and at mRNA levels. Brachyury expression in the cytoplasm correlates with highly aggressive tumors, whereas the presence of Brachyury in the nucleus is correlated with tumor invasion. We found that Brachyury-positive cells present higher viability, proliferation, migration, and invasion rates than Brachyury-negative cells. Microarray analysis further showed that genes co-expressed with Brachyury are clustered in oncogenic-related pathways, namely cell motility, cellcycle regulation, and cell metabolism. Conclusions: Collectively, the present study suggests that Brachyury plays an important role in prostate cancer aggressiveness and points, for the first time, to Brachyury as a significant predictor of poor prostate cancer prognosis. Our work paves the way for future studies assessing Brachyury as a possible prostate cancer therapeutic target.This study was supported by the ICVS internal research funds of participating authors and by the FCT project, ref. PTDC/SAU-MET113415/2009. F. Pinto and N. Pertega-Gomes received fellowships from the FCT, ref. SFRH/BD/81369/2011 and SFRH/BD/61027/2009, respectively. R. P. Andrade was funded by Ciencia2007 Program Contract and Programa Operacional Regional do Norte (ON. 2) - NORTE-07-0124-FEDER-000017

Clinical Study Retrospective Study of Selective Submandibular Neck Dissection versus Radical Neck Dissection for N0 or N1 Necks in Level I Patients with Oral Squamous Cell Carcinoma

Objective. To evaluate the efficacy of selective submandibular neck dissection (SMND) in patients with oral squamous cell carcinoma (OSCC) with or without nodal metastasis. Patients. From a total of 384 patients with untreated OSCC who underwent radical excision, we identified 229 with clinically N0 necks and 68 with clinically N1 necks in level I. Main Outcome Measures. The Kaplan-Meier 5-year regional control and 5-year disease specific survival (DSS) were compared for SMND, radical neck dissection (RND), and modified radical neck dissection (MRND). Results. In clinically node-negative necks, the regional control rates were 85.2% with SMND and 83.3% with MRND (P = 0.89), and 5-year DSS rates were 86.5% and 87.0%, respectively, (P = 0.94). In clinically N1 necks, the regional control rates were 81.3% with SMND and 83.0% with RND (P = 0.72), and the DSS rates were 81.3% and 80.0%, respectively, (P = 0.94). Type of neck dissection was not significantly associated with regional control or DSS on either univariate or multivariate analysis using Cox's proportional hazard model. Conclusions. SMND can be effectively applied in elective and therapeutic management to patients with OSCC that are clinically assessed as N0 or N1 to level I of the neck

Brachyury oncogene is a prognostic factor in high-risk testicular germ cell tumors

The T-box transcription factor Brachyury has been considered a cancer-specific marker and a novel oncotarget in solid tumors. Brachyury overexpression has been described in various cancers, being associated with epithelial-mesenchymal transition, metastasis, and poor prognosis. However, its clinical association with testicular germ cell tumor is unknown. We analyzed the expression of Brachyury by immunohistochemistry in a series of well-characterized testicular germ cell tumor samples and at transcript level by in silico analysis. Additionally, we aimed to investigate the clinical significance of Brachyury in testicular germ cell tumor. Brachyury cytoplasm immunostaining was present in 89.6% (86/96) of cases with nuclear staining observed in 24% (23/96) of testicular germ cell tumor. Bioinformatics microarray expression analysis of two independent cohorts of testicular germ cell tumors showed similar results with increased levels of Brachyury in testicular germ cell tumors and metastasis compared with normal testis. Clinically, Brachyury nuclear staining was statistically associated with lower event-free survival (p = 0.04) and overall survival (p = 0.01) in intermediate/high-risk testicular germ cell tumors. Univariate analysis showed that Brachyury nuclear subcellular localization was a predictor of poor prognosis (p = 0.02), while a tendency was observed by multivariate analysis (HR: 3.56, p = 0.06). In conclusion, these results indicate that Brachyury plays an oncogenic role in testicular germ cell tumors and its subcellular localization in the nucleus may constitute a novel biomarker of poor prognosis and a putative oncotarget for intermediate/high-risk testicular germ cell tumor patients.ICVS internal research funds, by the Portuguese FCT project (PTDC/SAU‐TOX/114549/2009‐FCOMP‐01‐0124‐FEDER‐016057) to Reis RM and Barretos Cancer Hospital Internal Research Fund. F. Pinto received a fellowship from FCT ref SFRH/BD/81369/2011 and SFRH/BPD/115730/2016). Project ON.2 SR&TD Integrated Program (NORTE‐07‐0124‐FEDER‐000017) cofinanced by Programa Operacional Regional do Norte (ON.2—O Novo Norte), Quadro de Referência Estratégico Nacional (QREN), Fundo Europeu de Desenvolvimento Regional (FEDER)info:eu-repo/semantics/publishedVersio

口腔癌におけるBrachyury発現と上皮間葉移行の関与 : 予後因子としての応用の可能性

要旨 緒言 材料と方法 考察 総括 謝辞 引用文献Made available in DSpace on 2012-06-07T07:14:09Z (GMT). No. of bitstreams: 1 dent554.pdf: 1878188 bytes, checksum: 005209acd04fbd4599095bb7e834bbe9 (MD5) Previous issue date: 2012-03-27歯学府_歯学癌浸潤・転移は治療を困難にする最も重要な因子である。転移には細胞生物学的にダイナミックな細胞特性の変化と多段階の過程を経ることが知られており、近年、その過程における上皮間葉移行（epithelial-mesenchymal transition:EMT）の関与が数多く報告されている。さらにT-box転写因子のひとつであるBrachyuryがEMTを誘導することが報告された。しかし、臨床検体を用いてBrachyury発現とEMTの関連を検討した報告は、これまでに口腔癌を含むすべての癌種において見られない。そこで本研究では、腺様嚢胞癌と扁平上皮癌の未治療生検組織を用いて、EMTおよびBrachyury発現と臨床的背景因子との関連、Brachyury発現とEMTの関連について検討した。 1．腺様嚢胞癌におけるBrachyury発現とEMTの関与 腺様嚢胞癌（AdCC）21例の未治療生検組織におけるBrachyury、E-cadherin、Vimentinの発現様式を免疫組織化学的に検索した。それぞれのタンパク質の陽性率はBrachyury:100％（21/21例）、E-cadherin:90.5％（19/21例）、Vimentin:90.5%（19/21例）と症例の分布に偏りがあったため、VimentinおよびBrachyury発現と臨床的背景因子との関連、Brachyury発現とEMTとの関連は検討できなかった。また、E-cadherin発現と臨床的背景因子との関連も認められなかった。患者の10年生存率および無病生存率についてKaplan-Meier法にて検討を行ったところ、Vimentin発現とは相関が認められなかったが、E-cadherin発現およびEMTと生存率に相関が認められた（p<0.001,p=0.001）。Brachyury発現には陰性症例がなく相関の検討が出来なかった。 2．扁平上皮癌におけるBrachyury発現とEMTの関与 扁平上皮癌（SCC）152例の未治療生検組織におけるBrachyury、E-cadherin、Vimentinの発現様式を免疫組織化学的に検索した。それぞれのタンパク質の陽性率はBrachyury:71.1％（108/152例）、E-cadherin:68.4％（104/152例）Vimentin:18.4%（28/152例）であった。臨床的背景因子のうちE-cadherin発現と関連を認めたものは、リンパ節転移、遠隔転移、腫瘍の分化度、腫瘍の浸潤様式（いずれもp<0.05）であり、Vimentin発現はリンパ節転移、遠隔転移、腫瘍の浸潤様式（いずれもp<0.05）と関連が認められた。Brachyury発現と関連を認めたものは、腫瘍の大きさ（T分類）、リンパ節転移、腫瘍の分化度、腫瘍の浸潤様式（いずれもp<0.05）であった。E-cadherinの発現低下とVimentinの発現をEMTと定義し、Brachyury発現とEMTの関連を検討したところ、Brachyury発現様式とVimentinの発現およびEMTに関連が認められた（p=0.002,p=0.035）。検索したBrachyury、E-cadherin、Vimentinの分子のうちどれが最もリンパ節転移、遠隔転移と相関するかロジスティック回帰分析を用いて検索したところ、単変量解析において、リンパ節転移はすべての分子と相関し、特にBrachyury発現（p=0.001, オッズ比4.390）と最も強く相関していた。遠隔転移はBrachyury発現との相関は認められず、E-cadherin発現（p=0.001,オッズ比0.113）と最も強く相関した。5年生存率、無病生存率についてKaplan-Meier法にて検討を行ったところ、Brachyury、E-cadherin、Vimentinの発現はすべて強い相関が認められた。AdCCは症例数が尐なく統計学的な解析が困難であったが、SCCと比較したBrachyury陽性率の高さはAdCCの高転移性を示す可能性があると考えられる。以上より、口腔癌におけるBrachyury発現とEMTの関与が示され、口腔癌特にSCCの予後因子として臨床応用が可能であると考えられた