tbuckley/cabot-search huggingface dataset:
Droplet‐Templated Antisolvent Spherical Crystallization of Hydrophilic and Hydrophobic Drugs with an in situ Formed Binder
Authors: Tonghan Gu, Eunice W. Q. Yeap, Zheng Cao, Denise Z. L. Ng, Yinying Ren, Ran Chen, Saif A. Khan, T. Alan Hatton
Journal: Advanced Healthcare Materials (2017)

This study presents a novel droplet-templated antisolvent spherical crystallization method applicable to both hydrophilic and hydrophobic drugs. In both cases, an alginate hydrogel binder forms in situ, concurrently with the crystallization process, effectively binding the drug crystals into monodisperse spheres. This study presents a detailed process description with mass transfer modeling, and with characterization of the obtained alginate/drug spheres in terms of morphology, composition, and drug loading. Although glycine and carbamazepine are used as model hydrophilic and hydrophobic drugs, this method is easily generalized to other drugs, and offers several benefits such as minimal thermal impact, fast crystallization rates, high drug-binder loading ratios, and high selectivity toward metastable polymorphs.
Hormone and targeted therapies in metastatic salivary duct carcinoma.
Authors: Thanh P. Ho, Ashish V. Chintakuntlawar, Scott H. Okuno, Katharine Andress Rowe Price
Journal: Journal of Clinical Oncology (2016)

e17557 Background: Salivary duct carcinoma (SDC) is an aggressive and rare cancer for which hormone and other targeted therapies are potential treatment options in the metastatic setting. Methods: A retrospective review was performed of patients (pts) with metastatic SDC treated at Mayo Clinic from 2010 to 2015. All pts had androgen receptor (AR) testing and 17 had HER2 testing by immunohistochemistry. Four pts had genomic testing through Foundation Medicine. Results: Eighteen male pts were found; median age of 64 (range 33 to 87). All patients were AR- positive. Ten pts were HER2 positive (56%), 5 were HER2 negative (28%), 2 equivocal (11%), and 1 unknown (5%). Fourteen (78%) pts received definitive therapy to the primary tumor including surgery, radiation, and/or chemotherapy (CT); 8 pts were metastatic at initial diagnosis. Ten pts (56%) received palliative CT prior to initiating hormone or targeted therapies. Sixteen (89%) pts received combined androgen blockade (CAB) with leuprolide and bicalutamide. The 2 pts who did not receive CAB received other local therapy for oligometastatic disease. Eleven of 16 pts responded to CAB (61%). Median time to progression on CAB was 6 months (0 to 14); two pts remain on CAB. Four pts who progressed on CAB received second line androgen therapy with abiraterone and prednisone. All 4 pts had a partial response; 3 remain on abiraterone with median length of treatment 3.5 months (1 to 8). Four pts with HER2-positive disease received HER-2 therapy (3 trastuzumab, 2 lapatinib) with clinical benefit for a median of 6 months (range 3 to 34). One pt had complete resolution of lung metastases with trastuzumab but later relapsed in the brain. Additional HER2 therapy with lapatinib, TDM-1 and neratinib resulted in stable intracranial disease for 8, 4, and 1 months, respectively. Targetable mutations identified included: ERBB2 (2 pts), PIK3CA (2 pts), HRAS (Q61K), and NF1 (A2644fs*35). The pt with the NF1 mutation was treated with everolimus with response. Median survival for all pts is 19 months (3 to 76) from time of diagnosis of metastases. Conclusions: Combined androgen blockade, second-line abiraterone, and HER2-directed therapies are treatment options. Genomic testing can lead to treatment options for pts with metastatic SDC.
Checkpoint kinase (CHK) 1/2 inhibitor LY2606368 in a phase I, dose-expansion study in patients (pts) with metastatic squamous cell carcinoma (mSCC) of the anus.
Authors: Johanna C. Bendell, Cathy Eng, Kathleen N. Moore, Howard A. Burris, Funda Meric-Bernstam, Suzanne Fields Jones, Sarina Anne Piha-Paul, Jeffrey R. Infante, Vivek Subbiah, Todd Michael Bauer, Lisa Golden, Ji Lin, Ricardo Martinez, Sameera Wijayawardana, Aimee K. Lin, David S. Hong
Journal: Journal of Clinical Oncology (2015)

3520 Background: LY2606368 is a CHK 1/2 inhibitor. CHK1 is a multifunctional kinase essential for checkpoint control, DNA repair, cell cycle replication, and proliferation. Potent inhibition of CHK1 is predicted to generate DNA damage and mitotic catastrophe. LY2606368 was evaluated as a single agent in an expansion cohort of pts with mSCC of the anus. Methods: This was a phase I study in pts with advanced cancer (NCT01115790). Preliminary signs of activity in the dose-escalation phase warranted a dose-expansion cohort of pts with mSCC of the anus given LY2606368 at the maximum tolerated dose (MTD) of 105 mg/m2 IV on day 1 of a 14-day schedule. Radiographic assessment every 6 weeks and pretreatment biopsies were obtained. Safety, tolerability, preliminary efficacy, and pharmacogenetic results are reported. Results: Of 26 pts enrolled, 62% had ≥ 2 prior regimens (median = 2 regimens; range: 1 - 13) and 92% of pts had prior radiotherapy. The most frequently reported adverse event (AE) was neutropenia, which occurred in 92% of pts (grade 4: 77%), but was of relatively brief duration; 1 pt experienced febrile neutropenia. Other drug-related AEs occurring in > 20% of pts were thrombocytopenia (58%), anemia (38%), and fatigue (31%). Nonhematologic AEs included nausea (19%), diarrhea (15%), anorexia and headache (12% each), which were mostly grade 1 or 2. One pt (4%) had a CR, 3 pts (12%) had a PR, and 11 pts (42%) had SD, for an overall response rate of 15% (90% CI: 5, 32) and a disease control rate of 58% (90% CI: 40, 74). Of the 4 pts with response, 3 pts (including the pt with a CR) remain on treatment, and 1 had a prolonged duration of response (10.1 mos) before discontinuing therapy. Tissue samples were available from 14 pts with evaluable response data. Alterations of genes in the PI3K pathway occurred in 5/8 (63%) pts with clinical benefit vs 1/6 (17%) pts without (p = 0.12). Conclusions: The CHK 1/2 inhibitor LY2606368 demonstrated an acceptable safety profile despite a relatively high rate of transient grade 4 neutropenia. Single-agent activity was observed in pretreated mSCC of the anus, a disease with a high unmet medical need. The MTD of 105 mg/m2 is confirmed as the recommended phase II dose. Clinical trial information: NCT01115790.
Large-scale identification of clinical and genetic predictors of motor progression in patients with newly diagnosed Parkinson's disease: a longitudinal cohort study and validation
Authors: Jeanne C Latourelle, Michael T Beste, Tiffany C Hadzi, Robert E Miller, Jacob N Oppenheim, Matthew P Valko, Diane M Wuest, Bruce W Church, Iya G Khalil, Boris Hayete, Charles S Venuto
Journal: The Lancet Neurology (2017)
Recombinant human IL-15 augments expression of complement restriction factors in human oral squamous carcinoma cells
Authors: Deborah A. Hopkins, Caterina Braun, Kristin Radzwill, Bruce Roberts, Srinivas Shankara
Journal: Cancer Research (2004)

4681   Traditionally IL-2 has been used as the cytokine of choice for the maintenance of antigen specific T cell proliferation  in vitro . However IL-2 and IL-15, which share the β and γ subunits of the IL-2 receptor but have private α chains to determine binding specificity, are both known to stimulate the proliferation of T cells  in vitro . These cytokines have both been shown to augment antitumor immunity and promote tumor regression in vivo. Additionally, IL-15 has been shown to enhance effector function and resistance to Fas induced apoptosis of T cells and TGFβ mediated immunosuppression. In this study, we wanted to compare the effect of various cytokines in the production of antigen specific T cells in vitro, in order to produce a better and more effectively educated T cell, a major component in the tools used for cancer immunotherapy. In order to access the immune response we utilize an  in vitro  T cell priming (IVP) technique, during which DCs from a naive healthy donor are transduced with adenoviral vector encoding tumor antigen, and then are placed in culture with autologous CD3+ T cells. Resulting T cells can then be analyzed by a number of methods to determine the potency of immune response to the antigen. Here we describe a comparison of IL-2, IL-15, and combination of IL-2/IL-7 as growth factors for T cells primed with tumor self antigen. Our data shows that culturing T cells in the presence of IL-15 while priming with tumor antigen results in a significant growth advantage when compared with IL-2. Within this growth advantage there is a significant shift from an equivalently mixed CD4+/CD8+ population (44%/42%) with IL-2 towards a population with a larger proportion of CD8+ T cells (>75%). Additionally when CD8+ T cells were isolated from each T cell population the cells raised with IL-15 present are more potent in cytolytic activity towards antigen positive tumor cells than are those raised with IL-2 present. These data suggest that IL-15 while possessing many of the same attributes as IL-2 may function better at promoting a successful cell mediated anti-tumor immune response.
Relationship Between Dietary Fat Composition and Colorectal Neoplasia
Authors: Elliot M. Berry, M.D., M.R.C.P., Joseph Zimmerman, M.D., Moshe Ligumsky, M.D.
Journal: JNCI Journal of the National Cancer Institute (1987)

Relationship Between Dietary Fat Composition and Colorectal Neoplasia Get access Elliot M. Berry, M.D., M.R.C.P., Elliot M. Berry, M.D., M.R.C.P. 1Department of Medicine B Hadassah University Hospital, P.O. 12000 Jerusalem, Israel Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph Zimmerman, M.D., Joseph Zimmerman, M.D. 2Department of Gastroenterology Hadassah University Hospital, P.O. 12000 Jerusalem, Israel Search for other works by this author on: Oxford Academic PubMed Google Scholar Moshe Ligumsky, M.D. Moshe Ligumsky, M.D. 2Department of Gastroenterology Hadassah University Hospital, P.O. 12000 Jerusalem, Israel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 78, Issue 2, February 1987, Pages 395–396, https://doi.org/10.1093/jnci/78.2.395-a Published: 01 February 1987
Prenatal Exposure to Nonpersistent Endocrine Disruptors and Behavior in Boys at 3 and 5 Years
Authors: Claire Philippat, Dorothy Nakiwala, Antonia M. Calafat, Jérémie Botton, Maria De Agostini, Barbara Heude, Rémy Slama
Journal: Environmental Health Perspectives (2017)

Background: Sex-specific associations have been reported between phthalates, bisphenol A (BPA), and child behavior. No data on large study populations are available for other phenols with possible endocrine-disrupting properties. Objectives: We aimed to study associations between prenatal exposure to phthalates and several phenols on behavior among male infants. Methods: We quantified 11 phthalate metabolites and nine phenols (four parabens, benzophenone-3, BPA, two dichlorophenols, triclosan) in spot urine samples collected during pregnancy among EDEN cohort mothers who delivered a boy. Mothers completed the Strength and Difficulties Questionnaire (SDQ) when their children were 3.1 (n=529) and 5.6 (n=464) y old. Results: BPA was positively associated with the relationship problems subscale at 3 y [incidence rate ratio (IRR): 1.11; 95% confidence interval (CI): 1.03, 1.20] and the hyperactivity–inattention subscale scores at 5 y (IRR: 1.08; 95% CI: 1.01, 1.14). Mono-n-butyl phthalate (MnBP) was positively associated with internalizing behavior, relationship problem, and emotional symptom scores at 3 y. Monobenzyl phthalate (MBzP) was positively associated with internalizing behavior and relationship problems scores at 3 y. After dichotomizing SDQ scores, triclosan tended to be positively associated with emotional symptom subscales at both 3 and 5 y. Conclusions: The observed associations between BPA, MnBP, and behavior in boys are consistent with previous findings. Further health impact assessment studies based on dose–response functions corrected for exposure misclassification are required to quantify the public health burden possibly entailed by such associations. https://doi.org/10.1289/EHP1314
Phase II clinical activity and tolerability of the SMAC-mimetic birinapant (TL32711) plus irinotecan in irinotecan-relapsed/refractory metastatic colorectal cancer.
Authors: Neil N. Senzer, Patricia LoRusso, Lainie P. Martin, Russell J. Schilder, Ravi K. Amaravadi, Kyriakos P. Papadopoulos, Zdenka E Segota, David Edward Weng, Martin Graham, Alex A. Adjei
Journal: Journal of Clinical Oncology (2013)

3621 Background: Birinapant (B) is a SMAC-mimetic that inhibits IAPs and has potent preclinical anti-tumor synergy combined with TNFa-inducing chemotherapies [i.e irinotecan (I)]. B and I combination is well-tolerated and has encouraging activity in a phase 1 study. This study tested B+I with an ascending dose strategy (ADS) of B to mitigate Bell’s palsy (BP) risk, an unusual and reversible side effect of SMAC mimetics. Methods: I at 350mg/m 2 IV q3weeks was administered with B weekly (2 of 3 weeks). The dose of B was titrated incrementally during Cycle 1: C1D1 at 5.6mg/m 2 and C1D8 at 11mg/m 2 for ADS. For Cycle 2 (C2) and ongoing treatment, the B dose was 22mg/m 2 or 35mg/m 2 , which were the MTD and DLT (BP) dose levels when combined with I from the Ph 1 study. Safety and clinical activity for KRAS mutant (KRAS-MT) and wild-type (KRAS-WT) were assessed in 3 cohorts: (1) at 22mg/m2 for CRC KRAS MT; (2) 22mg/m2 for CRC KRAS WT; (3) 35mg/m2 for CRC KRAS MT. Results: 51 patients (pts) with CRC had a median number of 4 prior regimens with 47 refractory/relapsed to irinotecan (92%). Tolerability was comparable to I alone. There were 2 PRs (4%), 27 SD (&gt;2 cycles; 53%, median 4.7 mo), 17 PD (33%), and 5 non- evaluable pts (9%) for an overall clinical benefit (CR+PR+SD) rate of 57%. Median progression-free survival (PFS) was 2.1 months, and 6 mo PFS was 20%. KRAS MT CRC with prior I had a median PFS of 2.9 mo and 6 mo PFS of 25% (n=20). KRAS WT CRC with prior I had a median PFS of 1.4 mo and 6 mo PFS of 17% (n=18). The ADS seemed to reduce BP risk. No BP events occurred among 40 pts (22mg/m 2 with ADS), compared to 1 of 7 pts (22mg/m2 without ADS). In the 35mg/m2 cohort, 1 BP event occurred among 12 pts (with ADS), compared to 3 of 6 (35mg/m2 without ADS). Conclusions: B + I demonstrated clinical benefit in pts refractory/relapsed to irinotecan, with greatest benefit in KRAS MT CRC. The ADS may provide a mitigation strategy for BP risk. Prior studies with I retreatment have showed no benefit in KRAS MT CRC. Comparable CRC pts with best supportive care have 6 mo PFS of 2%. Clinical activity supports the hypothesis for therapeutic synergy of B + I, with I as a TNFa-inducing agent. Further study of this combination is warranted. Clinical trial information: NCT01188499.
Effect of Nucleos(t)ide Analogue Therapy on Risk of Intrahepatic Cholangiocarcinoma in Patients With Chronic Hepatitis B
Authors: Teng-Yu Lee, Yao-Chun Hsu, Shi-Hang Yu, Jaw-Town Lin, Ming-Shiang Wu, Chun-Ying Wu
Journal: Clinical Gastroenterology and Hepatology (2017)
STREAM: A randomized discontinuation, blinded, placebo-controlled phase II study of sorafenib (S) treatment of chemonaïve patients (pts) with metastatic uveal melanoma (MUM).
Authors: Max E. Scheulen, Eckhart Kaempgen, Ulrich Keilholz, Lucie Heinzerling, Sebastian Ochsenreither, Annalena Abendroth, Ralf A. Hilger, Matthias Grubert, Axel Wetter, Nika Guberina, Sebastian Bauer, Gerold Schuler, Norbert Bornfeld, Martin H. Schuler, Heike Richly
Journal: Journal of Clinical Oncology (2017)

9511 Background: There is no established systemic treatment for pts with MUM. The STREAM study evaluated the efficacy of the oral multikinase inhibitor S in chemonaïve pts with MUM with the primary endpoint progression-free survival (PFS). Methods: During the initial 56d run-in period all pts received oral S 400 mg bid with concomitant monitoring by magnetic resonance imaging including diffusion weighted imaging (DWI-MRI). Pts with partial remission (PR) on d56 according to RECIST 1.1 were further treated with open-label S and monitored, pts with progressive disease (PD) were taken off study, and pts with stable disease (SD) were randomly assigned to blinded S or placebo (P) and were further monitored every 8 wks and unblinded in case of PD. Pts on S were taken off study and pts on P were offered S with further monitoring. Results: Altogether, 118 (79.2%) of 149 pts entering the run-in period were evaluable for response on d56. Two pts had PR (1.7%), 78 pts had SD (66.1%) and 38 pts had PD (32.2%), respectively. Median PFS from randomization was significantly longer with S (5.5 mths) than P (1.9 mths, HR = 0.527, p = 0.0079). S was readministered to 23 pts with PD under P (59.0%) with a median PFS of 2.0 mths (range 1.2-15.7 mths). Overall survival (OS) was not different between the S group (median 14.8 mths, range 3.7-38.3 mths) and the P group (median 14.4, range 3.3-37.3 mths). During the entire study there were 43 NCI-CTCAE grade 3 and 9 grade 4 adverse events requiring dose reduction of S to 200 mg bid or treatment discontinuation, respectively. No pt died from toxicity. The evaluation of the apparent diffusion coefficient (ADC) ratio derived from DWI-MRI in 47 pts of the run-in period showed a significant difference between pts with SD and pts with PD (p &lt; 0.05). Conclusions: The primary endpoint of STREAM was reached. S is clinically active and tolerable in first-line treatment of pts with MUM with an increase of median PFS from 1.9 mths for P to 5.5 mths for S (p = 0.0079). The median OS of 14.8 mths compares favorably with previous findings in pts with MUM. Besides morphological MRI features, ADC ratio may be used as an additional functional response criterion. Clinical trial information: NCT01377025.
Long-term Intra-articular Steroid Injections and Knee Cartilage
Authors: Pim A. J. Luijsterburg, Pieter K. Bos, Sita M. A. Bierma-Zeinstra
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Regorafenib (REG) versus trifluridine/tipiracil (TAS-102) as salvage-line in patients with metastatic colorectal cancer refractory to standard chemotherapies (REGOTAS): A propensity score analysis from a JSCCR multicenter observational study.
Authors: Shota Fukuoka, Toshikazu Moriwaki, Hiroya Taniguchi, Atsuo Takashima, Yosuke Kumekawa, Takeshi Kajiwara, Kentaro Yamazaki, Taito Esaki, Akitaka Makiyama, Tadamichi Denda, Yukimasa Hatachi, Takeshi Suto, Naotoshi Sugimoto, Kenji Katsumata, Toshiaki Ishikawa, Tomomi Kashiwada, Eiji Oki, Satoshi Yuki, Masahiko Gosho, Yasuhiro Shimada
Journal: Journal of Clinical Oncology (2017)

3540 Background: It is unclear which drug of REG or TAS-102 should be used earlier for the patients with metastatic colorectal cancer (mCRC) who have access to both drugs. This study investigated the comparison of the efficacy between REG and TAS-102 in patients with refractory to standard chemotherapies. Methods: The clinical data of patients who were treated with REG or TAS-102 among these drugs naive mCRC patients between Jun 2014 and Sep 2015 were retrospectively delivered from 24 institutions of Japanese Society for Cancer of the Colon and Rectum (JSCCR). The primary endpoint was overall survival (OS). Propensity score (PS) was calculated with a logistic regression, in which using baseline parameters were included. Two methods, adjusted and matched analysis, to take propensity score were used. The clinical outcomes were evaluated with Kaplan-Meier method and Cox models based on PS adjustment and matching. Results: Total of 589 patients were enrolled and 550 patients (223 patients in the REG group and 327 patients in the TAS-102 group) met criteria for inclusion in the analysis. The results from PS adjusted analyses showed that OS was similar between the two groups (HR of TAS-102 to REG, 0.96; 95% confidence interval, 0.78–1.18). There were also no statistically significant differences between two groups for progression-free survival (HR 0.94) and time to ECOG Performance status≥2 (HR 1.00), expect for time to treatment failure (HR 0.81; P = 0.025). In the subgroup analysis, REG showed favorable survival compared with TAS-102 in the age of &lt; 65 years patients and unfavorable survival in ≥65 years patients (P for interaction = 0.012). In the PS matched sample (174 patients in each group), the clinical outcomes were similar to the results of the PS adjusted analysis. Conclusions: Although REG and TAS-102 showed a similar efficacy in mCRC patients with refractory to standard chemotherapies, the choice of the drug by age might affect the survival. Supported by JSCCR. Clinical trial information: UMIN000020416
Long-Term Follow-Up of Elective Chronic Total Coronary Occlusion Angioplasty
Authors: Sudhakar George, James Cockburn, Tim C. Clayton, Peter Ludman, James Cotton, James Spratt, Simon Redwood, Mark de Belder, Adam de Belder, Jonathan Hill, Angela Hoye, Nick Palmer, Sudhir Rathore, Anthony Gershlick, Carlo Di Mario, David Hildick-Smith
Journal: Journal of the American College of Cardiology (2014)
Surfaceome profiling enables isolation of cancer-specific exosomal cargo in liquid biopsies from pancreatic cancer patients
Authors: J. Castillo, V. Bernard, F.A. San Lucas, K Allenson, M. Capello, D.U. Kim, P. Gascoyne, F.C. Mulu, B.M. Stephens, J. Huang, H. Wang, A.A. Momin, R.O. Jacamo, M. Katz, R. Wolff, M. Javle, G. Varadhachary, I.I. Wistuba, S. Hanash, A. Maitra, H. Alvarez
Journal: Annals of Oncology (2017)
Neonatal Thyrotoxicosis
Authors: Peter H Bisschop, A S Paul van Trotsenburg
Journal: New England Journal of Medicine (2014)

A 22-year-old woman was referred at 31 weeks of gestation for assessment of oligohydramnios. The fetal heart rate was 158 beats per minute. Ultrasonography was repeated every 2 weeks. At 35 weeks of gestation, intrauterine growth retardation was evident.
Human pluripotent stem cell–derived erythropoietin-producing cells ameliorate renal anemia in mice
Authors: Hirofumi Hitomi, Tomoko Kasahara, Naoko Katagiri, Azusa Hoshina, Shin-Ichi Mae, Maki Kotaka, Takafumi Toyohara, Asadur Rahman, Daisuke Nakano, Akira Niwa, Megumu K. Saito, Tatsutoshi Nakahata, Akira Nishiyama, Kenji Osafune
Journal: Science Translational Medicine (2017)

iPSC-derived cells can secrete functional erythropoietin in a physiological manner and ameliorate renal anemia in a mouse model.