tbuckley/cabot-search huggingface dataset:
SM-07 * A PILOT STUDY OF HIGH-DOSE INFLUENZA VACCINE IMMUNOGENICITY IN PATIENTS WITH PRIMARY CENTRAL NERVOUS SYSTEM MALIGNANCY
Authors: R. Strowd, G. Russell, M. Harmon, A. Carter, M. Chan, S. Tatter, A. Laxton, K. High, G. Lesser
Journal: Neuro-Oncology (2014)

BACKGROUND: In a previous investigation, we demonstrated reduced immunogenicity to the standard trivalent inactivated influenza vaccine in patients with primary central nervous system (CNS) malignancy (Neuro-Oncol 2014, PMID 24714522). Other populations with similar reduced responses have shown improved immunogenicity to a high-dose vaccine. OBJECTIVE: A pilot prospective cohort study was designed to evaluate the immunogenicity of the Fluzone® High-Dose influenza vaccine in patients with CNS malignancy. METHODS: Baseline data on diagnosis, chemotherapy, radiation, glucocorticoids, and timing of treatment were collected. All patients underwent vaccination with of the Fluzone® High-Dose influenza vaccine. Serum samples are actively being collected at baseline, day 28, and 3 months following vaccine administration. Hemagglutination inhibition (HAI) titers will be measured to determine seroconversion (4-fold rise) and seroprotection (titer 1:40). RESULTS: A total of 27 patients were enrolled. Mean age at baseline was 52.7 years (+/-12.6); 41% male; 93% white and 7% black. Diagnoses included high-grade glioma (85%), CNS lymphoma (11%), and meningioma (4%). At enrollment, 8 patients (30%) were taking glucocorticoids, 4 (15%) were undergoing active radiation, 14 (52%) were on chemotherapy, and 5 (19%) began chemotherapy following vaccine administration. Prior radiation (n = 19, 70%) and chemotherapy (n = 14, 52%) were common. Seven patients (26%) reported post-vaccination symptoms potentially attributable to vaccination; 6 experienced only local soreness or redness at the injection site and 1 suffered headache, nausea, vomiting. All symptoms were transient and resolved completely. At baseline, 8 patients (30%) had absolute CD4 < 300. Serum samples for HAI assay are being collected. Seroconversion and seroprotection rates are forthcoming. CONCLUSION: Studies have shown that populations known to respond poorly to standard yearly influenza vaccination (e.g. the elderly) can mount an effective immunologic response to the high-dose vaccine. This prospective cohort study will provide preliminary data regarding the immunologic response to high-dose vaccination in patients with primary CNS malignancy. Funding: The Fluzone® High Dose vaccine and HAI titer measurements were provided by Sanofi Pasteur. Acknowledgement: This research was supported by the Clinical Research Unit of the Wake Forest Translational Science Institute.
Detecting Near-the-Injection-Site Sentinel Nodes in Head and Neck Melanomas With a High-Resolution Portable Gamma Camera
Authors: Daan Hellingman, Linda J. de Wit–van der Veen, W. Martin C. Klop, Renato A. Valdés Olmos
Journal: Clinical Nuclear Medicine (2014)

Background In head/neck melanomas, near-the-injection-site sentinel nodes (NIS-SNs) may be missed on planar lymphoscintigraphy and/or SPECT/CT. The aim of the present study is to establish the performance of a portable gamma camera (PGC) to detect NIS-SNs in a simulation phantom set-up, and subsequently in head/neck melanoma patients scheduled for a SN procedure. Methods Five plastic Eppendorf tubes filled with technetium-99m-albumin nanocolloid were used to simulate 4 radiotracer deposit sites, as traditionally injected in melanoma patients, and 1 NIS-SN. A PGC was used with 2 pinhole collimators (2.5 and 4.0 mm). Image acquisition time was 1 minute with the camera positioned at various distances (range 1.5–15.5 cm). Results were compared with conventional lymphoscintigraphy and SPECT/CT acquired with a dual-head gamma camera as well with a gamma probe. Additionally, the same PGC setting was used in a case series of 3 patients with head/neck melanomas. Results The simulated NIS-SN was differentiated from the injection site at a distance of 3 mm with the 2.5-mm pinhole and at 5 mm with the 4-mm pinhole when the PGC was positioned at 1.5 cm distance. Planar lymphoscintigraphy, SPECT/CT, and the gamma probe depicted the NIS-SN separated from the injection site at distances of 7, 10, and 22 mm, respectively. In all 3 patients, 6 NIS-SNs were depicted with the PGC. Conclusion A high-resolution PGC, positioned close to the skin, is able to detect SNs at distances of at least 3 mm from the injection site. A further clinical evaluation of this device to establish its added value in reducing false-negative procedures and potential recurrences is necessary.
P5-17-01: Evaluation of Psychosocial Distress in Main Care-Givers of Patients with Metastatic Breast Cancer Who Receive Treatment in a Community Based Oncology Group Practice.
Authors: R Weide, S Feiten, V Friesenhahn, J Heymanns, K Kleboth, U Mergenthaler, J Thomalla, Roye C van, H Köppler
Journal: Cancer Research (2011)

Abstract Introduction: It is well-known that people who care for patients with a metastatic carcinoma are exposed to an above-average level of psychosocial distress. No data are available concerning the distress of main care-givers of female patients with metastatic breast cancer, who are treated in a community based oncology group practice. Methods: Standardized cross-sectional survey of main care-givers and patients with metastatic breast cancer who were treated in a community based oncology group practice in Germany between 04/2010-03/2011. Psychosocial distress of the patients and their main care-givers were evaluated using the German versions of the Distress Thermometer (DT) and the Problem List (PL). In addition anxiety and depression of the main care-givers were assessed using the Hospital Anxiety and Depression Scale (HADS-D). Results: 83 female patients with a median age of 65 (41-93) were interviewed. 6% did not have a main care-giver, 7% indicated that they needed no support, 48% reported one main care-giver and 39% several. Partners (60%), children (47%), siblings (11%) and friends (10%) were the most important care-givers. 47% of patients preferred visiting the practice in companion with their care-givers. The patients’ median score on the DT was 5 (0-10), with 34% scoring above cut-off (&amp;gt; 5) for psychosocial distress. 52 main care-givers (61% male, 39% female) with a median age of 57.5 (41-86) were interviewed. The relationships to the patients were as follows: partners 62%, children 27%, mothers, siblings and friends each with 4%. The main care-givers themselves were supported by partners (54%), children (21%) friends (17%) and siblings (8%), 23% did not receive any support. The median score on the DT was 5 (0-10), with 44% scoring above cut-off (&amp;gt; 5) for psychosocial distress. According to the HADS-D 37% (cut-off ≥ 8) of the care-givers reported anxiety, with a mean score of 6.6 (0-14). 15% could be regarded as depressed (cut-off ≥ 8), with a mean score of 4.1 (0-15). Conclusions: The main care-givers are distressed even more than the patients themselves. 37% of care-givers reported anxiety; depression can be observed too, but less frequently in 15%. Both issues should be addressed by healthcare professionals. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-17-01.
Acute Muscular Syndrome Associated with Administration of Clofibrate
Authors: Terry Langer, Robert I. Levy
Journal: New England Journal of Medicine (1968)

In 60 patients with hyperlipoproteinemia treated with clofibrate, five cases of elevated serum transaminase and creatine phosphokinase were observed. In two, severe myalgia, stiffness, weakness, and malaise coincident with drug administration developed. Cessation of therapy resulted in prompt resolution of symptoms. An identical clinical syndrome reappeared in one of these patients on rechallenge with clofibrate. Three patients had asymptomatic elevations in transaminase and creatine phosphokinase. In one case these abnormalities were clearly dose related. Usually, the abnormalities persisted throughout the period of therapy. In some cases, however, transaminase became normal but creatine phosphokinase remained elevated while treatment continued. Since creatine phosphokinase is absent from liver, these findings suggest that skeletal muscle is the major source of the elevated serum enzymes and that periodic examinations for evidence of muscle tenderness and dysfunction and frequent determinations of transaminase and creatine phosphokinase should be performed on all patients receiving clofibrate.
The Effect of Warfarin on Mortality and Reinfarction after Myocardial Infarction
Authors: Pål Smith, Harald Arnesen, Ingar Holme
Journal: New England Journal of Medicine (1990)

The use of oral anticoagulation in the long-term treatment of survivors of acute myocardial infarction has been highly controversial. We therefore randomly assigned 1214 patients who had recovered from acute myocardial infarction (mean interval from the onset of symptoms to randomization, 27 days) to treatment with warfarin (607 patients) or placebo (607 patients) for an average of 37 months (range, 24 to 63).
P229Tranexamic acid and aprotinin: antifibrinolytics in cardiac surgery
Authors: BT Nemeth, L Hidi, R Toth, G Veres, A Olah, C Matyas, G Merkely, B Merkely, G Szabo, T Radovits
Journal: Cardiovascular Research (2014)

Purpose: Anti-haemorrhagic drugs are being used to prevent and treat haemorrhagic complications in cardiac surgery. The serine-protease-inhibitor aprotinin is an antifibrinolytic agent that had been used in clinical practice for decades. In 2008, the BART-study revealed its unfavourable effects on postoperative mortality, which led to its withdrawal from the market. Today, the lysine-analogue tranexamic acid (TA) is available for the clinical routine. We compared the effects of aprotinin and TA on postoperative blood loss, hemodynamic, hemostaseologic and inflammatory parameters, using a canine model of cardiopulmonary bypass (CPB). Methods: Beagle dogs were randomized into three groups (n=8/group). Control dogs received placebo, treated groups were given aprotinin or TA. All animals received heparin and underwent 90min of CPB. The weaning from the heart-lung-machine was followed by administration of protamine and 130min of observation. We regularly determined blood loss and coagulation parameters, while hemodynamic parameters were continuously monitored. To assess the systemic inflammatory response induced by CPB, plasma levels of IL-6, IL-8 and TNF-α were determined by ELISA. Results: Compared to control, aprotinin significantly reduced blood loss (105±22ml vs. 41±8ml), while TA was found to be less effective (65±16ml). Regarding hemodynamic and coagulation parameters, no significant difference was detected among the groups. The elevation of proinflammatory cytokine levels during CPB was tendentially decreased by aprotinin, while a significant anti-inflammatory effect was observed in the TA group (TNFα 90min after starting CPB: 5.2±1.2ng/ml control vs. 3.7±0.9ng/ml aprotinin vs. 0.8±0.3ng/ml TA). Conclusions: Compared to aprotinin, TA is less effective in reducing blood loss, but has a stronger anti-inflammatory effect. Our work points out the need for the development of novel pharmacological tools for effective and safe postoperative blood loss reduction.
1381 INDICATION OF MRI LIVER IRON CONCENTRATION DETERMINATION WITHIN THE HIGH LIVER IRON OVERLOAD DIAGNOSTIC ALGORITHM
Authors: A. Castiella, J.M. Alústiza, E. Zapata, I. Urreta, J.I. Emparanza, M.D. De Juan, E. Zubillaga, A. Azkune, M.L. Rincon
Journal: Journal of Hepatology (2012)
Preliminary findings suggest hidradenitis suppurativa may be due to defective follicular support
Authors: F.W. Danby, G.B.E. Jemec, W.Ch. Marsch, M. von Laffert
Journal: British Journal of Dermatology (2013)

The initial pathology in hidradenitis suppurativa (HS)/acne inversa takes place in the folliculopilosebaceous unit (FPSU) and its surrounding tissue. The process involves follicular hyperkeratosis, inflammation and perifolliculitis. Identification of the exact origin of inflammation may shed new light on the pathogenesis and aetiology of the disease.To study the morphology of the basement membrane zone (BMZ) in patients with HS.In total, 65 operative specimens from 20 patients diagnosed with HS were cut stepwise. Within each specimen, the focus was set on heavily involved HS regions (centre) and clinically uninvolved regions (border). All specimens were stained with periodic acid-Schiff (PAS) to visualize the epithelial support structures of the FPSU (i.e. the BMZ), the sinus tracts (STs) and the interfollicular basement membrane (BM). The intensity of BMZ PAS staining was graded from 0 to 4+.Compared with the axillary skin of human controls, the sebofollicular junction in patients with HS was found to be almost devoid of PAS-positive material (grade 0/1+) in both the border and centre lesions of HS, whereas STs and BMs showed uniformly grade 2-3+ positivity irrespective of any inflammation present. The distribution of inflammatory cells around the sebofollicular junction occurred predominantly in areas of BMZ thinning.The BMZ PAS positivity of clinically uninvolved FPSUs of patients with HS appears to be wispy or not present at all. It is speculated that this may explain the apparent fragility of the sebofollicular junction. There is an increased concentration of inflammatory cells adjacent to these areas, while inflammatory cells are scarce in areas where the PAS-positive material is intact. It is hypothesized that the PAS gap identifies (i) areas susceptible to leakage, trauma and rupture, leading to release of materials that trigger inflammatory mediators, and (ii) the seeding of the dermis with free-living stem cells generating benign but invasive epithelialized sinuses, spreading horizontally in and below the dermis.
Elimination of the So-Called Amputation Neuromas of Divided Peripheral Nerves
Authors: Donald Munro, G. Kenneth Mallory
Journal: New England Journal of Medicine (1959)

THE possibility of preventing the formation of a so-called amputation neuroma on the distal end of the proximal part of a cut peripheral nerve is one that has to be commonly faced by general and orthopedic surgeons. The need for such prevention and the method of assuring it appear to be neither recognized nor practiced, however. For example, an orthopedic surgeon of considerable note stated publicly, in a meeting at which one of us was present, that it was impossible to prevent the formation of such neuromas. This was the more surprising because an infallible method devised to accomplish this . . .
Abstract 1629: A protein-protein interaction network for RalB-TBK1 signaling pathway in KRAS mutant non small cell lung cancer
Authors: Jae-Young Kim, Bin Fang, John Koomen, Guolin Zhang, Eric B. Haura
Journal: Cancer Research (2011)

Abstract KRAS mutation accounts for development of approximately 30% of Non Small Cell Lung Cancer (NSCLC) however therapeutic targets for KRAS mutant NSCLC have poorly been identified. A better understanding of the KRAS signaling network could uncover novel therapeutic targets or therapeutic strategies. RalB and TBK1 are important proteins used by KRAS to maintain tumor cell survival. To better understand oncogenic properties of RalB-TBK1 signaling for KRAS mutant lung cancer development, we are currently developing a protein-protein interaction network for RalB and TBK1 using Tandem Affinity Purification (TAP) coupled with Liquid Chromatography-Mass Spectrometry (LC-MS/MS). By interrelating protein-protein interactions and data from a RNA interference screen, a map of signaling will be constructed to highlight important components vulnerable to attack. Data from this mapping will be used to interrogate novel targets in a larger collection of lung cancer cell lines. We have expressed Strep-HA tagged versions of both RalB and TBK1 in KRAS mutant lung cancer cells using retroviruses. A two step purification coupled to LC-MS/MS is used to purify and identify protein complexes. Preliminary studies have identified the bait (TBK1) in the MS results along with HSP90 isoforms. Based on these results, we determined if HSP90 inhibition can modulate TBK1 levels. We found that 17-DMAG and AUY922, two HSP90 inhibitors, lead to reduced levels of TBK1 proteins. AUY922 also had potent effects on cell viability in vitro. Suppression of TBK1 expression using shRNA significantly induced cell death in KRAS mutant NSCLC cells, confirming that TBK1 signaling is essential for survival of those cancer cells, and loss of TBK1 by HSP90 inhibitors could in part lead to their cytotoxic effect. Collectively, we expect this network approach to KRAS-RalB-TBK1 signaling pathways will provide better insight into molecular mechanism by which TBK1 mediates KRAS mutant lung cancer cell survival and novel therapeutic targets for this cancer subtype. Updated work will be presented. Supported by the SPORE in Lung Cancer (P50-CA119997). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1629. doi:10.1158/1538-7445.AM2011-1629
Abstract P2-09-27: Predictive Factors of Complete Axillary Downstaging after Neoadjuvant Chemotherapy in Breast Cancer Patients
Authors: M Vidal, JM Perez-Garcia, E Muñoz, C Saura, L de Mattos, P Gomez, J Cortes, J Baselga, M. Bellet
Journal: Cancer Research (2010)

Abstract Background: The axillary status after neoadjuvant chemotherapy (NACT) is an important prognostic factor. Complete axillary downstaging (CAD) occurs in up to 20-30% of the patients, however, sentinel node biopsy after NACT is not recommended in patients with initial axillary nodal involvement and complete axillary response after NACT. Our aim was to investigate predictive factors of CAD after NACT to identify patients who could avoid an unnecessary axillary dissection. Patients and methods: From January 2004 to December 2008, 256 consecutive patients were diagnosed with invasive breast cancer and received NACT and breast surgery at our institution. Patients were eligible for this analysis if they met the following inclusion criteria: clinically and/or cytologically proven metastatic axillary nodes; complete axillary response after NACT; and complete axillary dissection after systemic treatment. CAD was defined as pN0 (isolated tumor cells and micrometastasis were excluded). Univariate and multivariate analyses were performed to assess the association between CAD and either tumor characteristics or intrinsic cancer subtypes. Results: 84 patients were included. Median age was 51.64 years. 75 (89,3%) received anthracyclines-and taxanes-based CT and 11 (13%). 38 (45,2%) had cytologically proven metastatic axillary nodes at diagnosis. According to intrinsic cancer subtypes, 22 (26%) were classified as HER2 positive, 17 (20,2%) as triple negative (ER, PR, and HER2 -), 6 (7,1%) as luminal A [estrogen receptor positive and/or progesterone receptor positive and (Ki67 &amp;lt; 20% and histological grade 1 or 2)], and 23 (27,4%) as luminal B [estrogen receptor positive and/or progesterone receptor positive and (Ki67 ≥20% or histological grade 3)]. In the univariate analysis, HER2 positivity (p=0,002) and neoadjuvant treatment with trastuzumab (p=0,019) were significantly associated with CAD. In the multivariate analysis only HER2 status maintained statistical significance (p=0,003). Among luminal A, luminal B, and triple negative tumors, complete axillary response after NACT did not significantly predict CAD. Conclusions: In our cohort of breast cancer patients, HER2 status is an independent predictive factor of CAD after NACT. Clinical trials, probably according to specific breast cancer subtypes, are required to identify patients with initial axillary metastatic involvement who could avoid an axillary dissection after systemic therapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-27.
Abstract 503: Curcumin protects UV-induced skin damage in SKH-1 hairless mouse
Authors: Jaw-Ming Cherng, Alice Yu-whay Yu, Jung-Chung Lin
Journal: Cancer Research (2010)

Abstract Exposure to ultraviolet (UV) light is the major etiologic factor leading to the development of cutaneous squamous and basal cell carcinoma and is also a risk factor for melanomas. UV elicits inflammation, epidermal hyperplasia and changes in the expression of numerous genes associated with proliferation and differentiation. Curcumin has been shown to exert an anti-inflammatory activity, interfere with multiple cell signaling pathways, and possess potential preventive effect against various cancers. The purpose of this study was to determine whether curcumin can protect UV-induced skin damage in hairless SKH-1 mice. Oral or topical application of curcumin prior to, or immediately after, UV irradiation resulted in a very strong protective effect against UV-induced thymine dimer expression in epidermis, accounting for 69-74% inhibition (p &amp;lt; 0.00). Curcumin treatment also resulted in upregulation of p53 and p21/Cip1 protein levels by 33-41% (p &amp;lt; 0.005) and 46-50% (p &amp;lt; 0.005), respectively. Oral or topical application of curcumin prior to, or immediately after UV irradiation strongly decreased the expression of proliferative cell nuclear antigen by 47- 56% (p &amp;lt; 0.005). In addition, curcumin treatment significantly suppressed UV-induced apoptosis as measured by TUNEL assays (p &amp;lt; 0.005). Furthermore, curcumin treatment also significantly inhibited NF-κB, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and nitric oxide (NO) levels. Our results suggest that curcumin possesses strong protective effect against UV-caused damage in epidermis. Taken together, these results provide a focus for the rational development of curcumin as a novel chemopreventive agent against UV-induced human skin cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 503.