tbuckley/cabot-search huggingface dataset:
CBIO-28NIX PROMOTES GLIOBLASTOMA CELL SURVIVAL UNDER STRESS THROUGH MITOPHAGY
Authors: Jinkyu Jung, Ying Zhang, Brian Williams, Jeremy Rich, Zhengping Zhuang, Deric Park
Journal: Neuro-Oncology (2015)

Nix (NIP3-like protein X, BNIP3L), a hypoxia-responsive member of the Bcl-2 family of proteins, is believed to play key roles in both hypoxia-mediated cell death and mitophagy. Because our previous work demonstrated that hypoxia, a potentially stressful condition, promotes preferential expansion of GBM stem-like cells in a HIF-1-dependent mechanism, we investigated Nix in GBM. We observed elevated levels of mitochondrial Nix and LC3B-II/I ratio in GBM tissues. Series of experiments revealed that Nix but not BNIP3, mediated hypoxia-induced mitophagy in an Nrf2 (critical regulator of the cellular antioxidant response)-dependent manner. Nix repression led to several striking observations: 1) Reversal of hypoxia-mediated GBM cell proliferation; 2) Down-regulation of both HIF-1α and HIF-2α; 3) Inhibition of Rheb and its downstream signaling; 4) Depletion of cellular ATP level; and 5) Decreased survival of animals in orthotopic xenograft GBM model. Both oncogenic and tumor suppressive actions of autophagy have been extensively discussed in the literature, supporting the notion that specific action is likely cell-type and context dependent. Our work suggests that Nix regulation of mitophagy is a critical mechanism of GBM cell survival particularly during stressful conditions. Such conclusion is further support by pronounced sensitivity of Nix depleted GBM cells to temozolomide and/or irradiation. Manipulation of the Nix pathway may provide novel therapeutic opportunities.
GM-CSF Mediates Mesenchymal–Epithelial Cross-talk in Pancreatic Cancer
Authors: Meghna Waghray, Malica Yalamanchili, Michele Dziubinski, Mina Zeinali, Marguerite Erkkinen, Huibin Yang, Kara A. Schradle, Sumithra Urs, Marina Pasca Di Magliano, Theodore H. Welling, Phillip L. Palmbos, Ethan V. Abel, Vaibhav Sahai, Sunitha Nagrath, Lidong Wang, Diane M. Simeone
Journal: Cancer Discovery (2016)

Pancreatic ductal adenocarcinoma (PDA) is characterized by a dense stroma consisting of a prevalence of activated fibroblasts whose functional contributions to pancreatic tumorigenesis remain incompletely understood. In this study, we provide the first identification and characterization of mesenchymal stem cells (MSC) within the human PDA microenvironment, highlighting the heterogeneity of the fibroblast population. Primary patient PDA samples and low-passage human pancreatic cancer-associated fibroblast cultures were found to contain a unique population of cancer-associated MSCs (CA-MSC). CA-MSCs markedly enhanced the growth, invasion, and metastatic potential of PDA cancer cells. CA-MSCs secreted the cytokine GM-CSF that was required for tumor cell proliferation, invasion, and transendothelial migration. Depletion of GM-CSF in CA-MSCs inhibited the ability of these cells to promote tumor cell growth and metastasis. Together, these data identify a population of MSCs within the tumor microenvironment that possesses a unique ability, through GM-CSF signaling, to promote PDA survival and metastasis.The role of stroma in pancreatic cancer is controversial. Here, we provide the first characterization of MSCs within the human PDA microenvironment and demonstrate that CA-MSCs promote tumorigenesis through the production of GM-CSF. These data identify a novel cytokine pathway that mediates mesenchymal-epithelial cross-talk and is amenable to therapeutic intervention. Cancer Discov; 6(8); 886-99. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 803.
Treatment of Head and Neck Cancer
Authors: Christopher M Nutting, Shreerang A Bhide, Kevin J Harrington
Journal: New England Journal of Medicine (2008)

To the Editor: In the report by Posner et al. (Oct. 25 issue)1 on the treatment of head and neck cancer, we question the authors’ implication that the 91-11 trial of the Radiation Therapy Oncology Group and Head and Neck Intergroup showed that cisplatin–fluorouracil (PF) induction followed by radiotherapy for laryngeal preservation is equivalent to or better than concomitant cisplatin and radiotherapy. The 91-11 trial was not designed to show equivalence.2 Both combinations resulted in better laryngectomy-free survival than did radiotherapy alone, but the composite end point does not account for a preserved larynx in patients whose death was not due to laryngeal cancer (over half the deaths). Rates of laryngeal preservation and locoregional control provide a much better assessment, and for both end points, the rates were significantly better with concomitant cisplatin and radiotherapy than with radiotherapy alone or PF induction followed by radiotherapy, whereas overall survival did not differ significantly.2,3 The results of the 91-11 trial do not justify the use of docetaxel–cisplatin–fluorouracil (TPF) sequential therapy for T3 and low-volume T4 laryngeal cancer. Arlene Forastiere, M.D.
A phase 2, multicenter study investigating ofatumumab and bendamustine combination in patients with untreated or relapsed CLL
Authors: Ian W. Flinn, Panayiotis Panayiotidis, Boris Afanasyev, Ann Janssens, Sebastian Grosicki, Wojciech Homenda, Lukas Smolej, Kazimierz Kuliczkowski, Michael Doubek, Natalia Domnikova, Sarah L. West, Chai‐Ni Chang, Alison M. Barker, Ira V. Gupta, Oliver J. Wright, Fritz Offner
Journal: American Journal of Hematology (2016)

The purpose of this study is to assess the safety and efficacy of the combination of ofatumumab and bendamustine in patients with previously untreated or relapsed chronic lymphocytic leukemia. Patients received IV ofatumumab (cycle 1: 300 mg day 1 and 1,000 mg day 8; cycles 2-6: 1,000 mg on day 1 every 28 days) and IV bendamustine 90 mg m(-2) (previously untreated) or 70 mg m(-2) (relapsed) on days 1 and 2 of each 28-day cycle, for up to 6 cycles. Forty-four previously untreated and 53 relapsed patients were enrolled. Median age was 62.5 years (previously untreated) and 68 years (relapsed); relapsed patients had received a median of 1 (range 1-11) prior therapy. The investigator-assessed overall response rate was 95% (43% complete response [CR]) for the previously untreated, and 74% (11% CR) for the relapsed patients. The regimen was well tolerated with 89% (previously untreated) and 85% (relapsed patients) receiving all 6 cycles. No unexpected toxicities were reported. Grade 3/4 events occurred in 57% of previously untreated, and 72% of relapsed patients. At ∼29 months' follow-up, the median progression-free survival (PFS) was not reached for the previously untreated population, and the 28-month PFS estimate was 72.3%. The median PFS for the relapsed population was 22.5 months (95% CI: 14.0-27.3 months). The combination of ofatumumab and bendamustine was well tolerated and effective in these previously untreated or relapsed populations. Am. J. Hematol. 91:900-906, 2016. © 2016 Wiley Periodicals, Inc.
The DSM-III-R personality disorders: an overview
Authors: T A Widiger, A Frances, R L Spitzer, J B Williams
Journal: American Journal of Psychiatry (1988)

The revision of DSM-III (DSM-III-R) includes substantial changes in the axis II personality disorders. The authors present and critically review these revisions and suggest directions for further research. The issues discussed include the multiaxial system, the use of a categorical rather than a dimensional format, the change from monothetic to polythetic criteria sets, the reduction in overlap among criteria sets, the decrease in the amount of unnecessary inferential clinical judgment required to make diagnoses, and the addition of two new personality disorders in an appendix. The criteria sets for many of the DSM-III personality disorders were also substantially revised in DSM-III-R. Changes in each of these are discussed in turn.
Blood Flow in the Renal Medulla
Authors: LAWRENCE S. LILIENFIELD, HERMAN C. MAGANZINI, MARK H. BAUER
Journal: Circulation Research (1961)

The accumulation of intra-arterially injected I 131 albumin in the papilla of the kidney was measured in a series of 33 anesthetized dogs producing hypertonic urine. Although the data were widely scattered, an estimate of the average rate of this accumulation during the first half-minute following the start of the infusion was made. From the data, the plasma perfusion rate in the papilla under the experimental conditions was calculated and appears to average 25 ml./100 Gm./min.
Myelin basic protein in CSF of children receiving intrathecal chemotherapy.
Authors: A Thyss
Journal: Journal of Clinical Oncology (1986)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1986.4.10.1569 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2428950 Myelin basic protein in CSF of children receiving intrathecal chemotherapy. A ThyssxA ThyssSearch for articles by this author https://doi.org/10.1200/JCO.1986.4.10.1569 PDF "Myelin basic protein in CSF of children receiving intrathecal chemotherapy.." Journal of Clinical Oncology, 4(10), p. 1569© 1986 by American Society of Clinical Oncology
Detection of Complement-Dependent Antibody to Tumor Cells in Sera of Strain-2 Guinea Pigs Cured of Their Tumors by BCG Treatment
Authors: Michael D. P. Boyle, Sarkis H. Ohanian, Tibor Borsos
Journal: JNCI Journal of the National Cancer Institute (1976)

Sera of strain-2 guinea pigs (cured of line-10 tumor by BCG therapy) were tested for complement-dependent, cytotoxic antibody. About 30% of the sera tested contained significant cytotoxic activity with the addition of human, but not syngeneic, complement. Using papain pretreated line-lO cells, we detected antibody in about 50% of the sera with syngeneic sera as the source of complement. Antibody to line-10 was also demonstrated in selected sera by indirect fluore,scence and the C1 fixation and transfer test.
Effect of Amp5q31 and Del12p13 on Survival of Patients with Multiple Myeloma Treated with Novel Agent-Based Regimens: A Single Center Experience on 172 Patients
Authors: Evangelos Terpos, Efstathios Kastritis, Despoina Iakovaki, Maria Gkotzamanidou, Magdalini Migkou, Georgia Bardi, Meletios Athanasios Dimopoulos
Journal: Blood (2011)
A High Throughput Exome Sequencing Approach To Analyse Events Within a Good Responder CML Patient Under Imatinib At Diagnosis and Under Remission
Authors: Anita Chacko, Shankarrao Patil, Atul Upadhayay, Deepak Arya, Ashwat Nagrajan, Rakesh Khatri, Sudhir Krishna, Ramanathan Sowdhamini, Cecil Ross, Rajesh Behl
Journal: Blood (2013)
Unsticky Neutrophils
Authors: Leonard H. Brubaker
Journal: New England Journal of Medicine (1974)

Nearly everyone knows that stickiness of platelets is essential to their function, but the importance of neutrophil stickiness may not be so well appreciated. Despite its long history of scientific observations, dating back to 1824,1 neutrophil stickiness has received relatively little attention. The recent scholarly review of phagocytosis (mostly about neutrophils) by Stossel2 in the Journal covered production, deployment, chemotaxis, recognition, ingestion, degranulation, peroxide formation, killing, and digestion, but it did not say much about variations in the sticky character of neutrophils. Thus, the article in this issue by MacGregor and his associates is welcome as a supplement to the . . .
Prediction of response to nortriptyline and phenelzine by platelet MAO activity
Authors: A Georgotas, R E McCue, E Friedman, T Cooper
Journal: American Journal of Psychiatry (1987)

Thirty-seven depressed patients over the age of 55 were treated for 5-7 weeks with either nortriptyline, a tricyclic antidepressant, or phenelzine, a monoamine oxidase (MAO) inhibitor. Patients' platelet MAO activity was measured following a drug washout period before treatment. Patients with higher MAO activity had a better response to treatment, regardless of which drug was used.
Four-year evaluation of a psychiatric clerkship: 1982-1986
Authors: L W Reiser, W H Sledge, M Edelson
Journal: American Journal of Psychiatry (1988)

The authors describe a psychiatric clerkship organized to achieve goals relevant to all medical students, regardless of their future specialty choice. The clerkship had been in place for 8 years in 1986, and standardized program evaluations were available for 4 years. A survey of the diverse clinical settings used for the clerkship showed that each had unique strengths and weaknesses but that each could meet the core goals of the clerkship, indicating that this clerkship design would also be feasible in a smaller department with any one or two of the settings available.
Myosin light chain phosphorylation, novel targets to repair a broken heart?
Authors: Danuta Szczesna-Cordary, Pieter P. de Tombe
Journal: Cardiovascular Research (2016)

This editorial refers to ‘Acute heart failure with cardiomyocyte atrophy induced in adult mice by ablation of cardiac myosin light chain kinase’, by M.T. Massengill et al ., pp. 34–43. 

This editorial refers to ‘Essential light chain S195 phosphorylation is required for cardiac adaptation under physical stress’, by L.-M. Scheid et al ., pp. 44–55. 

The process of ATP-dependent cyclic attachments and detachments of the myosin cross-bridges to actin-containing thin filaments forms the basis of muscle contraction.1 As such, the myosin cross-bridge is the molecular motor of the heart. It binds ATP and actin and myosin's lever arm region, supported by the regulatory light chain (RLC) and essential light chain (ELC) ( Figure 1A and B ), amplifies small conformational changes generated in the motor domain into the large movements needed to produce force and sarcomere shortening.2 As an EF-hand Ca2+-binding protein, the RLC contains a Ca2+–Mg2+ binding site that can be occupied by either Ca2+ or Mg2+, and a Ser15 phosphorylation site, a target for cardiac myosin light chain kinase (cMLCK) encoded by the MYLK3 gene. The ELC is also an EF-hand-like protein; however, cardiac muscle ELC has developmentally lost its ability to bind calcium. Proteomic analysis by the Van Eyk's group revealed that residue Ser195 of ELC can be phosphorylated in pharmacologically preconditioned cardiomyocytes, although no specific kinase responsible for Ser195-ELC phosphorylation has yet been identified.3 Two new articles, published in this issue of Cardiovascular Research by Massengill et al. 4 and Scheid et al. ,5 focus on the functional impacts of myosin RLC and ELC phosphorylation on heart function in a mouse model of …
Case 3-1974
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Adolph M. Hutter, Walter G. J. Putschar
Journal: New England Journal of Medicine (1974)

Presentation of CaseA 57-year-old man was admitted to the hospital because of painful swelling of the leg.The patient was known to have a heart murmur since birth, and his activity had always been limited by exertional dyspnea. Forty-one years before admission, at the age of 16 years, he came to this hospital for evaluation. Physical examination revealed a pectus excavatum deformity, with a harsh systolic murmur to the left of the sternum and a + + second heart sound to the left of the sternum. There was slight cyanosis of the digits, without clubbing. The hemoglobin was "90 . . .
High-needs hematology/oncology patients: A quality improvement project.
Authors: Swanee Tobin, Joyce Fenuta, Julie Kruchowski, Lisa K. Hicks
Journal: Journal of Clinical Oncology (2013)

197 Background: St. Michael’s Hospital (SMH) is an academic, inner-city hospital in Toronto, Canada. In the hematology/oncology (hem/onc) program, a small number of patients appeared to contribute disproportionately to hospital admissions and emergency department (ED) visits. We hypothesized that high needs hem/onc patients could be recognized early in their care and that ED visit and admission rates among these patients could be decreased through targeted interventions. Methods: Members of the hem/onc team were interviewed regarding characteristics, which they felt predicted higher needs and greater liklihood for hospital admission/ED visit. A list of high risk features was generated. ED visit and admission rates for a prospectively identified high needs cohort were compared to rates for the entire hem/onc clinic. An intervention targeting high needs hem/onc patients is on-going. Pre and post-intervention ED visit and admission rates will be compared. Results: Interviews with 3 nurses, 1 social worker, 1 discharge planner, and 4 physicians identified 10 factors that the hem/onc team believed were predictive of higher needs and subsequent higher ED visit and admission rates. Between December 1, 2012, and February 28, 2013, 42 high needs hem/onc out-patients were prospectively identified. The ED visit and admission rates for this cohort were retrospectively compared to those of the entire hem/onc clinic and found to be dramatically higher (Table). Begininng in June 2013, hem/onc patients identified as “high needs” were offered enrollment in a NP-based program offering telephone assessments following ED visits, hospital admissions or discharges. Assessment of the impact of this intervention is ongoing. Conclusions: It is possible to prospectively identify hem/onc patients who are at risk of higher than usual ED visit and admission rates. Identifying this population may provide an opportunity to decrease their ED visit and admission rates. An evaluation of an intervention targeting high needs hem/onc patients is ongoing. Preliminary data will be presented. [Table: see text]
Identification of a subset of human natural killer cells expressing high levels of programmed death 1: A phenotypic and functional characterization
Authors: Silvia Pesce, Marco Greppi, Giovanna Tabellini, Fabio Rampinelli, Silvia Parolini, Daniel Olive, Lorenzo Moretta, Alessandro Moretta, Emanuela Marcenaro
Journal: Journal of Allergy and Clinical Immunology (2016)
Incidental focal thyroid uptake on FDG positron emission tomographic scans may represent a second primary tumor.
Authors: CELSO DARIO RAMOS, ROLAND CHISIN, HENRY D. YEUNG, STEVE LARSON, HOMER MACAPINLAC
Journal: Clinical Nuclear Medicine (2001)

Purpose This article discusses the value of incidental thyroid uptake of fluorodeoxyglucose (FDG) on whole-body positron emission tomography (PET) scans performed in patients with cancer. This issue has been reported diversely in the literature. Materials and Methods Whole-body PET scans of four patients with cancer (two of them women; age, 49 to 78 years) in whom focal thyroid uptake was visualized and subsequently correlated with thyroid carcinoma based on cytologic or histopathologic data were reviewed. The clinical outcomes of these patients were analyzed retrospectively. Maximum and average standardized uptake values (SUVs) of thyroid accumulation were recalculated in all patients. Results Two of the four patients referred for FDG PET scans had lung adenocarcinomas, one had prostrate carcinoma, and one had an unknown primary tumor. Focal thyroid uptake was visualized, with maximum and average SUVs ranging from 3.7 and 2.3 to 53 and 34, respectively. These findings were correlated with cytologic (two patients) or histopathologic data (two patients) that indicated thyroid carcinoma. In two patients, their treatment was changed and total thyroidectomy was performed; in one of them the SUVs of the focal thyroid accumulation (maximum and average values of 7.9 and 4.8, respectively) were less than the cutoff values for thyroid cancer noted in the literature. The clinical condition of the other two patients did not permit additional investigation or treatment for thyroid carcinoma. Conclusion Increased focal thyroid uptake on whole-body FDG PET scans should not be overlooked, even when it is not marked, and should prompt further investigation to rule out cancer.
On Meddling
Authors: Lewis Thomas
Journal: New England Journal of Medicine (1976)

When you are confronted by any complicated living system, a seaboard city, for instance, or the United Nations, or even a hamster, with things about it that you're dissatisfied with and anxious to fix up, you cannot just step in and set about adjusting the parts that you particularly dislike. If you do, the whole thing may fall apart before your eyes. This realization is one of the sore discouragements of our century. Jay Forrester has shown it mathematically, with his computer models of urban societies in which any attempt to introduce helpful changes in the system, especially changes based . . .
Abstract P1-05-06: Essential role of notch-4/STAT3 signaling in epithelial-mesenchymal transition of tamoxifen-resistant human breast cancer
Authors: QT Bui, KW Kang
Journal: Cancer Research (2016)

Abstract Epithelial-mesenchymal transition (EMT) is process in which epithelial cells undergo unique morphologic changes characterized by a transition from epithelial cobblestone phenotype to elongated fibroblastic phenotype (mesenchymal phenotype) leading to increased motility and invasion. Our previous study demonstrated that tamoxifen (TAM)-resistant human breast cancer (TAMR-MCF-7) cells showed the increased expression of mesenchymal marker proteins compared to the parent MCF-7 cells. Notch plays a crucial role in the promotion of EMT during both development and tumor progression. Especially, Notch-1 and Notch-4 were reported as prognostic markers in human breast cancer. Here, we found that the basal expression and activity of Notch-4 were significantly increased in TAMR-MCF-7 cells compared to control MCF-7 cells. Suppression of Notch-4 by either Notch inhibitors or Notch-4 siRNA significantly attenuated the EMT signaling. Interestingly, long-term treatment with DAPT, a Notch inhibitor, eventually led to partial reversal of EMT by up-regulating E-cadherin expression. Activated or tyrosine-phosphorylated STAT3 (pYSTAT3) protein is supposed as a critical signaling molecule in the regulation of tumorigenesis and metastasis of cancer cells. We further found that TAMR-MCF-7 cells exhibited constitutive STAT3 phosphorylation. Suppression of Notch-4 activation attenuated the activated STAT3 elevation in TAMR-MCF-7 cells. We hypothesized that Notch-4 regulated EMT in TAMR-MCF-7 cells via STAT3 signaling. Intrasplenic injection model of liver metastases was performed using TAMR-MCF-7 cells. Mice were received subcutaneous injections daily with DAPT (10 mg/kg) formed smaller tumor size in spleens and showed less micrometastatic tumor burden in livers compared to group treated with vehicle. In conclusion, inhibition of Notch signaling may have efficacy in the treatment of breast cancer metastasis. Citation Format: Bui QT, Kang KW. Essential role of notch-4/STAT3 signaling in epithelial-mesenchymal transition of tamoxifen-resistant human breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-05-06.