tbuckley/cabot-search huggingface dataset:
Nano-gossypin, a novel cdk2/VEGF inhibitor formulation against breast cancer.
Authors: HB Nair, P Veerapaneni, DM Sophie, NB Kirma, RP Perla, RR Tekmal
Journal: Cancer Research (2009)

Abstract Abstract #3080 Cyclin-dependent kinases (CDKs) play essential roles in the intracellular control of the cell cycle. The encapsulated therapeutic drug molecules as nanoparticles will offer a sustained delivery of chemotherapeutics in to the target tissue. Nanoparticles enhance the therapeutic efficacy of an encapsulated drug by increased and sustained delivery of the drug inside the cell. Most anticancer drugs are taken up non-specifically by all types of cells, resulting in serious side-effects. Therefore, an ideal delivery carrier for an anticancer drug should be able to transport the drug specifically to cancer cells and release the drug molecules inside the cells to the site of their pharmacological activities. Most of the activity proven natural products were not entered in to the clinical practice due to lack of active formulation and/ or effective targeted delivery systems. In our study we found that gossypin (3,5,7,3',4'-Pentahydroxy-8-O-glucosylflavone) is inhibiting cell cycle progression by inhibiting cyclin dependent kinase-2 (cdk2) when compared with roscovitine, a known cdk2 inhibitor. Gossypin has been shown to induce the accumulation of the tumor suppressor p53, cell cycle arrest in G1 and G2/M phases of the cell cycle, and to induce apoptosis in MCF-7, SKBR-3, and MDA-MB-231 cells with a mean IC 50 of 40uM. Gossypin also found to inhibit vascular endothelial growth factor (VEGF) in vitro. Nanoparticle formulation of gossypin effectively inhibited the growth and colony formation in vitro when compared to parent compound. Gossypin might exert inhibition of tumor cell growth and invasion by cell cycle arrest as well as VEGF induced vascular permeability and tumor neovascularization. The dual mode of action of gossypin may results in highly efficacious inhibition of tumor growth and management of breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3080.
704 LIVER STIFFNESS CHANGES DETECTED BY ACOUSTIC RADIATION FORCE IMPULSE IMAGING (ARFI) IN PATIENTS WITH INTRAHEPATIC CHOLESTASIS
Authors: D. Attia, K. Rifai, S. Pischke, B. Schönemeier, A.A. Negm, A. Schneider, M.P. Manns, M.J. Gebel, T.O. Lankisch, A. Potthoff
Journal: Journal of Hepatology (2013)
FRI0468-HPR What does the language we use about arthritis mean to a patient?
Authors: K. Barker, C. Minns Lowe, M. Reid
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Research shows that more than 80 percent of patients have poor health literacy. To date, research has focussed on language associated with back pain, with less on general musculoskeletal complaints, although these account for a large amount of physiotherapy consultations. <h3>Objectives</h3> To determine patients' knowledge, awareness and comprehension of the language used to describe arthritis, including gaining feedback on the emotional impact of the terms. <h3>Methods</h3> Five qualitative focus groups of 6-8 respondents, and 6 individual in-depth interviews were conducted among a purposive sample of: Men and women (50/50 split across the sample); patients aged 45 years and over with a spread of ages in each group and within the overall sample of depth interviews and a range of socio-economic groupings. Key terms such as arthritis, degenerative, rheumatism, wear and tear and rehabilitation were used as stimulus materials. Focus groups and interviews were audio-recorded, transcribed verbatim and underwent line by line coding and thematic analysis using interpretative phenomenological analysis. <h3>Results</h3> Patients were familiar with many of the terms such as arthritis, osteoarthritis, rheumatism, inflammation etc, but their level of comprehension varied. Most terms had little emotional impact. Terms used to describe pathophysiology such as "wear and tear" and "degenerative" elicited negative emotional impact, especially in women. Terms such as rehabilitation and "self management" were poorly understood and produced negative emotional impact. <h3>Conclusions</h3> Health care professionals should not assume that patients' familiarity with medical terms correlate to understanding the term. They should be aware of the potential for negative emotional impact related to some terms. <h3>Disclosure of Interest</h3> None Declared
Abstract 713: Three-dimensional <i>in vivo</i> blood flow mapping in tumors using optical frequency domain imaging.
Authors: David Blauvelt, Nishant Mohan, Brett Bouma, Rakesh Jain, Timothy Padera, Benjamin Vakoc
Journal: Cancer Research (2013)

Abstract Angiogenesis in the tumor microenvironment is a chaotic process that results in a dysfunctional vascular network. Unlike normal blood vessels, tumor vessels are dense, tortuous, and leaky. The disorganized nature of the tumor vascular network often leads to unequal perfusion in different parts of the tumor. While some vessels see high blood flow rates, others can be virtually stagnant. This heterogeneity in blood flow can affect oxygen distribution, and, as a result, the efficacy of radiation and chemotherapy. Furthermore, knowing how blood flow varies as a tumor develops is critical for our comprehension of tumor angiogenesis. Finally, our understanding of how anti-angiogenic and chemotherapeutic treatments affect tumor vessels depends on our ability to monitor blood flow. Unfortunately, existing strategies for measuring blood flow are limited by low spatial resolution, long imaging times, or an inability to measure flow over whole tumor volumes. Here, we use optical frequency domain imaging (OFDI) to measure blood flow in individual vessels over an entire tumor volume growing in a mouse. Previously, we have used OFDI to obtain high-resolution images of tumor vasculature. Our new technique is based on an association between the speed of moving blood and the dynamics of optical speckle patterns that are intrinsically generated in OFDI. By employing novel methods to measure these speckle patterns and then relate them to an underlying flow velocity, we are able to generate high-resolution three-dimensional maps of blood flow within tumors. Our results expand the potential of OFDI to characterize the tumor microvasculature by adding wide-field blood flow measurements to its demonstrated ability to characterize microvascular morphology, tumor anatomy, tissue viability, and lymphatic vessel morphology. Citation Format: David Blauvelt, Nishant Mohan, Brett Bouma, Rakesh Jain, Timothy Padera, Benjamin Vakoc. Three-dimensional in vivo blood flow mapping in tumors using optical frequency domain imaging. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 713. doi:10.1158/1538-7445.AM2013-713
EFECTIVIDAD, SEGURIDAD Y TOLERANCIA DE 226 PACIENTES INTERVENIDOS DE GASTROPLASTIA ENDOSCÓPICA POR MÉTODO POSE (PRIMARY OBESITY SURGERY ENDOLUMENAL)
Authors: G Lopez-Nava, I Bautista-Castaño, A Jimenez-Baños, JP Fernandez-Corbelle
Journal: Endoscopy (2014)

Introducción: La gastroplastia endoscópica por el Método POSE es una de las nuevas técnicas desarrolladas para el tratamiento de la obesidad
BENDAVIA (ELAMIPRETIDE) RESTORES PHOSPHORYLATION OF CARDIAC MYOSIN BINDING PROTEIN C ON SERINE 282 AND IMPROVES LEFT VENTRICULAR DIASTOLIC FUNCTION IN DOGS WITH HEART FAILURE
Authors: Ramesh C. Gupta, Vinita Sing-Gupta, Hani N. Sabbah
Journal: Journal of the American College of Cardiology (2016)
Abstract 1159: Single molecule sequencing to detect and characterize somatic mutations in cancer genomes
Authors: Elaine Mardis, Rachel Maupin, Kevin Travers, Chen-Shan Chin, John Eid, Benson Chau, Jason Londry, Primo Baybayan, Vince Magrini, Mike McLellan, Todd Wylie
Journal: Cancer Research (2010)

Abstract One result of large-scale cancer genome characterization is the identification of sets of genes that are commonly mutated in specific tumor types or subtypes and have clinical relevance, e.g. are prognostic or diagnostic. In this paradigm, we have investigated the use of a novel, single molecular real time (SMRT) sequencing technology from Pacific Biosciences that enables targeted regions to be sequenced in real time as single molecules in a mixed population. Several experiments were performed to evaluate the performance of this technology in the context of testing for cancer-specific mutations in previously characterized samples. In the first experiment we assessed whether SMRT sequencing could detect the known mutations of PCR products derived from genomic DNA of tumor cells compared to normal cells. In the second experiment we investigated the impact of different neoplastic cellularity percentages on the ability to detect known mutations. The final experiment involved producing deep read count SMRT sequencing data from PCR products containing known variants to ascertain their different levels of prevalence in a discrete tumor cell population, and then comparing these results to deep read counts for the same variants obtained with the Illumina instrument. Our results indicate that the Pacific Biosciences instrument offers exquisite sensitivity and speed in detecting somatic single base mutations in tumor-derived genomic DNAs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1159.
Abstract 1489: Basal cell carcinomas express functional indoleamine 2,3-dioxygenase (IDO) which may confer immunoprotection
Authors: Blanche K. Lo, Reza B. Jalili, David Zloty, Aziz Ghahary, Bryce Cowen, Jerry Shapiro, Kevin J. McElwee
Journal: Cancer Research (2010)

Abstract Basal cell carcinoma (BCC) is the most common malignancy in humans worldwide. Besides genetic alterations, abrogation of host immune defense has been suggested to enable tumor growth. Cancer cells may express factors that confer resistance to inflammatory cell mediated activity and may actively suppress immune targeting mechanisms. BCCs can derive from hair follicle bulge region keratinocytes; a structure which exhibits elements of immune privilege (IP). As such, BCCs may also exhibit immunoprotective characteristics during tumorigenesis. Indoleamine 2,3-dioxygenase (IDO) suppresses T lymphocyte proliferation via tryptophan catabolism in the kynurenine pathway. IDO is used as an immune subversion strategy by several types of cancer such as ovarian carcinomas. Expression of IDO has also been identified in hair follicle keratinocytes. Taken together, we hypothesized that IDO might have an impact on the putative IP of BCCs. In a preliminary study, we identified increased expression of mRNA in BCCs for several IP related factors. In this study, real-time RT-PCR identified significant upregulation of IDO-1 and IDO-2 (12.5- and 19.1-fold change respectively) in human nodular BCCs (n=10) as compared to non-lesional skin epithelium tissues (n=10). Dual label immunohistochemistry revealed co-localization of IDO and keratin 17 (K17), which is a BCC keratinocyte marker, in human BCC tissues (n=5). Western blot detected IDO (42kDa) and a 30kDa IDO isoform in BCC tissues (n = 6). Activity of IDO was shown by significantly increased production of L-kynurenine in the conditioned medium from cell cultures. CXCL11 has recently been shown to be a supplement required for the survival and growth of primary human BCC cells in culture. Addition of CXCL11 to primary BCC cell cultures in increased concentrations promoted increased L-kynurenine in a dose dependent manner. However, there was no significant increase in L-kynurenine production by normal primary human keratinocytes under CXCL11 treatment. In conclusion, of several differentially expressed genes associated with IP, mRNA for IDO was identified with significantly increased expression. The co-expression of the peptide with K17, as well as the IDO-mediated L-kynurenine production in human BCC cell cultures, provides further evidence of functional IDO synthesis by BCCs during their growth. The results suggest that BCCs may exhibit IP characteristics through IDO production and induction of a local collapse of such IP systems in BCC tumors may be a novel strategy for promoting BCC regression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1489.
Novel Technologies for Cervical Cancer Screening Seen on the Horizon
Authors: C. McNeil
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Novel Technologies for Cervical Cancer Screening Seen on the Horizon Get access Caroline McNeil Caroline McNeil Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 11, 7 June 1995, Pages 789–790, https://doi.org/10.1093/jnci/87.11.789 Published: 07 June 1995
Abstract 2910: Oncogenic role of MUC1 in context of TGF-β production and signaling
Authors: Sritama Nath, Shanti Rao, Teresa L. Tinder, Sandra Gendler, Pinku Mukherjee
Journal: Cancer Research (2011)

Abstract Introduction: Pancreatic cancer is the fourth leading cause of cancer-related death in United States. Most human pancreatic cancers overexpress MUC1, which is associated with high metastasis and poor prognosis of the disease. We have recently shown that MUC1 initiates the process of epithelial to mesenchymal transition (EMT) and promotes metastasis in pancreatic cancer cells via signaling through the seven tyrosines present in its cytoplasmic tail (CT) motif. When the 7 tyrosines were mutated to phenylalanine, EMT was completely abrogated. Since TGF-β has been extensively studied as a mediator of EMT and invasion in pancreatic cancer, we hypothesized that MUC1 may be inducing its effect through regulating TGF-β production and signaling. We also aimed at identifying the specific tyrosine residue(s) responsible for MUC1 induced EMT. Method: We made the following plasmids containing a) full length MUC1 (MUC1), b) all 7 tyrosine residues of MUC1 CT were mutated to Phenylalanine (Y0), c) Y6 (Tyrosine 6 present, the rest replaced by Phenylalanine), d) Y7 (Tyrosine 7 present, the rest replaced by Phenylalanine), e) Y2,5 (Tyrosine 2 and 5 present, the rest replaced by Phenylalanine), f) Y3,6,7 (Tyrosine3, 6 and 7 present, the rest replaced by Phenylalanine) and g) empty vector (Neo). These plasmids were stably expressed in human pancreatic cancer cell lines, BxPC3 and Su86.86 that express low levels of endogenous MUC1. We first assessed the levels of functional TGF-β secreted by BxPC3 Neo, MUC1 and Y0 cells as well as the levels of TGF-βI and II receptors. We then treated these cells with exogenous human recombinant TGF-β and assessed both, the process of EMT and the capacity to invade through growth-reduced matrigel. Results: We found that BxPC3.MUC1 cells produced strikingly larger amounts of TGF-β compared to BxPC3 Neo and Y0 cells. We also found that MUC1-expressing cells became more invasive in response to exogenous TGF-β while the Y0 cells did not respond to exogenous TGF-β although the receptor levels were similar in all three cell lines. However, none of the mutants of MUC1 CT could rescue the function of full length MUC1, in the context of induction of EMT. Conclusion: 1) We believe that TGF-β mediated EMT and TGF-β signal propagation requires the tyrosine residue of MUC1, which is evident from the data that mutating the tyrosine residues in MUC1CT abrogates TGF-β mediated EMT in these cells. 2) Induction of EMT by MUC1 is a complex process, which involves a particular combination of tyrosine residues of MUC1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2910. doi:10.1158/1538-7445.AM2011-2910
AB0103 Polymyalgia rheumatica has a nocturnal rise in plasma interleukin-6 which is almost completely suppressed by night time administration of modified-release prednisone
Authors: S. Zakout, L. Clark, D. Jessop, R.H. Straub, J.R. Kirwan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Musculoskeletal stiffness in polymyalgia rheumatica (PMR) follows a circadian rhythm. In rheumatoid arthritis (RA) patients, a timed release tablet of prednisone taken at 10pm led to a significant decrease in morning stiffness which was correlated with decreased night time plasma IL-6 [1]. However, the effects of timed release glucocorticoids on morning stiffness and the circadian profile of IL-6 in PMR have not been investigated. Previous studies of cytokines in PMR only collected blood samples at one time point mainly in the morning, without specifying the exact timing [2]. <h3>Objectives</h3> To determine whether IL-6 follows a circadian rhythm in patients with newly diagnosed untreated PMR, and to compare the effects of morning and night time glucocorticoids on overnight IL-6 and morning stiffness. <h3>Methods</h3> 10 patients with newly diagnosed PMR were randomised to two treatment groups with either night time modified-release prednisone 7mg (Lodotra) or morning immediate-release prednisolone 7mg. Hourly blood samples over 24-hours were taken before (Night A) and after 2 weeks treatment (Night B) to measure plasma IL-6. Patients were then treated with morning prednisolone 15mg and after 2 weeks a single measurement of IL-6 was performed at 9am (Day C). Duration of morning stiffness was recorded on each occasion. IL-6 assays were performed in Germany using the MILLIPLEX MAP kit. <h3>Results</h3> IL-6 showed a marked circadian variation in PMR, with a rise during the early hours of the morning which was partially suppressed by 7mg morning prednisolone and almost completely suppressed by 7mg night time prednisone (Figure 1a and 1b). Night time prednisone reduced morning stiffness by 90% compared to 42% with the morning prednisolone (p=0.044, t-test, figure 1c). <h3>Conclusions</h3> PMR, like RA, has a marked circadian variation in plasma IL-6. Both IL-6 and symptoms of morning stiffness are suppressed more by night time low dose glucocorticoids. This observation raises the possibility that PMR may be controlled by lower doses of glucocorticoids given at night compared to current conventional morning treatment. <h3>References</h3> Buttgereit, F., et al., Efficacy of modified-release versus standard prednisone to reduce duration of morning stiffness of the joints in RA (CAPRA-1): a double-blind, randomised controlled trial. Lancet, 2008. 371(9608): p. 205-214. Spies, C.M., et al., More Night Than Day - Circadian Rhythms in Polymyalgia Rheumatica and Ankylosing Spondylitis. Journal of Rheumatology, 2010. 37(5): p. 894-899. <h3>Disclosure of Interest</h3> None Declared
Local Factors in Ascites Formation during Sodium Retention in Cirrhosis
Authors: M. S. Losowsky, D. P. Jones, C. S. Lieber, C. S. Davidson
Journal: New England Journal of Medicine (1963)

PREVIOUS studies have indicated that in patients with cirrhosis the presence or absence of ascites can be explained by a consideration of hydrostatic and osmotic forces, and a similar analysis can be used to explain the responses to various forms of treatment.1 , 2 It is well established that, in cirrhosis, an increased intake of sodium causes an increased rate of ascites formation,3 but the precise local forces leading to the transfer of fluid across the peritoneal membrane under these conditions have not been defined. The present study was undertaken to provide such information.Patients and MethodsFour patients with portal cirrhosis . . .
Phase II study of NGR-hTNF, a vascular targeting agent, in combination with doxorubicin in patients with relapsed small cell lung cancer (SCLC).
Authors: V. Gregorc, S. Novello, A. Santoro, F. Grossi, M. Giaj Levra, R. Cavina, M. Viganò, F. Caligaris-Cappio, A. Lambiase, C. Bordignon
Journal: Journal of Clinical Oncology (2010)

e18043 Background: NGR-hTNF consists of tumour necrosis factor (TNF) fused to the tumour-homing peptide NGR, which selectively binds an aminopeptidase N overexpressed on tumour blood vessels. Both preclinical synergism and safe clinical toxicity profile were previously shown by using low-dose NGR-hTNF combined with doxorubicin. SCLC patients (pts) failing front-line platinum-based combination therapy are poor responders to chemotherapy. Methods: SCLC pts previously treated with at least one chemotherapy regimen received low-dose NGR-hTNF given at 0.8 μ g/m2 plus doxorubicin 75 mg/m2 every 3 weeks. NGR- hTNF was continued until progression and doxorubicin until a lifetime cumulative dose of 550 mg/m2. Primary study endpoint was the 3-month progression-free rate, with RECIST-defined tumour restaging done every two cycles. A two-stage design was used, assuming that 7/16 and 13/27 progression-free pts at 3 months would warrant further testing. Results: 16 pts (13M/3F) with a median age of 67 years (range, 41-75) were entered onto the first study stage. The number of prior treatment lines ranged from 1 to 3, whereas the median treatment-free interval was 3.0 months (95% CI, 0.8-6.6). Eleven pts presented with a PS of 0 and 5 pts with a PS of 1 or 2. In total, 55 cycles (median, 3; range, 1-10) were delivered. NGR-hTNF did not apparently modify the doxorubicin-related toxicity profile. No grade 3 to 4 NGR-hTNF-related toxicities were observed, whereas most grade 1 to 2 events were short-lived infusion-time related chills (56%). Eight pts (50%; 95% CI, 25-75%) were progression free at 3 months, thus allowing to proceed to the second study stage. The median progression-free survival was 3.0 months (95% CI, 1.8-4.2). Four partial responses (25%) and four stable diseases (25%) were observed, yielding an overall disease control rate of 50% (95% CI, 25-75%). Six pts progressed at their first restaging and 2 pts discontinued early because of symptomatic deterioration. The study is currently completing the accrual in the second study stage. Conclusions: The combination of NGR-hTNF and doxorubicin can be safely administered in pretreated SCLC pts, showing preliminary evidence of activity. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MolMed
Clinical Phenotype of Microsatellite Instable Metastatic or Recurrent Colorectal Cancer in a Japanese Population
Authors: H. Takahashi, M. Takahashi, M. Inoue, H. Soeda, K. Ouchi, X. Zhang, S. Takahashi, H. Shimodaira, S. Kato, C. Ishioka
Journal: Annals of Oncology (2013)