tbuckley/cabot-search huggingface dataset:
Abstract 4117: Utilizing RNA aptamers for biomarker discovery in a novel cell culture system for hepatocellular carcinoma
Authors: Ibtehaj A. Naqvi, Rebekah R. White, Cynthia A. Moylan, Anna Mae Diehl, Steve S. Choi
Journal: Cancer Research (2014)

Abstract Introduction: Current serum biomarkers for hepatocellular carcinoma (HCC) lack the sensitivity and specificity to be effective screening tools. Aptamers are single-stranded RNA oligonucleotides that specifically bind to target proteins with high affinity and are generated by repeatedly screening complex RNA libraries for binding to protein targets. We have utilized this selection process to identify biomarkers from complex targets, such as secreted proteomes (secretomes). Our hypothesis is that aptamers that specifically bind the HCC secretome will identify serum protein biomarkers for HCC. Methods: We mirrored the microenvironments of HCC and normal liver tissue utilizing two co-culture systems: 1) human HCC cells (Huh-7) with normal hepatic stellate cells (HSCs) to model HCC livers and 2) normal human hepatocyte cells (THLE-2) with HSCs to model normal livers. Co-cultures were grown to confluence then switched to serum free media for collection of secreted cancer proteins (HCC secretome, HS) and normal secretome (NS). A nuclease-resistant RNA pool was then alternately incubated with NS (discarded for negative selection) and HS (recovered and amplified for positive selection). Results: Binding affinity for HS increased over 7 successive rounds, while binding affinity for NS decreased. The final RNA pool was cloned and sequenced yielding 3 candidate aptamers that were tested for binding to the secretomes and to human serum from patients with HCC and normal controls. In the samples tested we found that one candidate aptamer sequence (G-20) demonstrated increased binding to the sera of HCC pts (N=5) relative to normal sera (N=2) and to a non-binding control aptamer. The maximal percent fraction bound of the G-20 aptamer to cancer serum was 15% compared to only 7% in control. The maximal percent fraction bound of G-20 in normal serum was 8% compared to 6% in control. Conclusions: This co-culture system may better recapitulate the in vivo environment. Aptamers that specifically bind our cancer secretome over the normal secretome may bind to proteins that are specifically secreted by HCC tumors in vivo. The G-20 aptamer selectively binds to HCC patient sera. Future goals of this work are to utilize affinity purification techniques to identify the target of our G-20 aptamer and to continue testing our G-20 aptamer in patient sera to further validate its ability to differentiate between cancer and normal disease states. Citation Format: Ibtehaj A. Naqvi, Rebekah R. White, Cynthia A. Moylan, Anna Mae Diehl, Steve S. Choi. Utilizing RNA aptamers for biomarker discovery in a novel cell culture system for hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4117. doi:10.1158/1538-7445.AM2014-4117
MERTK rs4374383 polymorphism affects the severity of fibrosis in non-alcoholic fatty liver disease
Authors: Salvatore Petta, Luca Valenti, Fabio Marra, Stefania Grimaudo, Claudio Tripodo, Elisabetta Bugianesi, Calogero Cammà, Andrea Cappon, Vito Di Marco, Giovanni Di Maira, Paola Dongiovanni, Raffaela Rametta, Alessandro Gulino, Enrico Mozzi, Emanuele Orlando, Marco Maggioni, Rosaria Maria Pipitone, Silvia Fargion, Antonio Craxì
Journal: Journal of Hepatology (2015)
Patient access to Psychiatric Records: The Patients’ View
Authors: J Parrott, G Strathdee, P Brown
Journal: Journal of the Royal Society of Medicine (1988)

The passing of legislation relating to subject access to personal health data has been accompanied by concern about the possible harmful effects of this development on patients. Despite the lack of substantive evidence psychiatric patients have been regarded as the group most at risk. This study investigates the subjective views of patients on access to records on two psychiatric wards.
Plaque Composition in the Left Main Stem Mimics the Distal But Not the Proximal Tract of the Left Coronary Artery
Authors: Marco Valgimigli, Gastón A. Rodriguez-Granillo, Héctor M. Garcia-Garcia, Sophia Vaina, Peter De Jaegere, Pim De Feyter, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (2006)
Phase I dose-finding study of sorafenib in combination with capecitabine and cisplatin as a first-line treatment in patients with advanced gastric cancer
Authors: C. Kim, J. Lee, Y. Choi, B. Kang, M. Ryu, H. Chang, T. Kim, Y. Kang
Journal: Journal of Clinical Oncology (2009)

4559 Background: We conducted a phase I dose-finding study of sorafenib (S) in combination with capecitabine (X) and cisplatin (P) in patients with previously untreated metastatic or inoperable advanced gastric cancer. Methods: Four dose levels of S, X, and P combination were tested. The doses of S (p.o. daily), X (p.o. on days 1–14), and P (i.v. on day 1) were escalated at the following schedule; level 1: S 400 mg/d, X 1,600 mg/m 2 /d, P 80 mg/m 2 ; level 2: S 800 mg/d, X 1,600 mg/m 2 /d, P 80 mg/m 2 ; level 3: S 800 mg/d, X 2,000 mg/m 2 /d, P 80 mg/m 2 ; level 1A: S 800 mg/d, X 1,600 mg/m 2 /d, P 60 mg/m 2 . The cycle was repeated every 3 weeks. Dose limiting toxicities (DLTs) were evaluated only in the first cycles and a standard 3+3 dose escalation design was implemented. Results: A total 21 pts were enrolled in the study. No DLTs were observed at dose level 1 (n=3). One DLT (grade 3 diarrhea) was noted at dose level 2 (n=6), and 2 DLTs (two grade 4 neutropenias longer than 5 days in duration) were observed at dose level 3 (n=6), which made the level 3 dose the maximum tolerated dose (MTD). However, at cycle 2 and thereafter at dose level 2, the relative dose intensity (RDI) of S and X could not be maintained (mostly below 80%) due to the frequent dose reductions and cycle delays. So, we explored a new dose level (1A) between dose level 1 and 2. Since no DLTs were found in 6 patients at level 1A with RDI mostly above 80% throughout the treatment period, level 1A was determined as recommended dose (RD). Most frequent grade 3 and 4 hematologic toxicities were neutropenia (25.0% of cycles), and most frequent grade 2 and 3 non-hematologic toxicities were hand-foot syndrome (9.4%), asthenia (7.0%), and anorexia (5.5%). The objective responses were confirmed in 10 out of 16 patients with measurable lesions (62.5%; 95% CI, 38.8–86.2%). With a median follow-up of 8.1 months, estimated median progression-free survival was 10.0 months (95% CI, 1.6–18.4 months) and median overall survival has not been reached. Conclusions: Diarrhea and neutropenia were DLTs in this S, X, and P combination. The dose schedule of sorafenib 400 mg po bid daily with capecitabine 800 mg/m 2 po bid on days 1–14, and cisplatin 60 mg/m 2 iv on day 1 in every 3 weeks is recommended for further development in AGC. [Table: see text]
Long-term FEV1 decline and airway hyperresponsiveness in asthma
Authors: Bruno Sposato, Marco Scalese, Elisa Baldini, Maria Giovanna Migliorini
Journal: European Respiratory Journal (2014)

Our study investigated if airway hyperresponsiveness (AHR) at asthma onset could predict FEV1 decline in treated asthmatics. We retrospectively recruited 275 subjects that had performed a methacholine test at asthma onset and FEV1 measurements after 5-10 years. We subdivided subjects into three groups, according to their AHR level. 65 patents had normal reactivity (25 males; mean age 46±15; mean baseline FEV1%:96.1±20); 78 were borderline/mild AHR (PD20>400µg) (26 males; mean age 43±14; mean baseline FEV1%:102±12; mean PD20:1120±696) and 132 showed moderate/severe AHR (PD20≤400µg; 51 males; mean age 43±14; mean baseline FEV1%: 94±13; mean PD20:185±108). Annual FEV1 declines (the differences between the first and last measurements, divided by the number of years separating them) were compared. Average annual FEV1 declines (after 7±2 years) were similar in all groups: 46.2±81 ml/yr in normal reactivity subjects, 53±65 in borderline/mild AHR and 45±62.5 in moderate/severe AHR (p=0.645). No differences in FEV1 decline values were found either in males or females. When a logistic model was applied to investigate if AHR could predict a FEV1 decline (>30 ml/yr) - corrected for age sex, smoking habits and BMI - we found that AHR (compared to normal reactivity) was not a risk factor for a greater FEV1 decline (OR:0.76 [95%CI:0.40-1.44]; p=0.4 in borderline/mild AHR and OR:1.26 [95%CI:0.61-2.61]; p=0.54 in moderate/severe AHR). Moreover, no relationships between annual FEV1 declines and baseline PD20 values (r=0.05) were found. In conclusion, AHR severity, detected at asthma onset, does not seem to be associated with a worse FEV1 decline. Other factors may be involved.
Benzene and Leukemia
Authors: Robert A. Rinsky, Alexander B. Smith, Richard Hornung, Thomas G. Filloon, Ronald J. Young, Andrea H. Okun, Philip J. Landrigan
Journal: New England Journal of Medicine (1987)

To assess quantitatively the association between benzene exposure and leukemia, we examined the mortality rate of a cohort with occupational exposure to benzene. Cumulative exposure for each cohort member was estimated from historical air-sampling data and, when no sampling data existed, from interpolation on the basis of existing data. The overall standardized mortality ratio (a measure of relative risk multiplied by 100) for leukemia was 337 (95 percent confidence interval, 154 to 641), and that for multiple myeloma was 409 (95 percent confidence interval, 110 to 1047). With stratification according to levels of cumulative exposure, the standardized mortality ratios for leukemia increased from 109 to 322, 1186, and 6637 with increases in cumulative benzene exposure from less than 40 parts per million–years (ppm-years), to 40 to 199, 200 to 399, and 400 or more, respectively. A cumulative benzene exposure of 400 ppm-years is equivalent to a mean annual exposure of 10 ppm over a 40-year working lifetime; 10 ppm is the currently enforceable standard in the United States for occupational exposure to benzene. To examine the shape of the exposure–response relation, we performed a conditional logistic-regression analysis, in which 10 controls were matched to each cohort member with leukemia. From this model, it can be calculated that protection from benzene-induced leukemia would increase exponentially with any reduction in the permissible exposure limit. (N Engl J Med 1987;316:1044–50.)
Towards clinical VEGF imaging using the anti-VEGF antibody bevacizumab and Fab-fragment ranibizumab
Authors: W. B. Nagengast, M. N. Lub-de Hooge, G. A. Hospers, A. H. Brouwers, H. J. Hoekstra, P. H. Elsinga, N. H. Mulder, F. Warnders, E. G. de Vries
Journal: Journal of Clinical Oncology (2008)

3547 Background: VEGF, released by tumor cells, is an important growth factor in tumor angiogenesis as it induces tumor neovascularization. VEGF121 is freely soluble whereas splice variants such as VEGF165, 189, 206 are mainly located in the extra cellular matrix, resulting in high concentrations in the tumor micro-environment. Non-invasive assessment of VEGF-levels in the micro-environment of the tumor could guide in the development and follow up of anti-VEGF targeted therapy. For this aim, we radiolabeled the anti-VEGF monoclonal antibody bevacizumab and the Fab-fragment ranibizumab, both binding to all VEGF-A isoforms, with SPECT (111In) and PET (89Zr) isotopes. Methods: Labeling, stability and in-vitro immunoreactivity studies were performed. Thereafter, nude mice were inoculated with VEGF producing human SKOV-3 ovarian tumor cells. After tumor size reached 6–8 mm in diameter, microPET and biodistribution studies were performed at multiple time points corresponding with the different elimination half-lives of radiolabeled bevacizumab and ranibizumab. A feasibility study in patients with recurrent melanoma and metastatic colon cancer has been started. Results: Uptake was significantly higher for both SPECT- and PET-tracers compared to radiolabeled control (Fab)-IgG, namely 7.74 ± 1.99 %ID/g and 4.66 ± 1.91 %ID/g for respectively 111In-bevacizumab at 168 h and 111In- ranibizumab at 24 h post injection. MicroPET imaging with 89Zr-bevacizumab and 89Zr-ranibizumab showed clear tumor localization respectively 72 and 3 h post injection. Furthermore, uptake of 89Zr-bevacizumab was predominantly seen in liver and spleen whereas 89Zr-ranibizumab was mainly cleared by kidney. Preliminary results of SPECT imaging using 111In- bevacizumab revealed tumor lesions in both recurrent melanoma and metastatic colon cancer patients. Conclusions: Radiolabeled bevacizumab and ranibizumab showed to be specific tracers for non-invasive (pre)clinical VEGF imaging, with distinctive pharmacokinetics. Bevacizumab shows the highest tumor uptake whereas ranibizumab allows imaging shorter after injection of the tracer. Both tracers could potentially guide anti-angiogenic VEGF targeted therapy. Supported by a grant from the Dutch Cancer Society. No significant financial relationships to disclose.
Impact of a protein and energy dense nutritional supplement containing eicosapentaenoic acid on weight-losing patients with head and neck cancer
Authors: H. G. Weed, R. L. Gaff, M. L. Ferguson, K. S. Deluca, D. S. Hustead, V. L. Knox, A. C. Voss
Journal: Journal of Clinical Oncology (2005)

8112 Background: Patients with squamous cell cancer of the head and neck (HNSCCa) often lose weight. Under-nutrition is associated with increased postoperative complications and mortality (Nozoe, 2002). A protein and energy dense nutritional supplement (SUP) containing the omega-3 fatty acid eicosapentaenoic acid (EPA) can increase weight and lean body mass (LBM), and improve physical activity and quality of life in pancreatic cancer patients (Fearon et al, 2003; Moses et al, 2004). The purpose of this study was to determine the impact of pre- and peri-operative use of the SUP on weight-losing HNSCCa patients. Methods: Preoperatively, HNSCCa patients with at least 5% premorbid weight loss anticipating surgical resection with curative intent (+/- chemoradiation) were offered 2 cans of SUP (300 kcal, 16g protein, 1g EPA/can) daily beginning at least 2 weeks before surgery. Weight was measured at baseline, hospital admission, and discharge. LBM was measured using bioelectrical impedance at baseline and at hospital discharge. Weight and/or LBM were not available for all patients. Statistical comparisons were with the Wilcoxon Signed Rank Test. Results: Of the 38 patients who consented, 4 had disease progression and did not undergo surgery, 2 withdrew due to SUP intolerance, and 1 was unable to complete study diaries, yielding 31 subjects: Male: 74%, Mean Age: 62 years, Stage IV: 71%, Mean Pre-Study Weight Loss: 12%, Mean Supplement Consumption: Pre-admission: 1.8 cans/day, In-Hospital: 1.5 cans/day. 70% maintained or gained weight before admission: Mean weight gain pre-admission: 1.6 lb (n=27), at discharge: 1.5 lb (n=30). 23 subjects had LBM measured at discharge: Mean increase in LBM at discharge: 7 lb (p<0.001, n=23). Conclusions: A protein and energy dense, EPA-containing nutritional supplement can halt or reverse weight loss and increase LBM in HNSCCa patients. Because improving nutrition before surgery can decrease post-operative complications and length of stay (Gianotti et al, 2002), this supplement might be an appropriate component of a preoperative nutrition program. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ross Products Division Ross Products Division Ross Products Division
Randomized trials between behenoyl cytarabine and cytarabine in combination induction and consolidation therapy, and with or without ubenimex after maintenance/intensification therapy in adult acute myeloid leukemia. The Japan Leukemia Study Group.
Authors: T Kobayashi, S Miyawaki, M Tanimoto, K Kuriyama, H Murakami, M Yoshida, S Minami, K Minato, K Tsubaki, E Ohmoto, H Oh, I Jinnai, H Sakamaki, A Hiraoka, A Kanamaru, I Takahashi, K Saito, T Naoe, O Yamada, N Asou, S Kageyama, N Emi, A Matsuoka, M Tomonaga, R Ohno
Journal: Journal of Clinical Oncology (1996)

PURPOSE We analyzed complete remission (CR), disease-free survival (DFS), and event-free survival (EFS) rates in two groups of patients treated with either N4-behenoyl-1-beta-D-arabinosylcytosine (BHAC) or cytarabine, and analyzed DFS with or without ubenimex, a biologic response modifier. PATIENTS AND METHODS Newly diagnosed patients with acute myeloid leukemia (AML) were randomized to receive either BHAC or cytarabine as remission-induction combination chemotherapy and two courses of consolidation therapy. After maintenance/intensification therapy, patients in CR were randomized to receive either ubenimex and no drug. RESULTS Of 341 patients registered, 326 were assessable. The age of assessable patients ranged from 15 to 82 years (median, 48). The overall CR rate was 77%: 72% in the BHAC group and 81% in the cytarabine group, and there was a significant difference between the two groups (P = .035, chi 2 test). The predicted 55-month EFS rate of all patients was 30%: 23% in the BHAC group and 35% in the cytarabine group, with a significant difference between groups (P = .0253). The predicted 55-month DFS rate of all CR patients was 38% and that of CR patients less than 50 years of age was 47%. There was no significant difference in DFS between the ubenimex group and the group that did not receive ubenimex. CONCLUSION Analyses of our clinical trial showed that the use of BHAC in remission-induction therapy and in consolidation therapy resulted in poorer CR and EFS rates in adult AML patients compared with the use of cytarabine at the doses and schedules tested. Immunotherapy with ubenimex after the end of all chemotherapy did not improve DFS.
US poll finds strong support for Medicare and Medicaid
Authors: Michael McCarthy
Journal: BMJ (2015)

As the 50th anniversary of Medicare and Medicaid approaches, a new poll has found strong public support for both US government health insurance plans.

The survey,1 conducted by the non-partisan Kaiser Family Foundation, found that 77% of respondents considered Medicare a “very important” program—a similar proportion to the 73% who considered US military and defense programs very important. A somewhat smaller but substantial majority, 63%, said that they considered Medicaid to be very important.

The two health programs were signed into law by President Lyndon Johnson on 30 July 1965. Medicare, a …
Seasonal distribution of exacerbations in Dutch and Swiss COPD patients
Authors: Anja Frei, Alexandra Strassmann, Lara Siebeling, Patrick Muggensturm, Marco Zoller, Gerben ter Riet, Milo Puhan
Journal: European Respiratory Journal (2014)

Introduction 

In-depth knowledge of the natural occurrence of COPD exacerbations is important for clinicians to optimise the treatment and for researchers to plan and interpret clinical trials.

Aims and objectives 

To assess if the seasonal pattern of exacerbations in COPD patients from primary care setting differs between a northern European country with maritime climate (Netherlands) and an alpine country (Switzerland).

Methods 

We analysed data over 3 years from 409 primary care patients (≥40 years of age) participating the ICE COLD ERIC cohort from the Netherlands (n=258) and Switzerland (n=151) with COPD (GOLD stages II-IV). We used event-based definition of exacerbations that required newly prescribed systemic corticosteroids and/or antibiotics. All exacerbations, initially ascertained by patients' self-report and experts' review of patient charts, were centrally adjudicated in consensus by experts.

Results 

COPD patients suffered from 648 exacerbations during the 3 years. Most exacerbations occurred in November, December and January (10.0-11.3%) whereas they were less prevalent in the months May to September (6.3-6.8%). The variation of frequency of exacerbations per month was greater among Swiss patients (3.0-16.0%) compared to Dutch patients (6.7-11.6%)

![Figure][1] 



.

Conclusions 

Variation of exacerbation frequency between months was higher in Switzerland, which may be explained by the greater variation in temperature over the year.

 [1]: pending:yes
A phase I/II trial of a polysaccharide extract from <i>Grifola frondosa</i> (Maitake mushroom) in breast cancer patients
Authors: G. Deng, H. L. Smith-Jones, A. D. Seidman, M. Fornier, G. D'Andrea, K. Wesa, S. Cunningham-Rundles, K. S. Yeung, A. Vickers, B. R. Cassileth
Journal: Journal of Clinical Oncology (2008)

3024 Background: A polysaccharide extract from Grifola frondosa (Maitake extract) has shown immunomodulatory effects in preclinical studies and potentials for anticancer immunotherapy. However whether its oral administration in human is associated with measurable immunological change is unknown. Methods: In a phase I/II dose escalation trial, thirty postmenopausal breast cancer patients free of disease after initial treatment were enrolled sequentially into five cohorts of six patients each. Maitake extract was taken orally at 0.1, 0.5, 1.5, 3, or 5 mg/kg twice daily for three weeks. Peripheral blood was collected at day -7, 1 (prior to the first dosing), 7, 14, and 21 for ex vivo analyses. The primary endpoint was safety and tolerability. Results: No dose-limiting toxicity was encountered. Pharmacodynamic activities of the study agent did not follow a linear dose curve, as often seen with immunomodulatory agents. The following correlative endpoints showed significant changes compared to baseline. Quadratic dose curve analysis showed that a daily dosage of 2 mg/kg was associated with the greatest increases of CD3+CD25+ or CD4+CD25+ T cells in the peripheral blood (300% of baseline, p<0.001); a daily dosage of 6 mg/kg was associated with the most significant increases in intracellular IL-2 production by NK-T cells (237% of baseline, p=0.002); IL-10 production by T cells (360% baseline, p=0.002). Interferon gamma production by memory CD4+ T cells was attenuated to 27% of baseline at a daily dose of 7.4 mg/kg (p=0.002). Conclusions: Oral administration of a polysaccharide extract was associated with measurable changes in peripheral blood. The dose associated with the most significant changes varies by immunological parameter. The dose of 6 mg/kg is selected as the dose in future studies with clinical endpoints. No significant financial relationships to disclose.
Twenty years of MOPP therapy for Hodgkin's disease.
Authors: D L Longo, R C Young, M Wesley, S M Hubbard, P L Duffey, E S Jaffe, V T DeVita
Journal: Journal of Clinical Oncology (1986)

The results of treatment of 198 patients with MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) for Hodgkin's disease were analyzed after a median of 14 years of follow-up. Throughout the period of follow-up, 103 patients have remained continuously free of disease. Review of biopsy specimens of 43 patients originally classified as Hodgkin's disease, lymphocyte-depleted type, revealed that ten of these patients actually had diffuse immunoblastic or large cell non-Hodgkin's lymphomas. Of the 188 patients with Hodgkin's disease, 157 achieved a complete response (CR) (84%), and 66% of them (101 patients) have remained disease-free more than 10 years from the end of treatment. Absence of B symptoms and receiving higher doses of vincristine were factors associated with a higher CR rate and longer survival. Patients entering complete remission in five cycles or less had significantly longer remissions than those requiring six or more cycles. Forty-eight percent of the Hodgkin's disease patients have survived between 9 and 21 years (median, 14 years) from the end of treatment. Nineteen percent of the CRs have died of intercurrent illnesses, free of Hodgkin's disease.