tbuckley/cabot-search huggingface dataset:
Greater substrate activity of 4’-thio-arabinofuranosylcytosine (T-araC) 5’-monophosphate (T-araCMP) with UMP/CMP kinase as a likely factor for the longer intracellular retention of its triphosphate
Authors: Hitoshi Someya, William B. Parker
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

4104 

T-araC is a new cytosine analog that exhibits excellent in vivo antitumor activity against a variety of human solid tumor xenografts in mice. Our research goal is to elucidate the reason why T-araC shows profound difference in anti-solid tumor activity from arabinofuranosylcytosine (araC) in spite of the structural similarity of these compounds. Our previous studies indicated that there was a substantial difference in intracellular retention time between araC 5’-triphosphate (araCTP) and T-araC 5’-triphosphate (T-araCTP) in solid tumor cells, which correlated with the difference in cytotoxicity between araC and T-araC. In the current studies, we have studied the enzymes involved in nucleotide degradation to determine the reason why T-araCTP has a longer retention time than araCTP in HCT-116 (human colon cancer) cells. Because T-araC and T-araCMP are poorer substrates for Cyd deaminase and dCMP deaminase than araC and araC 5’-monophosphate (araCMP), respectively, we determined the intracellular half-life of araCTP in the presence of deoxytetrahydrouridine (a potent inhibitor of both deaminases). However, inhibition of these deaminases did not affect the retention time of araCTP, which indicated that the differences between araC and T-araC as a substrate for these deaminases were not responsible for the difference in retention time between araCTP and T-araCTP. The retention time of araCTP also did not change in the presence of aphidicolin (a potent inhibitor of DNA synthesis), which indicated that DNA incorporation/removal was also not rate-limiting for araCTP degradation. Moreover, the rates of disappearance of the triphosphates and monophosphates of araC and T-araC in a crude extract from HCT-116 cells were similar, which indicated that the enzymes responsible for dephosphorylation of araC or T-araC mono- and tri-phosphates also did not discriminate between these two compounds. However, when investigating the monophosphate degradation using ATP as a stimulator, we discovered that the rate of phosphorylation of T-araCMP was much greater than that of araCMP. Using crude extracts from HCT-116 and CEM (human leukemia) cells, the rate of phosphorylation of T-araCMP was comparable to that of CMP, which is a natural substrate of UMP/CMP kinase, and was about 10-fold greater than that of araCMP. These results suggested that the 10-fold greater activity of T-araCMP with UMP/CMP kinase was responsible for the 10-fold greater half-life of T-araCTP in solid tumor cells. When T-araCTP was degraded to T-araCMP there was a greater chance that it would be rephosphorylated by UMP/CMP kinase (thus maintaining triphosphate pool), whereas with araCMP more compound would be dephosphorylated or deaminated. This work was supported by NIH grant # CA 34200.
Development and Validation of an Inflammatory Bowel Diseases Monitoring Index for Use With Mobile Health Technologies
Authors: Welmoed K. Van Deen, Andrea E. van der Meulen-de Jong, Nimisha K. Parekh, Ellen Kane, Aria Zand, Courtney A. DiNicola, Laurin Hall, Elizabeth K. Inserra, Jennifer M. Choi, Christina Y. Ha, Eric Esrailian, Martijn G.H. van Oijen, Daniel W. Hommes
Journal: Clinical Gastroenterology and Hepatology (2015)
Oncologic Care and Pathology Resources in Africa: Survey and Recommendations
Authors: Ann M. Nelson, Danny A. Milner, Timothy R. Rebbeck, Yawale Iliyasu
Journal: Journal of Clinical Oncology (2015)

The connection of a clinician who identifies a patient with signs and symptoms of malignancy to an oncologist who has the tools to treat a patient's cancer requires a diagnostic pathology laboratory to receive, process, and diagnose the tumor. Without an accurate classification, nothing is known of diagnosis, prognosis, or treatment by the clinical team, and most important, the patient is left scared, confused, and without hope. The vast majority of deaths from malignancies occur in sub-Saharan Africa primarily as a result of lack of public awareness of cancer and how it is diagnosed and treated in the setting of a severe lack of resources (physical and personnel) to actually diagnose tumors. To correct this massive health disparity, a plan of action is required across the continent of Africa to bring diagnostic medicine into the modern era and connect patients with the care they desperately need. We performed a survey of resources in Africa for tissue diagnosis of cancer and asked quantitative questions about tools, personnel, and utilization. We identified a strong correlation between pathology staffing and capacity to provide pathology services. On the basis of this survey and through a congress of concerned pathologists, we propose strategies that will catapult the continent into an era of high-quality pathology services with resultant improvement in cancer outcomes.
Profile of Sensitization to Sunflower Seedin a Large Population Highly Exposed
Authors: María Luisa Macias Ramirez, Ana Aranda, Francisca Gomez, Natalia Blanca-López, Elena Seoane, Gabriela Canto, Jose Luis Rodriguez-Bada, Leticia Tordesillas, Araceli Diaz Perales, Miguel Blanca
Journal: Journal of Allergy and Clinical Immunology (2013)
Hirschsprung’s disease, Down syndrome, and missing heritability: too much collagen slows migration
Authors: Robert O. Heuckeroth
Journal: Journal of Clinical Investigation (2015)

Hirschsprung's disease (HSCR) causes functional intestinal obstruction due to the absence of the enteric nervous system (ENS) in the distal bowel and is usually diagnosed shortly after birth or during childhood. While several genetic and nongenetic factors have been linked to HSCR, the underlying mechanisms that prevent ENS precursors from colonizing distal bowel during fetal development are not completely understood in many affected children. In this issue of the JCI, Soret and colleagues identify a new mechanism that causes HSCR-like disease in mice and involves deposition of excess collagen VI in the intestine by migrating ENS precursors as they colonize fetal bowel. Remarkably, their findings may explain some of the so-called missing heritability of HSCR and suggest a mechanism for increased HSCR incidence in children with Down syndrome (trisomy 21).
Surgical Management of Tumors that produce Gastrointestinal Hormones
Authors: C M Townsend, J C Thompson
Journal: Annual Review of Medicine (1985)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Prenatal Sex Hormones and the Developing Brain: Effects on Psychosexual Differentiation and Cognitive Function
Authors: A A Ehrhardt, H F L Meyer-Bahlburg
Journal: Annual Review of Medicine (1979)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
How Do Cytotoxic Lymphocytes Kill Cancer Cells?
Authors: Luis Martínez-Lostao, Alberto Anel, Julián Pardo
Journal: Clinical Cancer Research (2015)

In the past few years, cancer immunotherapy has emerged as a safe and effective alternative for treatment of cancers that do not respond to classical treatments, including those types with high aggressiveness. New immune modulators, such as cytokines, blockers of CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) and PD-1(programmed cell death protein 1)/PD-L1 (programmed death-ligand 1), and interaction or adoptive cell therapy, have been developed and approved to treat solid and hematologic carcinomas. In these scenarios, cytotoxic lymphocytes (CL), mainly cytotoxic T cells (Tc) and natural killer (NK) cells, are ultimately responsible for killing the cancer cells and eradicating the tumor. Extensive studies have been conducted to assess how Tc and NK cells get activated and recognize the cancer cell. In contrast, few studies have focused on the effector molecules used by CLs to kill cancer cells during cancer immunosurveillance and immunotherapy. In this article, the two main pathways involved in CL-mediated tumor cell death, granule exocytosis (perforin and granzymes) and death ligands, are briefly introduced, followed by a critical discussion of the molecules involved in cell death during cancer immunosurveillance and immunotherapy. This discussion also covers unexpected consequences of proinflammatory and survival effects of granzymes and death ligands and recent experimental evidence indicating that perforin and granzymes of CLs can activate nonapoptotic pathways of cell death, overcoming apoptosis defects and chemoresistance. The consequences of apoptosis versus other modalities of cell death for an effective treatment of cancer by modulating the patient immune system are also briefly discussed. See all articles in this CCR Focus section, "Cell Death and Cancer Therapy."
12-Month Outcome of Patients With Bipolar Disorder Following Hospitalization for a Manic or Mixed Episode
Authors: P E Keck, S L McElroy, S M Strakowski, S A West, K W Sax, J M Hawkins, M L Bourne, P Haggard
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: The authors studied the 12-month course of illness following hospitalization for a manic or mixed episode of bipolar disorder to identify potential outcome predictors. METHOD: They recruited 134 patients with DSM-III-R bipolar disorder who were consecutively admitted for the treatment of a manic or mixed episode. Diagnostic, symptomatic, and functional evaluations were obtained at the index hospitalization. Patients were reevaluated at 2, 6, and 12 months after discharge to assess syndromic, symptomatic, and functional outcome. Factors associated with outcome were identified by using multivariate analyses. RESULTS: During the 12-month follow-up period, there were no significant differences in outcome between patients with manic compared with mixed bipolar disorder. Although syndromic recovery occurred in 48% of the overall group, symptomatic recovery occurred in only 26% and functional recovery in only 24%. Predictors of syndromic recovery included shorter duration of illness and full treatment compliance. Medication treatment compliance was inversely associated with the presence of comorbid substance use disorders. Symptomatic and functional recovery occurred more rapidly and in a greater percentage of patients from higher social classes. CONCLUSIONS: A minority of patients with bipolar disorder achieved a favorable outcome in the year following hospitalization for a manic or mixed episode. Shorter duration of illness, higher social class, and treatment compliance were associated with higher rates of recovery and more rapid recovery.
Carbohydrate‐Conjugated Hollow Oblate Mesoporous Silica Nanoparticles as Nanoantibiotics to Target Mycobacteria
Authors: Nanjing Hao, Xuan Chen, Seaho Jeon, Mingdi Yan
Journal: Advanced Healthcare Materials (2015)

Engineering nanomaterials with enhanced antibacterial activities remains a critical and practical challenge. Hollow oblate mesoporous silica nanoparticles (HOMSNs) are synthesized by a simple protocol of ammonia hydrothermal treatment of oblate mesoporous silica nanoparticles prepared using dibenzyl ether as a cosolvent. When conjugated with trehalose as the targeting ligand, the antibiotic-encapsulated HOMSNs exhibit high binding affinity and antibacterial efficacy toward mycobacteria. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Randomized Multicenter Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil (DCF) Versus DCF Plus Growth Factor Support in Patients With Metastatic Gastric Adenocarcinoma: A Study of the US Gastric Cancer Consortium
Authors: Manish A. Shah, Yelena Y. Janjigian, Ronald Stoller, Stephen Shibata, Margaret Kemeny, Smitha Krishnamurthi, Yungpo Bernard Su, Allyson Ocean, Marinela Capanu, Bhoomi Mehrotra, Paul Ritch, Charles Henderson, David P. Kelsen
Journal: Journal of Clinical Oncology (2015)

Purpose Docetaxel, cisplatin, and fluorouracil (DCF) is a standard first-line three-drug chemotherapy regimen for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma and is associated with significant toxicity. We examined the safety and efficacy of a modified DCF (mDCF) regimen in a randomized multicenter phase II study. Patients and Methods Previously untreated patients with metastatic gastric or GEJ adenocarcinoma were randomly assigned to receive either mDCF (fluorouracil 2,000 mg/m 2 intravenously [IV] over 48 hours, docetaxel 40 mg/m 2 IV on day 1, cisplatin 40 mg/m 2 IV on day 3, every 2 weeks) or parent DCF (docetaxel 75 mg/m 2 , cisplatin 75 mg/m 2 , and fluorouracil 750 mg/m 2 IV over 5 days with granulocyte colony-stimulating factor, every 3 weeks). The study had 90% power to differentiate between 6-month progression-free survival of 26% and 43%, with type I and II error rates of 10% each. An early stopping rule for toxicity was included, defined as grade 3 to 4 adverse event rate &gt; 70% in the first 3 months. Results From November 2006 to June 2010, 85 evaluable patients were enrolled (male, n = 61; female, n = 24; median age, 58 years; Karnofsky performance status, 90%; GEJ, n = 28; gastric, 57). mDCF (n = 54) toxicity rates included 54% grade 3 to 4 toxicity (22% hospitalized) within the first 3 months and 76% grade 3 to 4 toxicity over the course of treatment. The DCF arm (n = 31) closed early because of toxicity, with rates of 71% grade 3 to 4 toxicity (52% hospitalized) within 3 months and 90% grade 3 to 4 toxicity over the course of treatment. Six-month PFS was 63% (95% CI, 48% to 75%) for mDCF and 53% (95% CI, 34% to 69%) for DCF. Median overall survival was improved for mDCF (18.8 v 12.6 months; P = .007). Conclusion mDCF is less toxic than parent DCF, even when supported with growth factors, and is associated with improved efficacy. mDCF should be considered a standard first-line option for patients with metastatic gastric or GEJ adenocarcinoma.
Response to Letters Regarding Article, “Invasive Evaluation of Patients With Angina in the Absence of Obstructive Coronary Artery Disease”
Authors: Jennifer A. Tremmel, William F. Fearon, Bong-Ki Lee, Hong-Seok Lim, Andy S. Yong, Ryotaro Yamada, Shigemitsu Tanaka, David P. Lee, Alan C. Yeung
Journal: Circulation (2015)
Oxprenolol in the treatment of anxiety due to environmental stress
Authors: W P McMillin
Journal: American Journal of Psychiatry (1975)

The author conducted two trial studies to evaluate the use of oxprenolol in the treatment of symptoms resulting from environmental stress. Results indicated that on a three-times-a-day regimen, 80 mg of oxprenolol was superior to 20 mg of oxprenolol and equally as effective as 5 mg of diazepam. The author discusses the benefit of beta-blocking drugs and points to the need for further studies.
Orchiectomy alone in clinical stage I nonseminomatous testis cancer: a critical appraisal.
Authors: G Pizzocaro, F Zanoni, A Milani, R Salvioni, L Piva, S Pilotti, E Bombardieri, J D Tesoro-Tess, R Musumeci
Journal: Journal of Clinical Oncology (1986)

Sixty-two consecutive patients with clinical stage I nonseminomatous testicular cancer were entered into a prospective study to receive no treatment after orchiectomy until clinical evidence of recurrent disease. Of 59 evaluable cases, 41 (69.5%) remained continuously disease free for a median duration of 30 months (range, 18 to 46 months), and evidence of metastatic disease developed in 18 patients (30.5%) from 2 to 36 months after orchiectomy. The median disease-free interval for relapsing patients was 6 months. Retroperitoneal metastases developed in ten patients; seven patients had pulmonary metastases, and one patient had progressive elevation of the serum alpha-fetoprotein level. Relapses were significantly more frequent in patients with either embryonal carcinoma, infiltrating testicular cancer (pT greater than 1), peritumoral vascular invasion, or in those who underwent transscrotal biopsy. One patient with relapse refused salvage therapy and died. The remaining 17 patients have been rendered disease free with cisplatin combination chemotherapy and/or surgery. However, two patients showed further recurrence, with one in the lung and the other one also in the retroperitoneal nodes. In our opinion, surveillance following orchiectomy will provide useful information in clinical stage I nonseminomatous testicular cancer, but it is a difficult study. For the time being, it should be restricted to specialized centers only. In the meanwhile, retroperitoneal lymphadenectomy remains the standard treatment.
Postnatal Development of Vision in Human and Nonhuman Primates
Authors: Ronald G. Boothe, Velma Dobson, Davida Y. Teller
Journal: Annual Review of Neuroscience (1985)

In this chapter we summarize the growing literature on the optical , anatomical, physiological, and behavioral development of vision in human and nonhuman primates. The literature in this area is new and diverse, and to our knowledge it has not been previously reviewed as a whole . Emphasis is on postnatal development, in both its normal and its most common abnormal forms. All monkeys in the studies reviewed were Old World monkeys . References to the large body o f developmental studies o n nonprimate spe­ cies have been omitted (for reviews see Grobstein & Chow 1976, Tees 1976, Movshon & Van Sluyters 1981, Sherman & Spear 1982, Mitchell & Timney 1984). We have also omitted a large body of literature on embryology and prenatal anatomical development (see Rakic & Goldman-Rakic 1982, van Hof-van Duin & Mohn 1984). Of necessity, extended discussions of theoretical issues are precluded. Extended works on the topic of visual development can be found in Banks & Salapatek (1983), Aslin et al (1981), and the October 1983 issue of Behavioural Brain Research. A major reason for studying the development of vision in monkeys is to establish and use the monkey as a model for studying normal and abnormal human visual development. Many of the behavioral and anatomical studies reviewed below suggest major similarities of development, with rough parity at birth, and development proceeding about four times faster in Old World monkey infants than in human infants. To emphasize this 4: 1 conversion factor
Laminin-332 sustains chemoresistance and quiescence as part of the human hepatic cancer stem cell niche
Authors: Olivier Govaere, Jasper Wouters, Michaela Petz, Yves-Paul Vandewynckel, Kathleen Van den Eynde, Anke Van den broeck, Stefaan Verhulst, Laurent Dollé, Lies Gremeaux, An Ceulemans, Frederik Nevens, Leo A. van Grunsven, Baki Topal, Hugo Vankelecom, Gianluigi Giannelli, Hans Van Vlierberghe, Wolfgang Mikulits, Mina Komuta, Tania Roskams
Journal: Journal of Hepatology (2015)

Cancer stem cells (CSCs) are thought to be persistent in tumours due to their chemoresistance and to cause relapse and metastasis. Hepatic carcinomas displaying hepatic progenitor cell (HPC) features have been associated with a poor prognosis, though it remains unclear how CSCs relate to these different histological subtypes.Candidate CSCs were isolated using the side population (SP) technique from primary tissue samples diagnosed as keratin(K)19-negative or -positive hepatocellular carcinoma (HCC) or as combined hepatocellular/cholangiocarcinoma and analysed for gene and protein expression. The effect of laminin-332 was analysed in vitro by using HCC cell lines and in vivo using a xenograft mouse model.The size of the SP correlated with the degree of HPC features found in human hepatic cancer, and also showed an elevated mRNA expression of biliary/HPC markers and the extracellular matrix marker LAMC2, the gene encoding the laminin γ2-chain. Immunopositivity for the γ2-chain of laminin-332 was seen in the extracellular matrix surrounding small HPC-like tumour cells with a low proliferation rate. In vitro, laminin-332 increased K19 expression, phosphorylated mTOR and decreased phospho-histone H3 expression, indicating reduced cell mitosis. The effect of laminin-332 was enhanced upon mTORC1 inhibition and diminished when inhibiting mTORC1+C2. Resistance to doxorubicin and sorafenib treatment, and the SP fraction increased in the coated condition. In vivo, laminin-332 reduced tumour growth and sustained K19 expression.In this study we identified a prominent role for laminin-332 as part of the specialised CSC niche in maintaining and supporting cell 'stemness', which leads to chemoresistance and quiescence.
Quality-of-Life Analysis of the German Prospective Multicentre Trial of Single-cycle Adjuvant BEP Versus Retroperitoneal Lymph Node Dissection in Clinical Stage I Nonseminomatous Germ Cell Tumours
Authors: Hans-Henning Flechtner, Florian Fischer, Peter Albers, Michael Hartmann, Roswitha Siener
Journal: European Urology (2015)
Well-being Programs for Physicians and the Role of the “Doctors' Mess”
Authors: Dipesh P. Gopal, Charlotte Lee
Journal: JAMA Surgery (2015)

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Trophic Interactions in Neurogenesis: A Personal Historical Account
Authors: Viktor Hamburger
Journal: Annual Review of Neuroscience (1980)

Instead of introducing the topics in developmental neurobiology reviewed in this volume, I decided to focus on one issue that has intrigued me for more than half a century and provide a historical account by an eyewitness of the analysis of a limited but important issue that unfolded gradually and ramified unexpectedly. The story illustrates a particular style of scientific pursuit in biology and the inexorable historical continuity of the scientific process, the vision of which we often lose.