tbuckley/cabot-search huggingface dataset:
Stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC)
Authors: M. Dahele, S. Pearson, K. Franks, T. Purdie, J. Bissonnette, A. M. Brade, J. Cho, A. Sun, D. Jaffray, A. Bezjak
Journal: Journal of Clinical Oncology (2008)

7529 Background: About 20% of patients (pts) present with early-stage, localized NSCLC. Medically inoperable patients may receive radical RT. SBRT gives very high dose RT in far fewer fractions (fr) than conventional RT (≤5 vs ≥30), with the expectation of higher local control (LC) (>80% vs <45%). Methods: Since October 2004, patients at Princess Margaret Hospital with medically inoperable T1–2N0M0 NSCLC have been treated on REB approved SBRT protocols. Common regimens are 54 or 60Gy/3fr (peripheral tumor, n=45), 48Gy/4fr (T1 tumor close to organ at risk, n=23) and 50–60Gy/8–10fr (central tumor, n=14). Treatment plans use 7–10 conformal beams; on-treatment image-guidance with cone-beam CT accurately targets the tumor. Results: The cohort consists of 76 consecutive patients (39M, 37F, median age 73 years [48–90], 72% ECOG 0–1, median DLCO 52.5% [24–104, n=66]) with 82 lesions (57 ≤3cm, 25 >3cm, median 2.3cm [0.7–5.7]). Median follow up is 8m (1–36). 49 pts with 53 lesions have been followed for ≥6m (median 13m). Of these, 2/53 lesions (4%) have failed locally (8 and 10m). 11/49 pts (22%) have failed distantly (median 9m [2–21], 10/11 with LC), predominantly in thorax (n=5) and bone (n=5). 9/49 pts (18%) have died (median 11m, 7–22), 5 from NSCLC, 4 of other causes. Kaplan- Meier 2 yr LC (all patients) = 95%, freedom from metastases = 70% and overall survival = 68%. At 3m, 39/69 lesions (56%) had responded (CR = 9, PR = 30, remainder SD by RECIST). To date the most common acute toxicities (≤3m, 76 pts) are grade (G) 1–2 fatigue (41%), cough (21%), skin erythema (14%), and chest wall pain (8%) with 5% G1–2 pneumonitis. The most frequent late toxicities (>3m, 57 pts) are G1–2 chest wall pain (23%), G1–3 rib fracture (14%), and G1–2 atelectasis (9%). There have been 4 G3 events (3 rib fractures, 1 pneumonitis). Conclusions: SBRT is a promising treatment. It can deliver high rates of LC in patients with stage I NSCLC and is well tolerated even by elderly patients with co-morbidity and impaired lung function. Long-term outcome data will define the therapeutic ratio. Clinical indications are evolving and strategies to optimize patient selection and outcome merit further investigation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Impac/Elekta Physics Advisory Board Elekta, Elekta, Philips, Raysearch Elekta
Evidence That High-Mobility Group A2 (Hmga2) Expression Contributes to the Ontogeny-Dependent Properties of Fetal Hematopoietic Stem Cells.
Authors: Michael R. Copley, David G. Kent, Claudia Benz, Keegan M. Rowe, Stefan H. Woehrer, Connie J. Eaves
Journal: Blood (2010)
Epithelial-to-mesenchymal transition confers pericyte properties on cancer cells
Authors: Anitha K. Shenoy, Yue Jin, Huacheng Luo, Ming Tang, Christine Pampo, Rong Shao, Dietmar W. Siemann, Lizi Wu, Coy D. Heldermon, Brian K. Law, Lung-Ji Chang, Jianrong Lu
Journal: Journal of Clinical Investigation (2016)

Carcinoma cells can acquire increased motility and invasiveness through epithelial-to-mesenchymal transition (EMT). However, the significance of EMT in cancer metastasis has been controversial, and the exact fates and functions of EMT cancer cells in vivo remain inadequately understood. Here, we tracked epithelial cancer cells that underwent inducible or spontaneous EMT in various tumor transplantation models. Unlike epithelial cells, the majority of EMT cancer cells were specifically located in the perivascular space and closely associated with blood vessels. EMT markedly activated multiple pericyte markers in carcinoma cells, in particular PDGFR-β and N-cadherin, which enabled EMT cells to be chemoattracted towards and physically interact with endothelium. In tumor xenografts generated from carcinoma cells that were prone to spontaneous EMT, a substantial fraction of the pericytes associated with tumor vasculature were derived from EMT cancer cells. Depletion of such EMT cells in transplanted tumors diminished pericyte coverage, impaired vascular integrity, and attenuated tumor growth. These findings suggest that EMT confers key pericyte attributes on cancer cells. The resulting EMT cells phenotypically and functionally resemble pericytes and are indispensable for vascular stabilization and sustained tumor growth. This study thus proposes a previously unrecognized role for EMT in cancer.
Inflammatory Gene Expression Profile and Defective Interferon‐γ and Granzyme K in Natural Killer Cells From Systemic Juvenile Idiopathic Arthritis Patients
Authors: Karen Put, Jessica Vandenhaute, Anneleen Avau, Annemarie van Nieuwenhuijze, Ellen Brisse, Tim Dierckx, Omer Rutgeerts, Josselyn E. Garcia‐Perez, Jaan Toelen, Mark Waer, Georges Leclercq, An Goris, Johan Van Weyenbergh, Adrian Liston, Lien De Somer, Carine H. Wouters, Patrick Matthys
Journal: Arthritis & Rheumatology (2016)

Systemic juvenile idiopathic arthritis (JIA) is an immunoinflammatory disease characterized by arthritis and systemic manifestations. The role of natural killer (NK) cells in the pathogenesis of systemic JIA remains unclear. The purpose of this study was to perform a comprehensive analysis of NK cell phenotype and functionality in patients with systemic JIA.Transcriptional alterations specific to NK cells were investigated by RNA sequencing of highly purified NK cells from 6 patients with active systemic JIA and 6 age-matched healthy controls. Cytokines (NK cell-stimulating and others) were quantified in plasma samples (n = 18). NK cell phenotype and cytotoxic activity against tumor cells were determined (n = 10), together with their interferon-γ (IFNγ)-producing function (n = 8).NK cells from the systemic JIA patients showed an altered gene expression profile compared to cells from the healthy controls, with enrichment of immunoinflammatory pathways, increased expression of innate genes including TLR4 and S100A9, and decreased expression of immune-regulating genes such as IL10RA and GZMK. In the patients' plasma, interleukin-18 (IL-18) levels were increased, and a decreased ratio of IFNγ to IL-18 was observed. NK cells from the patients exhibited specific alterations in the balance of inhibitory and activating receptors, with decreased killer cell lectin-like receptor G1 and increased NKp44 expression. Although NK cells from the patients showed increased granzyme B expression, consistent with intact cytotoxicity and degranulation against a tumor cell line, decreased granzyme K expression in CD56bright NK cells and defective IL-18-induced IFNγ production and signaling were demonstrated.NK cells are active players in the inflammatory environment typical of systemic JIA. Although their cytotoxic function is globally intact, subtle defects in NK-related pathways, such as granzyme K expression and IL-18-driven IFNγ production, may contribute to the immunoinflammatory dysregulation in this disease.
Increased burden of ultra-rare protein-altering variants among 4,877 individuals with schizophrenia
Authors: Giulio Genovese, Menachem Fromer, Eli A Stahl, Douglas M Ruderfer, Kimberly Chambert, Mikael Landén, Jennifer L Moran, Shaun M Purcell, Pamela Sklar, Patrick F Sullivan, Christina M Hultman, Steven A McCarroll
Journal: Nature Neuroscience (2016)
Trends in mortality from respiratory system diseases in Greece during the financial crisis
Authors: Filippos T. Filippidis, Vasiliki Gerovasili, William D-C. Man, Jennifer K. Quint
Journal: European Respiratory Journal (2016)

As a result of the ongoing economic recession in Greece, gross domestic product and health expenditure declined by 25%, unemployment increased from 9.6 to 26.5% [1], while unmet needs for medical care increased between 2009 and 2014 [2, 3]. Among others, the decline in disposable income has transformed cigarettes into luxury goods [4], tobacco consumption has declined sharply [5–7], sales and use of private vehicles have declined [1, 5] and low economic and industrial activity has contributed to the decline in concentrations of major air pollutants in urban areas, such as Athens [8]. Mortality from nonmalignant respiratory diseases in Greece has declined during the economic crisis <http://ow.ly/igYv3034E8L>
Treatable Diabetic Retinopathy Is Extremely Rare Among Pediatric T1D Exchange Clinic Registry Participants
Authors: Giovanna Beauchamp, Claire T. Boyle, William V. Tamborlane, Kellee M. Miller, Ingrid M. Libman, Michael J. Haller, Roy W. Beck
Journal: Diabetes Care (2016)

The Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) studies demonstrated that intensive diabetes management provides for marked reduction in risk for diabetic retinopathy (DR) (1,2). Nevertheless, guidelines for DR screening in the post-DCCT era have remained largely unchanged. Current American Diabetes Association guidelines for youth with type 1 diabetes suggest annual eye exams at the start of puberty or at age ≥10 years, whichever is earlier, once the youth has had diabetes for 3–5 years (3). We sought to examine how often treatable DR was reported among youth enrolled in the TID Exchange Clinic Registry (4).

Information about treatment for DR was collected from T1D Exchange Clinic Registry participants via …
The association of chemotherapy induced thrombocytopenia with survival in epithelial ovarian cancer patients
Authors: R. P. Rocconi, K. S. Matthews, K. Hoskins, M. Kemper, M. Finan, M. N. Barnes III
Journal: Journal of Clinical Oncology (2008)

16572 Background: Chemotherapy induced neutropenia has been demonstrated to be a surrogate parameter for survival in epithelial ovarian cancer patients (EOC). Therefore, we sought to evaluate if chemotherapy induced thrombocytopenia (CIT) could also be predictive of survival in primary EOC. Methods: Patients who were treated for primary stage II-IV EOC with cytoreductive surgery followed by 6 cycles of carboplatinum-taxane based chemotherapy were identified by a computerized database. CIT was defined as platelet count of ≤ 100 mm3 at chemotherapy cycle nadir and severe CIT was considered ≤ 50 mm3. These variables were correlated to clinicopathologic data and survival outcomes. Results: 280 consecutive patients were eligible for evaluation. Patients with CIT (n = 148) were similar to patients without CIT (n= 132) in regards to age, race, BMI, stage, histology, grade, and debulking status. Compared to patients without CIT, patients with CIT failed to demonstrate improvements in PFS (11 vs. 15 months; p = 0.67), OS (40 vs. 42 months; p = 0.54), and platinum sensitivity rates (61 vs. 66%; p = 0.42). Survival was also similar when stratified by debulking status (optimal vs. suboptimal). Other parameters such as severe CIT and number of episodes of CIT lacked prediction of survival in this cohort. Conclusions: Our data demonstrates that chemotherapy induced thrombocytopenia is not associated with improved survival in primary epithelial ovarian cancer. Therefore, CIT should not be utilized as a treatment goal or prognostic indicator for survival. No significant financial relationships to disclose.
The association between octreotide dose and tumor control in gastroenteropancreatic neuroendocrine tumors (NETs).
Authors: Sally C Lau, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2014)

4108 Background: Gastroenteropancreatic NETs represent a heterogeneous group of cancers that are associated with an indolent, protracted course. Octreotide has been used as a mainstay in the symptom management of these tumors. However, the recent PROMID study showed that octreotide 30 mg contributed to disease stabilization in well-differentiated midgut NETs, but a meaningful survival analysis was limited due to insufficient events. Our aim was to examine the relationship between octreotide dose and overall survival (OS) in a population-based setting. Methods: Patients diagnosed with NETS from 1987 to 2013, referred to any 1 of 5 regional cancer centers in British Columbia, and who initiated octreotide were reviewed. To account for variations in the duration of therapy, we determined the mean octreotide dose per 28-day cycle and compared OS based on dose of octreotide. Dose was dichotomized into high vs. low based on the median as well as 30mg as per the PROMID study. Results: A total of 170 patients were included: mean age 60 years (SD=13) and 54% were men. NETs most commonly originated from the midgut (47%) and the pancreas (21%). A significant proportion had unresectable, metastatic disease (81%) among whom the majority (87%) had hepatic involvement. Carcinoid symptoms that included diarrhea, flushing and wheezing were prevalent (72%). Octreotide was offered to patients with the intent of symptom management (71%), disease stabilization (23%), and tumor marker control (6%). The mean dose per 28-day cycle was 27 mg (SD=9). After accounting for symptoms and tumor burden, patients who received > 27 mg (n=78) experienced significantly longer median OS when compared to those who received </= 27 mg (n=92) of octreotide (82 vs. 39 months, respectively, p<0.0001). Likewise, median OS was also superior among those who were given > 30 mg (n=65) of octreotide as per the PROMID study, relative to those on </= 30 mg (n=105) of the drug (83 vs. 46 months, p=0.0001). Conclusions: Our findings suggest that higher doses of octreotide may confer OS benefits in selected patients with gastroenteropancreatic NETs and that titration of this drug to manage symptoms may not represent the optimal treatment strategy for all patients.
Phase II trial of combination biotherapy of high-dose interferon alfa-2b and tremelimumab for recurrent inoperable stage III or stage IV melanoma
Authors: A. A. Tarhini, S. S. Moschos, J. J. Schlesselman, J. Shope-Spotloe, M. Demark, J. M. Kirkwood
Journal: Journal of Clinical Oncology (2008)

9009 Background: High dose IFNα-2b (HDI) and anti-CTLA4 blockade with tremelimumab are two immunomodulatory therapeutic approaches that demonstrate activity in advanced melanoma and induce autoimmunity in association with therapeutic benefit. We hypothesized that the combination of these agents would effect more potent antitumor immunity and antitumor responses. Methods: Tremelimumab was given at 15 mg/kg IV per course (12 weeks). HDI was given concurrently starting with IV induction at 20 MU/m2 IV, 5 days/week, for 4 weeks followed by maintenance with 10 MU/m2 SC three times a week (TIW), for 8 weeks per course. From course 2 onward, HDI was given only SC at 10 MU/m2 TIW. A 2-stage design was adopted. HDI dose modification guidelines as for adjuvant therapy were utilized. Dose delays up to 12 wks were allowed for Tremelimumab. Results: Sixteen patients (10 male, 6 female), age 32–75 (median 55) have been enrolled to date. All had AJCC stage IV melanoma (4 M1a, 2 M1b, 10 M1c) and all had previously received therapy for metastatic disease (range 1–5 prior regimens). Two patients had previously treated stable brain metastases. A total of 24 courses have been administered (median of 1 course per patient; 6 patients continue on therapy). The frequency of grade 3/4 toxicities does not exceed experience with the FDA-approved HDI regimen alone. Grade 3/4 toxicities included neutropenia (3 patients; 19%), hepatic enzyme elevations >5 fold ULN (2; 13%), fatigue (6; 38%), anxiety (2; 13%). One patient had grade 4 autoimmune colitis leading to treatment discontinuation, but recovered completely following steroid therapy. The overall response rate is 19% (3 partial responses lasting 2+ - 4+ months). Responses were seen in both M1a (1) and M1c (2) disease. Two of the PRs were associated with autoimmune manifestations (autoimmune colitis and marked vitiligo). Six patients have stable disease lasting 1+ - 4.5 months and 3 have had progression. Conclusion: The combination of HDI and Tremelimumab can be administered with acceptable toxicity, and exhibits antitumor efficacy that is promising. This study has now proceeded into a second stage in which 21 more patients will be treated. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology Pfizer Oncology
Maternal and child undernutrition : global and regional exposures and health consequences. Commentary
Authors: Josette Sheeran, Geert Tom Heikens, Beatrice C. Amadi, Mark Manary, Nigel Rollins, Andrew Tomkins, Robert E. Black, Lindsay H. Allen, Zulfiqar A. Bhutta, Laura E. Caulfield, Mercedes De Onis, Majid Ezzati, Colin Mathers, Juan Rivera
Journal: The Lancet (2008)
A phase Ib study to evaluate the fully human monoclonal antibody MNRP1685A (anti-NRP1) administered intravenously in combination with bevacizumab with or without weekly paclitaxel in patients with advanced solid tumors.
Authors: A. Patnaik, C. D. Weekes, P. Hegde, Y. Xin, R. Yu, H. Xiang, R. K. Brachmann, P. LoRusso
Journal: Journal of Clinical Oncology (2010)

TPS180 Background: This study seeks to determine whether the anti-angiogenic antibody anti-NRP1 can be safely combined with the anti-VEGF antibody bevacizumab with or without paclitaxel. The VEGF pathway is a validated target for oncology therapeutics. Additional approaches that target tumor vasculature may augment current therapies. Anti-NRP1 specifically targets neuropilin-1 (NRP1) and keeps tumor blood vessels in an immature, highly VEGF-dependent state. In preclinical studies, anti-NRP1 shows substantial anti-tumor activity in combination with anti-VEGF suggesting that anti-NRP1 provides an opportunity to improve upon the clinical activity of regimens containing anti-VEGF therapies. Methods: Seven patients have been enrolled in two dose-escalation cohorts of Arm A at anti-NRP1 doses of 7.5 and 15 mg/kg (estimated minimum efficacious exposure based on preclinical studies). The study uses a 3+3 design. In Arm A, anti-NRP1 is administered intravenously followed by bevacizumab intravenously at 15 mg/kg on Day 1 of 3- week cycles. Besides two already enrolled cohorts, two additional cohorts are planned (24 and 36 mg/kg). In Arm B, anti-NRP1 and bevacizumab (10 mg/kg) are administered on Days 1 and 15 and paclitaxel (90 mg/m2) intravenously on Days 1, 8 and 15 of 4-week cycles. Three dose-escalation cohorts (12, 16 and 24 mg/kg) and one expansion cohort are planned. All patients receive premedication for the anti-NRP1 infusion that includes dexamethasone on Days -1 and 1. Arm B will open once Cohort 2 of Arm A (anti-NRP1 15 mg/kg) has been cleared. Primary objectives are to evaluate the safety and tolerability, identify dose-limiting toxicities, estimate the maximum tolerated dose and identify a recommended phase II dose of anti-NRP1 when combined with bevacizumab with or without paclitaxel. Pharmacokinetics of anti-NRP1 and bevacizumab will be evaluated. Plasma samples will be used to measure Placental Growth Factor (PlGF), basic Fibroblast Growth Factor (bFGF) and other circulating factors for exploratory analyses and for comparison to results of a phase I study for anti-NRP1 as single-agent. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Roche Genentech Genentech
Risk factors for infections in myelofibrosis: role of disease status and treatment. A multicenter study of 507 patients
Authors: Nicola Polverelli, Massimo Breccia, Giulia Benevolo, Bruno Martino, Alessia Tieghi, Roberto Latagliata, Elena Sabattini, Mara Riminucci, Laura Godio, Lucia Catani, Maura Nicolosi, Margherita Perricone, Daria Sollazzo, Gioia Colafigli, Anna Campana, Francesco Merli, Umberto Vitolo, Giuliana Alimena, Giovanni Martinelli, Russell E. Lewis, Nicola Vianelli, Michele Cavo, Francesca Palandri
Journal: American Journal of Hematology (2016)

Although infectious complications represent a relevant cause of morbidity and mortality in patients with myelofibrosis (MF), little is known about their incidence, outcome and risk factors. We retrospectively evaluated a cohort of 507 MF patients, diagnosed between 1980 and 2014 in five Italian hematology centers, to define the epidemiology of infections and describe the impact of ruxolitinib (RUX) treatment. Overall, 112 patients (22%) experienced 160 infectious events (grade 3-4, 45%) for an incidence rate of 3.9% per patient-year. Infections were mainly bacterial (78%) and involving the respiratory tract (52% of cases). Also, viral (11%) and fungal infections (2%) were recorded. Overall, infections were fatal in 9% of the cases. Among baseline features, high/intermediate-2 IPSS category (HR 1.8, 95%CI:1.2-2.7; P = 0.02) and spleen length ≥10 cm below left costal margin (HR 1.6, 95%CI:1.1-2.5; P = 0.04) were associated with higher infectious risk in multivariate analysis. Overall, the rate of infections was higher in the cohort of 128 RUX-treated patients (44% vs. 20%, P < 0.001). In conclusion, IPSS-category and splenomegaly, emerged as the main risk factors for infections in MF. RUX-treated patients experienced significantly more infection episodes; however, future prospective studies are needed to isolate the confounding contribution of other risk factors such as disease stage. Am. J. Hematol. 92:37-41, 2017. © 2016 Wiley Periodicals, Inc.
Polyglycolic acid sheet application to prevent esophageal stricture after endoscopic submucosal dissection for recurrent esophageal cancer
Authors: Yeong Kim, Jun Park, Hyunsoo Chung, Sung Shin, Sang Lee, Young Lee
Journal: Endoscopy (2016)

Endoscopic submucosal dissection (ESD) is an accepted treatment for early esophageal cancer. However, for large early esophageal cancers, ESD is associated with an increased risk of stricture development.
US blood testing company cuts workforce by 40%
Authors: Michael McCarthy
Journal: BMJ (2016)

The controversial US biotechnology company Theranos, which is currently facing federal sanctions, has announced that it will close its clinical laboratories, shut its retail wellness centers, and lay off 40% of its workforce.

Theranos came under scrutiny last year when reports emerged that the company was using its technology to run only a fraction of the blood tests it conducted and was instead relying on traditional devices made by other companies to process the …
Mobilization Scheme With Cytarabine In Poor Mobilizers Patients Diagnosed With Lymphoma
Authors: Cristina Calderón-Cabrera, Magdalena Carmona González, Jesús Martín, Eduardo Ríos Herranz, Pilar Noguerol Novella, Fátima De la Cruz, Estrella Carrillo, Ildefonso Espigado, Jose Antonio Pérez-Simón
Journal: Blood (2013)