tbuckley/cabot-search huggingface dataset:
Abstract A22: Hypoxia-mediated translational control of hypoxia inducible factor 1 alpha through aldolase A feedback regulation in lung carcinogenesis
Authors: Yu-Chan Chang, Michael Hsiao
Journal: Cancer Research (2017)

Abstract Lung cancer cells grow in-situ during low-oxygen situation and usually results in invasion and is frequently recurrent after therapy. However, the oxygen-mediated translation control of the metabolic events in lung cancer remains largely unknown. By using the integrated transcriptomics data and the shRNA library against glycolytic enzymes, here we identified that Aldolase A (ALDOA) up-regulation is highly correlated with migratory/invasive activity of lung cancer cells and poorer clinical outcomes. Significantly, knockdown of Aldolase A inhibited in vitro and in vivo migratory/invasive activity of lung cancer cell line with high ALDOA expression. Complementary, enforced overexpression of exogenous ALDOA promoted migration/invasion. Furthermore, microarray and Ingenuity pathway analyses reveal that ALDOA-driven lung cancer metastasis likely recruits Hypoxia-inducible factor 1 alpha (HIF1α)-associated signaling pathway. There were no significance changes at the mRNA level of HIF1α in ALDOA two-way models. However, HIF1α protein was found stabilized in hypoxic or normoxic condition through ALDOA overexpression to decrease prolyl hydroxylase (PHD) activity for hydroxylation-form of HIF1α to activate downstream genes including CXCR4, MMP9 in lung carcinogenesis. Interesting, HIF1α also was found to bind hypoxia-response element (HRE) domain of ALDOA to activate its transcription and form a positive feedback loop. IHC staining results further demonstrate that Aldolase A and HIF1α expression is positively correlated in clinical lung cancer tissues and the signature of high-level Aldolase A and HIF1α; expression strongly associates with worst survival probability in lung cancer patients. Our results not only unveil molecular mechanism by which Aldolase A promotes lung cancer metastasis via inducing the HIF1α activity but also provide a novel therapeutic strategy to combat malignant lung cancer via targeting ALDOA. Citation Format: Yu-Chan Chang, Michael Hsiao. Hypoxia-mediated translational control of hypoxia inducible factor 1 alpha through aldolase A feedback regulation in lung carcinogenesis. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr A22.
Salvage therapy for metastatic acral or mucosal melanoma: Efficacy and safety analysis of nab-paclitaxel/carboplatin combined with bevacizumab in c-kit/BRAF wild-type pts.
Authors: Chuan Liang Cui, Si Ming Li, Lu Si, Zhihong Chi, Xi Nan Sheng, Li Li Mao, Bin Lian, Xuan Wang, Bi Xia Tang, Jun Guo
Journal: Journal of Clinical Oncology (2014)

e20017 Background: Metastatic acral or mucosal melanoma seems to be more aggressive and had little response to traditional chemotherapy. Nab-Paclitaxel (Abraxane) is clinically active in metastatic cutaneous melanoma, but its activity is still unknown in acral or mucosal melanoma. As acral or mucosal melanoma might have more abundant blood supply than cutaneous melanoma, we conducted this trial of abraxane /carboplatin combined with bevacizumab as 3rd line therapy in metastatic acral or mucosal melanoma pts. Methods: Pts with wild type BRAF/C-kit, stage IV acral or mucosal melanoma were enrolled; 1st and 2nd line chemotherapies were allowed. The salvage regimen abraxane 260 mg/m2 d1, carboplaitin (AUC 5) d1, and bevacizumab 5mg/Kg d1, 15, was continued in a 28 days cycle until disease progression or toxicity intolerable. Primary endpoints were objective response rate and safety analysis evaluated according RECIST 1.1 criteria every cycle and NCI CTC 4.0. Secondary endpoints included progression free survival (PFS) and overall survival (OS). Results: From Jan 2011 to May 2013, 30 pts were enrolled and evaluable, in which 16 were acral and 14 mucosal, with 26.7% M1a disease, 16.7% M1b and 56.7% M1c. The 1st and 2nd line chemotherapy included dacarbazine or temozolomide and paclitaxel/carboplatin. Mean cycle of salvage therapy was 2.3 (range1-8). There were 2pts got PR (6.7%), and 14 got SD (>8weeks), with the disease control rate 53.3%. Until last follow up of May 2013, the median PFS was 3.0 months (95%CI 2.0~3.9 months). The median OS was not reached. Grade 3-4 toxicities were relatively low, anemia (16.7%), leucopenia (33.3%), and thrombocytopenia (16.7%). No treatment related death occurred. Conclusions: For metastatic acral and mucosal melanoma, abraxane/carboplatin combined with bevacizumab might get a well disease control and improved median PFS even in the setting of 3rd line therapy, it was well tolerated and worthy of further study in treatment naïve pts.
Ultrasound contrast visualization of tumor vasculature in vivo by targeted microbubbles
Authors: M. K. K. Wong, R. A. Modzelewski, G. Weller, F. S. Villanueva, D. Henry, J. S. Kirk, C. K. Brown, W. R. Wagner
Journal: Journal of Clinical Oncology (2004)

3198 Background: Tumor endothelial cells (ECs) are phenotypically distinct and express unique surface molecular markers. Previous work show that a synthetic peptide containing the amino acid motif RRL will specifically bind (i) tumor ECs in vitro, (ii) the vasculature of experimental prostate and sarcoma tumors and (iii) the ECs within human prostate and sarcoma tumors. We hypothesized that ultrasound contrast microbubbles (MBs) linked to RRL peptide would preferentially and specifically adhere to tumor vasculature, allowing for direct, real-time, tumor imaging. Methods: Phospholipid MBs were conjugated via avidin/biotin bridging chemistry to cyclic peptides containing either RRL (MBRRL) or a glycine control sequence (MBControl). Solid 0.5 cm3 PC3 (human prostate) or Clone C (mouse sarcoma) tumors were established in the flank of 11 mice. MBRRL or MBControlwere injected i.v. (5x106 MBs/injection), and the tumors imaged with high-mechanical index triggered pulse inversion ultrasound at 120 and 135 sec. In 10 additional mice, the ventricular myocardium was likewise studied to assess MB behavior in high blood flow conditions. Videointensity (VI) was measured offline, and the VI difference between the 120 sec (adhered + circulating MBs) and 135 sec (circulating MBs) frames was defined as the signal attributable to MB adhesion only. Results: The mean VI for all tumors using MBControl was 2 ± 2 intensity units, suggesting that there was minimal adhesion. The VI difference for MBRRLwas significantly greater than that for MBControl(7±3 vs. 2±2 intensity units; p<0.02). There was no significant change in VI between MBRRL as compared to MBControl in the myocardium, thus suggesting the lack of preferential adhesion of MBRRL at this site. Conclusions: RRL peptide targeted microbubbles: Bind to tumor endothelium in vivo, via sequence-specific interactions; Selectively adhere to tumor vasculature versus normal vasculature in vivo; Cause persistent tumor contrast enhancement during ultrasound imaging. This is the first demonstration that targeted ultrasound contrast agents may enable noninvasive functional imaging of tumor vasculature. No significant financial relationships to disclose.
Serum Amyloid A (SAA) in Patients with Pancreatic Carcinoma
Authors: K. Yokoi, M. N. Raber, L.-C. N. Shih, D. Li, S. R. Hamilton, I. J. Fidler, J. L. Abbruzzese
Journal: Journal of Clinical Oncology (2004)

9649 Background: New biomarkers are essential for the diagnosis and monitoring of human pancreatic carcinoma. In our previous study, sera collected from nude mice implanted in the pancreas with human pancreatic cancer cells were analyzed by Surface Enhanced Laser Desorption Ionization (SELDI) mass spectrometry. The progressive growth of the tumors directly correlated with the level of Serum Amyloid A (SAA). In the present study, we determined whether plasma levels of SAA correlated with the stage of pancreatic carcinoma in patients. Methods: Plasma was collected from 113 normal volunteers and 134 patients with pathologically confirmed pancreatic adenocarcinoma. The plasma level of SAA was determined by enzyme linked immunosorbent assay (ELISA). Results: The concentration of SAA in plasma of pancreatic cancer patients was significantly higher than that in normal volunteers (mean value: 180.1 vs 27.9 mg/L; P<0.01), and had a tendency to increase in later stages of the disease. Specifically, the level of SAA in stage IV B patients was significantly higher than that in stage I patients and normal volunteers (282.9 vs 17.8 and 27.9 mg/L; P<0.01). Immunohistochemical analysis of pancreatic tumor specimen revealed intense expression of SAA in the malignat epithelium of the carcinomas with less intense staining of desmoplastic fibroblasts. Conclusions: SAA may be a useful biomarker for monitoring of patients with advanced pancreatic cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech; Novartis Pharma
High-Risk Histopathology Features in Primary and Secondary Enucleated International Intraocular Retinoblastoma Classification Group D Eyes
Authors: Ido D. Fabian, Andrew W. Stacey, Tanzina Chowdhury, Catriona Duncan, Esin K. Karaa, Irene Scheimberg, M. Ashwin Reddy, Mandeep S. Sagoo
Journal: Ophthalmology (2017)
A phase 1 study of veliparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, in combination with cisplatin and etoposide in extensive-stage small cell lung cancer (SCLC) patients: An Eastern Cooperative Oncology Group study (E2511).
Authors: Taofeek Kunle Owonikoko, Suzanne Eleanor Dahlberg, Saad A. Khan, David E. Gerber, Jonathan Dowell, Rebecca Anne Moss, Chandra Prakash Belani, Christine L. Hann, Charu Aggarwal, Suresh S. Ramalingam
Journal: Journal of Clinical Oncology (2014)

7523 Background: Veliparib is a small molecule inhibitor of PARP currently in advanced clinical testing. Based on promising preclinical evidence of therapeutic potentiation when combined with cisplatin and etoposide in SCLC, a phase 1 study was conducted to establish the safety of the 3-drug combination. Methods: The study employed the 3+3 dose escalation design to establish the safety and recommended phase 2 dose (RP2D) of veliparib when combined with fixed doses of cisplatin (75mg/m2 on D1) and etoposide (100mg/m2on D1-3) without prophylactic growth factor support in a 21-day cycle. The starting dose of Veliparib was 60mg (bid D1-7) with plan to escalate to 100mg (D1-7) if no dose limiting toxicity (DLT) or de-escalate to 40mg (bid D1-7) if DLT was observed in 2 of 3 or ≥2 of 6 treated patients. Patients with treatment-naïve, extensive stage SCLC were included. DLT was assessed during cycle 1. Results: The study enrolled 9 patients with extensive stage SCLC; Gender: M/F (4/5); Age: median/range (60, 51-78); Race: White/African American (8/1). Veliparib was well tolerated at the 60mg dose (0 of 3 patients with DLT). DLT was seen in 1 of 6 patients treated at the 100mg dose (grade 5 cardiac failure). We established the maximum tolerated dose of veliparib of 100mg bid on D1-7 in combination with standard doses of cisplatin and etoposide as the RP2D. Grades 3-5 adverse events irrespective of attribution included - G3: dehydration (1), febrile neutropenia (1), hyponatremia (1), diarrhea (1), nausea (3), thrombocytopenia (1), fatigue (2), neutropenia (1), leukopenia (3); G4: hyponatremia (1), respiratory failure (1), thrombocytopenia (1), neutropenia (5), leukopenia (2); G5: heart failure (1). Unconfirmed investigator-assessed efficacy outcome in 7 evaluable patients were stable disease in 2/7 (28.6%), partial response in 4/7 (57.1%) and complete response in 1/7 (14.3%) patients. Conclusions: The study demonstrated the safety of combining veliparib with cisplatin and etoposide in previously untreated SCLC patients. A randomized phase II efficacy study of this combination is currently ongoing. Clinical trial information: NCT01642251.
Hematopoietic Stem Cell Transplantation for Sickle Cell Disease in Childhood: A Single Center Experience with 45 Patients
Authors: Laurence Dedeken, Phu-Quoc Le, Nadira Azzi, Cecile Brachet, Catherine Heijmans, Sophie Huybrechts, Christine Devalck, Ngalula Mujinga Malou, Alina Ferster
Journal: Blood (2011)
Upfront treatment with temozolomide and bevacizumab (TEMOBEVA) in patients with bulky, multifocal glioblastoma and/or with severe neurological impairmen.
Authors: Ilan Darmon, Mathieu Boone, Marie Blonski, Emilie Le Rhun, Luc Taillandier, Bruno Chauffert, Alexandre Coutte
Journal: Journal of Clinical Oncology (2015)

e13037 Background: Optimal treatment of patients with bulky or multifocal glioblastoma, or with severe neurological impairment is not well established. We evaluated here the impact of upfront Temozolomide (TMZ) and bevacizumab (BEV) in such patients. Methods: This retrospective study included 43 patients from 3 French centres between December 2010 and December 2014. Patients were considered not eligible for surgery or initial chemoradiation either due to tumor volume precluding an upfront chemoradiotherapy with TMZ, or due to multifocality or severe neurological impairment. Initial combination of TMZ (150 to 200 mg/m2/d, 5d every 28d) plus BEV (10mg/kg every 14d) was delivered. Responding patients received radiotherapy (60 Gy in 30 fractions) plus concomitant TMZ (75mg/m2/d), with or without BEV (10mg/kg every 14d). Results: Forty-three patients were analyzed (median age 60 years, median Karnofsky Performance Status (KPS) 70). Thirty-two patients (74%) were classified in the RTOG RPA group V-VI. Median number of TMZ cycles was 3 [1-12], and the median number of BEV cycles was 6 [1-20] before disease progression or radiotherapy. Twenty six out of 36 patients (69%) received a complete dose of radiotherapy (60 Gy) and concomitant TMZ after a TMZ-BEV-induced diminution of the clinical target volume (CTV). Eight patients (19%) experienced grade 3-4 toxicity. PFS was 58.2% [95%CI (41.9 to 71.1)] at 6 months and 23.2% [95%CI (11.9 to 36.5)] at 12 month. OS was 67.4% [(95%CI (51.1 to 79.2)] at 6 month and 46.5% [95% CI (31.2 to 60.2)] at 12 month. Median OS and PFS were 10.6 months [95%CI (6.2 to 14.4)] and 7.1 months [95%CI (4.5 to 9.8)], respectively. Induction therapy allowed for dose reduction or cessation of steroid treatment in 60% of patients, and a stable dose in 24% of patients. An improvement in KPS was observed in 42% of patients, while KPS remained stable in 46%. Conclusions: For the majority of patients, a clinical benefit was obtained after upfront TMZ-BEV, with improved KPS and a decrease in steroid dose. Most patients were treated with optimal chemoradiotherapy after reduction of the CTV. OS and PFS compared favourably to historical series of RPA class V-VI patients.
LIPOPROTEINS, STATIN THERAPY, CAROTID ATHEROSCLEROTIC PLAQUE VULNERABILITY AND STIFFNESS: A STUDY OF NOVEL ULTRASOUND METHODS UTILIZING MICROBUBBLE CONTRAST ENHANCEMENT AND SHEAR WAVE ELASTOGRAPHY
Authors: Runqing Huang, Matthew W. Urban, J. Kevin DeMarco, Waleed Brinjikji, John Huston, Thanila A. Macedo, Eric J. Dailey, Mary E. Hagen, Sharon L. Mulvagh
Journal: Journal of the American College of Cardiology (2017)
IS MYOCARDIAL FIBROSIS A HALLMARK OF PARADOXICAL LOW GRADIENT AORTIC STENOSIS?
Authors: Alisson Slimani, Clotilde Roy, Christophe De Meester, Mihaela Amzulescu, Christophe Beauloye, Anne-Catherine Pouleur, David Vancraeynest, Agnes Pasquet, Bernhard Gerber, Jean-Louis Vanoverschelde
Journal: Journal of the American College of Cardiology (2017)
Concurrent chemoradiotherapy with S-1 and cisplatin for locally advanced esophageal cancer
Authors: H. Iwase, M. Shimada, T. Tsuzuki, M. Okeya, K. Kobayashi, H. Watanabe, Y. Hibino, N. Ryuge, H. Goto
Journal: Journal of Clinical Oncology (2007)

15007 Background: Both oral fluoropyrimidine anti-cancer agent (UFT, S-1) and cisplatin can enhance the effectiveness of radiotherapy. We previously reported a phase II trial of UFT and cisplatin combined with radiotherapy (Int J Clin Oncol 8 (2003): 305–311) and a phase I trial of S-1 and cisplatin combined with radiotherapy (Jpn J Cancer Chemother 33 (2006): 224–229) for advanced esophageal cancer. The present study analyzes the efficacy of concurrent chemoradiotherapy by using S-1 and cisplatin for locally advanced esophageal cancer. Methods: Chemoradiotherapy consisted of two courses. The first course included 30 Gy of radiotherapy given over 3 weeks, together with daily oral administration of S-1 (80 mg/m 2 /day) for 2 weeks and a 24-h infusion of cisplatin (70 mg/m 2 ) on day 8. The second course of chemoradiotherapy was administered after 2 weeks. For patients who exhibited an objective response to chemoradiotherapy, at least 2 four-week courses consisting of chemotherapy of S-1 and cisplatinon were administered. If a patient was unable to take S-1 as a capsule, S-1 was administered in the powdered form with water. Results: Fifty-nine patients were enrolled. They had the following characteristics: median age 65 years; M/F 52/7; PS 0/1/2: 33/19/7. There were 9 patients with stage II tumors and 50 with stage III. Fifty-four patients (92%) completed 2 courses of chemoradiotherapy. The major toxicity was myelosuppression. Fifteen patients (25%) developed grade 3 leukocytopenia, while 7 patients (12%) developed grade 4 leukocytopenia. Nonhematologic toxicity was moderate: grade 2 nausea/vomiting, pain, oral mucositis, and renal dysfunction occurred in 20%, 12%, 5% and 5% of patients, respectively. In stage II cases, complete response (CR), partial response (PR), and response rates were 78%, 22%, and 100%, respectively. In stage III cases, CR, PR, and response rates were 58%, 32%, and 90%, respectively. All stage II patients survived. In stage III cases, the 1-year survival rate was 70% and the 3-year survival rate was 44%. Conclusions: Chemoradiotherapy with S-1 and cisplatin is convenient, tolerable, and effective, and may be a promising nonsurgical management option for patients with locally advanced esophageal cancer. No significant financial relationships to disclose.
PULMONARY VASCULAR RESISTANCE PREDICTS MORTALITY IN END-STAGE RENAL DISEASE PATIENTS WITH PULMONARY HYPERTENSION
Authors: Jonathan Wolfe, Gavin Hickey, Andrew Althouse, Michael Sharbaugh, Deepak Kumar Pasupula, Dustin Kliner, Michael Mathier, Prem Soman
Journal: Journal of the American College of Cardiology (2017)
Lapatinib in combination with capecitabine plus oxaliplatin (CapeOx) in HER2 positive advanced or metastatic gastric (A/MGC), esophageal (EAC), or gastroesophageal (GEJ) adenocarcinoma: The LOGiC trial.
Authors: J. Randolph Hecht, Yung-Jue Bang, Shukui Qin, Hyun-Chul Chung, Jian-Ming Xu, Joon Oh Park, Krzysztof Jeziorski, Yaroslav Shparyk, Paulo M. Hoff, Alberto F. Sobrero, Pamela Salman, Jin Li, Svetlana Protsenko, Marc E. Buyse, Karen Afenjar, Tomomi Kaneko, Allison Kemner, Sergio Santillana, Michael F. Press, Dennis J. Slamon
Journal: Journal of Clinical Oncology (2013)

LBA4001 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Children's stress: associations with lifestyle and obesity
Authors: Nathalie Michels, Isabelle Sioen, Liesbet Boone, Caroline Braet, Els Clays, Barbara Vanaelst, Inge Huybrechts, Stefaan De Henauw
Journal: Psychotherapy and Psychosomatics (2013)

Introduction: Stress has been hypothesized to be involved in obesity development. Apart from a direct pathway through cortisol, stress may indirectly facilitate obesity by influencing other lifestyle factors: stressed persons may consume more comfort foods, may have a more sedentary behaviour and may suffer from sleep problems.
Methods: In 326 Belgian children (5-12y) of the ChiBS study, the longitudinal relation between stress and body composition was examined over two years. Stress was measured by salivary cortisol (4 samples/day, 2 days) and questionnaires concerning negative life events, problem behaviour and emotions. For body composition, BMI, waist-to-height and fat% estimation by air displacement were used. Furthermore, physical activity, screentime, food consumption, eating behaviour and sleep duration were measured as lifestyle factors. Cross-lagged analyses with Mplus and moderation by cortisol and lifestyle factors were tested.
Results: Children with higher stress scores had a less healthy lifestyle. They had an unhealthier diet especially due to more sweet food consumption, performed more emotional eating, were less active and slept less. Two years later, these stressed children maintained the same unhealthy life style except that they were more physical active instead of less. Salivary cortisol and lifestyle were moderators in the stress-obesity relation: stressed children had also more overweight or a higher fat percentage, but only when they had an unhealthier lifestyle or higher cortisol. 
Discussion: These results confirm that stress can deteriorate lifestyle and cortisol homeostasis already in childhood and that these changes make them vulnerable to overweight. Consequently, obesity prevention should target both lifestyle and stress.
Long-term follow-up in low-grade gastric MALT lymphoma (LGGML): Effect of persistent monoclonality (m+) on outcome
Authors: C. Pegoraro, A. Savio, S. Beghelli, A. Scarpa, G. Zamboni, A. Tomba, R. Sabbioni, F. Merlin, G. L. Cetto, F. Pasini
Journal: Journal of Clinical Oncology (2004)

6560 Background: limited data exist whether, in the long-term, the PCR for the rearranged immunoglobulin heavy chain region may define groups with different prognosis. Methods: 113 pts from the same area in the North East of Italy with stage I LGGML were prospectively monitored clinically and endoscopically. Wotherspoon score 0–3 was defined as histological remission (R) and score 4–5 as histological presence of lymphoma (P). Results: H. Pylori was eradicated in about 95% of the cases. After a median follow-up of 66 mo (24–132), three groups of pts were identified. Group A: 60 pts achieved R within 24 mo from diagnosis. Median time to R was very short (3 mo). At diagnosis 38/60 (63%) cases presented m+, 16/60 (27%) had negative monoclonality (m-) and in 6 data were not available. In the m+ subset median time to m- was 12 mo (3–24). In the m- subset, 2 pts presented isolated findings of m+. All remained in continuous R with m- at a median follow-up of 66 mo (24–120). Group B: 33/113 pts were in R, but with m+ at ≥ 24 mo; median time to R was 6 mo (3–24). 30 pts were m+ at diagnosis: 21 of these presented intermittently occurring monoclonality between 24 and 72 mo (median 42) while 12 presented more repeated positive samples between 36 and 90 mo (median 48). All are in continuous R. Group C: 18 pts presented P at 24–30 mo; median follow-up was 60 mo (36–132). 9/18 pts presented Pm+ at a median of 5 yrs (30–72), while 9 achieved R (either with m+ or m-) at a median of 42 mo (30–102). Median persistence of m+ was 48 mo (24–114). Conversion into high-grade lymphoma did not occur. 2 pts underwent gastrectomy after 1 yr and showed no evidence of relapse up to 84 mo. Overall, in groups B and C, we had evidence of m+ between 24 and 114 mo (median 48 mo) in 48 pts (43%) either in R (33) or P (15). Conclusions: i) monoclonality did not influence outcome, either in R or P ii) pts achieving rapid R are probably cured iii) in the P subset oncological therapies can be delayed, if not avoided, provided a close monitoring iii) for treatment decision making, routine histology remains the standard tool. No significant financial relationships to disclose.