tbuckley/cabot-search huggingface dataset:
Abstract 3219: DrIMS-3DCC: Drug imaging mass spectrometry of 3D cell culture systems.
Authors: Xin Liu, Eric Weaver, Amanda B. Hummon
Journal: Cancer Research (2013)

Abstract 3D cell cultures have increased complexity compared to simple monolayer and suspension cultures, recapitulating the cellular architecture in the body. For example, many colon cancer cell lines form rounded heterogeneous spheroid structures that mimic the pathophysiological properties of tumors when grown under appropriate cell culture conditions. Classical imaging methodologies, like immunohistochemistry, are commonly used to examine the distribution of specific species within the spheroids. However, there is a need for an unbiased discovery-based methodology that would allow examination of protein/peptide distributions in 3D culture systems, without a need for prior knowledge of the analytes. We have developed a MALDI imaging mass spectrometry approach to examine protein distributions in 3D culture models (MALDI IMS-3DCC), allowing us to map the spatiotemporal dynamics of proteins in these valuable model systems. We are currently expanding our approach to image the distribution of drugs within 3D cell cultures. We are using our MALDI IMS-3DCC to analyze the penetration of drugs within 3D cell cultures. With our mass-spectrometric based approach, we have the ability to map the distribution of the 1) the drug, 2) the metabolites produced from the drug, and 3) the spatiotemporal changes in proteins following treatment. Thus far, we have successfully evaluated the effects of two clinically relevant species, oxaliplatin and Irinotecan, on spheroids. In the future, we will expand our approach to evaluate new therapeutic compounds. We believe that our novel imaging strategy will drastically alter how new therapeutic compounds are evaluated, reducing the need for animal models in the early stages of drug development, thereby speeding up the drug evaluation process. Citation Format: Xin Liu, Eric Weaver, Amanda B. Hummon. DrIMS-3DCC: Drug imaging mass spectrometry of 3D cell culture systems. [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 3219. doi:10.1158/1538-7445.AM2013-3219
Increased Uptake of I-123 IMP in Peritoneal Metastases of Hepatocellular Carcinoma
Authors: FUMIKO KODAMA, YUJI SUTO, TAKASHI IWAMIYA, YOSHIO OHTA
Journal: Clinical Nuclear Medicine (1996)

I-123 IMP is now widely used as a radioactive agent for cerebral blood flow scintigraphy. It is also known to accumulate in certain types of tumors. The authors present a case in which I-123 IMP accumulated in peritoneal metastases of hepatocellular carcinoma.
The Atrial Arrhythmias
Authors: David Scherf
Journal: New England Journal of Medicine (1955)

MANY common arrhythmias observed in both atria and ventricles are similar although the atrial types have a few important distinguishing features. Thus, so far as therapy is concerned, the atrial arrhythmias are less responsive to procaine amide than the ventricular ones. On the other hand, quinidine exerts a stronger action on the atria.1 In general, atrial tachycardias do not, if present without complications, endanger life. Atrial paralysis from the failure of impulse formation in the sinus node or a failure of conduction of the impulse from its point of origin is usually compensated immediately by the escape of the deeper . . .
Abstract 3296: Cell survival in colon cancer metastatic progression
Authors: Wang Wang, Michael G. Brattain
Journal: Cancer Research (2010)

Abstract Colon cancer is the second most lethal malignancy in the United States. The majority of deaths are due to metastasis, for which no effective therapies are currently available. While much is known about oncogenic initiation of colon cancer, the mechanisms by which cancer cells survive and metastasize in spite of the cellular stresses associated with this process require further investigation. Resent studies indicated that deregulation of apoptosis contributes to metastasis and deregulation of Bcl-2 family members are correlated with cancer progression. We have initiated studies with a unique othotopic implant model based on closely related colon cancer cell lines. HCT116 and HCT116b cells were isolated from the same primary colon tumor. They both bear the H1047R PIK3CA mutation and form progressively growing invasive orthotopic primary tumors. However, only HCT116 cells exhibit robust metastatic potential. Interestingly, we found that Bcl-2 is highly expressed in HCT116 cells, but not in HCT116b cells. Overexpression of exogenous Bcl-2 in HCT116b cells enhanced their ability to withstand external stress, indicated by reduced levels of DNA fragmentation, reduced cytochrome c release from the mitochondria, and increased caspase activation. Immunoprecipitation assays revealed the formation of Bcl-2: Bax heterodimers, which has been shown to exert the anti-apoptotic property of Bcl-2. In complementary experiments, both shRNA-mediated stable knockdown and overexpression of dominant negative forms of Bcl-2 in metastatic HCT116 cells abolish its survival advantage against stress. These results indicate that modulation of Bcl-2 protein alone can reverse the sensitivity of HCT116 and HCT116b cells to stress-induced apoptosis. Current studies in our orthotopic model will determine whether alterations in Bcl-2 expression as well as complex formation of Bcl-2/Bax affect the metastatic potential of colon cancer in vivo, and consequently provide direct evidence as to whether cell survival control determines metastasis. 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 3296.
Abstract 4250: Deficiency of CD109, a negative regulator of TGF-β signaling, leads epidermal hyperplasia and appendage abnormalities in mice
Authors: Shinji Mii, Yoshiki Murakumo, Naoya Asai, Masato Asai, Masahide Takahashi
Journal: Cancer Research (2012)

Abstract CD109, a glycosylphosphatidylinositol (GPI)-anchored glycoprotein, is a member of the β2-macroglobulin/C3, C4, C5 family of thioester-containing proteins. It has been reported that CD109 is highly expressed in various tumor cell lines and in tumor tissues including squamous cell carcinomas (SCCs) of the lung, oral cavity, esophagus and uterine cervix, malignant melanoma of the skin, and urothelial carcinoma of the urinary bladder. CD109 is, therefore, thought to be a cancer-related gene. On the other hand, CD109 is a component of TGF-β receptor system and negatively regulates TGF-β signaling. However, its physiological function in vivo remains largely unknown. To investigate the physiological function of CD109 in vivo, we generated CD109-deficient (CD109-/-) mice in which exon 1 and 2 of CD109 genomic locus were replaced with the lacZ gene. CD109 protein is expressed in the skin, tongue, and testis of adult CD109+/+ mice, but not in CD109-/- mice. Macroscopically, CD109-/- mice showed hair growth impairment from postnatal day 7 (P7) and persisted until P28. Microscopically, hyperplasia of the epidermis and sebaceous glands became apparent at P7 in CD109-/- mice and sustained until P70, and the hair follicles of CD109-/- mice exhibited ectasia with kinked hair shafts at P14. The epidermis of CD109-/- mice showed apparent thickening of the basal / suprabasal layers, which are positive for CK14, compared with CD109+/+ mice, whereas no significant differences in Ki-67 or cleaved caspase-3-positive ratios were detected between the two groups. These results suggest that CD109 regulates the differentiation of keratinocytes in vivo, and impairment of hair growth and ectatic hair follicles may be secondary changes caused by narrowing of the infundibular portion of the hair follicles due to epithelial hyperplasia. 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 4250. doi:1538-7445.AM2012-4250
HIGH SENSITIVITY CARDIAC TROPONIN I IS ASSOCIATED WITH MENTAL AND CONVENTIONAL STRESS INDUCED MYOCARDIAL ISCHEMIA
Authors: Muhammad Hammadah, Ibhar Al Mheid, Kobina Wilmot, Ronnie Ramadan, Ayman Alkhoder, Mosaab Awad, Malik Obideen, Naser Abdelhadi, Shuyang Fang, Yasir Bouchi, Oleksiy Levantsevych, Heval Mohamed Kelli, Matthew Topel, Pratik M. Pimple, Kareem Hosny, Nancy Murrah, Paolo Raggi, Amit J. Shah, Ernest Garcia, Viola Vaccarino, Arshed Quyyumi
Journal: Journal of the American College of Cardiology (2016)
SP0194 Leveraging an Innovative TRIAL Design for A Rare Disease Context: the Cohort Multiple RCT (CMRCT) Design
Authors: B.D. Thombs
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Pragmatic randomized controlled trials (RCTs) are considered the gold standard for determining the effectiveness of interventions in actual clinical practice. Traditionally designed pragmatic RCTs have high internal validity, but have been criticized for having poor external validity. They often are able to recruit only a small portion of eligible patients, which reduces both power and the generalizability to actual practice, since patients who partake in trials may differ substantially from patients treated in practice. The most common reason why patients choose not to participate in clinical trials is that they are uncomfortable with being randomized to treatment or non-treatment, a practice that deviates from what would occur in actual clinical practice. The cohort multiple randomized controlled trial (cmRCT) design was developed to address this problem, as well as other shortcomings in traditional trial designs. In the cmRCT design, individuals consent to participate in a cohort for ongoing data collection and to allow their data to be used for comparison purposes to patients from the cohort who may be offered any number of trials that are conducted in the cohort framework. The objective of this presentation is to describe the cmRCT design and how it is being implemented in the CIHR-funded Scleroderma Patient-centered Intervention Network (SPIN), as well as how it could be used in other rheumatology clinical trials. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6105
Abstract 1412: Progesterone and calcitriol attenuate inflammatory cytokines CXCL1 and -2 in endometrial and ovarian cancer cells
Authors: Leyla Kavandi, Michael A. Collier, Huyen Nguyen, Viqar Syed
Journal: Cancer Research (2012)

Abstract Chronic inflammation has been shown to play a critical role in growth of cancers. NF-κB is a transcriptional factor that regulates diverse biological processes, including cell proliferation, survival and inflammation. We have previously shown inhibition of endometrial and ovarian cancer cell growth with progesterone and calcitriol. In the present study, we evaluated the effect of progesterone and calcitriol on the expression of inflammatory genes. Using RT-PCR array of inflammatory cytokine and receptor genes, we found two inflammatory cytokines, CXCL1 and -2 (GRO-A and -B), downregulated by both treatments. PCR array results were validated by Western blotting. Knockdown of NF-kB resulted in a reduced expression of CXCL1 and -2 and the inhibitory effect of progesterone and calcitriol on the expression of cytokines was abrogated in NF-kB-silenced cancer cells. Silencing of IkBα increased the expression of CXCL1 and -2 in cancer cells, which can be attributed to the increased activation of NF-kB-p65, caused by the lack of its inhibitor. Progesterone and calcitriol-induced inhibition was abolished in IkBα-knockdown cells. Our results demonstrate that suppression of IkBα phosphorylation by progesterone and calcitriol contributes to the reduced expression of CXCL1 and -2. We investigated the effect of CXCL1 and -2 downregulation on metastasis-promoting genes and found a marked inhibition of CXCR4, COX2 and matrix metalloproteinases (MMP2 and MPP-9). Overall, our results indicate that progesterone and calcitriol downregulate NF-kB in cancer cells, leading to the suppression of metastasis, thus providing the molecular basis for the treatment of endometrial and ovarian cancer patients with progesterone and calcitriol. 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 1412. doi:1538-7445.AM2012-1412
OC-008 Defining the genetic landscape of oesophageal adenocarcinoma by next-generation sequencing
Authors: J M J Weaver, N B Shannon, M Smith, M Dunning, C A Ong, C Ross-Innes, T Underwood, A Lynch, M Eldridge, C Caldas, P Edwards, S Tavare, R C Fitzgerald
Journal: Gut (2012)

<h3>Introduction</h3> Despite its dismal prognosis and steady increase in prevalence little is known about the genetic alterations that drive oesophageal adenocarcinoma. As part of the International Cancer Genome Consortium: Oesophageal Adenocarcinoma (ICGC-OAC) we performed a pilot study, sequencing the genomes of 32 OAC samples, to assess the feasibility of initiating a large scale project sequencing a total of 500 OAC genomes. <h3>Methods</h3> A total of 56 genomes were selected for sequencing including 32 OAC genomes—16 chemotherapy-Naive, 16 chemotherapy-treated—and 24 matched normal genomes. Whole genome sequencing was performed on the Illumina Hiseq 2000 platform. Initial bioinformatic analysis, run by Illumina using the Casava pipeline, detected single nucleotide variants (SNVs), small (&lt;50 bp) Insertion and Deletions events (INDELs) and large scale structural variants (SVs). Additionally, bioinformatic analysis of SVs was performed using a custom Perl script. To determine the specificity of the bioinformatic approach a subset of SNVs and SVs were selected for verification by Sanger capillary sequencing and PCR respectively. <h3>Results</h3> A minimum of 50-fold mappable sequence data were generated for each of the 56 genomes. 161/167 (96%) of predicted SNVs were confirmed as somatic, two were miscalled germline variants while four were undetectable in either sample. For 2/75 (3%) SVs PCR amplicons could not be generated, for 18 of 75 SVs (24%) a PCR amplicon was detectable in the normal showing them to be germline polymorphisms. The True positive rate for SV detection was therefore 73%. Comparison of SNV information across all 24 samples revealed many recurrently mutated genes. These include previously reported mutations in TP53, CDKN2A and APC among others. No genes were significantly associated with chemotherapy-treated or chemotherapy-naive samples. <h3>Conclusion</h3> Analysis of the Illumina bioinformatic pipeline suggests it is highly specific (96% true positive rate) for somatic SNVs. A true positive rate of 73% for SV detection is comparable to recent literature. Further analysis to determine the sensitivity of this pipeline is ongoing including resequencing of putatively non-mutated genes in samples sent for WGS and the application of alternative bioinformatic approaches for the calling of SNVs, INDELs and SVs. Initial analysis of the SNV data from 32 tumour genomes has revealed several recurrently mutated genes known to be altered in OAC validating the ability of our approach to detect candidate “driver” genes. <h3>Competing interests</h3> None declared.
Phthiriasis Palpebrarum in a Child
Authors: Giuseppe Micali, Francesco Lacarrubba
Journal: New England Journal of Medicine (2015)

A 6-year-old boy presented with erythema and pruritus of the eyelids, which had been previously diagnosed as atopic dermatitis and unsuccessfully treated with topical glucocorticoids and systemic antihistamines. Dermatoscopy showed crab lice and their nits, shown in a video.
Abstract P2-14-12: Contents Preferred for a Post Treatment Survivorship Care Plan for Breast Cancer Survivors
Authors: S Singh-Carlson, C Gotz
Journal: Cancer Research (2010)

Abstract Background: Current evidence indicates that the range of survivorship issues that patients can encounter is broad and can include physical, psychological, social and spiritual aspects. Studies also show that breast cancer survivors (BCS) may feel isolated and uninformed after completion of active treatment, when they have less interaction with health professionals. Although, Institute of Medicine's report on cancer survivorship recommends that cancer patients completing treatment should be provided with a comprehensive care summary and follow up plan that is clearly and effectively explained, it is not always practiced in oncology care. Methods: A qualitative approach was used to explore impacts of breast cancer on survivors at different life stages and to determine preferred content and format of survivorship care plan (SCP). Focus group and face-face interviews were audio-recorded and transcribed with women who had non-metastatic breast cancer, 3-48 months post-treatment and were 18-75 years of age. Groups were stratified by age into &amp;lt;44, 45-54, 55-64, and &amp;gt;65. Transcripts were subjected to thematic and content analysis by age group (life stage). Results: Results from16 women interviewed from the 4 age groups show that the impacts of breast cancer were broad and varied by age group. Physical, emotional and social effects were more intense in younger patients with women in the middle age group experiencing more concerns centered on financial and social support issues. Fatigue, fear of the unknown, and fear of recurrence were the most universal effects. Although customized SCP was preferred, important elements include: treatment summary, information on nutrition/exercise, expected side effects, signs/symptoms of recurrence, follow-up schedule, and updates on changes to recommended care. Preferred format for SCP is similar for all groups. Women preferred oncology nurses to provide the SCP at the beginning or at the end of the treatment and preferred written materials in lay language, telephone follow-up resource person and electronic bulletins for communicating updates. Discussions: BCS are diversely impacted by the breast cancer experience. Effects vary by life stage, which impacts preferred content of SCP, but not format. Qualitative information on the impact of breast cancer at different life stages can be used to help customize content of SCPs. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-14-12.
Abstract 1766: Investigating Chk1 biology with selective oral Chk1 inhibitor.
Authors: Zhenxiong Wang
Journal: Cancer Research (2013)

Abstract Chk1 inhibitor as a chemo-potentiator in cancer therapy was proposed more than 10 years ago. Most of the first generation i.v. dosing chk1 inhibitors were terminated in clinical trials recently. The second generation oral chk1 inhibitors were just launched by several companies. However, many questions in Chk1 biology remain unclear, which is important to guide Pfizer to develop oral chk1 inhibitor in the future. Chk1 biology team investigated preclinical scheduling, biomarker, combination strategy, TGI, primary indication and patient selection with chk1 tool compounds. Biomarker is critical in evaluating POM in clinical trial phase I. Significant target modulations and dose responses of biomarkers p-Chk1 345, r-H2AX, cleaved-PARP were observed in both in vitro and in vivo studies, suggesting their potential application in clinical setting. The scheduling study indicated its importance in chk1 project. Both administration of chk1 inhibitor soon after chemotherapy and sustained inhibition of chk1 robustly improved efficacy in Miapaca2 pancreatic cancer model. There was no clear patient selection strategy for Chk1 clinical trials in the past. To investigate the primary indication and patient selection, 6 indications were indentified according to clinical trial results and human tumor tissue genomics, more than 100 cancer cell lines were screened with either chk1 inhibitor alone or in combination with SOC. 75%(12/16) cell lines in mesothelioma and 44% (4/9) in endometrial carcinoma demonstrated significant synergy in the combination treatment. Next generation sequencing and SiRNA library screening in DNA damage repair genes (DDR) will be used to clarify the mechanisms. In summary, we have identified treatment schedule and potential new indications for Chk1 inhibitor, which could significantly increase efficacy, lower toxicity, and improve probability of success in clinical trials. Citation Format: Zhenxiong Wang. Investigating Chk1 biology with selective oral Chk1 inhibitor. [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 1766. doi:10.1158/1538-7445.AM2013-1766
FRI0333 Leflunomide as a corticosteroid-sparing agent in giant cell arteritis and polymyalgia rheumatica: a consecutive case series
Authors: H. Hetland, G. Myklebust, A. P. Diamantopoulos
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) affecting individuals older than 50 years and corticosteroids are the mainstay of treatment. Azathioprine and methotrexate have shown little or moderate efficacy as corticosteroid-sparing agents [1]. <h3>Objectives</h3> Our aim was to examine the role of leflunomide as a corticosteroid-sparing agent in difficult -to-treat GCA and PMR patients. <h3>Methods</h3> Patients with difficult-to-treat GCA and PMR were retrospectively identified in our vasculitis clinic between 2010 and 2013. The dose of corticosteroids and CRP values were recorded before and at the end of the treatment (for patients continuing treatment, censoring date was 1 January 2013). Side-effects were also registered. Student’s t-test was used to compare the means. Statistical significance was defined as p&lt;0.05. <h3>Results</h3> Twenty three patients were recruited (3 males, 20 females, mean age 69 years), 12 with PMR and 11 with GCA. All the patients fulfilled either the ACR classification criteria for GCA [2] or the EULAR/ACR classification criteria for PMR [3]. Mean duration of treatment was 10.7 months (SD 9.8). The mean value of CRP at starting point was 21.8 mg/dl (SD 27.3) and 18.8 mg/dl (SD 18.0) for the PMR and GCA groups respectively. Mean staring dose of corticosteroids was 10.6 mg (SD 4.3) and 10.5 mg (SD 4.2) for PMR and GCA groups respectively. Six patients (26%) discontinued treatment due to side-effects and 5 patients (21%) due to remission. A mean difference of 11.6 mg/dl in CRP (CI 95% -10.9-34.2, p=0.27) and 3.8 mg (CI 95% 0.5-7.0, p=0.03) in prednisolone dose was observed in PMR group. In GCA patients, the mean differences were 12.4 mg/dl (CI 95% -0.7-25.5, p=0.06) in CRP and 6.6 mg (CI 95% 2.8-10.3, p=0.003) in prednisolone dose. <h3>Conclusions</h3> Leflunomide seems to be effective as a corticosteroid sparing agent in patients with difficult-to-treat GCA and PMR. However, a high rate of withdrawals was observed in our study, with 1 in 4 patients discontinuing leflunomide treatment due to side-effects. Randomized controlled trials are warranted to examine the usefulness of leflunomide in the treatment of GCA/ PMR. <h3>References</h3> Schmidt J, Warrington KJ. Polymyalgia rheumatica and giant cell arteritis in older patients: diagnosis and pharmacological management. Drugs &amp; aging. 2011;28(8):651-66. Epub 2011/08/05. Hunder GG, Bloch DA, Michel BA, et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum. 1990;33(8):1122-8. Epub 1990/08/01. Dasgupta B, Cimmino MA, Kremers HM, et al. 2012 Provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Arthritis Rheum. 2012;64(4):943-54. Epub 2012/03/06. <b>Disclosure of Interest</b>: None Declared