tbuckley/cabot-search huggingface dataset:
Prevention and Treatment of Lymphatic Metastasis by Antilymphangiogenic Therapy
Authors: R. K. Jain, T. P. Padera
Journal: JNCI Journal of the National Cancer Institute (2002)

Cancer cells escape a tumor by two primary routes-blood vessels and lymphatic vessels-to establish distant metastases.Thus, it seems reasonable to hypothesize that blocking the growth of new blood vessels (angiogenesis) and lymphatic vessels (lymphangiogenesis) will inhibit hematogenic and lymphogenic metastases, respectively.An impressive array of preclinical studies has demonstrated prevention and suppression of hematogenic metastases by antiangiogenic and antivascular approaches.Whether antilymphangiogenic and antilymphatic approaches will yield similar results for lymphogenic metastases remains to be seen.Both vascular endothelial growth factor (VEGF)-C and VEGF-D induce angiogenesis (1,2) and lymphangiogenesis (1,(3)(4)(5) in tumors and are associated with lymphogenic metastasis in a variety of human tumors (6).Last year Stacker et al. (1) presented the first direct evidence for the prevention of lymphatic metastasis from a tumor grown in the mammary fat pad by blocking VEGF-D.In this issue of the Journal, He et al. (7) report similar findings in subcutaneously grown tumors that lack VEGF-D by blocking VEGF-C.Although Stacker et al. (1) used a blocking antibody against VEGF-D, He et al. ( 7) used a receptor-antibody fusion protein (VEGFR-3-Ig fusion protein) that can trap both VEGF-C and VEGF-D.The receptor-antibody was generated in vivo by cancer cells engineered to secrete soluble VEGFR-3-Ig or by the liver infected by an adenovirus expressing VEGFR-3-Ig.In both studies, treatment was initiated within a day after tumor implantation, before the primary tumor became established, and lymph nodes were examined for metastatic lesions 4-6 weeks later.Blocking VEGF-C or VEGF-D suppressed lymphangiogenesis associated with the primary tumor and regional lymph node metastasis.These are exciting and timely findings that raise many important questions about the biology and potential treatment of lymphatic metastases.First, how do VEGF-C and VEGF-D alter tumor biology to promote lymphatic metastasis?The current study used an ectopic (subcutaneous) model of lung cancer and found an association between lymphatic vessel density (measured as lymphatic vessel endothelial hyaluronan receptor [LYVE]-1-positive structures) and lymph node metastases in one of two tumor lines.Another recent study (4) used orthotopically grown tumors engineered to overexpress VEGF-C and found an increased diameter of functional lymphatic vessels in the tumor margin and a greater number of lymph node metastases compared with mocktransduced controls.Thus, by increasing the surface area of lymphatic vessels, VEGF-C and VEGF-D increase the opportunity for metastatic spread through lymphatic vessels.VEGF-C and VEGF-D may also serve as a survival factor for endothelial cells of newly formed or co-opted lymphatic vessels in a tumor (5).Furthermore, He et al. (7) show that trapping VEGF-C only inhibits lymphatic metastasis without affecting hematogenic
Abstract 5692: Targeted inhibition of cancer stem cells by self-assembled miRNA-nanovectors
Authors: Xiaojie Meng, Rebecca Marquez, Amber Smith, Blake Balcomb, Chad Highfill, Wenhua Tang, Liang Xu
Journal: Cancer Research (2012)

Abstract Cancer stem cells (CSCs) are a subpopulation of tumorigenic cells capable of self-renewal and differentiation. These cells are highly resistant to chemo/radiation therapy and may be responsible for tumor recurrence and metastasis. MicroRNAs (miRNAs) are involved in cancer initiation and progression by regulating genes responsible for cell proliferation and/or death. The tumor suppressor miRNA miR-34a is directly regulated by p53. miR-34a targets Notch and Bcl-2, both of which are involved in the self-renewal and survival of CSCs. We recently showed that miR-34a potently inhibits tumorsphere growth and tumor-initiation of p53-mutant pancreatic cancer, accompanied by reduction of CSCs and inhibition of Bcl-2/Notch signaling pathways. However, like other gene therapeutics, tumor-targeted delivery of miRNA, especially targeting to CSCs, remains a great challenge. We have established a self-assembled nanovector system that shows promising tumor specificity and efficiency for tumor-targeted gene/siRNA delivery (US Patent No. 6,749,863 and 7,479,276 with modification). The nanovectors show promising specificity and efficacy for systemic p53 tumor suppressor gene therapy in human cancer models. The first-in-human Phase I clinical trial of nano-p53 (NCT00470613, ClinicalTrails.gov) by Chang EH group shows a promising safety profile, efficient therapeutic gene expression in tumors and early tumor response. We have modified this nanotechnology and established a nanovector delivery system to deliver miR-34a, which resulted in a high transfection efficiency and significant Bcl-2/Notch downregulation in pancreatic, breast and prostate cancer cell lines, accompanied with reduced tumorsphere growth in vitro and tumor formation in vivo. More importantly, systemic injection of nano-miR-34a can delivermiR-34a to the established pancreatic, breast and prostate cancer xenograft tumors and reduce Bcl-2/Notch expression in these tumors. CSC population was also reduced in the treated tumors. Our studies demonstrate that our nano-miR-34a may provide a novel and effective molecular therapy for human cancers with high Bcl-2 and p53 loss of function, potentially by modulating cancer stem cells. Molecularly targeted miRNA therapy delivered by nanovectors could be a powerful tool to correct the cancer stem cell dysregulation. Supported in part by NIH grant CA121830(S1). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5692. doi:1538-7445.AM2012-5692
Short-chain carboxylic acids, a new class of teratogens: studies of potential biochemical mechanisms.
Authors: M E Coakley, S J Rawlings, N A Brown
Journal: Environmental Health Perspectives (1986)

Certain short-chain carboxylic acids (SCCA) appear to share a common teratogenic potential, although the structural requirements for activity remain obscure. By using a whole rat embryo culture model system, several biochemical processes have been examined, either as potential initial sites of teratogenic action or as early steps in the pathway to malformation. Valproate, methoxyacetate, and butyrate were the prototype SCCA examined. Measurement of [14C]glucose utilization and lactate production confirmed that energy production by the early organogenesis embryo is predominantly from glycolysis. While the positive control agent, iodoacetate, caused a significant inhibition of lactate production, none of the SCCA affected this process or glucose utilization at teratogenic concentrations. Valproate did not influence embryonic acetyl CoA levels, in marked contrast to the reported response of adult liver, the other major target of valproate toxicity. Pinocytosis by the visceral yolk sac (VYS) was measured by the uptake of [125I]polyvinylpyrrolidone. This process ultimately supplies the embryo with amino-acids and is essential for normal development. SCCA induce morphological abnormalities of the VYS in embryo culture. Pinocytosis was slightly reduced by valporate, but not the other SCCA. However, comparison with the action of an antiserum, for which inhibition of pinocytosis is the initial teratogenic insult, suggests that this is not the mechanism for valproate. Incorporation of [3H]thymidine into embryo or yolk sac was not affected after 3 hr of SCCA exposure, but there was a marked effect of the positive control, hydroxyurea. This suggests that DNA synthesis is not directly influenced by SCCA.(ABSTRACT TRUNCATED AT 250 WORDS)
A distinct glucose metabolism signature of acute myeloid leukemia with prognostic value
Authors: Wen-Lian Chen, Jing-Han Wang, Ai-Hua Zhao, Xin Xu, Yi-Huang Wang, Tian-Lu Chen, Jun-Min Li, Jian-Qing Mi, Yong-Mei Zhu, Yuan-Fang Liu, Yue-Ying Wang, Jie Jin, He Huang, De-Pei Wu, Yan Li, Xiao-Jing Yan, Jin-Song Yan, Jian-Yong Li, Shuai Wang, Xiao-Jun Huang, Bing-Shun Wang, Zhu Chen, Sai-Juan Chen, Wei Jia
Journal: Blood (2014)
Effects of Chlorpromazine in Patients with Hepatic Disease
Authors: A. E. Read, J. Laidlaw, C. F. McCarthy
Journal: BMJ (1969)

Patients with cirrhosis were found to be extremely sensitive to chlorpromazine as shown by slowing of the electroencephalograph (E.E.G.), which was particularly definite in those who had had hepatic encephalopathy previously. Patients showing the most definite E.E.G. changes were in general very sleepy and took some hours to recover after taking chlorpromazine. It is concluded that phenothiazine drugs should be used very cautiously in patients with alcoholic liver disease.
Primary health care in residential homes for the elderly
Authors: M E M Herford
Journal: BMJ (1982)

the investigation of all aged demented patients since the yield of "potentially reversible" causes will certainly be low and the yield of "actually reversible" causes even lower.There are patients of all ages (including aged demented patients) in whom computed tomo- graphy is a valuable procedure, but they will all have to wait a very long time for their scans if we all follow what appears to be Professor Millard's advice and seek computed tomo- graphy scans for all our aged demented patients.
Effect of Age at Onset on the Course of Major Depressive Disorder
Authors: Sidney Zisook, Ira Lesser, Jonathan W. Stewart, Stephen R. Wisniewski, G.K. Balasubramani, Maurizio Fava, William S. Gilmer, Timothy R. Dresselhaus, Michael E. Thase, Andrew A. Nierenberg, Madhukar H. Trivedi, A. John Rush
Journal: American Journal of Psychiatry (2007)

Objective: This report assesses whether age at onset defines a specific subgroup of major depressive disorder in 4,041 participants who entered the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Method: The study enrolled outpatients 18–75 years of age with nonpsychotic major depressive disorder from both primary care and psychiatric care practices. At study entry, participants estimated the age at which they experienced the onset of their first major depressive episode. This report divides the population into five age-at-onset groups: childhood onset (ages <12), adolescent onset (ages 12–17), early adult onset (ages 18–44), middle adult onset (ages 45–59), and late adult onset (ages ≥60). Results: No group clearly stood out as distinct from the others. Rather, the authors observed an apparent gradient, with earlier ages at onset associated with never being married, more impaired social and occupational function, poorer quality of life, greater medical and psychiatric comorbidity, a more negative view of life and the self, more lifetime depressive episodes and suicide attempts, and greater symptom severity and suicidal ideation in the index episode compared to those with later ages at onset of major depressive disorder. Conclusions: Although age at onset does not define distinct depressive subgroups, earlier onset is associated with multiple indicators of greater illness burden across a wide range of indicators. Age of onset was not associated with a difference in treatment response to the initial trial of citalopram.
The Natural History of Disease
Authors: Leonard Sinclair
Journal: BMJ (2008)

John Ryle came from the school of master clinicians who walked the wards and tended the needs of patients (at Guy’s Hospital, London). He was a physician who listened but was also noted for his clinical research on gastric function. “Ryle’s tube” was for many years the eponymous name for that tube used for emptying the stomach and for gastric lavage.

His mentor was Arthur Hurst, the doyen of gastroenterologists in the 1920s, and he dedicated this book to him. It was written at a time when Ryle had accumulated much clinical experience and was under …
Breast and Prostate Cancer: An Analysis of Common Epidemiological, Genetic, and Biochemical Features*
Authors: Carlos López-Otín, Eleftherios P. Diamandis
Journal: Endocrine Reviews (1998)

I. Introduction II. Epidemiological Evidence Associating Breast and Prostate Cancer III. Incidence of Breast and Prostate Cancer in Different Countries: Dietary Factors IV. Genetic Abnormalities Common to Breast and Prostate Cancer A. AR alterations in prostate cancer B. AR alterations in breast cancer C. BRCA1 and BRCA2 alterations in breast cancer D. BRCA1 and BRCA2 alterations in prostate cancer E. Other genes associated with breast or prostate cancer V. Common Biochemical Features of Breast and Prostate Cancer A. Prostate-specific antigen (PSA) B. Apolipoprotein D (apoD) C. Zn-α2-gp D. Gross cystic disease fluid protein-15 E. Pepsinogen C F. Other proteins VI. Growth Factors in Breast and Prostate Cancer A. AIGF B. KGF VII. Theories of Breast and Prostate Cancer Development: Role of Steroid Hormones VIII. Conclusions
Single daily dose of allopurinol.
Authors: I Brewis, R M Ellis, J T Scott
Journal: Annals of the Rheumatic Diseases (1975)

Allopurinol was administered to seven patients with gout to compare the effects of three different methods of administration. Allopurinol 100 mg given three times daily. Allopurinol given once daily as three 100 mg tablets. Allopurinol given once daily as a single 300 mg tablet. Allopurinol as a single dose in the morning gave as sustained control of plasma levels as did divided administration.
Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma
Authors: Miriam Benezra, Oula Penate-Medina, Pat B. Zanzonico, David Schaer, Hooisweng Ow, Andrew Burns, Elisa DeStanchina, Valerie Longo, Erik Herz, Srikant Iyer, Jedd Wolchok, Steven M. Larson, Ulrich Wiesner, Michelle S. Bradbury
Journal: Journal of Clinical Investigation (2011)

Nanoparticle-based materials, such as drug delivery vehicles and diagnostic probes, currently under evaluation in oncology clinical trials are largely not tumor selective. To be clinically successful, the next generation of nanoparticle agents should be tumor selective, nontoxic, and exhibit favorable targeting and clearance profiles. Developing probes meeting these criteria is challenging, requiring comprehensive in vivo evaluations. Here, we describe our full characterization of an approximately 7-nm diameter multimodal silica nanoparticle, exhibiting what we believe to be a unique combination of structural, optical, and biological properties. This ultrasmall cancer-selective silica particle was recently approved for a first-in-human clinical trial. Optimized for efficient renal clearance, it concurrently achieved specific tumor targeting. Dye-encapsulating particles, surface functionalized with cyclic arginine-glycine-aspartic acid peptide ligands and radioiodine, exhibited high-affinity/avidity binding, favorable tumor-to-blood residence time ratios, and enhanced tumor-selective accumulation in αvβ3 integrin-expressing melanoma xenografts in mice. Further, the sensitive, real-time detection and imaging of lymphatic drainage patterns, particle clearance rates, nodal metastases, and differential tumor burden in a large-animal model of melanoma highlighted the distinct potential advantage of this multimodal platform for staging metastatic disease in the clinical setting.
Nitric oxide synthases: which, where, how, and why?
Authors: T Michel, O Feron
Journal: Journal of Clinical Investigation (1997)

Ca 2 ϩ i ], intracellular Ca 2 ϩ concentration; NO, nitric oxide; NOS, NO synthase.2.Where possible, references in support of introductory material will cite recent review articles rather than the numerous primary publications that form the basis for our current understanding.
Clinical Studies on Veratrum Alkaloids
Authors: EDWARD MEILMAN, OTTO KRAYER
Journal: Circulation (1950)

The action of two pure veratrum alkaloids, veratridine and protoveratrine, in human hypertension is described for the first time. The vasodepressor reflex pathway involved in the response to these ester alkaloids is reviewed. Protoveratrine is found to produce a striking fall in blood pressure in both essential and renal hypertension after intravenous administration.
Abstract 4660: Temporal interrogation of EGFR signaling in head and neck cancer reveals highly distinct phosphorylation waves for individual EGFR inhibitors
Authors: Gopal Iyer
Journal: Cancer Research (2014)

Abstract Targeting the epidermal growth factor receptor (EGFR/HER) family is an effective target for cancer therapeutics with thousands of cancer patients treated annually with EGFR inhibitors. However, we are only beginning to appreciate the rapid and dynamic signaling impact of various EGFR inhibitors on cancer cell phosphorylation events. The purpose of this study was to characterize the temporal phosphoprotein kinetics in head and neck cancer cells treated with the anti-EGFR antibodies cetuximab and Sym004. For the first time, perturbation data were generated using reverse phase protein array probed with 183 phosphorylated proteins involved in various signaling pathways at 11 different time points starting as early as 5 min and up to 24 hours. A novel signaling module comprised of phospho-ATM at Ser-1981, p-53(Ser15), p-IkB-α (Ser32/36) and p-Bad (Ser112) was found to be highly upregulated following exposure to Sym004. Concomitantly, high resolution imaging also revealed rapid EGFR degradation and increased endosomal trafficking with Sym004 treatment. Correlation matrix on a temporal scale revealed distinct network topologies suggesting that phosphorylation occurs in distinct waves over time. These response patterns were highly distinct when comparing cetuximab with Sym004. Using this platform, we are able to quantify the strength of various signaling networks triggered by EGFR inhibition and are able to model new pathways. These findings may have significant implications for developing more personalized treatment strategies including logical combination with other molecular target inhibitors. Note: This abstract was not presented at the meeting. Citation Format: Gopal Iyer. Temporal interrogation of EGFR signaling in head and neck cancer reveals highly distinct phosphorylation waves for individual EGFR inhibitors. [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 4660. doi:10.1158/1538-7445.AM2014-4660
Chronic fatigue. A prospective clinical and virologic study
Authors: D. Gold
Journal: JAMA (1990)

To evaluate the clinical and virologic course of patients with chronic fatigue who had elevated Epstein-Barr virus (EBV) titers, we prospectively followed up 26 patients with serial cultures for EBV in blood and saliva and serial EBV serologic and clinical and psychiatric evaluations, and we compared these results with those for healthy controls. The frequency of isolating EBV in blood or demonstrating EBV infection by in situ hybridization in blood lymphocytes or in saliva was similar in patients and controls. The prevalence and titers of antibody to human herpesvirus type 6 were also similar in the two populations. Patients with chronic fatigue did demonstrate higher in vitro natural killer activity and lower in vitro interleukin 2 production than controls, and patients had a high frequency of DSM-III depressive illness. Over 50% of patients with chronic fatigue improved over the course of follow-up. Improvement was not associated with any discernible change in titers of EBV proteins. No evidence of ongoing EBV infection with either transforming or nontransforming strains was demonstrated in this population of patients with chronic fatigue. Clinically, most patients gradually improve over time.
PROLONGED COMA IN INSULIN THERAPY OF THE PSYCHOSES
Authors: HERVEY CLECKLEY, C. M. TEMPLETON
Journal: American Journal of Psychiatry (1941)

No adequate explanation can be offered by us for the occurrence of prolonged non-hypoglycemic coma in the six cases reported. Intensive treatment with thiamin chloride, nicotinic acid and with riboflavin failed to terminate the coma. Nicotinic acid apparently brought about a striking change in Case 2. This effect was not, however, on the initial coma but on a state of confusion associated with redness of the tongue many days after the coma had subsided. Despite prophylactic administration of these vitamins, which play important rôles in carbohydrate oxidation and in the absence of recognized signs of danger, patients undergoing insulin shock therapy sometimes fail to awaken from hypoglycemic coma when the hypoglycemia is terminated. This distressing complication sometimes arises even in patients who have not reached a level of deep coma or shock and who have been in coma or shock only for very short periods. Though nearly all of the procedures recommended in this emergency were carried out, no favorable effect was noted except in one instance when potassium chloride administration was followed by a prompt cessation of severe convulsive activity. Prolonged coma is to be regarded as a serious complication which not infrequently terminates fatally. Aside from pulmonary edema it has been the only dangerous complication that we have experienced in the use of insulin shock therapy. In the two reported cases which came to autopsy no adequate cause could be found for the failure to awaken. The status of patients in prolonged coma varies widely. Some may show only a mildly clouded consciousness and appear to be in excellent physical condition for many days but nevertheless proceed to a fatal termination. Since prolonged coma is at present an unpredictable complication and a very dangerous condition, opportunities to devise therapy are sporadic and limited. It seems worth while to make use of any harmless measure that offers a chance of success even on purely theoretical grounds. We therefore feel that it would be advisable to administer potassium to all patients who develop this complication. The possibility of favorable results from the use of lipocaic should be investigated. It is suggested that this preparation be used in cases of prolonged coma, on theoretical grounds, whenever the occasion arises. Since riboflavin and nicotinic acid are no less important in carbohydrate metabolism than thiamin chloride and since the demand for them is also increased during insulin therapy it is suggested that they, as well as thiamin chloride, be used prophylactically in all cases undergoing treatment.
LET'S GET THE LEAD OUT
Authors: Samuel L. Andelman
Journal: JAMA (1964)

In the last decade, lead intoxication in preschool children has become an increasingly serious problem. Institution of measures to prevent deaths, crippling, and encephalopathy tax the ingenuity of the health officer who has the responsibility of combatting them. To a toddler, paint scales look good enough to eat. That's where most of the trouble starts. Unfortunately, the cause for pica is in doubt and no adequate therapy is as yet available. As pointed out by Griggs and colleagues elsewhere in this issue ofThe Journal(p 703), the cases of lead poisoning seen in most large cities every summer are the result of a combination of factors: (1) the natural tendency for toddlers to put anything they can reach into their mouths, (2) substandard housing in which paint and paint-impregnated plaster have flaked off the walls and ceilings, (3) lack of adequate supervision of preschool children, (4) lack of full
Partial deletions of long arm of chromosome 6: biologic and clinical implications in adult acute lymphoblastic leukemia
Authors: M Mancini, ML Vegna, GL Castoldi, C Mecucci, F Spirito, L Elia, A Tafuri, L Annino, F Pane, G Rege-Cambrin, M Gottardi, P Leoni, E Gallo, A Camera, L Luciano, G Specchia, G Torelli, M Sborgia, A Gabbas, A Tedeschi, I Della Starza, N Cascavilla, F Di Raimondo, F Mandelli, R Foà
Journal: Leukemia (2002)