tbuckley/cabot-search huggingface dataset:
Interesting antitumor activity of lenalidomide in a patient with hepatic epithelioid hemangioendothelioma (HEH).
Authors: Maria Caterina Pallotti, Maria A. Pantaleo, Cristian Lolli, Margherita Nannini, Maristella Saponara, Anna Mandrioli, Lidia Gatto, Valerio Di Scioscio, Stefano A Pileri, Luigi Bolondi, Guido Biasco
Journal: Journal of Clinical Oncology (2013)

e21511 Background: Epithelioid hemangioendothelioma (HEH) is a rare malignant vascular soft tissue tumor occurring mostly in the liver. The molecular background is still unkonwn and therefore the medical treatment has not been established. Some case reports treated with angiogenesis inhibitors are described. Lenalidomide has anti-proliferative and cytotoxic effects, immunomodulatory properties but also anti-angiogenic activity. In literature there are few case of patient with solid tumors treated with lenalidomide.We report a patient affected by HEH treated with lenalidomide for long time. Methods: In 2010, a 73 year old man arrived our attention with multiple hepatic lesions diagnosed with contrast computed tomography (CT), abdominal magnetic resonance (MR) imaging and contrast enhanced ultrasound (CEUS) of the liver. An ultrasound guided biopsy of an hepatic lesion was made and histopathology exam deposed for the diagnosis of HEH. We decided to treat the patient with lenalidomide 25 mg daily on 1- 21 every 28 days, because a liver transplantation was not inidcated for the age of the patient. The follow up of disease was made by abdominal ultrasound and MR every three/four months. Results: The patient was treated with lenalidomaide for thirty months totally. After six months the imaging showed a stable disease and after ten months MR also demonstrated an intralesional structure modification as colliquative necrosis. In February 2012, after 24 months of continuos therapy, we decide to stop the treatment for fatigue and for other comorbidity of the patient. After five months of suspension, the ultrasound showed a dimensional increase of a target hepatic lesion &amp; so we restarted lenalidomide for other six months. MR imaging demonstrated a stable disease and abdominal ultrasound showed a decrease of the dimension of a target hepatic lesion. The patient is still under treatemnt with a control of disease. Conclusions: HEH is a rare tumors with probably an indolent natural history but this case report suggests an interesting activity of lenalidomide and antiangiogentic drugs in the treatment of this solid tumor. More patients treated with lenalidomide are encouraged and a small phase II study should be proposed.
Hepatitis C virus-induced MiR-21 activation triggers steatosis and promotes hepatitis C virus life cycle
Authors: S. Clément, C. Sobolewski, A. Rojas, G. Bonifacio, N. Goossens, S. Conzelmann, D. Gomes, N. Calo, F. Negro, M. Foti
Journal: Journal of Hepatology (2017)
Aggressive care at the end-of-life for younger patients with cancer: Impact of ASCO's Choosing Wisely campaign.
Authors: Ronald C. Chen, Aaron David Falchook, Fang Tian, Ramsankar Basak, Laura Hanson, Nandini Selvam, Stacie Dusetzina
Journal: Journal of Clinical Oncology (2016)

LBA10033 Background: Aggressive medical care at the end of life is widely recognized to be harmful to cancer patients. This includes cancer-directed procedures and therapies; emergency room and ICU admissions; and in-hospital deaths. Prevalence of its use in patients younger than 65 has not been previously examined. We evaluated use of aggressive care within the last 30 days of life from before to after ASCO’s 2012 Choosing Wisely campaign aimed at reducing aggressive end-of-life care. Methods: Claims data from the HealthCore Integrated Research Database were analyzed, which overall includes ~60 million individuals enrolled in Blue Cross and/or Blue Shield licensed plans across 14 states. Patients aged ≤ 65 who died between 2007-2014 and who had diagnoses for metastatic lung, colorectal, breast, pancreatic, and prostate cancers were included. Poisson multivariable regression models assessed the associations between age group, geographic region, gender, and regional education and income measures with aggressive care. Results: 28,731 patients were analyzed. 71-76% of patients across different cancers received aggressive care within the last 30 days of life (Table), including 30-35% of patients who died in the hospital. Rates of aggressive care use between early 2012 before Choosing Wisely vs. 2014 were unchanged in patients with colorectal and breast cancers; and increased in lung, pancreatic and prostate cancers. On the other hand, hospice use ranged from 14-18% across cancers. Multivariable models showed regional variations in aggressive care and hospice use. Conclusions: There is substantial overuse of aggressive end-of-life care among younger patients with incurable cancers. Aggressive care did not decrease following the 2012 ASCO Choosing Wisely recommendations. [Table: see text]
So Sheep May Safely Graze: Honing in on Culprit behind Fleece Variation in Domesticated Sheep
Authors: Joseph Caspermeyer
Journal: Molecular Biology and Evolution (2017)

a delightful cantata, "Sheep May Safely Graze," whose opening lyric boasts of shepherds protecting sheep from the ravages of the hunt.Fast forward a few centuries, where now, from a large genome study, a team of French and Argentinian scientists may have successfully identified the mutations behind the sheep traits that shepherds began saving from the huntfor their prized wool.Corresponding author Demars, from the
Survival analysis and response to ursodeoxycholic acid in patients with primary biliary cholangitis
Authors: A. Raga, M. García-Retortillo, A. García-Rodríguez, T. Broquetas, M. Puigvehí, S. Coll, J. Gimeno, M.D. Giménez, F. Bory, R. Solà, J.A. Carrión
Journal: Journal of Hepatology (2017)
Impact of multidisciplinary team approach to liver tumors in a tertiary center: 5-years experience
Authors: S. Okolicsanyi, V. Pontecorvi, G. Bonato, A. Ciaccio, R. Perego, F. Romano, F. Uggeri, D. Leni, F. Vacirca, A. Gambini, A. Mariani, M. Ratti, M. Acquati, N. Zucchini, G. Bovo, R. Corso, P. Invernizzi, M. Strazzabosco
Journal: Journal of Hepatology (2017)
Cabozantinib (XL184) in chemotherapy-pretreated metastatic castration resistant prostate cancer (mCRPC): Results from a phase II nonrandomized expansion cohort (NRE).
Authors: Matthew Raymond Smith, Christopher Sweeney, Dana E. Rathkopf, Howard I. Scher, Christopher Logothetis, Daniel J. George, Celestia S. Higano, Evan Y. Yu, Andrea Lynne Harzstark, Eric Jay Small, A. Oliver Sartor, Michael S. Gordon, Nicholas J. Vogelzang, David C. Smith, Maha Hussain, Johann Sebastian De Bono, Naomi B. Haas, Christian Scheffold, Yihua Lee, Paul G. Corn
Journal: Journal of Clinical Oncology (2012)

4513 Background: Cabozantinib (cabo) inhibits MET and VEGFR2. High rates of bone scan resolution, pain relief and overall disease control, independent of PSA changes, were previously reported in a phase II study in mCRPC patients (pts). This is a NRE cohort in docetaxel (D)-pretreated pts with a novel primary endpoint of bone scan response based on computer-aided quantitative assessment of bone scan lesion area (BSLA) and a double-reader, independent, blinded review (Nucl Med Commun, in press). Methods: D-pretreated (≥225 mg/m 2 ) CRPC pts with bone metastasis were required to have progressed in soft-tissue or bone within 6 months of last dose of D. Pts received 100 mg cabo qd. Tumor response was assessed q6 wks. Bone scan response (BSR) was defined by a ≥30% decline in BSLA. Pain intensity (worst pain over the past 24 hrs; BPI scale 0-10) and interference with sleep and daily activity were prospectively assessed using an IVR system. Analgesic use was collected by diary. Bone turnover markers and CTCs were assessed. Results: 93 D-pretreated pts were enrolled (89 evaluable with ≥6 wks f/u). Median age was 67, 46% received cabazitaxel and/or abiraterone, 32% had visceral disease, 51% had fatigue, and 18% had anemia. 44% had worst pain ≥4 of which 95% were taking narcotics. Median CTC count was 49 and 80% had ≥5. Median f/u was 125 days (range, 23-305). Of 85 pts evaluable for BSR, 51 (60%) had a PR, 24 (28%) SD, 5 (6%) PD and 5 (6%) d/c’d prior to f/u scan. 21/30 pts (70%) had reduction of measurable disease.16/33 pts (49%) with BPI ≥4 and ≥12 wks f/u had pain reduction durable for ≥6 wks; 46% had decreased narcotic use, including 27% who discontinued use. Sleep and daily activity were improved in pts with pain relief. Among pts with elevated serum levels, 74%, 67% and 47% had declines on treatment of ≥30% in CTx, NTx and bALP, respectively. In 59 pts with CTCs ≥5, 92% had a decrease of ≥30% and 39% converted to &lt;5 CTCs at weeks 6 or 12. 12% discontinued cabo due to AEs. Most common Gr 3/4 AEs were fatigue (19%), nausea (10%) and anemia (10%). Conclusions: Cabo treatment resulted in high rates of bone scan response, durable pain relief, and reductions in bone turnover markers and CTCs in D-pre-treated CRPC pts with bone metastases.
Diet high in vegetables, fruit, and whole grains may reduce risk of gout
Authors: Susan Mayor
Journal: BMJ (2017)

Eating a diet high in fruit, vegetables, and whole grains and low in salt, sugary drinks, and red meat is associated with a lower risk of gout than a typical Western diet, a long term follow-up study has found.1

Gout is the most common inflammatory arthritis and is caused by hyperuricemia. The Dietary Approaches to Stop Hypertension (DASH) diet has been shown to reduce uric acid levels in the blood, …
Association of Pre-Allogeneic Hematopoietic Stem Cell Transplant 25-Hydroxy-Vitamin D Level and Development of Acute Skin Graft-Versus-Host-Disease: A Retrospective Analysis of 154 Patients
Authors: Ranjit Joseph, Seema Jabbar, Manasa Reddy, Damon E. Houghton, Yun Trull, Xainming Tan, Ibrahim Hashim
Journal: Blood (2016)
Current status and perspectives of patient-derived xenograft models in cancer research
Authors: Yunxin Lai, Xinru Wei, Shouheng Lin, Le Qin, Lin Cheng, Peng Li
Journal: Journal of Hematology & Oncology (2017)

Cancers remain a major public health problem worldwide, which still require profound research in both the basic and preclinical fields. Patient-derived xenograft (PDX) models are created when cancerous cells or tissues from patients' primary tumors are implanted into immunodeficient mice to simulate human tumor biology in vivo, which have been extensively used in cancer research. The routes of implantation appeared to affect the outcome of PDX research, and there has been increasing applications of patient-derived orthotopic xenograft (PDOX) models. In this review, we firstly summarize the methodology to establish PDX models and then go over recent application and function of PDX models in basic cancer research on the areas of cancer characterization, initiation, proliferation, metastasis, and tumor microenvironment and in preclinical explorations of anti-cancer targets, drugs, and therapeutic strategies and finally give our perspectives on the future prospects of PDX models.
The SO(H)L(H) “O” drivers of oocyte growth and survival but not meiosis I
Authors: T. Rajendra Kumar
Journal: Journal of Clinical Investigation (2017)

The spermatogenesis/oogenesis helix-loop-helix (SOHLH) proteins SOHLH1 and SOHLH2 play important roles in male and female reproduction. Although previous studies indicate that these transcriptional regulators are expressed in and have in vivo roles in postnatal ovaries, their expression and function in the embryonic ovary remain largely unknown. Because oocyte differentiation is tightly coupled with the onset of meiosis, it is of significant interest to determine how early oocyte transcription factors regulate these two processes. In this issue of the JCI, Shin and colleagues report that SOHLH1 and SOHLH2 demonstrate distinct expression patterns in the embryonic ovary and interact with each other and other oocyte-specific transcription factors to regulate oocyte differentiation. Interestingly, even though there is a rapid loss of oocytes postnatally in ovaries with combined loss of Sohlh1 and Sohlh2, meiosis is not affected and proceeds normally.
Abstract 27: Psychometric Testing of Instruments for Use in Women’s Cardiovascular Recovery Globally
Authors: Lucia Gonzales, Koci Anne, Rose Mary Gee, Ariko Noji, Dale Glaser, Allison Marsh, Kathy K Marsh, Amara M Altman, Nasser Al Salmi, Sulaiman Al Sabei
Journal: Circulation Research (2015)

Worldwide, 3.4 million women die each year from cardiovascular disease. After experiencing a cardiovascular event, a woman’s physical health, the women’s likelihood of being treated with coronary artery bypass graft surgery, likelihood for referral for cardiac rehabilitation are less favorable than men. An established conceptual model depicts psychosocial stressors and the influence of behavioral risk factors on the pathogenesis of atherosclerosis and the occurrence of CV events. The woman’s social stressors of role quality and behavioral risk factors of low self-efficacy for physical activity are associated with physical and mental health outcomes following cardiovascular crises. The study aimed to evaluate the reliability of the translated versions (Japanese, Ukrainian, Tagalog, Hispanic and Arabic) of the worker, partner, mother Role Quality and the Self Efficacy of Lifestyle Physical Activity indices among 282 women (aged 35-92 years) representing seven cultures. The study was performed in a multi-center, multicultural context. Translations followed an established process. Results showed reliability was strong (coefficient alphas of 0.93 and 0.88). These instruments underwent first-time confirmatory factor analyses with acceptable, though borderline fit, thus providing valuable input for strengthening in future studies. Understanding a woman’s role quality and self-efficacy for lifestyle physical activity provides valuable information that assists health-care professionals to co-develop with the woman an individualized plan to reduce role stress and to initiate increased physical activity following cardiovascular episodes.
Abstract P137: Metabolomic Analysis of the Early and Late Hypertrophic Heart
Authors: Alan C Brooks, Brian E Sansbury, Zhengzhi Xie, Robert E Brainard, Lewis J Watson, Kenneth R Brittian, Sumanth D Prabhu, Steven P Jones, Aruni Bhatnagar, Bradford G Hill
Journal: Circulation Research (2011)

The metabolic adaptations to acute myocardial pressure overload are characterized by alterations in metabolism that drive the hypertrophic response and that balance workload with energy demand. Under conditions of chronic pressure overload, it is known that substrate utilization becomes less flexible and that the heart shifts energy preference from fatty acids to glucose. Nevertheless, the metabolic changes that underlie the progression of compensated hypertrophy to heart failure are incompletely understood and attempts to correct the known metabolic defects to delay decompensation have been largely unsuccessful. To identify key changes in metabolic phenotype that could underlie progression to heart failure, we measured metabolites in a transverse aortic constriction (TAC) mouse model using an unbiased metabolomic approach. Hearts were harvested 1 d, 1 wk and 8 wks after sham or TAC operation, and metabolites were extracted from the hearts and analyzed via GC/MS and LC/MS/MS. The signal intensities of 288 named metabolites were re-scaled to median values. Welch’s t-test and two-way ANOVA were used to identify metabolites that changed significantly with pressure overload and progression to heart failure. Echocardiographic measurements showed a significant decrease in ejection fraction after 1 d (65±2% vs. 49±5%) and 8 wks (61±2% vs. 34±8%) of TAC; 1 wk of TAC showed a compensated phenotype characterized by a largely preserved ejection fraction. One day after TAC, only 1.7% of the metabolites changed significantly; however, nearly all amino acids measured were increased by 1 wk. By 8 wks, amino acids returned to near sham levels and a significant and robust decrease in phospholipid, carnitine, inositol, sterol, and fatty acid metabolites occurred. These findings demonstrate that the temporal changes in metabolic phenotype are more complex than previously thought. The preservation of pathways involved in lipid and amino acid metabolism may be important for maintaining myocardial energetics and preventing pump failure under conditions of chronic pressure overload.
Treatment of refractory/relapse vitreoretinal lymphoma: Result of a multicenter retrospective study from the LOC network on temozolomide in monotherapy.
Authors: Sylvain Choquet, Marine Baron, Carole Soussain, Caroline Houillier, Emmanuel Gyan, Nathalie Cassoux, Valerie Touitou, Christine Fardeau, Veronique Leblond, Khê Hoang-Xuan
Journal: Journal of Clinical Oncology (2015)

8546 Background: Vitreoretinal lymphoma (VRL) is a rare subset of non Hodgkin lymphoma. Its overall survival (OS) is from 35% to 68% at 5 years (Riemens et al Jama ophtalmol 2014) in first line, but relapse/refractory (R/R) VRL survival is usually of few months. Temozolomide (Tz) has been described effective in some cases of CNS lymphoma. Methods: VRL not eligible for IV chemotherapy or local treatment were proposed to be treated by Tz at 150mg/m²/j 5 days/month. Diagnosis of VRL was made by vitrectomy with a cytological, phenotypical and molecular analysis, dosages of IL10 and IL6 were also made. Extra-ocular localizations were searched by brain RMI, lombar puncture and CT-scan or PET-scan. Results: 16 patients were included, mean age was 75 years [35-90]. 12 previously received systemic chemotherapy with high dose methotrexate or cytarabin, 8 were in second line, 3 in third, 2 in forth, and 1 in fith who relapsed after autologous stem-cell transplantation (ASCT). The 2 patients treated in first line where more than 80 years old. All but one had an isolated VRL, one an association with a cerebral localization. Median duration of treatment was 5 months. The median follow-up (fu) is 16 months. Overall response rate is 75%, with 10 CR (63%) and 2 PR (13%). At the last fu, 6 patients are still in CR. The median disease free survival is 12,3 months. The patient treated after ASCT relapse is still in CR at 77 months. The two old patients treated in first line are in CR at last fu. One patient with cerebral localization had a persistent ocular and cerebral CR. Three patients were treated a second time by Tz after relapse, obtaining 2 new CR, one of 4 months and one persistent at 12 months, and one new persistent PR. Median OS is not reached. Only 2 patients experienced hematological grade 3/4 toxicity. There was no treatment related deaths. Conclusions: This work represents the biggest study with an homogeneous treatment in R/R VRL. Temozolomide appears as a safe and efficient treatment of R/R VRL and first line VRL in patients in bad condition, even after high dose chemotherapy and/or in elderly patients. Longer follow-up, prospective and larger studies are necessary to confirm these data.
Increased expression of folate receptor-α (FRA) in triple-negative breast cancer: A potential therapeutic target.
Authors: Jennifer A. Crozier, Brian M. Necela, E Aubrey Thompson, Xochiquetzal Geiger, Alvaro Moreno-Aspitia, Ann E. McCullough, Barbara A. Pockaj, Heather Cunliffe, Zhifu Sun, Krishna R. Kalari, Jennifer M. Kachergus, Daniel J. O'Shannessy, Julia D. Maltzman, Karla V. Ballman, Cathy A. Andorfer, Edith A. Perez
Journal: Journal of Clinical Oncology (2013)

1037 Background: Folate receptor alpha (FRA the product of the FOLR1 gene) has been identified as a potential prognostic and therapeutic target in a number of cancers. A correlation has been shown between intense expression of FRA in breast tumors and poor prognosis, yet little is known about FOLR1/FRA expression across clinically relevant breast cancer subtypes. Methods: 131 breast cancer tumors including 4 benign, 33 ER+, 26 HER2+, and 68 triple negative (TN) were constructed into tissue microarrays (TMAs). FRA expression was analyzed by immunohistochemistry (IHC) using a high affinity FRA antibody. Tumor membrane staining intensity was scored by a pathologist as negative (0), weak (1+), moderate (2+) and strong (3+). The percent of cells within each tissue core stained at each intensity was recorded to calculate an H-score. The H-score is a weighted score that captured both the proportion of positive staining and intensity for each tumor. H-score values can range from zero (no membrane staining) to a maximum of 300 (100% membrane staining at 3+). H-scores for each patient sample were averaged over 3 TMA cores. The mean H-scores for each tumor subtype and the percentage of 3+ staining in &gt;30% of tumor cells were compared by a Mann-Whitney test. The distribution of FOLR1 mRNA was completed using a TCGA RNA-seq dataset from 691 breast tumors classified as ER+, HER2+ and TN. FOLR1 levels of TN versus ER+ and HER2+ were compared by a Mann-Whitney test. Results: The mean H-score for the benign tumors was 0, ER+ (13.31), HER2+ (39.36), TN (119.02). The median H-score for the benign tumors was 0, ER+ (0), HER2+ (7.5), TN (127.5). The TN tumors mean and median H scores were significantly higher than benign, ER+ or HER2+ (p&lt;0.001). The largest percentage of 3+ staining in &gt;30% of tumor cells was observed in TN tumors (36.7%) and lowest in ER+ tumors (0%) (p&lt;0.001). TN tumors had significantly higher levels of FOLR1 mRNA compared to ER+ and HER2+ subtypes (p&lt;0.0001). Conclusions: Our data indicate that expression of FRA is highly prevalent in TN tumors and is supported by FOLR1 mRNA levels. Anti-FRA therapy may represent an important therapeutic intervention in TNBC who to this point have no active targeted treatment options.
Effects of Plasma Exchange (PE) Therapy in a Severe Fever with Thrombocytopenia Syndrome (SFTS) Patient with High Virus Quantities
Authors: Kazuhito Tsutsumi, Toshiro Takafuta, Michiko Kida, Tatsuji Mino, Miki Kido, Masayuki Shimojima, Masayuki Saijo, Takuo Ito
Journal: Blood (2016)