tbuckley/cabot-search huggingface dataset:
IGF-1 Child-Turcotte-Pugh score as a predictor of overall survival to therapy in CTP-A, BCLC stage C patients with advanced hepatocellular carcinoma.
Authors: Yehia I. Abugabal, Aliya Qayyum, Manal Hassan, Lianchun Xiao, Dan G. Duda, Rikita Hatia, Sunyoung S. Lee, Robert A. Wolff, Roberto Pestana, Jeffrey Morris, James C. Yao, Hesham M. Amin, Ahmed Omar Kaseb
Journal: Journal of Clinical Oncology (2020)

488 Background: Child-Turcotte-Pugh (CTP) A is the standard population for active HCC therapy. The IGF-CTP score, comprises levels of type 1 insulin-like growth factor (IGF-1), bilirubin, INR, and albumin, significantly improved the prediction of overall survival (OS) in recently published studies. Our current study aimed to investigate the accuracy of the IGF-CTP score in predicting OS in HCC Child-Pugh A patients (pts) treated with local and/or systemic therapies (tx). The overall hypothesis is that the IGF-CTP score can further distinguish CP-A pts in terms of overall survival, PFS. Methods: Between 2014 and 2018, a total of 274 pts with new advanced HCC BCLC stage who had available baseline plasma IGF-1 level were retrospectively enrolled. Clinicopathologic features and treatment history were collected. We calculated IGF-CTP scores, used Kaplan-Meier method and log rank test to estimate and compare time to event outcomes between subgroups of patients. Results: 198 pts were CTP Class A, 209 patient underwent systemic tx, 65 underwent local tx [see table]; 161 were re-classified as IGF-CTP-A with a median OS of 16.09 months (95% CI = 13.06 to 23.29 months) (p &lt;0.0001), whereas 37 patients were reclassified as intermediate risk (IGF-CTP-B) and had significantly shorter OS of 10.66 months (95% CI = 5.49 to 26.51) (p &lt;0.0001). Conclusions: The results of this study support our biologically-driven hypothesis that IGF-CTP score is predictive of overall survival to therapy in advanced HCC treated with local and/or systemic therapy. Among HCC pts with CTP-A class, some are reclassified as IGF-CP-B/C and were found to have significantly poorer prognosis in terms of shorter OS. Future validation of the predictive ability of our IGF-1 score may lead to adopting it as a stratification tool in clinical trials as well as to predict HCC outcome and guide therapy decision in routine practice. [Table: see text]
Clustering of anthracycline-containing lysosomes in drug-resistant MCF-7 cells in response to tesmilifene
Authors: Baoqing Guo, Jason Sprowl, Stacey Hembruff, David Villeneuve, Amadeo Parissenti
Journal: Cancer Research (2008)

3223  A clinical trial by the National Cancer Institute of Canada Clinical Trials Group has shown that N,N-Diethyl-2-[4-(Phenylmethyl)Phenoxy] Ethanamine (tesmilifene) in combination with doxorubicin was superior to doxorubicin alone in patients with metastatic breast cancer in terms of overall survival (p=0.021. J. Clin. Oncol.22: 269-276). To address the mechanism for tesmilifene-induced clinical potentiation of drug cytotoxicity, doxorubicin-resistant (MCF-7DOX-2) and paclitaxel-resistant (MCF-7TAX-2) variants of MCF-7 cells were established in our laboratory. Clonogenic assays revealed that tesmilifene could effectively augment the cytotoxicity of a variety of chemotherapy agents specifically in these drug-resistant cell lines and this potentiation was independent of P-glycoprotein status. To better understand the mechanism of action of tesmilifene, confocal fluorescence microscopy was used to examine the distribution and localization of doxorubicin and epirubicin in drug-resistant cells in the absence or presence of tesmilifene. In wildtype MCF-7 cells, lysosomes were well distributed throughout the cytoplasm, while doxorubicin and epirubicin were consistently observed within the nucleus. In contrast, both drugs were located in the cytoplasm of some or all of MCF-7TAX-2 and MCF-7DOX-2 cells, respectively, where they co-localized with lysosomes (as visualized by LysoTracker staining). Addition of tesmilifene to the drug-resistant cells induced a very striking clustering of doxorubicin- or epirubicin-containing lysosomes to the perinuclear region. Clustering of lysosomes around the nucleus is a hallmark feature of necrosis, suggesting that tesmilifene may induce necrotic death in drug-resistant tumour cells. To identify genes which may be related to this phenomenon, a survey of gene expression using Operon Human Genome arrays (AROS V4) containing 35035 oligonucleotide probes was conducted in order to identify tesmilifene-induced changes in gene expression in the drug resistant cell lines in the presence of either doxorubicin or paclitaxel. Sixty-two genes were upregulated and 29 genes down-regulated by tesmilifene in MCF-7DOX-2 cells in the presence of doxorubicin. Tesmilifene upregulated 9 genes in MCF-7TAX-2 cells in the presence of paclitaxel. Two of the tesmilifene-dependent genes in MCF-7DOX-2 cells were found to be related to lysosome function and may play a role in the above-described phenomenon. These include the overexpression of cathepsin C (CTSC) and Lysozyme G-like Protein Precursor (LYG2). In MCF-7TAX-2 cells, Bcl-2 like 13 protein (BCL2L13) was induced by tesmilifene and is known to promote paclitaxel-induced cell death. Further studies are underway to identify the precise mechanism by which tesmilifene induces lysosomal clustering and the above changes in gene expression.
Abstract 15086: Associations Between Apolipoprotein A-I Proteoforms and Markers of Cardiometabolic Health
Authors: John T Wilkins, Henrique Seckler, Jonathan S Rink, Colby Thaxton, Philip Compton, Allan D Sniderman, Luca Fornelli, Richard LeDuc, David R Jacobs, Donald M Lloyd-jones, Neil Kelleher
Journal: Circulation (2019)

Introduction: Apolipoprotein A-I (apoA-I) is a central structural and functional protein of high-density lipoprotein (HDL) particles. ApoA-I undergoes post-translational modification at specific am...
Association of CXCR2+ granulocytic myeloid derived suppressor cells with the development of cholangiocarcinoma: A possible target for intervention.
Authors: Nicholas A. Ullman, Luis I. Ruffolo, Katherine M. Jackson, Alexander Chacon, Rachel Jewell, Mary Georger, Brian A. Belt, David Linehan
Journal: Journal of Clinical Oncology (2020)

565 Background: Cholangiocarcinoma (CCA) is the second most common primary liver malignancy, with increasing incidence. Currently, surgical resection offers the only chance for cure, however the prognosis remains poor in part due to high rates of unresectability, recurrence, and poor response to conventional therapy. Thus, new systemic therapies represent an unmet medical need. Few preclinical models exist for identifying and testing new targeted or immune based therapies. Here we present our findings of the immune infiltrate in human CCA tumor microenvironment (TME) and a spontaneous murine model that faithfully recapitulates human disease. Methods: Histology and immunohistochemistry (IHC) staining was performed on human CCA and adjacent normal liver. Mice with targeted hepatic Kras activation and loss of p53 (KPPC) spontaneously develop CCA. KPPC hepatic tumors and normal livers from littermate controls underwent histological and gene expression studies. Flow cytometric analysis was performed on bone marrow, spleen, peripheral blood, CCA tumors and normal littermate livers. Results: Digital IHC quantification of archival human CCA specimens demonstrated elevated levels of CD15 + CXCR2 + granulocytic myeloid derived suppressor cells (G-MDSC) compared to adjacent normal liver (p = &lt; 0.05). In addition, the CXCR2 ligand, CXCL5, was significantly elevated in CCA tumors compared to adjacent normal liver. In KPPC mice, flow cytometric analysis of hepatic tumors showed an abundance of CD45 + leukocytes comprised of immunosuppressive G-MDSC vs normal littermate controls (p = 0.0007) which recapitulates human disease. qRT-PCR demonstrated significantly increased expression of G-csf, Csf1, Cxcl1, Cxcl2, and Cxcl5 (p = &lt; 0.0001) in CCA KPPC tumors compared to normal livers. Accordingly, granulocytes in KPPC mice were elevated in both the bone marrow and blood compared to normal littermate controls. Conclusions: These data suggest CCA co-opts the ELR+ cytokine/CXCR2 axes to mobilize and recruit immunosuppressive G-MDSC to the TME. Targeted therapy against tumor infiltrating neutrophils can be tested in this pre-clinical model to inform clinical translation.
Regorafenib as second-line therapy for imatinib-resistant gastrointestinal stromal tumor (GIST).
Authors: Tsuyoshi Takahashi, Toshirou Nishida, Toshihiro Kudo, Narikazu Boku, Yoshitaka Honma, Yoshito Komatsu, Hiroshi Nakatsumi, Koji Matsumoto, Takuma Onoe, Eiji Oki, Masako Nakamoto, Miki Fukutani, Shogo Nomura, Akihiro Sato, Yoichi Naito, Toshihiko Doi
Journal: Journal of Clinical Oncology (2020)

823 Background: Imatinib is a standard first line treatment for advanced gastrointestinal stromal tumor (GIST); however eventually almost all the GISTs become resistant to imatinib. Secondary mutation in KIT is the most relevant cause of imatinib-resistant, as high as 70% of cases. Sunitinib is standard of care for imatinib-resistant GIST with median progression-free survival (PFS) of 24.6 weeks; however, in a preclinical study sunitinib is not active for approximately half of secondary mutations. Regorafenib is active for some secondary mutations resistant to sunitinib in the preclinical study. Therefore, we conducted a phase II study evaluating regorafenib for imatinib-resistant GIST. Methods: Patients with imatinib-resistant advanced GIST were enrolled. Key eligibility criteria were ECOG PS of 0-1 and adequate organ function. Prior exposure of sunitinib was not allowed. The primary endpoint was PFS rate at 24 weeks. ctDNA for KIT was evaluated prior to regorafenib administration. Results: A total of 38 patients were enrolled as planned. Median age was 64.5 (39 - 80). Twenty-five patients were male. Primary site was stomach in 17, small intestine in 16. Median PFS was 36.3 weeks and PFS rate at 24 weeks was 47.4% (primary endpoint was not met). Best overall response was PR for 6 (16 %), SD for 25 (63 %) and PD for 5 (13 %) patients. Grade 3 or more adverse events (AE) were observed in 25 (66 %) patients. Common grade 3 or more AE were hand-foot-skin reaction (n = 9), hypertension (n = 9), hepatotoxicity (n = 4). ctDNA was evaluated in 32 patients and among them secondary mutations were observed in 15 patients (47%). PFS was shorter (15.6 weeks) in patients with exon 13 mutation than that in patients without second mutation (49.3 weeks, not statistically significant). Conclusions: Regorafenib demonstrated favorable activity in patients with imatinib-resistant GIST as second line therapy with acceptable toxicity. Secondary mutation in KIT might be a predictor of the efficacy of regorafenib. Clinical trial information: UMIN000016115.
ヒト浸潤性乳癌において,miR-125bはメチル化され,ETS1癌原遺伝子を制御することにより腫瘍抑制因子として機能する | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Zhang Yan, Yan Li-Xu, WU Qi-Nian, DU Zi-Ming, Chen Jing, Liao Ding-Zhun, Huang Ma-Yan, Hou Jing-Hui, WU Qiu-Liang, Zeng Mu-Sheng, Huang Wen-Lin, Zeng Yi-Xin, Shao Jian-Yong
Journal: Cancer Research (2011)
Persons Evaluated for 2019 Novel Coronavirus — United States, January 2020
Authors: Kristina L. Bajema, Alexandra M. Oster, Olivia L. McGovern, Stephen Lindstrom, Mark R. Stenger, Tara C. Anderson, Cheryl Isenhour,, Kevin R. Clarke, Mary E. Evans, Victoria T. Chu, Holly M. Biggs, Hannah L. Kirking, Susan I. Gerber, Aron J. Hall, Alicia M. Fry, Sara E. Oliver, Glen Abedi, William Bower, Kevin Chatham-Stephens, Laura Conklin, Laura Cooley, Margaret Cortese, Aaron Curns, Kathleen Dooling, Runa Gokhale, Jeremy Gold, Gavin Grant, Julie Gutman, Elisabeth Hesse, Shifaq Kamili, Lindsay Kim, Robert Kirkcaldy, Emily Koumans, Stephanie Kujawski, Gayle Langley, Joana Lively, Xiaoyan Lu, Brian Lynch, Sheryl Lyss, Lakshmi Malapati, Michael Martin, Sarah Mbaeyi, Paul McClung, Claire Midgley, Maureen Miller, Michelle Morales, Janna' Murray, Amy Parker Fiebelkorn, Manisha Patel, Georgina Peacock, Taran Pierce, Brian Rha, Senthilkumar Sakthivel, Eileen Schneider, David A. Siegel, Brittany Sunshine, Megan Wallace, Lijuan Wang, John Watson, Brett Whitaker, Anna Yousaf
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

In December 2019, a cluster of cases of pneumonia emerged in Wuhan City in central China's Hubei Province. Genetic sequencing of isolates obtained from patients with pneumonia identified a novel coronavirus (2019-nCoV) as the etiology (1). As of February 4, 2020, approximately 20,000 confirmed cases had been identified in China and an additional 159 confirmed cases in 23 other countries, including 11 in the United States (2,3). On January 17, CDC and the U.S. Department of Homeland Security's Customs and Border Protection began health screenings at U.S. airports to identify ill travelers returning from Wuhan City (4). CDC activated its Emergency Operations Center on January 21 and formalized a process for inquiries regarding persons suspected of having 2019-nCoV infection (2). As of January 31, 2020, CDC had responded to clinical inquiries from public health officials and health care providers to assist in evaluating approximately 650 persons thought to be at risk for 2019-nCoV infection. Guided by CDC criteria for the evaluation of persons under investigation (PUIs) (5), 210 symptomatic persons were tested for 2019-nCoV; among these persons, 148 (70%) had travel-related risk only, 42 (20%) had close contact with an ill laboratory-confirmed 2019-nCoV patient or PUI, and 18 (9%) had both travel- and contact-related risks. Eleven of these persons had laboratory-confirmed 2019-nCoV infection. Recognizing persons at risk for 2019-nCoV is critical to identifying cases and preventing further transmission. Health care providers should remain vigilant and adhere to recommended infection prevention and control practices when evaluating patients for possible 2019-nCoV infection (6). Providers should consult with their local and state health departments when assessing not only ill travelers from 2019-nCoV-affected countries but also ill persons who have been in close contact with patients with laboratory-confirmed 2019-nCoV infection in the United States.
Survivorship care engagement with American Indian and Alaska Native survivors of gastrointestinal (GI) cancers.
Authors: Christine E. Hill-Kayser, Carolyn Vachani, Isabella Amaniera, Christina Bach, Karen Arnold-Korzeniowski, Margaret K. Hampshire, James M. Metz
Journal: Journal of Clinical Oncology (2020)

814 Background: American Indian and Alaska Native (AI/AN) survivors are at significant risk for GI cancers, and also represent an underserved medical population. Gastrointestinal cancers represent the third most commonly diagnosed cancers in the AI/AN population and are a leading cause of death. Survivorship resources tailored for the AI/AN population are sparse and patterns of survivorship care poorly understood. Methods: The OncoLife survivorship care plan has been through the OncoLink website since 2007. The tool is free and publically available. It asks survivors to enter data regarding diagnosis, demographics, and treatments, and provides customized guidelines for future care. All research is IRB approved. Results: Over the past 12 years, the OncoLife tool has been utilized by &gt;85,000 persons, with survivors of GI cancer representing 10-12% of users each year. Most users are women (75%) and Caucasian (80%). American Indian and Alaska Native survivors represent &lt;1% of users since the launch of the tool. Of 519 AI/AN users, median age was 54 years, and 76% identified as female. Of plans created for AI/AN survivors, 13% were for survivors of GI cancers, with the most common GI diagnosis being colorectal cancer (74%), followed by pancreas (11%) and anal (6%). Most plans (73%) were created by HCP, with the remainder by survivors themselves; 20% of AI/ AN users completing plans requested information on smoking cessation as part of their care plan. Conclusions: American Indian and Alaska Native survivors represent a very small minority of survivors utilizing this free Internet-based tool, with most plans for this population being created by healthcare providers and not by survivors themselves. Future efforts should be directed at supporting this underserved population with survivorship information, particularly given high risk of morbidity and mortality related to GI cancers.
DS-Screen: Prospective analysis of the expression status of FGFR2 and HER2 in colorectal and gastric cancer population.
Authors: Hiroki Hara, Atsushi Takeno, Hisateru Yasui, Hiroshi Imamura, Hiroki Akamatsu, Kazumasa Fujitani, Minoru Nakane, Chihiro Kondoh, Seigo Yukisawa, Junichiro Nasu, Yoshinori Miyata, Akitaka Makiyama, Hiroyasu Ishida, Norimasa Yoshida, Eiji Matsumura, Masato Ishigami, Masahiro Sugihara, Atsushi Ochiai, Toshihiko Doi
Journal: Journal of Clinical Oncology (2020)

431 Background: FGFR2 and HER2 proteins are well-known molecular targets for cancer therapy, and there are emerging attractive protein-targeted agents such as second generation antibody-drug conjugates. However, there are still limited information about the expression status of FGFR2 and HER2 in gastrointestinal cancer and their relationship to patient background with cancer. In this study, expression status of FGFR2 and HER2 in advanced/metastatic gastric cancer (GC) and colorectal cancer (CRC) were prospectively analyzed in clinical setting. Moreover, eligible patients for the clinical trials of DS-1123 or DS-8201, which are FGFR2- or HER2-targeting anti-cancer agent respectively, were screened. Methods: Patients with advanced/metastatic GC, gastroesophageal junctional cancer (GEJ), and CRC were enrolled. Expression status of FGFR2 and HER2 were prospectively analyzed by IHC and/or FISH. Results: A total of 565 patients (GC; 160, GEJ; 16, CRC; 389) have been enrolled in this study from November 2016 to June 2018. FGFR2 expression (IHC 1+~3+) was observed in 24%, 44%, and 3% of GC, GEJ, and CRC respectively. HER2 expression (IHC 2+, 3+) was observed in 24%, 44%, and 17% of GC, GEJ, and CRC respectively. Expression levels of FGFR2 and HER2 seemed to be not correlated with each other in all 3 types of cancer. Distributions of expression level of FGFR2 or HER2 were slightly different among the histological types in GC. In CRC, distribution of HER2 expression level was also slightly different among the histological types and HER2 expression level was higher in KRAS/NRAS wild type compared to KRAS/NRAS mutant. There was no association between HER2 expression level and primary tumor sites in patients with CRC. Slight concordance of HER2 expression was observed between IHC and FISH in CRC. A total of 7 patients have been enrolled in clinical trials of DS-1123 or DS-8201 through this study based on the analysis findings. Conclusions: This study showed insights into the expression status of FGFR2 and HER2 in GC and CRC as a large-scale prospective analysis. Seven patients who had no standard therapy could access exploratory new drug based on targetable agents through this study. Clinical trial information: 163380.
Efficacy and safety of yttrium-90 ibritumomab tiuxetan in the treatment of non-Hodgkin lymphoma.
Authors: Catherine Doyle, Johnna Smith, Celeste M. Bello, Lubomir Sokol, Ghassan El-Haddad
Journal: Journal of Clinical Oncology (2020)

103 Background: Yttrium 90-labeled ibritumomab tiuxetan (Zevalin) is a radioimmunotherapy agent which combines the action of a beta-emitting isotope, yttrium-90, with the anti-CD20 monoclonal antibody, rituximab. The purpose of this study was to evaluate the efficacy of Zevalin in the treatment of Non-Hodgkin Lymphoma (NHL) in terms of response to therapy, overall survival (OS) and progression free survival (PFS). Methods: A total of 171 patients with NHL referred for treatment with Zevalin between September 2005 and January 2017 were identified for retrospective analysis. Clinical characteristics, treatments, and outcomes were extracted from clinical chart review. Survival rates and survival curves were generated using Kaplan-Meier analysis. Chi-square and independent student t test were used for comparison of categorical variables. Multivariate analysis (MVA) Cox proportional hazards ratios (HR) model was used to assess OS and PFS. Results: Of the 171 patients referred for treatment, median age was 70 years old, 54% were male (n = 93), and each patient had received a median of 2 prior chemotherapy regimens. The majority of patients were treated for follicular lymphoma (n = 107) and diffuse large B-cell lymphoma (n = 34). Seventy-three patients (53%) achieved complete response, and 23 patients achieved partial response (17%). One-year progression free survival was 71%, and median PFS was 31 months. Adverse events included cytopenic events, GI side effects, and mucocutaneous toxicity. Conclusions: Use of Zevalin for treatment of NHL demonstrated a significant improvement in PFS. In addition to improved efficacy, Zevalin was well-tolerated in this study and demonstrated an adequate safety profile. Further considerations will be given as to which treatment factors are associated with a complete response and improved PFS.
Nationwide large-scale investigation of microsatellite instability status in more than 18,000 patients with various advanced solid cancers.
Authors: Kiwamu Akagi, Eiji Oki, Hiroya Taniguchi, Kaname Nakatani, Daisuke Aoki, Takeshi Kuwata, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2020)

803 Background: The recent success of immunotherapy in high-frequency microsatellite instability (MSI-H) and/or mismatch repair protein deficient (MMR-D) tumors now supports testing for MSI in all advanced solid tumors. We previously reported using the quasi-monomorphic variation range (QMVR), the MSI status can be determined without matched normal DNA (Bando H, et al. Cancer Sci. 2018). Here, we investigate the proportion of the MSI status across various advanced solid tumors by this method. Methods: The MSI analysis was performed centrally by CLIA-certified, CAP-accredited, the single laboratory using tumor DNA from formalin-fixed paraffin embedded (FFPE) tissues with the MSI test kit (FALCO), which includes fluorescent-labelled primers for co-amplification of five mononucleotide markers (NR-21, BAT-25, MONO-27, NR-24 and BAT-26). The MSI-H was defined as positive if 2 or more makers showed instable. Results: A total of 18,250 patients with advanced solid tumors were registered from Dec 2018 to Aug 2019, and the MSI status was confirmed in 18,088 patients (99%). Among them, 51.9% were male, with median of 62.0 y/o. Overall prevalence of the MSI-H was3.3% (2.3% in male and 4.5% in female); the highest was 16.2% (149/916) in endometrial cancer, followed by 13% (13/100) in small intestinal cancer, 5.9% (74/1277) in gastric cancer, 3.3% (236/7190) in colorectal cancer, 2.6% (4/154) in prostate cancer, 2.5% (20/806) in ovarian cancer, 2.1% (9/426) in cervical cancer, 1.6% (13/831) in biliary tract cancer, 1.5% (4/271) in hepatocellular carcinoma, 0.9% (16/1852) in pancreas cancer. Interestingly, among biliary tract cancers, all MSI-H cases were arising from gall bladder (13/152) but no other sites. High prevalence was observed in cancer of teens or twenties (7.9%) and over 80y/o (5.6%), compare with others (3.0%) in this study (p &lt; 0.001, both). Conclusions: These data show the MSI-H advanced solid tumors are distributed across a much broader tumor spectrum, and confirm the clinical relevance of the screening in patients with most advanced solid tumors, which can select patients sensitive to immune checkpoint blockade, regardless of the cancers' tissue of origin.
38P Evolution of Estrogen Receptor (ER) and ErbB2 Expression Between Primary Tumor and Circulating Tumor Cells (CTC) of Metastatic Breast Cancer Patients
Authors: S. Doisneau-Sixou, C. Bock, C. Kuhn, L. Majunke, B. Jäger, C. Theil, U. Jeschke, B. Rack
Journal: Annals of Oncology (2012)