tbuckley/cabot-search huggingface dataset:
Abstract 4420: Matriptase-mediated proteolytic regulation of biological activity and spatial distribution of PDGF-D
Authors: Wei Huang, Hyeong-Reh C. Kim
Journal: Cancer Research (2014)

Abstract The oncogenic roles of platelet-derived growth factor D (PDGF-D) and its proteolytic activator, matriptase, have been strongly implicated in human prostate cancer. The latent full-length PDGF-D consists of N-terminal CUB domain, C-terminal growth factor domain, and hinge region in between. Matriptase processes the full-length PDGF-D dimer (FL-D) into PDGF-D growth factor domain dimer (GFD-D) in a step-wise manner, involving generation of hemidimer (HD), which is an intermediate product containing one full-length PDGF-D subunit and one growth factor domain subunit. In this study, we showed that HD acts as a dominant-negative ligand of PDGF/PDGFR signaling in fibroblasts whereas it has its own unique function in pre-osteoclasts. The regulation of PDGF-D's activity by matriptase is biphasic as demonstrated by the event that active PDGF-D GFD-D can be further cleaved into a smaller and yet inactive form if the enzymatic action of matriptase persists. By mutagenesis analyses, we identified amino acid residues R340R341GR343A at the C-terminus of PDGF-D growth factor domain to be the matriptase cleavage site through which PDGF-D is inactivated. Based on the sequence analysis in comparison with the published crystal structure of PDGF-B, we suggest that R340R341GR343A is within the loop III of PDGF-D growth factor domain, a critical domain for its binding to the PDGF receptor. When the positively charged arginine residues of R340R341GR343A were mutated to alanine residues, PDGF-D GFD-D lost its biological activity in activating β-PDGFR. Further, we found that proteolytic processing of latent PDGF-D to remove CUB domain and hinge region is tightly linked with the storage of PDGF-D GFD-D within extracellular matrix (ECM) in vitro. These results indicate the increased affinity to the ECM from FL-D, HD, to GFD-D and also suggest that CUB domain and hinge region of PDGF-D prevent the sequestration of PDGF-D in ECM. Interestingly, the matriptase cleavage site R340R341GR343A within the growth factor domain is also critical for PDGF-D association with ECM. Taken together, the present study reports structural elements crucial to the biologically function of PDGF-D and its association with ECM, suggesting that proteolytic processing is a crucial mechanism for PDGF-D to establish its tissue gradient. Citation Format: Wei Huang, Hyeong-Reh C. Kim. Matriptase-mediated proteolytic regulation of biological activity and spatial distribution of PDGF-D. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4420. doi:10.1158/1538-7445.AM2014-4420
Abstract 9594: Case Report of Vasopressin Induced Hyponatremia in a Patient With Pulmonary Hypertension, Hypotension and Sepsis
Authors: Andrew Peters, Yevgeniy Brailovsky, Vladimir Lakhter, Paul Forfia
Journal: Circulation (2014)

Introduction: Vasopressin induced hyponatremia is a rare occurrence that can pose a diagnostic dilemma. Vasopressin is commonly used in the setting of septic shock as the endogenous stores of vasopressin are depleted. On the contrary, patients with heart failure exhibit elevated levels of endogenous vasopressin, which contributes to water retention and hyponatremia. Clinical Vignette: A 55 year-old woman with chronic thromboembolic pulmonary hypertension, persistent pulmonary hypertension (PH) and right heart failure 13 days status post pulmonary thromboendarterectomy was transferred to the intensive care unit for hypoxic respiratory failure and presumed septic shock. She was febrile, tachypneic, tachycardic and in respiratory distress. Examination revealed an elevated jugular venous pressure and a right ventricular heave. Labs were notable for a leukocytosis and a mixed venous oxygen saturation of 51% (hemoglobin 10gm/dL). A transthoracic echocardiogram demonstrated a normal left ventricular ejection fra...
Depressions in the Activity of Liver Catalase in Mice Injected with Homogenates of Normal Mouse Spleen&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Eugene D. Day, Frederick C. Gabrielson, Jason B. Lipkind
Journal: JNCI Journal of the National Cancer Institute (1954)

Journal Article Depressions in the Activity of Liver Catalase in Mice Injected with Homogenates of Normal Mouse Spleen Get access Eugene D. Day, Eugene D. Day Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine, and Brandeis University, Waltham, Mass. Search for other works by this author on: Oxford Academic PubMed Google Scholar Frederick C. Gabrielson, Frederick C. Gabrielson Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine, and Brandeis University, Waltham, Mass. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jason B. Lipkind Jason B. Lipkind Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine, and Brandeis University, Waltham, Mass. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 2, October 1954, Pages 239–252, https://doi.org/10.1093/jnci/15.2.239 Published: 01 October 1954 Article history Received: 02 April 1954 Published: 01 October 1954
"Promiscuous" Anticancer Drugs That Hit Multiple Targets May Thwart Resistance
Authors: Tracy Hampton
Journal: JAMA (2004)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
"No" vote frees pound250m
Authors: Z. Kmietowicz
Journal: BMJ (2002)

The health secretary, Alan Milburn, vowed last week to press ahead with reforms in the health service and to use money promised in the consultants' contract to buy more of doctors' time for the NHS.

Speaking in front of the health select committee, Mr Milburn told ministers that the £250m ($400m;€390m) promised in the proposed contract for consultants and “liberated” by the doctors' rejection of the contract could now be used to “incentivise” doctors to do more work for the NHS.

After expressing disappointment that the long negotiated contract …
Salvage lung resection for local recurrence after stereotactic body radiotherapy for primary and metastatic lung cancers
Authors: Takuya Terashi, Hiroshi Hamakawa, Shinya Neri, Ei Miyamoto, Keisuke Tomii, Nobuyuki Katakami, Masaki Kokubo, Yutaka Takahashi
Journal: European Respiratory Journal (2011)

Introduction:  Stereotactic body radiotherapy (SBRT) has been proposed as an alternative to surgical resection for primary and metastatic lung cancers, for patients under inoperable condition based on poor lung function and/or senility. Sometimes, such patients refuse surgery and chose SBRT for the first treatment as a less invasive therapeutic option. However, surgical outcomes for local recurrence after SBRT were still unclear.   Methods:  To further understand the indication for salvage lung resection, we retrospectively reviewed 9 patients (3 with stageInon-small cell lung cancer and 6 with metastatic lung tumors) who underwent salvage surgical resection for local recurrence after SBRT.   Results:  Of the 9 patients, 7 underwent lobectomy, and the remaining 2 did bilobectomy and segmentectomy, respectively. 2 with metastatic lung tumors had pleural adhesion resulted from SBRT-related fibrosis. However, there was no case in which SBRT made surgical procedure impossible. Retrospectively considering the course after SBRT, once all 9 irradiated tumors resulted in disease progression, they grew in size rapidly.   Conclusions:  We have treated all patients without major technical difficulties by SBRT-related change. SBRT did not close the door to perform salvage surgical resection, and surgical resection might be feasible for local recurrence after SBRT. However, close follow-ups are mandatory for patients treated with SBRT because tumor regrowth after SBRT is thought to occur at a rapid rate. And if patients are medically fit for surgery as the first line treatment, the use of SBRT should not be decided by only reason of its less invasiveness.
The MOGE(S) Classification for a Phenotype–Genotype Nomenclature of Cardiomyopathy
Authors: Eloisa Arbustini, Navneet Narula, G. William Dec, K. Srinath Reddy, Barry Greenberg, Sudhir Kushwaha, Thomas Marwick, Sean Pinney, Riccardo Bellazzi, Valentina Favalli, Christopher Kramer, Robert Roberts, William A. Zoghbi, Robert Bonow, Luigi Tavazzi, Valentin Fuster, Jagat Narula
Journal: Journal of the American College of Cardiology (2013)
The Task of Medicine: Dialogue at Wickenburg.
Authors: Kerr L. White, J. Kaiser, George Engel
Journal: Annals of Internal Medicine (1988)

This book is  summary byDr Kerr L. White of  4-day conference sponsored by the Kaiser Foundation at which the future of medicine and medical education was discussed in depth. The conference's point of departure, actually its focus, was  monograph by Charles E. Odegaard, former president of the University of Washington, entitled Dear Doctor.1 Additionally, the conference members were given a series of commissioned papers and published reprints, many (all?) of which are included in the appendix to this book. There
A Review of: “Sheldon Krimsky and Peter Shorett (eds.), Rights and Liberties in the Biotech Age: Why We Need a Genetic Bill of Rights.”
Authors: Judith F. Daar
Journal: The American Journal of Bioethics (2006)

"A Review of: “Sheldon Krimsky and Peter Shorett (eds.), Rights and Liberties in the Biotech Age: Why We Need a Genetic Bill of Rights.”." , 6(2), pp. 92–93
Abstract 829: Prevalence of Cardiac Dysfunction in the Population: Results From the Community-Based Gutenberg-Heart Study
Authors: Philipp S Wild, Christoph R Sinning, Sandra Wilde, Andreas Schulz, Francisco Ojeda, Renate B Schnabel, Tanja Zeller, Till Keller, Edith Lubos, Maria Blettner, Karl J Lackner, Thomas F Munzel, Stefan Blankenberg
Journal: Circulation (2009)
Oncogenic pathways in breast cancer downstream of Pten
Authors: Rajwinder Lehal, Ming-Sound Tsao, Tak W. Mak, Eldad Zacksenhaus
Journal: Cancer Research (2006)

3987   The tumor suppressor protein Pten is commonly inactivated in human malignancies, including breast cancer. Pten has lipid phosphatase activity that antagonizes the function of PI3K and affects the PKB pathway. Comparative studies on breast cancer mouse models, MMTV-Wnt1 and MMTV-neu tumors show induction of both cyclinD1 and D2 in MMTV-Wnt1 tumors, but not in MMTV-neu tumors (Yu et al., Nature, 2001). Accordingly, MMTV-Wnt1, but not MMTV-neu tumor development is independent of cyclinD1. Li et. al. (2003) has shown that MMTV-Wnt1 tumors consists of both myo- and luminal- epithelial cells. These tumors also exhibit an expansion of Sca-1 and keratin 6 positive cell population suggesting stem cell origins of these tumors. On the other hand, MMTV-neu tumors do not possess these properties. To elucidate the oncogenic pathways downstream of Pten in breast cancer and the role of D-type cyclins in cancer progression, We are analyzing mouse mammary tumors in conditionally knock-out Wap-Cre:Ptenf/f mice. Preliminary data suggest that both cyclinD1 and D2 are induced in some of the Pten mutant tumors. To further elucidate the importance of cyclinD1 in tumor initiation and progression downstream of Pten, Wap-Cre:Ptenf/f mice were crossed with CyclinD1 -/-  mice to generate Wap-Cre:Ptenf/f:CyclinD1 -/-  mice; incidence of tumor is monitored. Histological analyses revealed that mutations in Pten give rise to at least two types of tumors: adenocarcinoma and adenosarcoma. Immunostaining of these tumors show the presence of both myo- and luminal epithelial cells and keratin6 positive cells in a fraction of these tumors. FACS analyses of Pten tumors also suggest an expansion of Sca-1 positive cells compared to mammary gland from virgin or pregnant mice. These observations suggest that aberrant signaling of Pten may induce at least two distinct oncogenic pathways, one of which like MMTV-Wnt1 tumors, may target the stem cell population and the other pathway, like MMTV-neu tumors, may targets more committed progenitor cells. To further analyze oncogenic pathways downstream of Pten, we have generated tumorspheres from Pten mutant tumors. These tumourspheres can be propagated in ultra-low attachment plates in DMEM/F12 media supplemented with EGF, FGF and B-27. These tumorspheres express both luminal and myo-epithelial cell markers when plated on collagen-coated slides. Understanding Pten-dependent tumor initiation may open new avenues for therapeutic interventions for breast cancer treatment.
Abstract 420: Tet family proteins and 5-hydroxymethylcytosine in esophageal squamous cell carcinoma
Authors: Asuka Murata, Yoshifumi Baba, Ryuichi Karashima, Satoshi Ida, Yu Imamura, Takatsugu Ishimoto, Shiro Iwagami, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Hideo Baba
Journal: Cancer Research (2014)

Abstract Objective: DNA methylation is a fundamental epigenetic process that modulates gene expression. Cancer cells exhibit two types of DNA methylation alterations: global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Although the base 5-methylcytosine (5mc) and the DNA methyltransferase (DNMT) family of enzymes that catalyze DNA methylation are well-studied, the mechanisms of DNA demethylation are poorly understood. The Ten-eleven translocation (Tet) family of enzymes (Tet1, Tet2, and Tet3) has been implicated in DNA demethylation. These enzymes possess the dioxygenase activity and convert 5-mC to 5-hydroxymethylcytosine (5-hmC). Frequent Tet mutational inactivation or reduction has been reported to associate with decreased 5-hmC levels in various types of myeloid leukemia and melanoma. However, the status of 5hmC and Tet expression in esophageal squamous cell carcinoma (ESCC) remains still unknown. Method: We analyzed the 5-hmC status in DNA from ESCC frozen tissues utilizing the ELISA test, and 5-hmC expression was evaluated by immunohistochemistry. We next examined the expression levels of Tet family mRNA in both normal and tumor tissues by RT-qPCR. Results: 5-hmC level was significantly lower in ESCC than in paired normal tissue in ELISA test (n=33, P&amp;lt;0.0001). The similar result was observed in immunohistochemistry. We found that the Tet2 mRNA expression was significantly lower in ESCCs than paired normal tissues (n=32, P&amp;lt;0.0001). The expression level of Tet2 mRNA was significantly associated with the 5hmC status (n=31, r=0.54, P=0.0085). Finally, 5-hmC status did not correlate with overall survival (P = 0.65). Conclusion: The 5hmC expression was decreased in ESCC tissues, and was associated with Tet2 expression level, suggesting that 5hmC and Tet2 might play a crucial role in the development of ESCCs. Citation Format: Asuka Murata, Yoshifumi Baba, Ryuichi Karashima, Satoshi Ida, Yu Imamura, Takatsugu Ishimoto, Shiro Iwagami, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Hideo Baba. Tet family proteins and 5-hydroxymethylcytosine in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 420. doi:10.1158/1538-7445.AM2014-420
Abstract 2498: Detection of S-nitrosylated heat shock protein 90 in renal cell cancer
Authors: Fumiya Hongo, Takashi Ueda, Saya Ito-Ueda, Masakatsu Oishi, Terukazu Nakamura, Yoshio Naya, Tsuneharu Miki
Journal: Cancer Research (2014)

Abstract Purpose: Nitric oxide (NO) is a versatile signaling molecule. Its roles in a variety of physiological functions in mammals are beginning to be understood. It has been demonstrated that NO up-regulates the expression of the Fas receptor on human tumor cells via specific inactivation of transcription repressor YY1 DNA binding activity to the silencer region of the Fas promoter (Hermes G., et al. 2001). We also showed that inactivation of YY1 via protein S-nitrosylated by NO in prostatic cancer could be identified (Hongo F., et al. 2005). This post-translational modification, known as S-nitrosylation, has emerged as a highly conserved and spatiotemporally specific signaling mechanism. The objective of our study was to examine the effect of NO donor treatment on renal cell cancer. Methods: We examined the effect of the NO donor DETA-NONOate (100-500uM) on the following renal cell cancer cell lines; CAKI-1, NC65, and ACHN. Anti-S-nitroso-Cysteine antibody in the rabbit (SIGMA-ALDRICH) was applied as a primary antibody for immunohistochemistry. The biotin-switch technique was applied to detect specific S-nitrosylated proteins. Whole cell lysates were extracted from ACHN cells employed with DETA-NONOate. Using an S-nitrosylated detection kit (Cayman Chemical Company), S-NO was replaced by Biotin. Cell lysates were incubated at 4 oC with 30 μL of Dynabeads M-280 Streptavidin (Invitrogen) for 3 hrs. After five washes with wash buffer (S-Nitrosylation Wash buffer), the protein complex was eluted from anti-biotin dynabeads by incubation with 1x volume of elution buffer (0.1M glycine (pH2.0)) twice for 15 min. Each sample was added to an SDS-polyacrylamide gel for mass spectrometry. Results: Significant up-regulation of S-nitrosylated proteins employed with DETA-NONOate was observed by immunohistochemistry. Specific S-nitrosylated proteins in ACHN cells were detected by the biotin-switch technique and included HSP90 (heat shock protein 90), GRP78 (HSP70 family), HSP70, and pyruvate kinase M2. In ACNH cells, Significant up regulation of S-nitrosylated HSP90 by western blot. Conclusions: Our data showed that NO treatment significantly increased S-nitrosylation of several proteins. S-nitrosylation should be considered as one of the mechanisms by which NO acts on cancer cells. Citation Format: Fumiya Hongo, Takashi Ueda, Saya Ito-Ueda, Masakatsu Oishi, Terukazu Nakamura, Yoshio Naya, Tsuneharu Miki. Detection of S-nitrosylated heat shock protein 90 in renal cell cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2498. doi:10.1158/1538-7445.AM2014-2498
Abstract 3611: Stromal transforming growth factor-beta 1 is crucial for reinforcing the invasive potential of low invasive cancer
Authors: Young Sun Hwang, Kwang-Kyun Park, Won-Yoon Chung
Journal: Cancer Research (2014)

Abstract Comparative analyses of gene expression profiles between metastatic and non-metastatic cells have revealed that various genes are differentially expressed in association with the metastatic potential of cancer cells. Interactions between tumor cells and their adjacent microenvironment are intimately associated with tumor growth and the development of metastasis. Cancer-associated fibroblasts (CAFs) are a source of various paracrine and autocrine growth factors that regulate growth of surrounding cells as well as themselves. Thus, there is an increasing interest to study CAFs as drug targets for anticancer therapies. In the present study, we investigated the existence of molecular crosstalk between cancer cells and surrounding stromal cells to reinforce the invasive potential of low invasive cancer. Molecular crosstalk between cancer cells and tumor microenvironment components suggests potential targets for new therapeutic approaches. Material and methods: Isolated normal fibroblasts (NFs) or CAF was co-cultured with low invasive HSC-2 cells to evaluate whether stromal TGF-β1 induced PDPN expression by Transwell invasion and influenced tumor growth in orthotopic xenografts. Results: Stimulation by TGF-β1 promoted PDPN expression and Transwell invasion through SMAD signaling as well as activation of Src, P38 mitogen activated protein kinase, and extracellular regulated kinase 1/2. PDPN induction was TβRII-dependent. Tumor growth of HSC-2 OSCC in a mouse orthotopic xenograft was intensified in the tumor CAF microenvironment. Conclusions: Stromal TGF-β1 signaling promoted PDPN expression in cancer cells, thereby enhancing tumor growth and leading to a more invasive phenotype. Citation Format: Young Sun Hwang, Kwang-Kyun Park, Won-Yoon Chung. Stromal transforming growth factor-beta 1 is crucial for reinforcing the invasive potential of low invasive cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3611. doi:10.1158/1538-7445.AM2014-3611
Abstract 12559: Combined Evaluation of Left Atrial Volume Index and Heart-Type Fatty Acid-Binding Protein is a Feasible Prognostic Predictor in Heart Failure Patients With Preserved Ejection Fraction
Authors: Shintaro Sasaki, Tetsu Watanabe, Harutoshi Tamura, Satoshi Nishiyama, Masahiro Wanezaki, Takanori Arimoto, Hiroki Takahashi, Tetsuro Shishido, Takehiko Miyashita, Takuya Miyamoto, Joji Nitobe, Isao Kubota
Journal: Circulation (2010)

Certain parameter predicting prognosis of heart failure with preserved ejection fraction (HFpEF) remains to be determined. It was reported that left atrial volume index (LAVI) is associated with th...
The differential expression of the LIV-1 family of zinc transporters in anti-hormone resistant breast cancer cell lines
Authors: Normawati Zahari, Kathryn Taylor, Robert Nicholson
Journal: Clinical Cancer Research (2007)

C66   All nine members of the LIV-1 family of proteins belongs to the ZIP superfamily of zinc transporters. Our Affymetrix Human Genome U133A GeneChips ®  analysis of ZIP7/HKE4/LZT-Hs1, LIV-1, ZIP14/LZT-Hs4, ZIP4/LZT-Hs5 and pS2 in MCF-7 breast cancer cells confirmed that ZIP7/HKE4/LZT-Hs1, LIV-1 and ZIP14/LZT-Hs4 were regulated by estradiol. This study was extended to investigate the expression of all nine LIV-1 family members in breast cancer cells treated with oestradiol, tamoxifen and faslodex. Additionally, we investigated the expression of the LIV-1 family members in our MCF-7 based models of tamoxifen and faslodex resistance using semi-quantitative PCR. Differential expression of these family members was seen with some members constitutively expressed whilst others were either elevated or reduced in the different conditions. This analysis demonstrated that ZIP7/HKE4/LZT-Hs1 was considerably elevated in tamoxifen resistance. In an effort to investigate a possible role for ZIP7/HKE4/LZT-Hs1 in tamoxifen resistant cells siRNA was used to reduced the expression of ZIP7/HKE4/LZT-Hs1. Interestingly, in the presence of siRNA for LZT-Hs1, it was not possible to demonstrate the activation of EGFR or Src as previously observed in the tamoxifen resistant phenotype using Western blotting analysis. This is an exciting result, which suggests a role for ZIP7/HKE4/LZT-Hs1 in driving the growth of tamoxifen resistant breast cancer cells.