tbuckley/cabot-search huggingface dataset:
Zoledronic acid effect on circulating RANK/RANK-l/OPG axis in cancer patients.
Authors: Toni Ibrahim, Laura Mercatali, Marianna Ricci, Emanuela Scarpi, Francesca Fabbri, Chiara Liverani, Stefania Vittoria, Luisa Nicoletti, Rossana Ricci, Patrizia Serra, Dino Amadori
Journal: Journal of Clinical Oncology (2012)

10615 Background: Bone metastasis disrupts bone integrity through loss of the balance between osteoclastic-mediated osteolysis and osteoblastic osteogenesis. The RANK/RANK-L/OPG axis governs osteoclastogenesis and bone resorption. We evaluated the trend of markers over time. Secondary aims were to study the predictive role of different circulating markers in the response to Zoledronic Acid (ZA) with respect to objective response and to skeletal-related events (SREs). Methods: The study prospectively evaluated levels of RANK, RANKL and OPG transcripts by Real-Time PCR and VEGF and NTX expression by ELISA in the peripheral blood of 49 consecutive patients with advanced breast, prostate or lung cancer (36, 7 and 6, respectively). Enrolled patients were at first diagnosis of bone metastases and had not previously undergone treatment with bisphosphonates. Patients received the standard schedule of ZA (4 mg infusion every 28 days) for about 12 months, undergoing blood tests and instrumental evaluation before the first infusion of ZA and every 4 months thereafter. Results: Median RANKL values after 12 infusions of ZA had decreased by 22% with respect to baseline whereas OPG, had increased by about 96%, with a 56% decrease in the RANKL/OPG ratio. NTX decreased over time (p&lt;0.0001). On the basis of ROC curve analysis, RANKL was the most accurate marker for bone response with an AUC of 0.74 (95% CI 0.54-0.93). No correlations were found between circulating markers and SREs. Conclusions: The present work is one of the few prospective studies carried out on the circulating markers that are potentially associated with bone metastases. Our findings would seem to indicate that ZA decreases osteoclast activity through RANK/RANKL/OPG pathway modulation and that RANKL may play a role in the prediction of objective response to ZA. Confirmation of results is needed in a larger case series.
Predictive scoring systems for brain metastasis at diagnosis and at recurrence in non-small cell lung cancer
Authors: S. T. Maunglay, W. J. Fulp, A. Chiappori, G. R. Simon
Journal: Journal of Clinical Oncology (2009)

e19020 Background: Brain metastasis (BM) is a major cause of mortality and morbidity in Non Small Cell Lung Cancer (NSCLC) but large studies analyzing potential factors that could be predictive of BM at diagnosis or recurrence are lacking. We have developed 2 predictive scoring models to identify the patients at risk. Methods: A retrospective analysis on 4,294 NSCLC cases, seen between 1994 and 2006, at the Moffitt Cancer Center and Research Institute, Tampa, FL was performed utilizing the cancer center's registry data. 477 (11.12%) patients had BM at the time diagnosis and additional 252 (5.82%) patients developed new BM as first recurrence. Results: For patients with BM at diagnosis, age younger than 63 years, non squamous histology and current or never smoking status were all significant in both univariate and multivariate analysis (N= 4174). Based on calculated odds ratios, a scoring system of 0 to 6 points was developed for these patients. Higher scores predicted higher risk for BM (0- 2=3.38%, 3- 4=9.93%, 5=13.65% and 6=21.03%; p &lt;.0001). For patients with new BM at first recurrence, age younger than 63 years, non squamous histology, and the stage at diagnosis (i.e., BM risk in stage III&gt;IV&gt;II&gt;I), were all significant in both univariate and multivariate analysis (N=4291). Based on calculated odds ratios, a scoring system of 0 to 7 points was developed for these patients. Higher scores predicted higher risk for BM (0–1=3.38%, 2–3=4.72%, 4–5= 8.76%, and 6–7=11.83%; p&lt;.0001). Similar risk percentage results were seen after testing the 2 scoring systems in 3 chronologically divided patient groups. Conclusions: The 2 scoring systems developed based only on clinical data were predictive of BM in NSCLC at diagnosis and recurrence. These scoring systems should be helpful for establishing initial and follow up cranial imaging schedules in NSCLC patients. [Table: see text] No significant financial relationships to disclose.
Perceptions and barriers towards clinical trials participation in Asian cancer patients.
Authors: I Peng Thomas Soh, Cheong Kiat Julian Tay, Gui Yi Ho, Angela Pang, Pei Jye Voon, Winnie Hui Yee Ling, Chee Seng Tan, Soo-Chin Lee
Journal: Journal of Clinical Oncology (2012)

e19523 Background: There is currently limited data on the perceptions and attitudes of Asian cancer patients towards therapeutic clinical trials (CTs). Understanding this is crucial to their successful execution. Methods: From May to December 2011, we surveyed cancer outpatients at the National University Cancer Institute, Singapore, and collected data on patient demographics, tumor information, awareness, perceptions, and willingness to participate in CTs. Results: 240 patients were surveyed, including 85 (35%) who had previously participated, 141 (59%) who had never participated, and 14 (6%) who had refused participation in a CT. The majority was Chinese (78.8%) or Malay (16.7%), 57.5% was female and median age was 56 years (range 22-83). There were no differences in demographics between patients who had, had not or refused participation in a CT. 135 patients (56%) had prior awareness of CTs, and were more likely to be female (p=0.027) or had metastatic disease (p=0.002). 111 (46%) patients were willing to participate in CTs given the opportunity, and were more likely to have prior awareness of CTs (76.6% vs 38.8%, p&lt;0.001), to believe that CT sponsorship covers only the cost of trial drugs (52.3% vs 24%, p&lt;0.001), and to state that paying for non-trial related or standard expenses was reasonable (35.1% vs 19.4%, p=0.006), compared to patients who were not willing to participate. Patient age, gender, education, income, or availability of health insurance did not influence willingness to participate. The majority of patients who had participated in CTs (66/85, 78%) reported only positive experiences, while 13 (15%) reported mixed experiences, and only 2 (2.4%) reported only negative experiences. The feeling of being treated as ‘guinea pigs’ (n=7), and fear of toxicities (n=5) were the main reasons cited for refusal to participate in CTs. Conclusions: Asian patients have moderate awareness of CTs, and slightly less than half the patients surveyed were willing to participate in CTs. Prior knowledge of CTs was associated with increased willingness to participate, and improving awareness through education could facilitate enrollment.
Abstract 3319: Rare cell isolation by enhanced microfluidic filter using wing-shaped micro posts
Authors: Nanda Kasani, Manjunath Yeriswamy, Guangfu Li, Jussuf Kaifi, Jae W Kwon
Journal: Cancer Research (2019)

Abstract Purpose: Study of effective isolation of rare cells using specially designed microfluidic filter. Design: A novel microfluidic filter chip is proposed to enhance the isolation efficiency on rare cells, and has been successfully tested with micro beads and A549 cell lines using our unique designs of micro-posts. While most of the other filtration techniques have serious issues of channel clogging and prolonged processing, we have successfully accomplished outstanding improvements from such problems by utilizing inertial displacement through curved structures, built-in bypassing routes, and dedicated trapping zones. A solution containing polystyrene micro beads of 9.9 μm in diameter was successfully separated at the isolation efficiency of 96% with a high flow rate of 1ml/min. Additional experiments were also carried out, with A549 cell-lines in a PBS solution to see the filtration feasibility on bio-particles. Our device may offer an effective and reliable label free separation technique without channel blockage issues. By far, we have studied two design configurations called Model I and Model II. (Model II is an improved version of Model I). Results: Capture efficiency of 96% was recorded from Model II for microbeads at the flowrate of 1ml/min. The capture efficiency of 85% was marked from Model I for microbeads at the flowrate of 1 ml/min. The relationship between the flowrate and capture efficiency has also been studied as shown in Table.1 Conclusion: Our studies demonstrate the excellence of our microfluidic devices with a capture efficiency of 96% and exhibits potential capabilities of isolating circulating tumor cells from peripheral blood of cancer patients. Table 1: Flow rate vs Filtering efficiency of microbeads and A549 cells Flow rate (ml/min)Model - I Filtering efficiency % (Standard Error Mean)Model II Filtering efficiency % (Standard Error Mean)MicrobeadsA549 cellsMicro beadsA549 cells185 (±4.5%)78 (±4.0%)96 (±3.4%)92 (±4.0%)1.580 (±4.0%)71 (±3.5%)90 (±3.1%)85 (±3.4%)273 (±3.5%)65 (±3.1%)84 (±2.8%)80 (±3.0%)2.556 (±2.6%)48 (±2.5%)80 (±2.3%)73 (±2.2%)345 (±2.2%)38 (±1.8%)70 (±2.0%)65 (±1.5%) Citation Format: Nanda Kasani, Manjunath Yeriswamy, Guangfu Li, Jussuf Kaifi, Jae W Kwon. Rare cell isolation by enhanced microfluidic filter using wing-shaped micro posts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3319.
Contemporary Debates in Adult Papillary Thyroid Cancer Management
Authors: Donald S A McLeod, Ling Zhang, Cosimo Durante, David S Cooper
Journal: Endocrine Reviews (2019)

An ever-increasing population of patients with papillary thyroid cancer is engaging with health care systems around the world. Numerous questions about optimal management have arisen that challenge conventional paradigms. This is particularly the case for patients with low-risk disease, who comprise most new patients. At the same time, new therapies for patients with advanced disease are also being introduced, which may have the potential to prolong life. This review discusses selected controversial issues in adult papillary thyroid cancer management at both ends of the disease spectrum. These topics include: (i) the role of active surveillance for small papillary cancers; (ii) the extent of surgery in low-risk disease (lobectomy vs total thyroidectomy); (iii) the role of postoperative remnant ablation with radioiodine; (iv) optimal follow-up strategies in patients, especially those who have only undergone lobectomy; and (v) new therapies for advanced disease. Although our current management is hampered by the lack of large randomized controlled trials, we are fortunate that data from ongoing trials will be available within the next few years. This information should provide additional evidence that will decrease morbidity in low-risk patients and improve outcomes in those with distant metastatic disease.
reGISTry: An observational registry of gastrointestinal stromal tumor (GIST) patients (pts) in the USA
Authors: J. C. Trent, C. D. Blanke, P. W. Pisters, M. Von Mehren, D. S. Davis, R. Ruxer, L. T. McWhorter, A. J. Salvado
Journal: Journal of Clinical Oncology (2006)

9543 Background: The management of pts with GIST dramatically changed after the discovery of the biologic role of dysregulated KIT and PDGFR receptor tyrosine kinases. However, published data on the epidemiology and patterns of diagnosis and management of GIST are limited. To fill this gap, the reGISTry, an observational, internet-based database designed to understand evolving patterns of care for pts with GIST, overall and by pt and provider characteristics, was established. Methods: Up to 200 physicians are expected to participate; recruitment of centers is stratified by geographic area and institution size/type. The reGISTry will be active for at least 4 years with expected accrual of 1800 pts. Pts must have a diagnosis of GIST and give written informed consent. Collected data include pt demographics, clinical characteristics, clinical/economic outcomes and medical care provided to treat GIST. Data analyses are performed every 6 months. Results: The first pt was enrolled in Jan 2005. As of Nov 2005 there were 108 pts enrolled from 39 centers. Eighty five pts (79%) were from community-based practices and 23 (21%) from university/academic centers. Fifty-five pts (51%) were male. Median age was 62 years (range 37–85). At diagnosis, 84 pts (78%) had a primary tumor and 24 (22%) metastatic disease. At diagnosis, 101 pts (94%) had immunohistochemical KIT testing, 95% with positive results. Only 2% of pts had genotyping performed. Surgery was the most common first-line treatment (85 pts, 79%). Eighty-nine percent of those with primary disease and 42% of those with metastatic disease underwent surgical resection as their initial therapy. Fifty percent of pts with metastatic disease and 7% of pts with primary disease underwent systemic therapy as their initial treatment. Forty-seven pts (44%) had imatinib mesylate therapy with 400 mg daily the most commonly prescribed dose. Therapeutic efficacy was more commonly assessed by CT size with radiodensity (55.6%) than positron-emission tomography (0%). Conclusions: The reGISTry is a useful tool for determining evolving practice patterns in the management of GIST. Iterative data analyses over the next 4 years will allow for comparison of management patterns as advances in the understanding of GIST evolve. [Table: see text]
Prolonged Clotting Time Among Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Harold L. Dauerman, Christine M. DeStephan, Heidi Taatjes Sommer, Kathryn C. Kurchena, Michael DeSarno, Erika G. Mendoza, Amy Henderson, David J. Schneider
Journal: Journal of the American College of Cardiology (2019)
Basophil degranulation in response to IgE ligation is controlled by a distinctive circadian clock in asthma
Authors: Giuseppe Spadaro, Giorgio Giurato, Cristiana Stellato, Gianni Marone, Vincenzo Casolaro
Journal: Allergy (2019)

Abstract Background Several factors may contribute to the circadian variability of clinical manifestations in asthma and allergy. Basophils play a pivotal role in allergic inflammation. However, evidence for a functional clock governing the effector function of these cells is sparse and contradictory. We have systematically sampled the 24‐hour response of basophils to IgE‐ and non‐IgE‐dependent ligands in asthma to understand their possible contribution to the diurnal variations of allergic symptoms. Methods Leukocytes were collected every 4 hours for 24 hours from 10 patients with moderate, persistent asthma and 10 matched, nonallergic controls, and then incubated with concentrations of anti‐IgE, formyl‐methionyl‐leucylphenylalanine (fMLP), or the Ca 2+ ionophore, A23187. Histamine release (HR) was tested for time‐of‐day‐ or disease‐related variability by conventional statistics and for 24‐hour rhythmicity by the cosinor method. Results HR induced by anti‐IgE was significantly increased at 08:00 vs. 20:00 in basophils from asthmatics but not controls. No significant differences were seen at any time in the response to A23187, while the response to fMLP was significantly higher at 08:00 vs. 20:00 in controls but not asthmatics. The basophil response to anti‐IgE, but not fMLP or A23187, varied significantly across the 24 hours in asthma, and its amplitude, percent rhythm, and acrophase were comparable to those of peak expiratory flow or serum cortisol. Conclusion Using an integrated statistical approach, we show that basophil responsiveness undergoes significant circadian variability and that distinct patterns of rhythmicity can be recognized depending on the signal delivered, the activation parameters assessed, and the disease status.
Predictive significance of VEGF and HIF-1α expression in metastatic colorectal cancer patients receiving chemotherapy combined with bevacizumab.
Authors: Veli Berk, Kemal Deniz, Halit Karaca, Mevlude Inanc, Oktay Bozkurt, Ayse Ocak Duran, Metin Ozkan
Journal: Journal of Clinical Oncology (2013)

e14672 Background: There is no suggested molecular indicator in identifying which patients will benefit from anti-angiogenic treatment in metastatic colorectal cancer. Over expression of vascular endothelial growth factor (VEGF) and Hypoxia Inducible Factor 1-alpha (HIF-1α) are associated with bad prognosis. In this study, VEGF and HIF-1α expression and their clinical significance are studied in tumor tissues of patients with colorectal cancer receiving treatment with bevacizumab. Methods: VEGF and HIF-1α were observed immunohistochemically in primary tumors of 53 patients. The expressions were separated by evaluating low and high of VEGF and HIF-1α expression. We evaluated whether expression of VEGF and HIF-1α can help to predict treatment response, progression free survival (PFS), and overall survival (OS). Results: Fifty-three patients were enrolled in the study. Median age was 55. VEGF was strongly expressed in 30 patients (57%) whilst low expression was observed in 23 of them (43%). When VEGF expression was evaluated in association with therapy response rates; the clinical benefit rate was 38% in the low expression group whereas it was 62% in high expression group. This difference was statistically significant (p=0.01). In the group with strong VEGF expression PFS was 10 months whereas it was 8 months in the low expression group (p=0.009). When evaluated for OS, 26 months versus 15 months was in favor of highly expressed VEGF group (p=0.03). Highly expressed HIF-1α was found in 29 patients (55%), on the other hand low expressed HIF-1α was detected in 24 (%45) patients. For clinical benefit rates, PFS and OS there was no difference between high and low expressed HIF-1α groups. Conclusions: It has been demonstrated that VEGF and HIF-1α expressions are associated with poor prognosis in several tumors, mainly colorectal carcinomas. With the better understanding of carciogenesis and angiogenesis at molecular level, especially VEGF and HIF-1α became target molecules of the therapy. According to results of our study, VEGF expression is a predictive factor in designating the metastatic colorectal cancer treatment.
Novel cancer vaccines in combination with oxaliplatin-based chemotherapy as first-line therapy in advanced colorectal cancer: A randomized phase II study.
Authors: Hiroaki Tanaka, Shoichi Hazama, Ko Tahara, Ryoichi Shimizu, Fumiaki Sugiura, Kiyotaka Okuno, Furuya Takumi, Taku Nishimura, Koichiro Sakata, Kazuhiko Yoshimatsu, Yuka Inoue, Shinsuke Kanekiyo, Shigefumi Yoshino, Yoshitaro Shindo, Koji Yoshida, Hirokazu Shinozaki, Hiroyuki Furukawa, Kosei Hirakawa, Yusuke Nakamura, Masaaki Oka
Journal: Journal of Clinical Oncology (2013)

3006 Background: A phase I cancer vaccination trial using five novel HLA-A24-binding peptides derived from not only three oncoantigens, RNF43 (ring finger protein 43), TOMM34 (34 kDa translocase of the outer mitochondrial membrane), and KOC1 (IMP-3; IGF-II mRNA binding protein 3) but also antiangiogenic cancer vaccine targeting VEGFR1 (vascular endothelial growth factor receptor 1) and VEGFR2 had revealed safety and immunogenicity in advanced colorectal cancer (CRC) as presented at 2011 ASCO Oral Abstract Session (No. 2510). We further performed a phase II trial to evaluate the benefit of the cancer vaccination in combination with oxaliplatin-based chemotherapy as first-line therapy. Methods: Ninety-six chemotherapy naïve CRC pts were enrolled to evaluate primarily response rates (RR), and secondarily OS and PFS. Each of the five peptides (3 mg each) was mixed with 1.5 ml of IFA and subcutaneously administered weekly for 12 weeks and after then biweekly. Chemotherapy was performed simultaneously as mFOLFOX6 or XELOX with/without bevacizumab. All enrolled pts had received the therapy without knowing HLA-A status double-blindly, and the HLA genotype were key-opened at analysis point and then, the endpoints are evaluated between HLA-A*2402 positive and HLA-A*2402 negative group. Results: Between February 2009 and November 2012, a total of 96 pts were enrolled in this study. The cutoff date for the main analysis was January 31, 2013 (median duration of follow-up of 26.5months). mFOLFOX6 and XELOX were administered to 93 and 3 pts, respectively. Bevacizumab was used for 5 pts. RR, the primary study end point, was 61.5% (CR 1, PR 58, SD 33, PD 4). It seemed superior as compared to other reports. The median duration to reach the best responses (14 weeks; range 8-69) was surprisingly long and indicated the delayed effect of vaccination. PFS and OS were 8.2 m and 20.7 m, respectively. The HLA genotype will be key-opened at March 2013 and the endpoints will be presented between HLA-A*2402 positive and negative group at the meeting. Conclusions: The phase II cancer vaccine therapy demonstrated the promising response, and warrants further clinical studies. Clinical trial information: UMIN000001791.
Intranasal micro-optical coherence tomography imaging for cystic fibrosis studies
Authors: Hui Min Leung, Susan E. Birket, Chulho Hyun, Timothy N. Ford, Dongyao Cui, George M. Solomon, Ren-Jay Shei, Adegboyega Timothy Adewale, Andrew R. Lenzie, Courtney M. Fernandez-Petty, Hui Zheng, Justin H. Palermo, Do-Yeon Cho, Bradford A. Woodworth, Lael M. Yonker, Bryan P. Hurley, Steven M. Rowe, Guillermo J. Tearney
Journal: Science Translational Medicine (2019)

Micro-optical coherence tomography with an intranasal imaging probe detects defects in the mucociliary transport of people with cystic fibrosis.
2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Part 1, Lifestyle and Behavioral Factors
Authors: Donna K. Arnett, Amit Khera, Roger S. Blumenthal
Journal: JAMA Cardiology (2019)

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