tbuckley/cabot-search huggingface dataset:
Abstract P2-04-06: Transgenic expression of a breast-cancer specific GATA3 mutant leads to mammary hyperplasia
Authors: PA Kenny, N Chandiramani
Journal: Cancer Research (2012)

Abstract GATA3 is expressed in normal luminal breast epithelial cells and is a key transcription factor in mammary gland development. In human breast tumors, high GATA3 protein levels are associated with estrogen receptor (ER) positivity and low grade. Recent published reports indicate that somatic mutations of GATA3 occur in up to 21% of ER+ tumors. These authors suggest, but do not demonstrate, that these GATA3 mutations are loss-of-function null alleles and that GATA3 is a haploinsufficient tumor suppressor gene. The published mutational data indicate a striking enrichment of GATA3 mutations in exons 5 and 6 (amino acids 309–443) which encode the second of two DNA binding zinc fingers. This suggests that mutant proteins lacking this zinc finger may confer a survival advantage on breast cancer cells. Given this apparently strong selective pressure for mutations in this hotspot, it seems unlikely that these mutations are loss-of-function alleles. We explored this directly by generating a MMTV-GATA3mutant mouse which specifically expresses a mutant GATA3 protein in the mammary gland. Non-parous pubertal transgenic mice exhibit a pronounced mammary hyperplasia and have increased ductal branching compared to wildtype littermates. These data confirm that the mutant GATA3 mutations commonly found in breast cancer are not null alleles, but that they instead have a gain-of-function phenotype. We are currently evaluating the effect of mutant GATA3 on the kinetics of mammary tumorigenesis by crossing these mice to the MMTV-PyMT model. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-04-06.
Studies on the Antibody Response in Splenectomized Persons
Authors: Samuel Saslaw, Bertha A. Bouroncle, Robert L. Wall, Charles A. Doan
Journal: New England Journal of Medicine (1959)

TO date, relatively little work has been done on the humoral antibody response in splenectomized persons. Rowley,1 using a single intravenous injection of 2 per cent sheep red blood cells, reported that 13 of 14 splenectomized patients failed to respond with a significant antibody titer nine to fourteen days after injection whereas all of 14 controls showed a significant rise. McFadzean and Tsang2 also used the intravenous injection of sheep red blood cells, and noted that the antibody response in 10 splenectomized patients was inferior to that observed in 11 controls. However, the same workers3 found that 15 splenectomized patients . . .
Signet-ring cell cancer of the colon presenting as facial and gastroduodenal metastasis 7 years after sigmoidectomy
Authors: Bin Li, Qian Li, Xiang Li, Guiying Zhang, Liangfang Shen
Journal: Endoscopy (2014)

A 46-year-old man presented with a red, nonpainful, fast-growing nodule with ulceration in the face, along with nausea and weight loss. Seven years ago, he had undergone sigmoidectomy for signet-ring cell adenocarcinoma (stage T2N0M0) in the sigmoid colon, and he had been followed up and appropriately screened regularly for cancer recurrence after the surgical intervention.
P42 Does pulmonary rehabilitation improve exercise capacity and HRQoL in patients with asthma?: Abstract P42 Table 1.
Authors: RJ Tanner, AK Boutou, Y Raste, VM Lord, LJ Grillo, A Menzies-gow, J Hull, Hopkinson NS
Journal: Thorax (2013)

<h3>Introduction</h3> Pulmonary rehabilitation (PR) benefits patients with COPD, however to date there is limited evidence demonstrating its effectiveness in patients with chronic asthma. We hypothesised that patients with asthma would have a significant improvement in exercise capacity and HRQOL following a standard PR programme. The aim of this study was a) to evaluate the impact of PR on exercise capacity and HRQoL in patients with asthma and b) to identify the factors influencing attendance and completion. <h3>Methods</h3> We retrospectively audited PR outcome in a cohort of asthmatic patients referred for PR at the Royal Brompton Hospital between 2008 and 2012. Exercise capacity (ISWT), quadriceps maximal volitional contraction (QMVC) and HRQoL (HADS, SGRQ, LINQ, MRC) were assessed before and following PR. Logistic regression analysis was used to determine factors predicting PR completion. <h3>Results</h3> 49 patients were referred of whom 25 completed (69.2% female; mean age: 58.7 ± 12.5 years; mean BMI: 31.27 ± 30.1) Completers were moderately obstructed (mean FEV<sub>1</sub>% pred: 57 ± 22.9, FEV<sub>1</sub>/FVC: 0.63 ± 0.14). 4% of them were current smokers and 8% were ex-smokers (mean history of 11.25pack/yrs). Mean classes attended were 15.3 1 ± 5.4 per patient. There was a significant improvement in QMVC (p = 0.02) and ISWT (p = 0.036) following PR. Other than LINQ score (p = 0.016), there was no improvement in HRQoL measures following PR. Patients with a higher%Fat, according to bioelectrical impedance, were less likely to complete PR once they had been referred. No other statistically significant differences were found between completers and non-completers. <h3>Conclusions</h3> Asthmatic patients benefit from attending a PR course in terms of functional capacity and muscle strength. Further prospective studies utilising asthma specific quality of life indices are required to evaluate disease specific benefits of PR and delineate factors predicting successful PR. <b>Does pulmonary rehabilitation improve exercise capacity and HRQoL in patients withasthma?</b>
Abstract 81: Role of GRM1 in breast cancer
Authors: Madhura S. Mehta, Sonia Dolfi, Roman Bronfenbrener, Erhan Bilal, Daniel Medina, Bruce Haffty, Deborah Toppmeyer, Shridar Ganesan, Kim M. Hirshfield
Journal: Cancer Research (2012)

Abstract Despite epidemiologic studies suggesting a link between melanoma and breast cancer, molecular mechanisms leading to these associations have not been elucidated. Overexpression of metabotropic glutamate receptor 1 (GRM1) has been implicated in melanomagenesis. Its primary action occurs through activation of the MAPK signaling pathway and other pathways through intracellular calcium release. A recent study implicated GRM1 as playing a role in angiogenesis in hormone receptor negative breast cancer. However, the role of GRM1 in hormone receptor positive disease is yet to be described. Given the associations between melanoma and breast cancer, we evaluated three SNPs in GRM1 for genotype associations with breast cancer clinicopathologic variables using DNA isolated from peripheral blood of 1,096 breast cancer patients. Our study found that a SNP in GRM1 resulting in a proline to serine substitution correlates with age at diagnosis of breast cancer and reflects the receptor status of the breast cancer, e.g. for progesterone receptor positive (PR+) disease, proline carriers were diagnosed 8 years earlier than serine carriers. Genotype-specific associations with risk of developing specific molecular subtypes of breast cancer were observed, i.e. serine carriers were twice as likely to develop estrogen receptor positive (ER+) and PR+ disease. Furthermore, carrying the proline isoform also correlated with higher risk of recurrence of breast cancer and shorter time to recurrence. Immunohistochemical evaluation of breast microarrays showed that GRM1 expression is higher in breast cancers as compared to normal tissue and is higher in ER+ as compared to ER- breast cancers. This parallels higher expression observed in ER+ breast cancer cells lines in comparison to ER- lines. In vitro studies with breast cancer cell lines were also performed to evaluate the expression of GRM1 as a function of hormone exposure and cell line receptor status. Treatment of ER+ cell lines with estradiol resulted in increased GRM1, while tamoxifen decreased expression. Gene expression data on ER+ breast cancers treated with tamoxifen were reanalyzed for association between GRM1 expression and recurrence. Analysis of breast cancers treated with tamoxifen from an independent cohort demonstrated that high expressors of GRM1 have a worse distant recurrence free survival. The results of these studies implicate GRM1 in hormone receptor positive breast cancer biology. Additional knowledge regarding the interaction between GRM1 and hormone signaling could have significant implications in breast cancer risk, prevention, and treatment. 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 81. doi:1538-7445.AM2012-81
Bone Scintigraphy of Drug-Induced Rhabdomyolysis:
Authors: TERUHIKO TAKAYAMA, SHIRO TSUJI, JUNICHI TAKI, TAKATOSHI MICHIGISHI, NORIHISA TONAMI
Journal: Clinical Nuclear Medicine (1996)

A 61-year-old man had drug-induced rhabdomyolysis caused by an antihyperlipidemia agent (Bezafibrate). A bone scan showed abnormal soft tissue accumulation that was compatible with muscle necrosis.
Potentiation of hepatic and renal toxicity of various compounds by prior exposure to polybrominated biphenyls.
Authors: W M Kluwe, K M McCormack, J B Hook
Journal: Environmental Health Perspectives (1978)

Mice ingesting a standard rodent diet supplemented with polybrominated biphenyls (PBBs) were more susceptible to chlorinated hydrocarbon solvent-induced renal and hepatic damage, as well as the lethal effects of CHCl3 and CCl4, than were mice consuming control diet. As little as 0.025 ml/kg CHCl3 caused a significant increase in serum glutamic oxaloacetic transaminase (SGOT) and blood urea nitrogen (BUN) and a significant decrease in renal cortical slices accumulation of p-aminohippurate (PAH) in PBB-pretreated but not control mice. SGOT and serum glutamic pyruvate transaminase (SGPT) were greater in PBB-pretreated mice than in control mice after 0.125 and 0.005 ml/kg CCl4, respectively. Renal cortical PAH accumulation was greatly reduced in PBB-pretreated but not control mice aftter 0.125 ml/kg CCl4. The solvent-induced decrease in PAH accumulation was also greater in PBB-pretreated mice than in control mice following administration of 1.0 ml/kg trichloroethylene (TRI) and 0.15 ml/kg 1,1,2-trichloroethane (TCE).
Benefits of Point-Spread Function and Time of Flight for PET/CT Image Quality in Relation to the Body Mass Index and Injected Dose
Authors: Go Akamatsu, Katsuhiko Mitsumoto, Kaori Ishikawa, Takafumi Taniguchi, Nobuyoshi Ohya, Shingo Baba, Koichiro Abe, Masayuki Sasaki
Journal: Clinical Nuclear Medicine (2013)

The PET image quality of overweight patients and patients who receive low injected doses deteriorates because of increases in statistical noise. The purpose of this study was to investigate the benefits of the point-spread function (PSF) and time-of-flight (TOF) for PET/CT image quality in such patients.The PET images were reconstructed using the baseline ordered-subsets expectation-maximization algorithm (OSEM), OSEM + PSF, OSEM + TOF, and OSEM + PSF + TOF. In the phantom study, we used a National Electrical Manufacturers Association body phantom with different radioactivity concentrations and analyzed image quality using the coefficient of variance in the background (CVphantom). In the clinical study, we retrospectively studied 39 patients who underwent clinical F-FDG PET/CT. The patients were classified into groups based on body mass index and injected dose. Image quality was evaluated using the CV in the liver (CVliver).In the phantom study, PSF and TOF improved the CVphantom, especially in low-activity models. Among all of the reconstructions, the best CVphantom was obtained with OSEM + PSF + TOF. In the clinical study, the CVliver of the low-dose group with OSEM + PSF + TOF was comparable to that of the high-dose group with conventional OSEM.Point-spread function and TOF improved PET/CT image quality for overweight patients who received a lower injected dose. Therefore, the use of PSF and TOF is suggested to maintain the image quality of such patients without extending scanning times. It is greatly beneficial to obtain sufficient image quality for larger patients, especially in delivery institutions where the injection dose cannot be easily increased.
Abstract 639: Inhibition of HER2 signaling using targeted therapeutics in breast cancer cell lines
Authors: James Korkola, Nora Bayani, Brian Cooper, Laura M. Heiser, Paul T. Spellman, Heidi S. Feiler, Richard Wooster, Joe W. Gray
Journal: Cancer Research (2011)

Abstract ERBB2/HER2 amplification occurs in 20-30% of all breast cancers and is associated with an aggressive clinical behavior. Therapeutics that target HER2 offer a modest survival benefit when given as monotherapy. Recent studies indicate that in the case of the HER2/EGFR inhibitor lapatinib, there is an initial down-regulation of the PI3K-AKT signaling pathway followed by reactivation of the pathway through p-HER3. Inhibition with much higher doses of lapatinib in vitro prevents the reactivation of the pathway, implying that more effective inhibition of HER2 could lead to more durable responses. To explore this phenomenon more fully, we examined response to lapatinib in a panel of 22 HER2 amplified breast cancer cell lines. Of the 22, there were 5 that were resistant to lapatinib, failing to reach 50% growth inhibition (GI50) even at doses as high as 5 uM. These lines have also been reported to be resistant to trastuzumab. However, all the cell lines in the panel were sensitive to BIBW-2992, which is an irreversible EGFR/ERBB2 inhibitor, with GI50 values in the nanomolar range. Initial western blot analysis indicated that in response to BIBW-2992, there was down-regulation of p-AKT and p-HER3, but that there was recovery of both over time to levels that were comparable to untreated cells. Finally, we observed strong synergistic interactions between BIBW-2992 in combination with a PI3K inhibitor in almost every HER2+cell line tested. These results suggest that even in the setting of resistance to lapatinib and trastuzumab, all HER2 amplified cell lines in our panel are still addicted to HER2 signaling, and that more efficient inhibition of HER2 can result in significant inhibition of growth and loss of viability in HER2 positive breast cancer cell lines. BIBW-2992 was effective against HER2 amplified cells even though inhibition of p-AKT and p-HER3 was not complete. However, addition of PI3K pathway inhibitors resulted in strong synergism in combination with BIBW-2992. These studies set the stage for clinical investigations into the efficacy of such irreversible HER2 inhibitors in patients with HER2 positive breast cancer. 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 639. doi:10.1158/1538-7445.AM2011-639
P1310 HEPATOCELLULAR CARCINOMA (HCC) INVADING PORTAL VENOUS SYSTEM IN CIRRHOSIS: 7 YEAR RESULTS OF PERCUTANEOUS RADIOFREQUENCY ABLATION OF HCC AND MAIN PORTAL VEIN TUMOR THROMBUS (MPVTT)
Authors: A. Giorgio, G. Calisti, C. Coppola, F. Scarano, U. Scognamiglio, N. Farella, L. Montesarchio, G. de Stefano, P. Gatti, V. Giorgio
Journal: Journal of Hepatology (2014)
In vivo diagnosis and characterization of gastric Crohn's disease using endomicroscopy and virtual chromoendoscopy
Authors: G. Hundorfean, A. Agaimy, A. Hartmann, M. Chiriac, J. Siebler, M. Neurath, J. Mudter
Journal: Endoscopy (2012)

Confocal laser endomicroscopy (CLE) and virtual (dyeless) chromoendoscopy are sophisticated, so-called advanced imaging techniques within contemporary endoscopy. I-Scan (Pentax, Tokyo, Japan) is a computer-based color program that enhances the contrast of mucosal details, especially the superficial vascularization [1]. In contrast, CLE provides a deeper view, meaning that a real-time and in vivo visualization of a plethora of cellular and subcellular details can be achieved, which correlates with conventional histology [2] [3]. Both techniques have an immense impact on modern endoscopic diagnosis and surveillance.
Patient-to-Patient Transmission of Hepatitis C Virus during Colonoscopy
Authors: Jean-Pierre Bronowicki, Véronique Venard, Christine Botté, Nathalie Monhoven, Isabelle Gastin, Laurence Choné, Hervé Hudziak, Bertrand Rhin, Christophe Delanoë, Alain LeFaou, Marc-André Bigard, Pierre Gaucher
Journal: New England Journal of Medicine (1997)

Invasive diagnostic or therapeutic procedures may be a route for the transmission of the hepatitis C virus (HCV).1–5 In a study of patients in a gastrointestinal-disease unit, endoscopic biopsies were found to be an independent risk factor for HCV infection.6 We report the transmission of HCV during colonoscopy from a person known to have HCV infection to two other patients. The patient-to-patient transmission was ascertained by sequencing the nucleotides in the various HCV isolates. Case Report A 55-year-old man (Patient 1) and his 54-year-old wife (Patient 2) were referred in October 1995. In June 1995, both had had hepatitis-like . . .
Abstract C3: Selective denuding of nanoparticles for tumor targeting
Authors: Jacob M. Berlin
Journal: Cancer Research (2011)

Abstract Targeted delivery of therapeutics to tumors is highly desired both to deliver fragile compounds that cannot reach the tumor on their own and to limit off-target toxicity. Nanovectors, nanoparticles capable of transporting and delivering one or more bioactive molecules, are an emerging class of targeted drug delivery platforms. Targeting of nanovectors to tumors is conventionally achieved both by designing them to be approximately 50–200 nm in diameter in order to take advantage of the enhanced permeation and retention (EPR) effect common to tumors and/or functionalizing the nanovectors with ligands that bind specifically in the tumor environment. In order for these strategies to be successful, the nanovectors must have an extended circulation time in the blood. One result of this is accumulation and prolonged retention of many nanovectors in the liver and spleen, which raises toxicity concerns. Here we demonstrate a dramatically different strategy making use of nanovectors composed of insoluble ultrasmall nanoparticles cores functionalized with responsive solubilizing polymer shells. The responsive polymers are designed to be cleaved from the insoluble nanoparticles core in the tumor microenvironment, which results in the deposition of the insoluble nanoparticles at the tumor site. On the other hand, because the particles are ultrasmall, if they remain unchanged they are rapidly cleared from the body, dramatically reducing potential side effects. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C3.
Abstract P5-10-19: The Influence of Time to Completion of Chemotherapy on Survival in Patients with Triple Negative Stage III Breast Cancer
Authors: J De Los Santos, B Hinton, J Carpenter, A LoBuglio, C Falkson, K Keene, R Meredith, H Krontiras, K Bland, C Wang, Y Kim, A. Forero
Journal: Cancer Research (2010)

Abstract Background: Neoadjuvant chemotherapy is increasingly delivered to facilitate breast conserving surgery through tumor downstaging. Prospective trials of neoadjuvant chemotherapy from the NSABP suggest no difference in survival outcomes in patients receiving neoadjuvant versus adjuvant therapy; however, subset analysis in 2 combined trials (B-18 and B-27) demonstrated a trend in DFS improvement in young patients (&amp;lt;50 yrs), who often have more aggressive variant tumors. This study explores the possibility that patients with aggressive variant molecular subtypes [triple receptor negative (TN)] treated with modern chemotherapy, may significantly benefit from earlier completion of drug delivery. Methods: Billing codes for all breast cancer patients treated with chemotherapy between 1/1998 and 5/2005 at the University of Alabama at Birmingham were reviewed to comprehensively capture all Stage II and III patients with intact data. Patient, tumor, and treatment related variables were recorded and patients were divided to 4 molecular subtypes based on receptor status: hormone receptor (HR) positive, Her2 negative; HR+/− , Her2+; and triple receptor negative (TN). Kaplan Meier curves to assess survival were performed by dividing the TN group into 2 groups: those completing chemotherapy ≥5 vs &amp;gt; 5 months from diagnosis. Results: 409 patients with Stage II-III disease with were identified: 124 received neoadjuvant and 285 received adjuvant chemotherapy. Out of this group, 81 patients had TN breast cancer (60 Stage II and 21 Stage III). Median age was 49 years. Median follow-up was 72 months. Chemotherapy consisted of adriamycin, taxol and cytoxan for a median of 9 cycles. Stage III patients who completed chemotherapy within 5 months had a statistically significant improvement in OS and DFS (p=0.03), and had a trend towards improvement in DMFS (p=0.10) when compared with those who took longer than 5 months to complete chemotherapy. Conclusion: Completion of chemotherapy in a shorter time interval in patients with Stage III, TN breast cancers was associated with an improvement in DFS and OS. Consideration of timing of chemotherapy warrants further study. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-19.
Abstract 4973: Recurrent chimeric RNAs enriched in human prostate cancer identified by deep-sequencing
Authors: Kalpana Kannan, Liguo Wang, Jianghua Wang, Michael Ittmann, Wei Li, Laising Yen
Journal: Cancer Research (2011)

Abstract Chimeric transcripts unrelated to chromosomal rearrangement are primarily generated by two transcription-induced mechanisms: read-through/splicing and trans-splicing. Both mechanisms result in fused transcripts that possess sequences from both genes. Although the exact cause and regulation of chimeric transcripts are unknown, chimeric RNAs, like fusion genes, are expected to increase the proteomic diversity in cells through chimeric proteins or altered regulation of participating mRNAs. Despite its importance, few studies have reported on chimeric RNAs, especially regarding their presence and roles in human cancers. In this study, we took advantage of the analytical power of paired-end high throughput sequencing to characterize chimeric transcripts enriched in human prostate cancer. By deep-sequencing the transcribed mRNA (transcriptome) of 20 clinical prostate cancer tissues, in addition to 10 matched benign prostate tissues from the same patients, we obtained greater than 500 million useful sequence reads. This strategy combined with stringent bioinformatic criteria enabled the identification of 27 novel and highly recurrent chimeric RNAs that have never been described before. The novel chimeric transcripts were experimentally validated to be present in human prostate cancer samples in a recurrent manner. Further experimental analysis identify several chimeric transcripts are present in the human prostate cancer cell lines, but not in primary human prostate epithelium cells, implying their associations with cancer mechanisms. Importantly, one of these chimeras appeared to be highly cancer-enriched, as it is confirmed to be expressed at significantly higher levels in human prostate cancers but present at very low levels in non-cancer prostates. Our results suggest that chimeric RNAs are more abundant than previously estimated. The RNA fusion junctions of these novel recurrent chimeras, as determined experimentally, suggest that many of them would generate altered or aberrant protein sequences, potentially leading to abnormal functions in cancer. 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 4973. doi:10.1158/1538-7445.AM2011-4973