tbuckley/cabot-search huggingface dataset:
Differential biological activity of quercetin-3-sulfate in normal and cancerous human breast cells
Authors: Kayoko Shimoi, Isamu Tomita, Tsutomu Nakayama, Bao Ting Zhu
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

1377 

It is known that the sulfate metabolites of estrogens and bioflavoniods have relatively long half-lives and could still exert biological functions following their metabolic desulfation. Recent studies by us and others have shown that cultured human cells appear to have the ability to re-uptake sulfated estrogens and bioflavonoids. In the present study, we used quercetin and quercetin-3-sulfate as model compounds to probe the roles of cellular transporter activity and metabolic desulfation in modulating the actions of drug sulfates in human mammary cells. Experimentally, since quercetin is a growth inhibitor whereas quercetin-3-sulfate is inactive (unless desulfated), we thus have chosen to measure cell growth as a reliable parameter for their biologic activity. Our data showed that quercetin inhibited growth of normal human mammary epithelial cells (HMECs) and MDA-MB-231 breast cancer cells in a concentration-dependent manner. The IC50 values for quercetin in inhibiting the growth of HMECs and MDA-MB-231 cells were ∼20 and 50 uM, respectively. Quercetin also showed a higher efficacy in inhibiting the growth of HMECs than the growth of MDA-MB-231 cells. Interestingly, quercetin-3-sulfate, when tested under the same experimental conditions, displayed exactly the opposite potency and efficacy in inhibiting the growth of these two human cell lines. As part of our continuing effort to search for the underlying mechanisms, we systematically analyzed the expression of genes encoding various organic anion transporters (OATs) and organic anion-transporting polypeptides (OATPs) by using the real time RT-PCR assay. Our data showed that a number of the transporters (such as OATP-B, D, and E) were expressed in HMECs and MDA-MB-231 cells, and their levels of expression did not appear to differ markedly. Although more studies are needed, the results of our present study, along with our other data on the sulfatase activity, suggest that cellular desulfation activity plays a more important role than the drug sulfate transporter activity in determining the biologic activities of various sulfated endobiotics, xenobiotics, as well as sulfated metabolites of anticancer drugs in human mammary cells. [Supported by Special Coordination Funds from the Ministry of Education, Culture, Sports, Science, and Technology of the Japanese government.]
Estimating influenza vaccine effectiveness in Spain using sentinel surveillance data
Authors: S Jiménez-Jorge, S de Mateo, C Delgado-Sanz, F Pozo, I Casas, M García-Cenoz, J Castilla, C Rodriguez, T Vega, C Quiñones, E Martínez, J M Vanrell, J Giménez, D Castrillejo, J M Altzíbar, F Carril, J M Ramos, M C Serrano, A Martínez, N Torner, E Pérez, V Gallardo, A Larrauri
Journal: Eurosurveillance (2015)

We aimed to estimate influenza vaccine effectiveness (VE) against laboratory-confirmed influenza during three influenza seasons (2010/11 to 2012/2013) in Spain using surveillance data and to compare the results with data obtained by the cycEVA study, the Spanish component of the Influenza Monitoring Vaccine Effectiveness (I-MOVE) network. We used the test-negative case–control design, with data from the Spanish Influenza Sentinel Surveillance System (SISS) or from the cycEVA study. Cases were laboratory-confirmed influenza patients with the predominant influenza virus of each season, and controls were those testing negative for any influenza virus. We calculated the overall and age-specific adjusted VE. Although the number of patients recorded in the SISS was three times higher than that in the cycEVA study, the quality of information for important variables, i.e. vaccination status and laboratory results, was high in both studies. Overall, the SISS and cycEVA influenza VE estimates were largely similar during the study period. For elderly patients (> 59 years), the SISS estimates were slightly lower than those of cycEVA, and estimates for children (0–14 years) were higher using SISS in two of the three seasons studied. Enhancing the SISS by collecting the date of influenza vaccination and reducing the percentage of patients with incomplete information would optimise the system to provide reliable annual influenza VE estimates to guide influenza vaccination policies.
Abstract 2711: Regulation of the IGF-1R signaling by angiotensin signaling pathway
Authors: Hye-Jin Boo, Hyun-Ji Jang, Yujin Jung, Hye-Young Min, Ho-Young Lee
Journal: Cancer Research (2015)

Abstract Lung cancer is one of the most commonly diagnosed cancers in the world. Tobacco smoking is the most predominant risk factor for the development of lung cancer. Carcinogenic compounds in tobacco smoke are thought to be responsible for lung cancer, at least in part, by activating G-protein coupled receptor (GPCR)-mediated signaling pathways. GPCR signaling has been suggested to cross-talk with the IGF-1R signaling pathway, a key pathway for cell survival, transformation and growth. However, the mechanisms underlying the crosstalk between GPCR and IGF-1R signaling pathways remain poorly understood. Here we show that tobacco carcinogen (TC) contributes to the lung carcinogenesis by activating the angiotensin signaling and subsequent IGF-1R signaling pathways. We observed that a potent tobacco carcinogen, nitrosamine 4-(methylnitro-samino)-1-(3-pyridyl)-1-butanone (NNK, nicotine-derived nitrosamine ketone), induced transformed phenotypes, including foci formation, viability in the absence of growth factors, and anchorage-dependent and -independent colony formation, and activation of the IGF-1R in normal human bronchial epithelial cells. The NNK treatment also induced lung tumor formation in mice. Losartan, an angiotensin type-1 receptor blocker, and captopril, an angiotensin converting enzyme (ACE) inhibitor, disrupted NNK-induced IGF-1R activation and transformed phenotypes in normal human bronchial epithelial cells and reduced lung tumor formation in mice. These findings indicated that TC-induced angiotensin signaling pathway can enhance lung carcinogenesis by activating the IGF-1R signaling. Our results suggest that targeting IGF-1R by using angiotensin signaling inhibitors may be an effective strategy for the chemoprevention of lung cancer. Citation Format: Hye-Jin Boo, Hyun-Ji Jang, Yujin Jung, Hye-Young Min, Ho-Young Lee. Regulation of the IGF-1R signaling by angiotensin signaling pathway. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2711. doi:10.1158/1538-7445.AM2015-2711
Phase I/II trial of Arginine Butyrate and ganciclovir in Epstein-Barr virus-associated lymphoid malignancies
Authors: D. V. Faller, O. Hermine, T. Small, F. Suarez, R. O’Reilly, F. Boulad, J. Fingeroth, S. J. Mentzer, C. Klein, S. Horwitz, S. P. Perrine
Journal: Journal of Clinical Oncology (2006)

7542 Background: Malignancies associated with latent Epstein-Barr virus (EBV) are resistant to nucleoside-type anti-viral agents because the viral enzyme target of these drugs, thymidine kinase (TK), is not expressed. Short-chain fatty acids, such as butyrate, induce EBV-TK expression in latently-infected B cells. In preclinical studies, we have shown that butyrate sensitizes EBV(+) lymphoblastoid cells, tumor lines and primary lymphoma cultures to apoptosis induced by ganciclovir. Methods: We conducted a Phase I/II trial of Arginine Butyrate in combination with ganciclovir in patients with refractory EBV(+) lymphoid malignancies to evaluate toxicity, pharmacokinetic parameters, and clinical responses. Fifteen patients with heavily-pretreated, refractory EBV(+) lymphoid malignancies, consisting of monoclonal refractory lymphoproliferative disease (PTLD), B cell non-Hodgkin’s lymphomas (NHL) (including one HIV-associated anaplastic B cell lymphoma), T cell NHL (including one cutaneous lymphoma), T/NK cell lymphomas, and Hodgkin disease were studied. Ganciclovir was administered twice daily and Arginine Butyrate was administered in an intra-patient dose-escalation. Arginine Butyrate was instituted at 500 mg/kg/day by continuous infusion, and escalated to 2000 mg/kg/day, as tolerated. Results: The MTD for Arginine Butyrate was established as 1000 mg/kg/day. Overall the combination was well-tolerated, with the most common toxicities being nausea and headache. Complications from rapid tumor lysis occurred in three patients, including acute hepatic necrosis in one patient. Reversible grade 3–4 somnolence or stupor occurred in three patients at Arginine Butyrate doses of greater than 1000 mg/kg/day. Ten of fifteen patients showed significant anti-tumor responses, with 5 CR and 5 PR. In certain patients who demonstrated a clinical CR, subsequent pathological analysis showed elimination of all tumor cells. Conclusions: The combination of Arginine Butyrate and ganciclovir was reasonably well-tolerated and appears to have significant biological activity in vitro and in vivo against refractory EBV(+) lymphoid malignancies. No significant financial relationships to disclose.
Chronic Coronary Occlusions: Age, Morphology and Chance of Reopening
Authors: Christian Vallbracht, Martin Unverdorben, Christoph Kadel, Hartmut Oster, Jens Otto, Gisbert Kober, Martin Kaltenbach
Journal: Journal of the Royal Society of Medicine (1997)

In chronic coronary occlusions the chance of successful reopening by angioplasty can be judged from the age of the occlusion. Often, however, time since occlusion cannot be accurately assessed. Therefore we determined whether the chance of reopening can be predicted from angiographic morphology. In cineangiograms from 60 consecutive patients with chronic coronary occlusions morphological details in at least two projections were evaluated in relation to the rate of success and the estimated age of occlusion. Morphological features associated with a higher rate of success (type A) were a clearcut proximal stump, absence of side branches at the site of occlusion, absence of bridging collaterals, and only slight filling of the distal part of the vessel. Features associated with a low success rate (type B) were absence of proximal stump, side branches at the site of occlusion, bridging collaterals, and rapid high-contrast filling of the distal part of the vessel. 48/60 (80%) of occlusions could be classified as type A or type B. The success rate was 17/21 (81%) in type A versus 5/27 (18.5%) in type B (P < 0.0002). The estimated age of type B occlusions was higher than that of type A medians 8 and 4 months (P < 0.002). Thus in chronic coronary occlusions the likelihood of successful reopening can be judged in many patients from morphological features.
Abstract 15734: Contrast Induced Nephropathy after Primary PCI for STEMI: usefulness of a new definition
Authors: Johanne Silvain, Vincent Spagnoli, Olivier Barthelemy, Anne Bellemain-Appaix, Farzin Beygui, Nicolas Vignolles, Guillaume Cayla, Stephen O'Connor, Jean-Philippe Collet, Gilles Montalescot
Journal: Circulation (2011)

BACKGROUND: Renal impairment and contrast-induced nephropathy (CIN) have been shown to have an impact on outcome in STEMI patients. OBJECTIVES: The aim of this study was to assess the prevalence an...
Abstract 2170: Unipolar Pace Mapping With the Medtronic SelectSecure 3830 Lead System can Accurately Locate the HIS Bundle for Permanent HIS Bundle Pacing
Authors: Stanley Tung, Kesava Rajagopalan, Jonathan Affolter, Santabhanu Chakrabarti, Lynn Davenport
Journal: Circulation (2008)

Introduction: Permanent HIS Bundle pacing (HBP) is one of the most physiological ventricular pacing strategies available. Its wide spread adoption is limited due to challenges in HIS mapping, and requires femoral EP mapping to guide lead placement. We investigate whether unipolar pace mapping (PM) using the lead alone is a viable technique to locate the HB for lead deployment. Methods: Patients indicated for ventricular pacing were approached for HBP. An active fixation lead (SelectSecure®3830, Medtronic) inserted through its deflectable sheath was advanced to the right atrium via left pectoral approach.The cathode tip was positioned just outside the tip of the sheath. Unipolar PM was applied at 5V/0.5ms along the tricuspid septal annulus in anterior posterior direction. At the location with 12/12 ECG match to intrinsic QRS, and with pace to QRS delay &gt;30ms, the lead was fixed. Unipolar sensing for HB electrogram was performed with the Medtronic 2090 analyzer (unfiltered, variable gain, sweep speed 50mm/sec). HBP implant thresholds, HB lead implant and fluoroscopy times, intrinsic and paced HV intervals, pre and post QRS and PR intervals were collected. Paired Student t -test was used for analysis. Results: 22 patients (16 male, mean age 69 yrs) underwent HBP. 19 patients had successful HBP, with 3 patients having para-Hisian septal pacing. The mean HBP implants threshold, HB lead implant and fluoroscopy times were 1.67±44V/0.6ms, 43±26min, and 13±12min respectively. The mean intrinsic and paced HV intervals were 60 and 44 ms respectively. After HBP, the QRS duration decreased from 160±44 to 132±43ms (p&lt;0.01). HBP corrected one RBBB, one LBBB, and three right ventricular apical pacing complexes to normal (&lt;120ms) and accounted for the shorter post HBP mean QRS duration. 8 patients presented with PR intervals ≥200msec and had their PR interval narrowed from a mean of 326±141 to 174±21ms (p&lt;0.05). Conclusions: Unipolar PM of the His bundle using the Medtronic SelectSecure® lead system alone can accurately locate the HB for HBP with acceptable implant time and pacing thresholds. HBP also has the potential value of AVN and ventricular electrical resynchronization benefit. More data with longer-term follow up are needed before considering wide spread adoption.
The impact of signal transduction pathways in a hormone dependent prostate cancer model (LNCaP cells).
Authors: Adam B. Schayowitz, Gauri Sabnis, Aashvini Belosay, Vincent Njar, Angela Brodie
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5353 

Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer related deaths in US men. Initially, the majority of prostate cancer patients present with localized hormone dependent disease. As such, primary treatment consisting of androgen ablation is often successful in preventing or delaying the progression of disease. It is widely accepted that hormone dependent prostate cancer growth occurs through the androgen receptor (AR) which activates transcription of androgen responsive genes and proliferation of cancer cells. The human hormone dependent prostate cancer cell line (LNCaP) is an established model for in vitro investigation of hormone dependent prostate cancer. Despite a mutated AR, LNCaP cells stimulated by 10 pM of dihydrotestosterone (DHT) increase cell growth 200% compared to vehicle treated control. LNCaP cells are also sensitive to hormone therapy such as casodex and VN/85-1, a novel CYP17/lyase inhibitor (IC50=1.29nM) and anti-androgen synthesized in our laboratory. In this study we investigated whether growth factor receptor pathways are also responsible for growth of the hormone dependent LNCaP cells. Many signal transduction proteins including p-Akt, p-mTOR and other downstream proteins are expressed in LNCaP cells and are responsible for cell growth. Compared to control, we found that wortmannin (IC50=249nM) and rapamycin (IC50=21nM) inhibit Akt and mTOR pathways respectively and cell growth. The expression of these proteins and their impact on cell survival indicate that the pathways are essential for cell growth in addition to AR mediated growth. We next investigated the effect of growth inhibition of both pathways by combination treatment with wortmannin plus VN/85-1 (IC50=2.3μM) as well as rapamycin plus VN/85-1. Both combinations significantly (p<0.001) inhibited cell growth compared to single agent treatment. This indicated that inhibition of both the PI3K axis and the AR was more effective than inhibition of either one alone. Using co-immunoprecipitation, we then found an interaction between the p-Akt and the AR. Whether the AR phosphorylates the Akt or vise versa remains to be determined. The activation of various signal transduction pathways in addition to the AR in the growth of hormone dependent prostate cancer has clinical implications and could at least in part account for the progression to androgen independent prostate cancer. Furthermore, inhibition of these pathways also has the potential to impact treatment of localized early stage prostate cancer and prolong the time of progression to androgen independent prostate cancer.
Abstract #4601: Phosphorylation and degradation of Mcl-1 in vinblastine-induced apoptosis
Authors: Rong Chu, David Terrano, Timothy Chambers
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Microtubule inhibitors such as vinblastine are important anticancer drugs that inhibit the dynamics of microtubules, arrest cells in M phase, and induce subsequent apoptosis. Apoptosis is regulated by Bcl-2 family proteins including the anti-apoptotic protein Mcl-1. Mcl-1 is an important survival factor for many cancers and the expression of Mcl-1 is related to chemo-resistance. In this study, we investigated the role of Mcl-1 in vinblastine-induced apoptosis in KB-3 cells. Vinblastine and other microtubule inhibitors promoted Mcl-1 phosphorylation and subsequent degradation. However, no changes in Mcl-1 phosphorylation or expression were observed when cells were treated with lethal concentrations of DNA-damaging agents, doxorubicin or VP-16, suggesting that these modifications are specific responses to microtubule damage. The degradation of Mcl-1 was inhibited by the proteosome inhibitor MG-132. The phosphorylation of Mcl-1 in synchronized cells was inhibited by treatment with different CDK inhibitors including roscovitine, purvalanol A and RO-3306. These results suggest that CDK-dependent phosphorylation and degradation of Mcl-1 may be an important regulatory mechanism in microtubule inhibitor-induced apoptosis. Supported by NIH CA109821.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4601.
In Vitro Development of Erythroid and Megakaryocytic Cells From a UT-7 Subline, UT-7/GM
Authors: Norio Komatsu, Keita Kirito, Ritsuko Shimizu, Masae Kunitama, Minami Yamada, Mie Uchida, Masaaki Takatoku, Mituoki Eguchi, Yasusada Miura
Journal: Blood (1997)
Validity of the familial and sporadic subtypes of schizophrenia
Authors: M A Roy, R R Crowe
Journal: American Journal of Psychiatry (1994)

A common means of subtyping schizophrenia is to use family history. Familial schizophrenia is defined by a family history of psychotic disorders, and sporadic schizophrenia is defined by the absence of such a history. Some writers have proposed that familial cases are mostly genetic, while the causes of sporadic schizophrenia are primarily environmental. The object of this report is to consider the theoretical and empirical support for the validity of this classification.A review of studies examining the familial-sporadic distinction in schizophrenia was based on papers located through a MEDLINE search and published bibliographies. Because of the great variation in the methodological rigor of the studies, the authors rated them on a scale assessing 10 methodological features. Studies achieving at least 50% of the maximum possible score were selected for review.Only 29 of 69 studies located met the selection criteria, and even among the studies selected, important methodological shortcomings were noted. Despite an impressive number of comparisons between groups of subjects with familial and sporadic schizophrenia, few differences were found. In addition, few differences were replicated and supported by studies using designs other than the familial-sporadic distinction.The scarcity of studies with adequate methodology precludes any definitive judgment about the validity of the familial-sporadic distinction in schizophrenia. The delineation of predominantly genetic and predominantly environmental subtypes of schizophrenia will likely require large sample sizes, valid methods for the diagnosis of relatives, and stringent definitions of familiarity and sporadicity. Moreover, research strategies other than the familial-sporadic distinction may be better suited to identify such subtypes.
Outcome of patients with chronic affective disorder: a five-year follow- up
Authors: W Coryell, J Endicott, M Keller
Journal: American Journal of Psychiatry (1990)

Patients with major depression, mania, or schizo-affective disorder that had been present without remission for 2 years or more at intake (N = 129) were followed prospectively for 5 years, as were 580 patients who had been ill for shorter periods at intake. Despite very substantial durations of episode, three-quarters of the chronic patients recovered, although recovery occurred much later in the follow-up period than it did among the nonchronic patients. Factors associated with recovery were less severe illness at intake, lack of psychotic features, good friendship patterns in adolescence, and, most important, a relatively high maximum level of functioning in the 5 years preceding intake.
Babes and boobs? Analysis of JAMA cover art Commentary: An inconclusive study
Authors: J. P Clark, E. Showalter
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objective:</b> To determine the representation of the sexes in <i>JAMA</i> cover art. <b>Design:</b> Review of 50 consecutive issues. <b>Setting:</b><i>JAMA</i>, March 1997-March 1998. <b>Main outcome measures:</b> Numbers and nature of covers portraying men and women. <b>Results:</b> Of the 50 covers, 34 depicted humans. 15 depicted women, 13 men, and 6 were of mixed or indeterminate sex 11 pictures of women included a child and five included nudity One cover showed a man with a child (not as a father) and none depicted nudity. Men were depicted exclusively in authoritative roles. <b>Conclusions:</b> Much of the cover art gives strong messages about sexual stereotypes that are inappropriate in modern society. <i>JAMA</i> should consider reviewing its policy for choosing cover art.
New small-molecule drug design strategies for fighting resistant influenza A
Authors: Zuyuan Shen, Kaiyan Lou, Wei Wang
Journal: Acta Pharmaceutica Sinica B (2015)

Influenza A virus is the major cause of seasonal or pandemic flu worldwide. Two main treatment strategies–vaccination and small molecule anti-influenza drugs are currently available. As an effective vaccine usually takes at least 6 months to develop, anti-influenza small molecule drugs are more effective for the first line of protection against the virus during an epidemic outbreak, especially in the early stage. Two major classes of anti-influenza drugs currently available are admantane-based M2 protein blockers (amantadine and rimantadine) and neuraminidase (NA) inhibitors (oseltamivir, zanamivir, and peramivir). However, the continuous evolvement of influenza A virus and the rapid emergence of resistance to current drugs, particularly to amantadine, rimantadine, and oseltamivir, have raised an urgent need for developing new anti-influenza drugs against resistant forms of influenza A virus. In this review, we first give a brief introduction of the molecular mechanisms behind resistance, and then discuss new strategies in small-molecule drug development to overcome influenza A virus resistance targeting mutant M2 proteins and neuraminidases, and other viral proteins not associated with current drugs.