tbuckley/cabot-search huggingface dataset:
Krill oil to improve blood lipids status in advanced cancer patient with cachexia.
Authors: Roberto Serpe, Clelia Madeddu, Filomena Panzone, Giorgia Antoni, Maria Chiara Cau, Antonio Macciò, Giovanni Mantovani, Sebastiano Banni
Journal: Journal of Clinical Oncology (2012)

e19634 Background: Cancer patients with cachexia symptoms often show a lipid profile disorder, consisting in severe hypertriglyceridemia due to increased circulating free fatty acids and variable total cholesterol levels, decreased activity of lipoprotein lipase and increased lipolysis, which is correlated with proinflammatory cytokines levels, particularly IL-6 and TNFα. Recent evidence further confirms impairment of adipose tissue metabolism in inflammatory condition like cancer cachexia. The aim of this study was to assess the effect of nutritional supplementation with Omega 3 fatty acids (EPA and DHA) in the form of Krill Oil, on main parameters of blood lipid profile and on IL-6 and TNFα blood levels. Methods: In 2011, 34 IV stage cachectic patients (M/F 20/14; age range 55-85 y) with cancer at different sites were enrolled. 21 healthy subjects were studied as controls. All patients had high blood tryglicerides, low total cholesterol levels , high levels of blood IL-6 and TNFα compared to controls. Patients received 3 capsules (3 g/day) of krill oil (Superba™ Krill Oil, Aker Biomarine, Norway), which is an oil extract from the crustacean krill (Euphausia Superba) which contains Omega-3 series unsaturated fatty acids in phospholipidic form, of which 98 % are EPA and DHA mainly in phospholipid form. Treatment duration was 2 months. Results: A significant reduction of tryglicerides blood levels (148.23 ± 88.06 vs 114 ± 55.8 mg/dl) and a significant improvement of HDL cholesterol (42.5 ± 15.6 vs 60.9 ± 12.3 mg/dl) and Total Cholesterol (135.6 ± 46.3 vs 159 ± 41.1 mg/dl) was observed after treatment. Cytokines Il-6 and TNFα blood levels did not change significantly after treatment Conclusions: Nutritional supplementation with krill oil showed a positive activity in the regulation of blood lipid profile, involving different metabolic and inflammatory pathways, probably mainly affecting hormone-sensitive lipase activity. Our data suggest that krill oil could be useful in multi-targeted combined pharmaco-nutritional approaches to treat cancer-cachexia. Additional phase III clinical studies are warranted.
Using patient-reported outcomes to assess prostate brachytherapy technique
Authors: J. A. Talcott, J. A. Clark, J. Manola, A. L. Zietman, I. Kaplan, A. V. D’Amico, J. Coen, S. P. Mitchell, C. E. Reilly
Journal: Journal of Clinical Oncology (2005)

4697 Background: Brachytherapy technique may affect prostate cancer treatment outcomes. One attempts to reduce urinary dysfunction by excluding the periurethral transitional zone from the target volume using MRI localization (MRB). In a small study, we found less short-term urinary and sexual function in patients after MRB, but worse bowel function. To assess the affect of technique, we compared patient-reported outcomes after MRB with those in 2 different academic practices using ultrasound and conventional target volumes (USB). Methods: In an ongoing cohort study, we surveyed patients with validated instruments to measure treatment-related urinary, bowel and sexual dysfunction before treatment (BL) and at 3 and 12 months. We abstracted clinical data from medical records. We report 12-month follow-up results. Results: Other than age, MRB and USB patient groups had similar favorable pretreatment demographic and clinical characteristics. MRB patients tended to increase urinary dysfunction less and bowel dysfunction more, without clear differences in sexual dysfunction. In addition, trends suggested changes in urinary and bowel dysfunction also differed between USB patient groups. Conclusions:These early results are consistent with our earlier observation that MRB patients have less short-term urinary dysfunction but more bowel dysfunction. We also found evidence that 2 different USB techniques in academic settings may produce different treatment-related outcomes. These observational data suggest that both intentionally distinct and apparently similar techniques may produce different treatment-related outcomes. Patient-reported data may contribute to technology assessment. No significant financial relationships to disclose.
Retroviral-Mediated Gene Transduction of c-kit Into Single Hematopoietic Progenitor Cells From Cord Blood Enhances Erythroid Colony Formation and Decreases Sensitivity to Inhibition by Tumor Necrosis Factor- and Transforming Growth Factor-β1
Authors: Li Lu, Michael C. Heinrich, Li-Sheng Wang, Mu-Shui Dai, Amy J. Zigler, Lin Chai, Hal E. Broxmeyer
Journal: Blood (1999)
Can Radiological Parameters Predict the Outcome in Metastatic Renal Cell Carcinoma (Mrcc) Patients Treated with Sunitinib? Usefulness of Normalized Arterial Density and Blood Flow
Authors: O. Reig, I. Victoria Ruiz, B. Paño, M. Campayo, C. Nicolau, B. Mellado, M.C. Sebastia
Journal: Annals of Oncology (2014)
Effect of intensity modulated radiotherapy delivery technique on integral dose in normal healthy tissue
Authors: A. Bahl, K. J. Basu, D. N. Sharma, V. Subrama, P. K. Julka, G. K. Rath, G. Kumar
Journal: Journal of Clinical Oncology (2008)

17009 Background: Integral dose (ID) delivered to the normal tissues during intensity modulated radiotherapy (IMRT) treatment is clinically relevant because of the increased risk of second malignancies. One method of reducing the ID is by fluence modulation using different IMRT delivery techniques. The aim of the present study was to evaluate any change in the ID received by normal healthy tissues in patients of carcinoma nasopharynx planned by dynamic versus static IMRT. Methods: Dosimetric data from ten cases of carcinoma nasopharynx, treated by simultaneous integrated boost IMRT was evaluated in this prospective study. The inclusion criteria included (1) patients with biopsy proven disease (2) patients planned for definitive radiotherapy. Target volume and organs at risk were contoured using Eclipse TPS version 6.5 (Varian Associates, Palo Alto, CA). A dose of 70 Gy to the GTV, 59.4 Gy to CTV1 and 54 Gy to the CTV2 was prescribed. A 5-mm margin was given to the CTV to achieve the planning target volume. For each patient IMRT plans using DMLC (dynamic multileaf collimator) and SMLC (static MLC) with 5L, 10L and 15L intensity level were generated with 6 MV photons and nine equispaced coplanar beams. To calculate the ID to the normal healthy tissue all the target volumes were subtracted from the body volume. The integral dose was calculated as the mean- dose times the volume of the structure. The statistical tests applied included paired t test, one-way ANOVA and agreement analysis. P value <0.05 was considered significant. Results: A total of forty IMRT plans were available for evaluation. The mean ID received by healthy normal tissue using 6X photons with dynamic MLC and segmental MLC with 5L, 10L and 15L intensity levels was 143.58 ± 28.61 (mean ± Standard deviation), 139.25 ± 27.39, 139.87 ± 28.74 and 143.11 ± 28.97 Liter-Gray respectively. A mean percent difference of −2.96% (p<0.001, paired t test), −2.67% (p<0.016), −0.39% (p<0.430) was observed between the two techniques. However on agreement analysis the difference with 5L and 10L intensity levels was not statistically significant. Conclusions: Dynamic IMRT was not associated with a significant increase in the integral dose to healthy normal tissue as compared to static IMRT. No significant financial relationships to disclose.
NHS should look to Alaska for model of reform, conference is told
Authors: Nigel Hawkes
Journal: BMJ (2015)

Could the model for reform of the NHS lie in distant Alaska? That may sound improbable, but Ben Collins, of the King’s Fund health charity, made a persuasive case at the fund’s annual conference on November 19.

Collins is the author of a new study1 of the Southcentral Foundation’s Nuka system of care run by Alaska Native people, which has evolved in the past 20 years into an international exemplar of the approach backed in NHS England’s Five Year Forward View 2: holistic care delivered by a tax based system that combines high quality, universal clinician and public approval, and affordable costs.

In the mid-1990s the healthcare system in Alaska looked rather like the NHS today, Collins said. Controlled from afar by a division of the US Department of Health and Human Services, it had long waiting times, …
Targeting the mitotic spindle in the treatment of adrenocortical cancer
Authors: E. A. Stephan, P. Gonzales, H. Han, C. S. Grant, S. Gately, D. D. Von Hoff, J. M. Trent, M. J. Demeure
Journal: Journal of Clinical Oncology (2007)

10572 Background: Adrenocortical carcinoma (ACC) is a rare and lethal cancer with an average incidence of 1 in 1.4 million. Response to current standard therapy including mitotane is approximately 22%. Herein we use gene expression profiling to identify novel targets for therapeutic intervention. Methods: The transcriptomes of 29 ACC tumors and 4 normal adrenal glands were profiled on Affymetrix Human Genome and Agilent 22K element expression arrays in order to identify genes that could represent potential therapeutic targets. Agents known to inhibit the selected targets were tested in comparison with mitotane in two ACC cell lines (H295R and SW-13) in vitro and are currently being tested in a Scid mouse xenograft system. Results: Expression of numerous kinesin family members is dysregulated within the ACC tumor population. Of interest in the ACC cells EG5 (KIF11, KSP), a kinesin important for mitotic spindle formation, is up-regulated 5.81+ 4.42 (μ+SD) and 6.48 + 0.99 fold on the Agilent and Affymetrix platforms respectively. In addition, SPARC, an albumin binding matrix associated protein is up-regulated in ACC tumors by 3.69 + 2.37 (μ+SD) and 1.56 + 0.44 on the two platforms. The anti-microtubular drugs paclitaxel and albumin bound paclitaxel (abraxane) exhibited in vitro inhibition of H295R and SW-13 cells at IC50 concentrations of 0.33 μM and 0.0078 μM for paclitaxel and 0.35 μM and 0.0087 μM for Abraxane compared to mitotane concentrations of 15.9 μM and 46.4 μM. Treatment effects of monastrol, paclitaxel, and Abraxane are currently being tested in xenograft murine models. Testing of the EG5 inhibitor S-trityl-L- cysteine is ongoing in the in vitro system. Conclusions: KIF11 inhibitors have been proposed in the treatment of cancer. These compounds may offer better anti-mitotic activity than other tubulin interacting agents with less neurotoxic side effects. Based on biological insight garnered through expression profiling of ACC tumors, the current ongoing research is investigating the use of abraxane and EG5 inhibitors in the in vitro and in vivo treatment of ACC. No significant financial relationships to disclose.
Four Proposals to Help Improve the Medical Research Literature
Authors: David Moher, Douglas G. Altman
Journal: PLoS Medicine (2015)

Points• The evidence base underpinning clinical practice is deeply flawed.• There must be better value gained from resources invested in medical research.• We make four proposals: (1) introducing publications officers; (2) developing core competencies for editors and peer reviewers, around which (3) training can be tailored; and (4) training authors to write articles fit for purpose.• All of these ideas need to be piloted and evaluated, and implemented if proven effective.• We suggest dedicated funding for initiatives aimed at understanding and improving the way that
Abstract 11082: Exome Sequencing Implicates the Burden of Rare Potassium Channel Variants in the Risk of Drug Induced Long QT Syndrome
Authors: Peter Weeke, Jonathan D. Mosley, David Hanna, Christian Shaffer, Jessica T. Delaney, Quinn S. Wells, Sara Van Driest, Jason H. Karnes, Christie Ingram, Yan Guo, Yu Shyr, Kris Norris, Prince J. Kannankeril, Andrea H. Ramirez, Joshua D. Smith, Elaine R. Mardis, Deborah Nickerson, Alfred L. George, Dan M. Roden
Journal: Circulation (2013)

Peter Weeke, 2013 Finalist and Presenting Author
Chemotherapy for adenocarcinoma of the lung (WHO III): A randomized study of vindesine versus lomustine, cyclophosphamide, and methotrexate versus all four drugs.
Authors: J B Sørensen, H H Hansen, P Dombernowsky, E Bork, R Malmberg, K Aabo, B Bødker, M Hansen
Journal: Journal of Clinical Oncology (1987)

Two hundred seventy-nine patients with previously untreated nonresectable adenocarcinoma of the lung (ACL) entered a prospective randomized trial, comparing vindesine (VDS) to a combination of lomustine (CCNU), cyclophosphamide (CTX), and methotrexate (MTX), and to a regimen including all four drugs. Response assessment was possible in 218 patients, while 259 were evaluable for survival. Response rates were similar (22%, 23%, and 27%, respectively) as were median durations of response (15 weeks overall) and survival (29 weeks overall). Patients with dose-limiting toxicity had significantly higher response rate and longer survival than patients without toxicity. The major toxicity was peripheral neuropathy with VDS treatment and myelosuppression with the other two regimens. The VDS single-agent activity in ACL was confirmed, but addition of VDS to the three-drug regimen did not increase activity. Future studies of VDS in combination with other active agents, and comparison to a matched control group on supportive care, are indicated.
AB1230-HPR Baseline Characteristics of the Liège Hand Osteoarthritis Cohort (LIHOC)
Authors: A. Neuprez, O. Bruyère, N. Dardenne, S. Distèche, E. Maheu, N. Burlet, J.-Y. Reginster
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Whereas hand osteoarthritis (OA) is a frequent disease, which may lead to considerable pain and physical limitations, limited research has been performed, compared to lower limbs OA. <h3>Objectives</h3> To better understand the impact of hand osteoarthritis on quality of life and health resources utilization of interdigital osteoarthritis. <h3>Methods</h3> We decided to prospectively follow a cohort of 203 individuals, diagnosed with hand OA during consultations held at a tertiary care facility specialized in bone and cartilage metabolism and called the Liège Hand Osteoarthritis Cohort (LIHOC). <h3>Results</h3> As expected, the vast majority of patients (90.1%) were of female gender with 46.8% having a family history of hand OA. The median age of the population was 69.1 years (Q1 61.9-Q3 75.6). Body Mass Index (kg/m<sup>2</sup>) median was 25.6 (22.9-28.9). Hand OA was associated with other joint involvement in 87.1% of the cases {mainly spine (70.8%) and knee (69.0%)}. On a Visual Analog Scale reflecting pain in hand joints, graded from 0 to 100, the median score was 50.0 (29.0-59.0), with a median number of painful joints at pressure of 5.0 (2.0-10.0). The median number of swollen joints and of joint with bony deformations was respectively 2.0 (1.0-4.0) and 10.0 (6.0-15.0). The total normalized Auscan score (0-300) median value was 129.0 (71.1-182.5) while the median Functional Index for Hand Osteoarthritis (FIHOA) score (0-30) was 5.0 (2.0-11.0). Radiologic assessment of hand OA showed a Verbruggen total score (0-218) median value of 31.6 (20.9-48.2) whereas the Kellgren-Lawrence total score (0-128) median value was 54.0 (40.0-66.0). <h3>Conclusions</h3> The LIHOC will be followed for a total duration of 5 years, with the objective to better understand the determinants of clinical and radiologic progression as well as the impact of hand OA on quality of life and health resources utilization. <h3>Disclosure of Interest</h3> None declared
Preoperative chemoradiation with oxaliplatin and 5-fluorouracil in locally advanced rectal carcinoma
Authors: V. Alonso, A. Salud, P. Escudero, J. Valencia, M. Mira, A. Ruiz de Lobera, J. Lambea, R. Grandez, A. Tres, A. Anton
Journal: Journal of Clinical Oncology (2004)

3607 Background: The aim of this phase II trial was to assess the impact of preoperative external radiation therapy combined with 5-Fluorouracil (5-FU) and oxaliplatin (LOHP) on pathologic tumor response, sphincter preservation and tumor control in patients with locally advanced rectal carcinoma. Methods: Fifty-three patients with locally advanced rectal carcinoma (T3/T4 or N+) received radiotherapy (50.4 Gy/28 fractions) and chemotherapy with continuous infusion of 5-FU 200 mg/m2/day on days 1–5 + LOHP 60 mg/m2 on day 1 every week (weeks 1–6). Surgery was performed between 5–7 weeks after the end of the treatment. Adjuvant chemotherapy with 5-FU + Folinic Acid (NCCTG) x 4 cycles was administered after surgery. Results: Patients have been recruited since May 2002 to November 2003. 35 male/18 female. Median age 66 years (range 32–78). Clinical stage (determined by EUS+CT or RMI): cT3 43p, cT4 10p, cN+ 32p. Tumor location (from anal verge): ≤ 5 cm in 26p, >5 cm in 27p. Surgery (performed in 43 patients) consisted of low anterior resection in 27p, abdominal perineal resection in 15 and 1 palliative colostomy. Tumor downstaging was observed in 33p (75.6%), 34 (79%) had negative lymph nodes, including 10p with complete pathological response (22.7%). 36% of patients with tumors in distal rectum had sphincter-saving surgery. Main adverse effects (NCI-CTC): diarrhea G3 7.5%, sensitive peripheral neurotoxicity G1 60%, skin G2 10%, skin G3 2%, nausea/vomiting G2 7.5%, asthenia G2 20%, cardiac (miocardial infarct) G4 2%. No G3–4 hematolgic toxicity was observed. Conclusions: Preoperative chemoradiotherapy with 5FU+LOHP is a feasible and well tolerated treatment. Our results are comparable to the best series of preoperative treatment. No significant financial relationships to disclose.
Mitoxantrone, fluorouracil, and high-dose leucovorin: an effective, well-tolerated regimen for metastatic breast cancer.
Authors: J D Hainsworth, M B Andrews, D H Johnson, F A Greco
Journal: Journal of Clinical Oncology (1991)

Between September 1988 and August 1990, we treated 35 women with metastatic breast cancer with a novel regimen containing mitoxantrone, fluorouracil (5-FU), and high-dose leucovorin. This regimen was designed to take full advantage of the favorable toxicity profiles of these agents while maintaining a high level of activity. All patients had received previous chemotherapy (adjuvant only, 15 patients; at least one metastatic regimen, 20 patients). Seven patients had received previous doxorubicin, but none within 6 months of study entry. Of 31 assessable patients, 20 (65%) had objective responses (two complete, 18 partial), with a median response duration of 6 months (range, 3 to 16+ months). Four patients with bone metastases (abnormal bone scan only) and pain were not considered assessable by strict response criteria; two of these patients had sustained symptomatic relief for 6 and 8 months, respectively. Myelosuppression was the most frequent toxicity but was mild in most patients; only four hospitalizations for fever and neutropenia were required (2% of courses). No severe thrombocytopenia occurred and no RBC transfusions were required. Alopecia, mucositis, and nausea/vomiting were uncommon and were not severe in any patient. The combination of mitoxantrone, 5-FU, and high-dose leucovorin is well tolerated and active as a first- or second-line treatment for metastatic breast cancer. Comparison with other standard regimens for breast cancer is indicated.
Immunolocalization of Protein Kinase C Isoenzymes α, βI and βII in Rat Kidney
Authors: IMKE L. PFAFF, HANS-JOACHIM WAGNER, VOLKER VALLON
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Protein kinase C (PKC) significantly contributes to the control of renal function, but little is known about the renal function or localization of PKC isoenzymes. Therefore, the localization of PKC isoenzymes α, βI, and βII was studied in rat kidney. Immunoblot analysis identified immunoreactive bands corresponding to PKC α, βI, and βII in total cell extracts of both renal cortex and medulla. Immunohistochemistry using confocal laser scanning microscopy revealed immunostaining for PKC α within the glomerulus including podocytes and mesangial cells. PKC βI was detected in mesangial cells, whereas anti-PKC βII labeled neither podocytes nor mesangial cells. PKC βII, however, was detected in cells within the mesangial area, which expressed MHC II, a marker for antigen-presenting cells. None of the three isoforms was detected in glomerular endothelial cells. A prominent immunostaining with anti-PKC α and βI was localized to the brush border of S2 and S3 segments of proximal tubule, whereas S1 segments were not stained. Along the loop of Henle, both PKC α and PKC βI were found in the luminal membrane of cortical and medullary thick ascending limb. In addition, anti-PKC βI labeled the luminal membrane of thin limbs. In the cortical collecting duct (CCD), immunofluorescence for PKC α was observed at the apical membrane of both peanut agglutinin (PNA)-negative cells and part of PNA-positive cells, whereas in the medullary collecting duct (MCD), PKC α was detected at the basolateral membrane. In comparison, PKC βI was localized at the luminal membrane of PNA-positive cells only in CCD and at the luminal membrane of MCD. Unlike PKC α or βI, there was ( 1 ) no detectable immunostaining with anti-PKC βII in the proximal tubule, the loop of Henle, or the CCD and ( 2 ) a distinct staining for PKC βII of interstitial cells in cortex and medulla (including MHC II-positive dendritic cells). Furthermore, PKC βII was detected in the luminal membrane of MCD. In summary, a distinct and differential expression pattern for PKC α, βI, and βII was shown in rat kidney, which may contribute to a better understanding of the specific role of these isoenzymes in the control of renal function.