tbuckley/cabot-search huggingface dataset:
Abstract 4769: Inhibition of ribosomal protein L9 expression suppresses colorectal carcinoma cell growth in vitro and in vivo
Authors: In Hye Baik, Keon Uk Park, Ilseon Hwang, Hun-Mo Ryoo, Yun-Han Lee
Journal: Cancer Research (2016)

Abstract Background: Ribosomal protein L9 (RPL9), a component of the 60S subunit, is upregulated in human colorectal cancer (CRC). We thus hypothesized if targeting of RPL9 with small interfering (si) RNA could inhibit CRC progression. We also investigated molecular mechanism to mediate CRC cell death caused by RPL9 silencing. Methods: HCT116 and HT29 human CRC cells were transfected with RPL9 siRNA and tested for growth inhibition and apoptotic induction using MTS, FACS and microscopic analysis. To obtain insights into the molecular changes in response to RPL9 knockdown, global changes in gene expression were examined using RNA sequencing. Results: RPL9 silencing caused inhibition of CRC cell growth through induction of apoptotic cell death. RNA sequencing revealed that RPL9-specific knockdown led to dysregulation of 622 genes in HCT116 and 2882 genes in HT29 cells. Among those, 256 genes showed the same directional regulation (128 up- and 168 down-regulated genes), including up-regulation of tumor suppressors such as KLF6 and ATF3, and were considered as a common RPL9 knockdown signature. Western blotting proved that downregulation of RPL9 was accompanied with the decrease in the levels of PARP-1 and pro-caspase 3 delaying cell cycle progression and accelerating apoptotic signaling. Of importance, targeting RPL9 significantly inhibited CRC growth in a murine xenograft model. Conclusion: These results suggest that inhibition of RPL9 expression could be an attractive option for molecular targeted therapy of colorectal cancer. Citation Format: In Hye Baik, Keon Uk Park, Ilseon Hwang, Hun-Mo Ryoo, Yun-Han Lee. Inhibition of ribosomal protein L9 expression suppresses colorectal carcinoma cell growth in vitro and in vivo. [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 4769.
NCCN Framework for Resource Stratification: A Framework for Providing and Improving Global Quality Oncology Care
Authors: Robert W Carlson, Jillian L Scavone, Wui-Jin Koh, Joan S McClure, Benjamin E Greer, Rashmi Kumar, Nicole R McMillian, Benjamin O Anderson
Journal: Journal of the National Comprehensive Cancer Network (2016)

More than 14 million new cancer cases and 8.2 million cancer deaths are estimated to occur worldwide on an annual basis. Of these, 57% of new cancer cases and 65% of cancer deaths occur in low- and middle-income countries. Disparities in available resources for health care are enormous and staggering. The WHO estimates that the United States and Canada have 10% of the global burden of disease, 37% of the world's health workers, and more than 50% of the world's financial resources for health; by contrast, the African region has 24% of the global burden of disease, 3% of health workers, and less than 1% of the world's financial resources for health. This disparity is even more extreme with cancer. NCCN has developed a framework for stratifying the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) to help health care systems in providing optimal care for patients with cancer with varying available resources. This framework is modified from a method developed by the Breast Health Global Initiative. The NCCN Framework for Resource Stratification (NCCN Framework) identifies 4 resource environments: basic resources, core resources, enhanced resources, and NCCN Guidelines, and presents the recommendations in a graphic format that always maintains the context of the NCCN Guidelines. This article describes the rationale for resource-stratified guidelines and the methodology for developing the NCCN Framework, using a portion of the NCCN Cervical Cancer Guideline as an example.
Breast cancer risk estimates using the Gail Model in women from an annual screening program in Southern Brazil
Authors: V. Belo Reyes, G. Skonieski, J. Zignani, A. Bedin, R. Giugliani, E. I. Palmero, L. Kalakun, L. Schuler-Faccini, P. Ashton-Prolla, M. Caleffi
Journal: Journal of Clinical Oncology (2006)

20045 Background: The Gail model is widely used to estimate breast cancer (BC) risk. It has been validated as a reliable risk predictor in North America, but very few studies have been done in other countries. This study intends to examine the estimated BC risk using the Gail Model in a sample of women from Southern Brazil a region with the highest BC incidence and mortality rates of the country. Methods: Lifetime and 5-year BC risk estimates were obtained for the first 1002 asymptomatic women (ages 40–69 years) enrolled in an annual BC screening program. The frequency of each of the model’s variables was recorded and compared to other studies. Information about family history (FH) included: presence of bilateral BC, male BC, first degree relative with BC and/or ovarian cancer (OC), relative with BC under age 50 and ≥ 2 relatives with either BC, OC or colorectal cancer (CRC). Other potential risk factors for BC such as body mass index and smoking were recorded. Results: Mean (± SD) values for age, age at menarche and age at birth of the first live child were 50.4 (± 7.75), 13.0 (± 1.80), and 21.6 (± 5.00) years, respectively. Only 50 (5.0%) women were nulliparous and 62 (6.2%) reported their first live birth after age 30. History of at least one first-degree relative (FDR) affected with BC was reported by 52 (5.2%), and 31 (3.1%) had a previous breast biopsy. The mean estimated BC risk in 5 years was 0.92% (± 0.49); for those under age 60, 24 (2.8%) had an estimated 5-yr risk over 1.66%. The mean estimated lifetime BC risk was 7.80 (± 3.2). Interestingly, a history of cancer in a FDR was reported by 32.6% of the women, and evidence of familial BC was observed in 20.4%. The estimated BC risk using the Gail model was significantly higher in women with a family history of BC &lt; 50ys and with ≥ 2 relatives with either BC, OC or CRC. Smoking and overweight were reported by 28% and 65% of the women, respectively. Conclusions: BC risk estimates obtained with the Gail Model did not differ significantly from those described in other populations. However, specific findings in cancer FH were associated with higher risk estimates. The importance of FH and overweight will be further explored in a larger sample. Population-specific risk factors for BC should be sought in different communities to ensure proper risk estimates. No significant financial relationships to disclose.
Effects of vasodilators on the systemic capacitance vessels, a study with the measurement of the mean circulatory pressure in dogs.
Authors: Hiroyasu Ito, Senri Hirakawa
Journal: Circulation (1984)

There have been yet only a few studies on the action of vasodilators on the entire systemic capacitance vessels of the living body. In the present study, we studied the action of the vasodilators on the systemic capacitance vessels by measuring the mean circulatory pressure (MCP), introduced by Guyton, and that on the systemic resistance vessels from total peripheral resistance, in anesthetized open chest dogs. We also studied the venous return curves. Depending n vasodilators and the dosages used, resistance vessels could be dilated, but capacitance vessels could not be dilated. The reverse was never true. It was also found frequently that capacitance vessels could be dilated only when the tone of the capacitance vessels have been previously elevated by norepinephrine. Again, depending on vasodilators and their dosages, the venous return curves were changed in position and/or slope. We constructed a venous return curve by connecting 2 points on the venous return-right atrial pressure (VR-RAP) plane, one, VR-RAP plot, and the other, the point of VR=0, RAP=MCP. Changes in the venous return curve caused by these vasodilators were classified into three types; (a) a clockwise rotation with a constant MCP, where one sees no change in MCP and decreased resistance to venous return (RVR), so that one may call this RVR-type, (b) a parallel shift of the venous return curve to the left, where one sees no change in RVR but a decreased MCP, so that one may call this MCP-type and (c) a shift to the left plus clockwise rotation, where one sees a decrease in MCP and decrease in RVR, so that this is a mixture of patterns (a) and (b). One may call this the mixed-type. The existence of the response of mixed-type is worth special attention, because, in this type, cardiac output (CO) was increased by the predominant decrease in RVR in spite of a decreased MCP, leading to an important condition that the CO does not necessarily decrease when systemic capacitance vessels were dilated by the vasodilators.
Abstract 5153: Dual inhibition of STAT3 and IL-8 pathways as a novel therapeutic approach in osteosarcoma
Authors: Yang Cao, Hui Xiao, Xiaojuan Wu, Jiayuh Lin
Journal: Cancer Research (2016)

Abstract Abstract Objective: Targeting STAT3 signaling represents a potential therapeutic approach to treatment of osteosarcoma. However, the use of STAT3 inhibitor as a single agent may not be effective for cancer therapy. Identify the pathway(s) that may generate synergy in tumor suppression may be more effective in osteosarcoma therapy. Methods: Inflammatory cytokines IL-6, IL-11, and IL-8 secretion of osteosarcoma after STAT3 inhibition were determined by ELISA assay. The sensitivity to STAT3 inhibitor was examined by cell viability assay. Cell migration and colony forming ability were evaluated when combination treatment. Results: In this study, we observed that the levels of IL-11 were significantly decreased and IL-6 was slightly decreased by STAT3 inhibitor. Interestingly, IL-8 levels were increased upon STAT3 inhibition. IL-8 was originally discovered as one of the major chemokines associated with the promotion of neutrophil chemotaxis and inflammatory responses. Previous studies have demonstrated that IL-8 contributes to cancer progression through its induction of tumor cell proliferation, survival, migration, and angiogenesis. Knocking down IL-8 expression using RNA interference resulted in enhanced sensitivity to STAT3 inhibitor. ELISA assay showed that MEK inhibitor (AZD6244 or Trametinib) and P38α inhibitor (LY2228820) had the ability to reduce the levels of IL-8 induced by STAT3 inhibition. Combination treatment of STAT3 and with a MEK inhibitor or with a P38α inhibitor showed more effective cytotoxic effect on osteosarcoma cell lines compared to single agent alone. Furthermore, the combination treatment exhibited stronger inhibition of cell migration and colony forming ability than single agent alone. Conclusion: These results suggest the IL-8 induction as a possible feedback mechanism for resistance to STAT3 inhibitor and suggest that simultaneous inhibition of STAT3 and IL-8 may be a more effective therapeutic approach in osteosarcoma. Citation Format: Yang Cao, Hui Xiao, Xiaojuan Wu, Jiayuh Lin. Dual inhibition of STAT3 and IL-8 pathways as a novel therapeutic approach in osteosarcoma. [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 5153.
Abstract 829: Chemoprevention of oxidative stress-associated oral carcinogenesis by sulforaphane depends on NRF2 and the isothiocyanate moiety
Authors: Aixian Lan, Wenjun Li, Yao Liu, Xinyan Zhang, Shanshan Zhou, Olesya Palko, Hao Chen, Mayanga Kapita, Justin Prigge, Edward Schmidt, Xin Chen, Zheng Sun, Xiaoxin Luke Chen
Journal: Cancer Research (2016)

Abstract Oxidative stress is known to play an important role in oral cancer development. In this study we aimed to examine whether a chemical activator of NRF2, sulforaphane (SFN), may have chemopreventive effects on oxidative stress-associated oral carcinogenesis. We first showed that Nrf2 activation and oxidative damage were commonly seen in human samples of oral leukoplakia. With gene microarray and immunostaining, we found 4-nitroquinoline 1-oxide (4NQO) in drink activated the Nrf2 pathway and produced oxidative damage in mouse tongue. Meanwhile whole exome sequencing of mouse tongue identified mutations consistent with 4NQO's mutagenic profile. Using cultured human oral keratinocytes and 4NQO-treated mouse tongue, we found that SFN pre-treatment activated the NRF2 pathway and inhibited oxidative damage both in vitro and in vivo. On the contrary, a structural analogue of SFN without the isothiocyanate moiety did not have such effects. In a long-term chemoprevention study using wild-type and Nrf2-/- mice, we showed that topical application of SFN activated the NRF2 pathway, inhibited oxidative damage, and prevented 4NQO-induced oral carcinogenesis in an Nrf2-dependent manner. Our data clearly demonstrate that SFN has chemopreventive effects on oxidative stress-associated oral carcinogenesis, and such effects depend on Nrf2 and the isothiocyanate moiety. Citation Format: Aixian Lan, Wenjun Li, Yao Liu, Xinyan Zhang, Shanshan Zhou, Olesya Palko, Hao Chen, Mayanga Kapita, Justin Prigge, Edward Schmidt, Xin Chen, Zheng Sun, Xiaoxin Luke Chen. Chemoprevention of oxidative stress-associated oral carcinogenesis by sulforaphane depends on NRF2 and the isothiocyanate moiety. [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 829.
Abstract 2909: Correlation between the expression of Sox2, Oct4 and deltaNp63 in clinical samples of resected esophageal cancers
Authors: Yoshikuni Inokawa, Kenichi Inaoka, Fuminori Sonohara, Hisaharu Oya, Masamichi Hayashi, Yukiko Niwa, Naoki Iwata, Daisuke Kobayashi, Masahiko Koike, Yasuhiro Kodera, Shuji Nomoto
Journal: Cancer Research (2016)

Abstract Background. DeltaNp63 is the oncogenic isoform in several squamous cell carcinomas including esophageal cancer (EC), however, the mechanisms of regulation of the expression are still unclear. Sox2 and Oct4 are well known transcription factors which function in cancer stemness. We supposed that these two molecules work as transcription factors on deltaNp63, and verified the expression of these genes in cases of resected squamous cell EC. Methods. In 78 surgical specimens of squamous cell EC with no prior neoadjuvant therapy, messenger RNA (mRNA) expression of deltaNp63, Sox2 and Oct4 in EC tissues and corresponding normal tissues was analyzed by quantitative real-time reverse transcription-polymerase chain reaction assay. The mRNA expression was standardized to that of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA. The expressions were compared in terms of clinicopathological factors and prognosis of postoperative survivals. Results. Peason correlation analysis showed significant correlations between expression of deltaNp63 and Sox2 in tumor tissues (r = 0.67, P&amp;lt;0.001), and between deltaNp63 and Oct4 (r = 0.71, P&amp;lt;0.001). The deltaNp63 expressions in tumor tissues were significantly higher than that in corresponding normal tissues (P&amp;lt;0.001), whereas Sox2 and Oct4 did not show significant differences between cancer and non-cancerous tissues. Univariate analysis identified poor differentiation, lymphatic involvement and higher ratio (Tumor/Normal) of expression of Oct4 as significant prognostic factors for poor overall survival, however, lymphatic involvement was the only independent prognostic factor in multivariate analysis (hazard ratio: 5.34; P&amp;lt;0.001). Conclusions. Expression of deltaNp63 in EC tumor tissues showed positive correlation with expression of Sox2 and Oct4. Therefore, these two transcription factors may regulate the expression of deltaNp63. The deltaNp63 is not a strong prognostic factor, however, Oct4 might be a significant predictor for poor prognosis for overall survival in squamous cell EC. Citation Format: Yoshikuni Inokawa, Kenichi Inaoka, Fuminori Sonohara, Hisaharu Oya, Masamichi Hayashi, Yukiko Niwa, Naoki Iwata, Daisuke Kobayashi, Masahiko Koike, Yasuhiro Kodera, Shuji Nomoto. Correlation between the expression of Sox2, Oct4 and deltaNp63 in clinical samples of resected esophageal cancers. [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 2909.
When the time matters: Metastatic Castration Resistant Prostate Cancer (mCRPC) patients long responders to Abiraterone acetate (AA) in post-docetaxel setting
Authors: G. Procopio, L. Porcu, P. Grassi, U. De Giorgi, L. Galli, O. Caffo, F. Boccardo, G. Facchini, F. De Vincenzo, A. Zaniboni, V. Chiuri, L. Fratino, D. Santini, V. Adamo, R. De Vivo, A. Di Nota, C. Messina, R. Ricotta, F. de Braud, E. Verzoni
Journal: Annals of Oncology (2015)
Self-Other Mergence in the Frontal Cortex during Cooperation and Competition
Authors: Marco K. Wittmann, Nils Kolling, Nadira S. Faber, Jacqueline Scholl, Natalie Nelissen, Matthew F.S. Rushworth
Journal: Neuron (2016)

To survive, humans must estimate their own ability and the abilities of others. We found that, although people estimated their abilities on the basis of their own performance in a rational manner, their estimates of themselves were partly merged with the performance of others. Reciprocally, their ability estimates for others also reflected their own, as well as the others', performance. Self-other mergence operated in a context-dependent manner: interacting with high or low performers, respectively, enhanced and diminished own ability estimates in cooperative contexts, but the opposite occurred in competitive contexts. Self-other mergence not only influenced subjective evaluations, it also affected how people subsequently objectively adjusted their performance. Perigenual anterior cingulate cortex tracked one's own performance. Dorsomedial frontal area 9 tracked others' performances, but also integrated contextual and self-related information. Self-other mergence increased with the strength of self and other representations in area 9, suggesting it carries interdependent representations of self and other.
Phase I/II study of PCI-27483, a coagulation factor VIIa (FVIIa) inhibitor, in combination with gemcitabine in patients with advanced pancreatic cancer.
Authors: Sameer A. Mahesh, Nashat Y. Gabrail, Jitendra G. Gandhi, Alok A. Khorana, Robert Manges, Satish Shah, Gary W. Thomas, Ahmed M. Hamdy, Michelle Stevens-Brogan, Cathy Zhou, Laurence Elias, David Loury, Ramesh K. Ramanathan
Journal: Journal of Clinical Oncology (2013)

e15014 Background: Tissue factor (TF) up-regulation is associated with increased tumor invasiveness and progression, worsened prognosis and increased thromboembolism (VTE). Activation of protease activated receptors by TF:FVIIa complex leads to increases in IL-8, VEGF and other invasiveness promoting factors. PCI-27483 (P), a selective FVIIa inhibitor, reduced pancreatic adenocarcinoma (PCa) xenograft growth in mice at doses producing 2.5 - 3.0 x PT changes. Methods: Escalating doses of P combined with gemcitabine (G) targeting peak (2 hr post) INR = 3.0 was studied in Phase I preceding randomization to G+P at the determined dose vs. G alone in Phase II. Eligible patients (pts) had measurable locally advanced or metastatic PCa, ECOG PS 0-1, and normal PT/aPTT, and no history of VTE. G was given IV at 1 G/m 2 q wk X3 every 4 wks, and P was self-administered SC bid continuously. Tumor evaluation including spiral CTs were performed at baseline and q 8 wks. Results: In phase I, 8 pts were enrolled and the targeted INR was attained at 1.2 mg/kg. In phase II, 34 patients were randomized, 16 to G and 18 to G+P. The randomized arms were well balanced; overall 88% had metastatic disease; most had liver involvement. Among pts randomized to P+G, mean ± SD 2-hr post injection INR was 3.1 ± 1.2 on D8 and 2.8 ± 1.0 on D22 (n=13). P dosing was continued for up to 96 wks; mean ± SD: 17 ± 24 wks. Dose reduction to maintain target INR was required for 6 pts. Overall tolerability and safety of G+P was similar to that of G, with a higher incidence of mostly low grade bleeding events and decreased Hgb. Efficacy measures of G vs G+P pts were not significantly different (Table). Conclusions: PCI-27483 +G was well tolerated at doses of P up to 1.5 mg/kg bid. The safety profile of the combination was consistent with that expected of each agent. While the clinical endpoints were not achieved in pancreatic cancer, the targeted inhibition of the coagulation cascade was achieved. Clinical trial information: NCT01020006. [Table: see text]
Randomized phase 2 study of paclitaxel (PTX), trastuzumab (T) with or without MM-111 in HER2 expressing gastroesophageal cancers (GEC).
Authors: Crystal Shereen Denlinger, Maria Alsina Maqueda, David J. Watkins, Sun Jin Sym, Johanna C. Bendell, Se Hoon Park, Hendrik-Tobias Arkenau, Tanios S. Bekaii-Saab, Art J. Kudla, Charlotte Fenton McDonagh, Akos Gabor Czibere, Benoist Chibaudel, Michael F. Press, Harry H. Yoon, J. Randolph Hecht, David Cunningham, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2016)

4043 Background: HER2 overexpression occurs in < 20% of GEC, and T-based front-line therapy improves survival. HER3 is overexpressed in < 87% of GEC and is associated with poor prognosis. HER3 is activated by its ligand heregulin (HRG) to form a potent signaling heterodimer with HER2 and is emerging as a key tumorigenic node. MM-111, a bispecific antibody designed to inhibit HRG-activated HER3 signaling in HER2+ tumors, was evaluated in second-line treatment of advanced HER2+ GEC in combination with weekly PTX and TRAS. Methods: Patients (pts) who progressed following fluoropyrimidine/platinum-based therapy +/- T for advanced disease or within 6 months of neoadjuvant/adjuvant therapy were randomized 1:1 to 80 mg/m2 PTX on days 1, 8 and 15 of a 28 day cycle; T at 4 mg/kg load/2 mg/kg/weekly; with (Arm A) or without (Arm B) MM-111 at 20 mg/kg/weekly. Primary endpoints were progression-free survival (PFS) in the intent-to-treat (ITT) population and HRG-high population (pts with HRG ≥ median). Enrollment of 120 pts was planned with 70 or 38 PFS events required to detect a 67% or 50% PFS improvement in the ITT- or HRG-high population, respectively (80% power, alpha = 0.1). Results: The study was closed early by the Data Monitoring Committee based on lack of efficacy within the ITT. 88 pts were randomized; 71 pts received prior T; 54 pts had HER2+ status centrally confirmed; 57 pts had assessable HRG mRNA. Median PFS in the ITT was 9.6 weeks (95% CI 8.0-15.7) for Arm A and 23.3 weeks (95% CI 12.1-27.0) for Arm B, HR 2.08 (p = 0.01; 95% CI 1.17-3.68). Median OS in ITT was 32.1 weeks (95% CI 20.4-48.0) and 56.1 weeks (95% CI 40.7-NR) for Arm A and Arm B respectively, HR 2.12 (p = 0.045, 95% CI 1.0-4.5). Any grade treatment emergent adverse events with > 15% incidence across both arms were diarrhea, anemia, decreased appetite, alopecia, fatigue, nausea, vomiting, asthenia, neutropenia, constipation, and cough. Conclusions: MM-111 did not improve PFS or OS in HER2+ GEC when added to PTX/T. HRG expression was lower than anticipated in the study population, potentially contributing to the effect of MM-111 on PFS and OS in the ITT. PTX/T alone appears promising in second-line therapy of GEC and further investigation is warranted. Clinical trial information: NCT01774851.