Two cases of radiation-associated angiosarcoma of the breast

Abstract Background The incidence of radiation-associated angiosarcoma (RAA) of the breast has been increasing, and its prognosis is reportedly poor. It is important to remove tumor tissues completely to prevent recurrence. Case presentation We report two cases of patients with RAA of the breast. Both patients had a nodule in their remaining breast a few years after undergoing breast-conserving surgery and radiation therapy for breast cancer. The nodules were diagnosed as angiosarcoma by skin biopsy and open biopsy, respectively. To determine the extent of lesion spread, mapping biopsy was performed before surgery. Both patients underwent mastectomy, extensive skin resection, and split skin grafting. Pathological findings showed that their tumors could be completely resected. After surgery, chemotherapy was performed. Conclusion In our cases, no local or distant recurrence has been detected in either patient for over 4 years. We identified the range of tumor invasion by preoperative mapping biopsy and completely resected all tumor tissue

Recurrent malignant peritoneal mesothelioma treated by a second resection: A case report

Key Clinical Message Malignant peritoneal mesothelioma, a rare and poor prognosis disease, is seldom treated surgically, especially for recurrence. However, early diagnosis and aggressive treatment of primary and recurrent tumors can achieve long‐term patient survival. Abstract Malignant peritoneal mesothelioma (MPM) is a rare and aggressive tumor, and rarely indicated for surgery, especially for recurrence. In the present case, we report a rare case who could survive long‐term after two surgeries in 4 years for MPM

An Integrative Analysis to Identify Driver Genes in Esophageal Squamous Cell Carcinoma

<div><p>Background</p><p>Few driver genes have been well established in esophageal squamous cell carcinoma (ESCC). Identification of the genomic aberrations that contribute to changes in gene expression profiles can be used to predict driver genes.</p><p>Methods</p><p>We searched for driver genes in ESCC by integrative analysis of gene expression microarray profiles and copy number data. To narrow down candidate genes, we performed survival analysis on expression data and tested the genetic vulnerability of each genes using public RNAi screening data. We confirmed the results by performing RNAi experiments and evaluating the clinical relevance of candidate genes in an independent ESCC cohort.</p><p>Results</p><p>We found 10 significantly recurrent copy number alterations accompanying gene expression changes, including loci 11q13.2, 7p11.2, 3q26.33, and 17q12, which harbored <i>CCND1</i>, <i>EGFR</i>, SOX2, and <i>ERBB2</i>, respectively. Analysis of survival data and RNAi screening data suggested that <i>GRB7</i>, located on 17q12, was a driver gene in ESCC. In ESCC cell lines harboring 17q12 amplification, knockdown of <i>GRB7</i> reduced the proliferation, migration, and invasion capacities of cells. Moreover, siRNA targeting <i>GRB7</i> had a synergistic inhibitory effect when combined with trastuzumab, an anti-<i>ERBB2</i> antibody. Survival analysis of the independent cohort also showed that high <i>GRB7</i> expression was associated with poor prognosis in ESCC.</p><p>Conclusion</p><p>Our integrative analysis provided important insights into ESCC pathogenesis. We identified <i>GRB7</i> as a novel ESCC driver gene and potential new therapeutic target.</p></div

Identification of Genes that Predict Lymph Node Metastasis in Colorectal Cancer Cases

大腸癌の罹患率は依然高いが，早期癌の発見率も増加し，主にピットパターンなど腫瘍の表面性状から得る深達度の診断能も向上したことで内視鏡的粘膜切除術(Endoscopic mucosal resection：EMR)や腹腔鏡下手術は急速に拡大してきている．大腸癌におけるリンパ節転移は予後規定因子として重要であり治療方針決定においても重要な因子となるが，リンパ節転移の評価に広く用いられているcomputed tomography (CT)，magnetic resonance imaging (MRI)のリンパ節転移検出の感度は決して高くない．術前病期分類を正確に判定する上で，リンパ節転移を含む遠隔転移を予測する高精度の指標が求められている．今回，大腸癌157例の遺伝子プロファイルからリンパ節転移を予測するマーカー遺伝子の検索を行った．遺伝子を同定する上で，その発現異常がゲノムコピー数異常に起因し，安定した発現解析が可能な遺伝子をターゲットとし，解析により同定されたマーカー遺伝子のリンパ節転移との関連と臨床的意義を検討した．Introduction : Currently, Endoscopic mucosal resection (EMR) and laparoscopic surgery with colorectal cancer (CRC) and has been expanding rapidly. In handling of colon cancer, adaptation of EMR is determined by the depth of tumor invasion. It is important to identify genes to predict lymph node metastasis in early CRC tumors precisely in a reproducible fashion to determine the adaptation of EMR treatment. We performed the comprehensive analysis of gene expression and genomic copy number simultaneously in CRC primary tumors to identify the bona-fide indicator of lymph node metastasis. Materials and Methods : We collected cancer cells specifically by Laser Microdissection (LMD) on 157 cases of primary colorectal cancer, and performed oligo microarrays for gene expression (GE) and aCGH for copy number aberration. As for candidate genes to be associated with lymph node metastasis, we examined reprodicibility by quantitative RT-PCR using cDNA created from the RNA extracted from 172 cases of CRC. Results : As for the association of lymph node metastasis, we found that 240 genes and 54 genes by aCGH and by oligo GE microarray, respectively. According to database of those two arrays, 501 genes were significantly correlated (correlation coefficient > 0.7) with each other, and we found that 11 out of 501 genes were identified as lymph node metastasis related genes with copy number alteration. Of these 11 genes, we focused on PCM1, MTUS1, ASAH1 on 8p22. Then, we confirmed that the decreased expression and genomic deletion of MTUS1 were observed in lymph node positive cases (p = 0.0195) in another subset of 172 cases of CRC. Conclusions : To measure the expression of MTUS1 of the tumor by PCR, we can predict the presence of lymph node metastasis. We expected that the loss of MTUS1 should be an important marker in determining the adaptation of endoscopic resection

Results of analysis on RNA interference screening data of Project Achilles.

<p>Results of analysis on RNA interference screening data of Project Achilles.</p

Results of univariate and multivariate analysis of clinicopathlogical factors for 5-year overall survival in the validation set.

<p>CI: confidence interval, well: well differentiated squamous cell carcinoma, mod: moderately differentiated squamous cell carcinoma, poor: poorly differentiated squamous cell carcinoma.</p><p>Results of univariate and multivariate analysis of clinicopathlogical factors for 5-year overall survival in the validation set.</p

Knockdown of <i>GRB7</i> expression in ESCC cell lines.

<p>(a) Reductions in mRNA and protein levels of GRB7 at 48 hours after siRNA transfection in KYSE410 and TE4 cells. The results are the mean ± SD from 3 replicates of a single experiment. (b) <i>GRB7</i> inactivation reduced proliferation of KYSE410 and TE4 cells. Cell growth was measured on days 2, 3, and 4 by MTT assay. Absorbance at day 0 was assigned a value of 1. The results are the mean ± SD from 6 replicates of a single experiment. (c) Migration and invasion assays using <i>GRB7</i>-knockdown cells. Each bar represents the average of 3 measurements. (d) Inhibitory effects of siRNA targeting <i>GRB7</i> in combination with trastuzumab. Cells were transfected with siRNA targeting <i>GRB7</i> or negative control siRNA and treated with or without trastuzumab (0.1 and 1.0 μg/mL). Cells were then seeded in 96-well plates, and cell growth was monitored every 24 hours using MTT assays. Absorbance at day 0 was assigned a value of 1. The results are the mean ± SD from 6 replicates of a single experiment.</p

GISTIC-defined peaks associated with altered expression in ESCC.

<p>Q value indicated the significance of copy number alteration in each region.</p><p>The % aberration included any gain over 0.1 or loss under −0.1 (log2 ratio).</p><p>Candidate targets were genes that have actual correlations between expression and copy number alterations in 'genes in peak'.</p><p>GISTIC-defined peaks associated with altered expression in ESCC.</p