tbuckley/cabot-search huggingface dataset:
Abstract 4192: The association between gastric Mucin 5AC (MUC5AC) expressions, transforming growth factor-β (TGF-β) signal, and histopathological phenotypes of lung cancer in xenograft models
Authors: Ryo Sato, Takashi Semba, Hirotsugu Kohrogi, Hideyuki Saya, Yoshimi Arima
Journal: Cancer Research (2016)

Abstract According to the 2015 World Health Organization (WHO) classification of lung tumors, invasive lung adenocarcinomas are pathologically classified as lepidic, acinar, papillary, micropapillary, or solid types. Adding the cribriform pattern as an additional subtype to the original WHO classification has recently been proposed, because patients with cribriform predominant tumors have a poorer prognosis than that for patients with acinar or papillary predominant tumors. Understanding the molecular mechanisms contributing to the pathological subtypes may provide a basis for the development of new therapeutic strategies and an improved prognosis for lung cancer patients. We found that the human lung adenocarcinoma A549 cells developed distinct histological types of tumors; acinar types and mucinous cribriform types, when cells were inoculated into immunodeficient mice. Acinar type tumors showed a gland-like pattern containing stromal cells, and cribriform type tumors contained abundant acidic mucins stained with Alcian blue. We also found that the cribriform type tumors, but not acinar type tumors, expressed Mucin 5AC (MUC5AC), which is one of the common mucin core proteins. In contrast, acinar type tumors upregulated the phosphorylation of Smad3, which is the downstream of the transforming growth factor-β (TGF-β) signal, indicating that the TGF-β/Smad pathway is activated in acinar type tumors. We went on to culture A549 cells in several conditions and found that MUC5AC is upregulated in serum-free floating culture conditions. To determine the relationship between TGF-β and MUC5AC expressions, TGF-β1 was added to the culture medium, and we found that TGF-β1 completely inhibited MUC5AC induction. These data imply that cancer cells and/or cancer associated fibroblasts (CAFs) release TGF-β1 and inhibit MUC5AC expressions, leading to acinar type tumor formations. Citation Format: Ryo Sato, Takashi Semba, Hirotsugu Kohrogi, Hideyuki Saya, Yoshimi Arima. The association between gastric Mucin 5AC (MUC5AC) expressions, transforming growth factor-β (TGF-β) signal, and histopathological phenotypes of lung cancer in xenograft models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4192.
The Third National Cancer Survey
Authors: J C Bailar, R N Grant
Journal: CA A Cancer Journal for Clinicians (1969)

conducting this survey?DR.BAILAR: It will consist of reports on all forms of cancer occurring in over tion with a number of contracting organizations.They are listed in Table 1. DR. GRANT:Will it include all cancer cases in this country?DR.BAILAR: It will consist of reports on all forms of cancer, occurring in over 13 percent of the population of the United States.It will cover much the same geographic areas as the two earlier surveys: namely, the first in 1937, and the second in 1947-48, which were known as the Ten-City Surveys.In addition, two states plus Puerto Rico will be included.(See Table 2.)
Re: Helicobacter pylori and Atrophic Gastritis: Importance of the cagA Status
Authors: MASSIMO RUGGE, MAURO CASSARO, FABIO FARINATI, ALFREDO SAGGIORO, FRANCESCO DI MARIO
Journal: JNCI Journal of the National Cancer Institute (1996)

Epidemiologic, biological, and clinical evidence have emerged to suggest that the etiology of both epithelial and nonepithelial gastric tumors involves infectious agents (7,2). Kuipers et al. (3) have recently added interesting data to support this hypothesis; in particular, they have stressed the possible relevance of the Helicobacter pylori cag-A-positive strains in the etiology of the subset of mucosal lesions most closely related to gastric carcinogenesis (4). These data expand on their previous observations and appear to be particularly relevant to the selection of patients with the highest risk of gastric cancer. Assuming that the described association is real, such patients deserve particular effort to eradicate cag-A-positive H. pylori infections.
Oxidized Phospholipids on Lipoprotein(a) Elicit Arterial Wall Inflammation and an Inflammatory Monocyte Response in Humans
Authors: Fleur M. van der Valk, Siroon Bekkering, Jeffrey Kroon, Calvin Yeang, Jan Van den Bossche, Jaap D. van Buul, Amir Ravandi, Aart J. Nederveen, Hein J. Verberne, Corey Scipione, Max Nieuwdorp, Leo A.B. Joosten, Mihai G. Netea, Marlys L. Koschinsky, Joseph L. Witztum, Sotirios Tsimikas, Niels P. Riksen, Erik S.G. Stroes
Journal: Circulation (2016)

Elevated lipoprotein(a) [Lp(a)] is a prevalent, independent cardiovascular risk factor, but the underlying mechanisms responsible for its pathogenicity are poorly defined. Because Lp(a) is the prominent carrier of proinflammatory oxidized phospholipids (OxPLs), part of its atherothrombosis might be mediated through this pathway. In vivo imaging techniques including magnetic resonance imaging, (18)F-fluorodeoxyglucose uptake positron emission tomography/computed tomography and single-photon emission computed tomography/computed tomography were used to measure subsequently atherosclerotic burden, arterial wall inflammation, and monocyte trafficking to the arterial wall. Ex vivo analysis of monocytes was performed with fluorescence-activated cell sorter analysis, inflammatory stimulation assays, and transendothelial migration assays. In vitro studies of the pathophysiology of Lp(a) on monocytes were performed with an in vitro model for trained immunity. We show that subjects with elevated Lp(a) (108 mg/dL [50-195 mg/dL]; n=30) have increased arterial inflammation and enhanced peripheral blood mononuclear cells trafficking to the arterial wall compared with subjects with normal Lp(a) (7 mg/dL [2-28 mg/dL]; n=30). In addition, monocytes isolated from subjects with elevated Lp(a) remain in a long-lasting primed state, as evidenced by an increased capacity to transmigrate and produce proinflammatory cytokines on stimulation (n=15). In vitro studies show that Lp(a) contains OxPL and augments the proinflammatory response in monocytes derived from healthy control subjects (n=6). This effect was markedly attenuated by inactivating OxPL on Lp(a) or removing OxPL on apolipoprotein(a). These findings demonstrate that Lp(a) induces monocyte trafficking to the arterial wall and mediates proinflammatory responses through its OxPL content. These findings provide a novel mechanism by which Lp(a) mediates cardiovascular disease. URL: http://www.trialregister.nl. Unique identifier: NTR5006 (VIPER Study).
Abstract 1404: Pemetrexed decreases circulating S100A9-myeloid derived suppressor cells in patients with non-small cell lung cancer
Authors: Po-Hao Feng, Kang-Yun Lee
Journal: Cancer Research (2016)

Abstract Background: We previously reported that S100A9-myeloid derived suppressor cells (MDSCs) are negatively associated with chemotherapy effect in non-small cell lung cancer (NSCLC) patients. Pemetrexed-cisplatin chemotherapy is a standard treatment for advanced lung adenocarcinoma. The effect of chemotherapy on MDSCs is still not clear. Methods: We prospectively enrolled nineteen stage 4 lung adenocarcinoma patients without known driving mutation before chemotherapy. Fourteen patients received pemetrexed-cisplatin and five with docetaxel-cisplatin as first line chemotherapy. Peripheral blood MDSCs percentage was evaluate by flow cytometry before first cycle and second cycle of chemotherapy. In vitro migration assay with transwell MDSC/A549 cell co-culture system was used to test the effect of chemotherapy on chemotactic ability of A549 cell. Chemotherapy pretreated-A549 cells were cultured in the bottom chamber, and MDSCs, isolated from PBMC with CD14+ magnetic bead, were cultured in the upper chamber. Results: MDSCs percentage decreased after patients received first cycle pemetrexed-cisplatin treatment (mean ±SD MDSC% in PBMC: 25.9±13.9% vs 16.3±11.3%, p&amp;lt;0.05, n = 5). In the subgroup patients that had partial response to pemetrexed and cisplatin, the MDSCs percentage decreased most significantly. (25.0±9.1 to 7.1±5.2, p&amp;lt;0.05, n = 5) In vitro study confirmed that pemetrexed reduced numbers of CD14+ MDSC (pemetrexed vs control: 15.0±6.6 vs 107.8± 56.8, p0.05) or cisplatin (96.7±98.2 vs 107.8 ±56.8, p&amp;gt;0.05) Conclusion: Pemetrexed-cisplatin, but not docetaxel-cisplatin, decreased S100A9-MDSC in patients with lung adenocarcinoma, an effect might be due to a reduction in chemotactic ability of tumors by pemetrexed. In addition to cytotoxic effect, clinical benefit of pemetrexed might be also due to the effect on microenvironment. Citation Format: Po-Hao Feng, Kang-Yun Lee. Pemetrexed decreases circulating S100A9-myeloid derived suppressor cells in patients with non-small cell lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1404.
Long-term outcome in stage I and II follicular lymphoma following treatment with involved field radiation therapy alone
Authors: P. M. Petersen, M. Gospodarowicz, R. Tsang, M. Pintilie, W. Wells, D. Hodgson, A. Sun, M. Crump, B. Patterson, D. Bailey
Journal: Journal of Clinical Oncology (2004)

6521 Background: Patients with localized follicular lymphoma (FL) are usually treated with radiation therapy (RT). The aim of this study was to assess the long-term overall survival (OS), local disease control and pattern of relapse after involved-field RT in stage I/II FL Methods: 669 patients with stage I and II FL were seen between 1968 and 1999. The records on these patients were systematically collected in an institutional database. The analysis focused on the outcome of treatment in terms of OS, relapse and local disease control in those initially treated with involved-field RT alone (n=460). Median RT dose was 35 Gy (16.0 –47.5 Gy) given over 3–4 wks Results: In 460 patients treated with RT alone, the median age at diagnosis was 59 yrs (17 - 86 yrs); median follow-up duration was 12.5 yrs (range 1.1 –32.2 yrs). The clinical stage was: stage IA: 337 pts, stage IIA: 115 pts, IB: 2 pts and IIB: 5 pts. Histology was: follicular grade 1: 35%, grade 2: 38%, and grade 3: 27%. 75% had nodal disease alone, and 25% presented with extranodal disease. 43% had Karnofsky performance status (KPS) of 100% and 55% KPS of 90%. OS at 5 and 10 yrs were 79% and 62% and DFS 56% and 41%, respectively. Local disease control was excellent; 450 patients achieved complete response and only 5.5% relapsed in radiation fields. Most relapses occurred in distant sites. The cumulative incidence rates for relapse at 5, 10, 15, 20, and 25 yrs were 38%, 48%, 54%, 56%, and 56% respectively. For those at risk of relapse, the probability of relapse between 5 and 10 yrs was only 11%, for 10–15 yrs 6%, and beyond 15 yrs, 2%. Conclusions: Involved-field radiation therapy provides excellent local control in stage I and II follicular lymphomas. Long-term clinical disease control is observed in over 40% of pts. While 30% of all relapses occur after 5 years, risk of very late relapse is low. Long-term follow-up is recommended. No significant financial relationships to disclose.
Abstract 582: Novel insights into the antitumor activity of an antibody specific for transferrin receptor 1 (ch128.1) in an <i>in vivo</i> model of human multiple myeloma
Authors: Lai Sum Leoh, Yoon Kyung Kim, Otoniel Martinez-Maza, Tracy R. Daniels-Wells, Manuel L. Penichet
Journal: Cancer Research (2016)

Abstract The transferrin receptor 1 (TfR1), also known as CD71, is a type II transmembrane homodimeric protein involved in cellular iron uptake and regulation of cell growth. The high levels of TfR1 expression on cancer cells, its extracellular accessibility, and its central role in cancer pathology make it an attractive target for antibody-mediated cancer therapy. We have previously developed a mouse/human chimeric IgG3 specific for human TfR1 (ch128.1), which exhibits direct cytotoxic activity against certain human malignant B cells in vitro through TfR1 degradation and iron deprivation. In addition, we showed that ch128.1 is capable of inducing antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-mediated cytotoxicity (CDC) against malignant B cells in vitro. Importantly, ch128.1 shows exceptional antitumor activity in xenograft models of disseminated multiple myeloma (MM) in immunosuppressed mice (SCID-Beige) in an early disease setting. Intriguingly, this activity is observed even in malignant cells that show no sensitivity to the direct cytotoxic activity of ch128.1 in vitro. In order to study the mechanism of the in vivo antitumor activity, we generated a ch128.1 mutant with abolished binding to FcγR and the complement component C1q (L234A/L235A/P331S). Interestingly, this antibody mutant exhibited a total lack of in vivo protection against MM. This lack of antitumor activity is not due to increased clearance as determined by bioavailability studies. If fact, the two antibodies showed comparable affinity for the mouse FcRn (the neonatal Fc receptor, also known as the Brambell receptor) as determined via surface plasmon resonance analysis. This result suggests a critical role for the antibody Fc fragment in ch128.1-mediated antitumor activity. However, preliminary in vivo studies showed that depletion of complement using cobra venom factor (CVF) does not decrease the antitumor activity of ch128.1, suggesting that CDC is not a relevant mechanism of action, at least in the model used. Furthermore, we recently found that treatment with ch128.1 also significantly increased survival in late MM disease. Further studies aiming to provide a better understanding of the in vivo activity conferred by this antibody are in progress. Our results suggest that ch128.1 can be effective in the therapy of incurable human B-cell malignancies such as MM. Citation Format: Lai Sum Leoh, Yoon Kyung Kim, Otoniel Martinez-Maza, Tracy R. Daniels-Wells, Manuel L. Penichet. Novel insights into the antitumor activity of an antibody specific for transferrin receptor 1 (ch128.1) in an in vivo model of human multiple myeloma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 582.
Impact of BMI on genetic variation in ovarian cancer.
Authors: Tara Castellano, Dario R. Roque, Leslie Horn Clark, Rashid Naim, Victoria Lin Bae-Jump, Weiya Zhang Wysham, David N. Hayes
Journal: Journal of Clinical Oncology (2016)

e17090 Background: We examined the effect of body mass index (BMI) on genetic mutations in ovarian cancer (OC) patients enrolled on UNCseq. Methods: Snap-frozen and FFPE tissue samples were collected from OC patients enrolled on UNCseq (NCT01457196). Illumina libraries were prepared separately from tumor and matched normal samples from each patient and sequenced on Illumina HiSeq machines. Relevant targets were enriched by a custom Agilent SureSelect hybrid capture enrichment library. Mutations with a quality score < 100 were filtered from the data set, and only mutations rated to have a moderate to high impact were retained. Single gene mutations were tested for association via Fisher’s Exact and Wilcoxon Two-Sample tests for binary and continuous correlates, respectively. Mutational Counts were associated with clinical correlates via negative binomial regression. Results: Data for 70 OC cases was collected. Histologic breakdown was 43 high-grade serous (HGS), 6 clear cell (CC), 6 endometrioid (EO), 2 mucinous (MO), 4 granulosa cell (GC), 3 ovarian carcinosarcoma (CS), 3 low grade serous (LGS) and 2 borderline tumors (LMP). In total, 469 mutations appeared in at least one individual across all patients. By histology the top observed mutations were: 1) HGS (TP53, NF1, MLL2, MLL, cbl-b), 2) CC (TP53, BRCA1, PIK3CA), 3) EO (TP53, CTNNB1, AHNAK2, CIITA, RICTOR), 4) LGS (KRAS, SCN5A, and SETD2), 5) MO (TP53, BRCA1, STAT2, and ARHGAP26), 6) LMP (KRAS, MAP3K1, CHEK2, and KRT6C), 7) CS (TP53, KRAS and ARID1A), 8) GS (ROS1, HECW1, SCNN1G, and STAG2). Advanced stage (III and IV) was associated with greater frequency of genetic mutations in HGS (p < 0.001). HGS histology was associated with increased total numbers of genetic mutations (p = 0.004). LGS (p = 0.01) and GC (p = 0.004) had fewer genetic mutations. In HGS, BMI ≥ 25 was associated with fewer mutations than BMI < 25 (p = 0.001). After adjusting for stage, this no longer retained statistical significance. Conclusions: We did not detect a difference in genetic mutations according to BMI, but our analysis is likely limited by sample size. Further collection of OCs through UNCseq is ongoing. We identified 3 frequently mutated genes in OC (SETD2, cbl-b, AHNAK2) that have not been previously associated with OC that warrant further evaluation.
Toremifene citrate versus placebo for treatment of bone loss and other complications of androgen deprivation therapy in patients with prostate cancer
Authors: M. S. Steiner, A. Patterson, R. Israeli, K. G. Barnette, R. Boger, D. Price
Journal: Journal of Clinical Oncology (2004)

4597 Background: Patients with prostate cancer receiving androgen deprivation therapy (ADT) may experience side effects including bone loss (osteoporosis), hot flashes, and gynecomastia. Bone loss is of particular significance as a bone fracture in this population has been associated with a significant decrease in length of survival. Toremifene citrate (Acapodene™), a selective estrogen receptor modulator (SERM), has the potential to ameliorate many of these side effects of ADT and to improve quality of life. Methods: 46 consenting patients who had been on ADT for at least 12 months were randomized to 20 mg, 40 mg, or 60 mg of toremifene citrate or placebo administered orally once daily for 6 months. Assessments included bone mineral density (BMD) determination by dual energy X-ray absorptiometry (DEXA), bone turnover markers, and hot flashes. Results: Toremifene was well tolerated at all doses studied. Based on our own observations and recent reports in the literature, the antiandrogen bicalutamide can affect bone metabolism. To avoid confounding effects from bicalutamide, patients on bicalutamide were excluded from the analysis. Administration of 60 mg/day of toremifene (but not 20 mg/day or 40 mg/day) resulted in an increase of BMD after 6 months of therapy compared to a decrease in the placebo group (p < 0.01 ), as well as beneficial effects on other side effects of ADT. Conclusion: Toremifene administration resulted in a statistically significant increase in BMD after just 6 months of therapy in patients with prostate cancer, suggesting that toremifene, a SERM, is a promising agent to improve bone mineral density and quality of life in patients with prostate cancer receiving ADT. A long-term large scale trial is in progress to demonstrate the long term benefits of toremifene in prostate cancer patients receiving chronic ADT. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GTx, Inc. GTx, Inc. GTx, Inc. GTx, Inc.
Abstract 964: Circulating biomarker miRNA-150 promotes tumor cell proliferation and progression by targeting SRC kinase signaling inhibitor 1 (SRCIN1) in non-small cell lung cancer
Authors: Jing Lin, Liren Zhang, Yuanqing Ye, Taro Oba, Emanuela Gentile, Emanuela Gentile, Jing Wang, Yang Zhao, Jian Gu, Ignacio Wistuba, Jack A. Roth, Xifeng Wu, Lin Ji
Journal: Cancer Research (2016)

Abstract Circulating microRNAs (c-miRNAs) expression ratio (ER) signatures were evaluated as prognostic biomarkers and therapeutic targets in early stage non-small cell lung cancer (NSCLC) patients. In a population study with 171 stage I and II NSCLC patients, the miR-150 and associated ER signature miR27A/miR-150 (ER ≥0.86, HR = 3.92, p = 1.46E-4) were significantly associated with 5-year survival. The upregulated expression of miR-150 was detected in primary tissue samples (n = 245) by miRNA microarray profiling analysis and significantly associated with cancer recurrence (p = 0.027) and overall survival (HR = 0.88, p = 0.04). Ectopic expression of miR-150 in NSCLC H1299, A549, and H2023 cells transfected by miR-150 expression plasmids promoted tumor cell proliferation, tumor cell-induced colony formation and migration/invasion, while blocking the action of miR-150 with a synthetic miR-150 inhibitor or transduction with a miRZip-150 inhibitor expressed by a lentiviral vector significantly inhibited these biological activities. The SRC kinase signaling inhibitor 1 (SRCIN1) was predicted to be a potential target of miR-150 by bioinformatics tools.miR-150-targeted binding and cleavage in the 3’-UTR of SRCIN1 mRNA were confirmed by a novel stem-loop array-reverse transcription-PCR assay. Both SRCIN1 gene and protein expression were significantly downregulated by ectopic expression of miR-150 and upregulated by miR-150 inhibitors in H1299 and H2023 NSCLC cells, as demonstrated by qRT-PCR and Western-blotting assays, respectively. Modulation of key elements in the SRCIN1 signaling pathway by ectopic expression or inhibition of miR-150 were further determined by qRT-PCR and predicted by ingenuity pathway analysis. Our findings suggest that circulating miR-150 and its associated ER signatures could serve as novel prognostic biomarkers for early stage NSCLC and function as an oncogenic miRNA that promotes lung cancer cell proliferation, invasion, and metastasis by direct targeting SRCIN1signaling pathway thus identifying SRCIN1 as a potential therapeutic target. Citation Format: Jing Lin, Liren Zhang, Yuanqing Ye, Taro Oba, Emanuela Gentile, Emanuela Gentile, Jing Wang, Yang Zhao, Jian Gu, Ignacio Wistuba, Jack A. Roth, Xifeng Wu, Lin Ji. Circulating biomarker miRNA-150 promotes tumor cell proliferation and progression by targeting SRC kinase signaling inhibitor 1 (SRCIN1) in non-small cell lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 964.
Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose
Authors: Natalie R. Johnston, Ryan K. Mitchell, Elizabeth Haythorne, Maria Paiva Pessoa, Francesca Semplici, Jorge Ferrer, Lorenzo Piemonti, Piero Marchetti, Marco Bugliani, Domenico Bosco, Ekaterine Berishvili, Philip Duncanson, Michael Watkinson, Johannes Broichhagen, Dirk Trauner, Guy A. Rutter, David J. Hodson
Journal: Cell Metabolism (2016)

The arrangement of β cells within islets of Langerhans is critical for insulin release through the generation of rhythmic activity. A privileged role for individual β cells in orchestrating these responses has long been suspected, but not directly demonstrated. We show here that the β cell population in situ is operationally heterogeneous. Mapping of islet functional architecture revealed the presence of hub cells with pacemaker properties, which remain stable over recording periods of 2 to 3 hr. Using a dual optogenetic/photopharmacological strategy, silencing of hubs abolished coordinated islet responses to glucose, whereas specific stimulation restored communication patterns. Hubs were metabolically adapted and targeted by both pro-inflammatory and glucolipotoxic insults to induce widespread β cell dysfunction. Thus, the islet is wired by hubs, whose failure may contribute to type 2 diabetes mellitus.