tbuckley/cabot-search huggingface dataset:
Abstract 3686: Antibody-functionalized single-walled carbon nanotubes for detection and selective destruction of breast and pancreas cancer cells
Authors: Yan Xiao, Xiugong Gao, William Cheung, Aaron Urbas, Oleh Taratula, David Holbrook, Richard E. Cavicchi, Joshua J. Souchek, Paul D. Wagner, Sudhir Srivastava, Thomas Avedisian, Huixin He, Surinder Batra
Journal: Cancer Research (2010)

Abstract Nanocarrier-based antibody targeting is a promising modality in therapeutic and diagnostic oncology. Single-walled carbon nanotubes (SWNTs) exhibit two unique optical properties that can be exploited for such applications, i.e., strong Raman signal for cancer cell detection and near-infrared (NIR) absorbance for selective photothermal ablation of tumors. In the present study, we constructed a HER2 IgY-SWNT complex and a MUC4 IgG-SWNT complex, and demonstrated in vitro their dual functionality for both detection and selective destruction of breast and pancreas cancer cells. The two complexes were constructed by covalently conjugating carboxylated SWNTs with anti-HER2 chicken polyclonal IgY antibody and with anti-MUC4 mouse monoclonal IgG antibody, respectively. Raman signals were recorded on a Raman spectrometer with a laser excitation at 785 nm. NIR irradiation was performed using a diode laser system, and cells with or without nanotube treatment were irradiated by 808 nm laser at 50 W/cm2 for 5 min. Cell viability was examined by calcein AM/ethidium homodimer-1 (EthD-1) staining. Immunohistochemical studies showed that HER2 IgY-SWNT complex specifically targeted receptor-expressing SK-BR-3 cells but not receptor-negative MCF-7 cells; MUC4 IgG-SWNT complex specifically targeted pancreatic cancer cells but not normal pancreas cells. Using a Raman optical microscope, we found the Raman signal collected at single-cell level from the complex-treated breast or pancreatic cancer cells was significantly greater than that from various control cells. NIR irradiation selectively destroyed the complex-targeted breast and pancreatic cancer cells without harming receptor-free cells. The death rate after NIR irradiation were 94.1% and 96.6% respectively for complex-treated breast and pancreatic cancer cells, but only 1.3% and 1.8% for the untreated controls of the two cancer cell types, respectively. These results demonstrated that the antibody-SWNT complexes have the potential to detect cancer cells at the early stages of tumor development. In addition, the complexes are potentially useful for selectively killing cancer cells while sparing healthy ones. Thus, the unique intrinsic properties of SWNTs combined with high specificity and sensitivity of antibodies can lead to new strategies for cancer detection and therapy. 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 3686.
Randomized phase II trial of two dose schedules of carboplatin/paclitaxel/cetuximab in stage IIIB/IV non-small cell lung cancer (NSCLC)
Authors: M. N. Saleh, M. A. Socinski, D. Trent, T. Dobbs, L. M. Zehngebot, M. A. Levine, P. J. Stella
Journal: Journal of Clinical Oncology (2007)

7586 Background: Cetuximab, an IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR) on both normal and tumor cells, has been investigated in advanced NSCLC as a single agent and in combination with chemotherapy. This ongoing randomized phase II open-label trial evaluates cetuximab in combination with carboplatin (Cb) and paclitaxel (Pac) when given in two dose schedules to patients (pts) with previously untreated stage IIIB/IV NSCLC. Methods: Eligible pts were randomized to 1 of 2 treatment arms. Cetuximab treatment was identical in both arms: 400 mg/m 2 IV on day 1 and 250 mg/m 2 weekly thereafter. Beginning on day 8, a schedule of Cb AUC=6 IV and Pac 225 mg/m 2 IV given on a 3-week cycle was compared with a schedule of Cb AUC=6 IV q4 weeks and Pac 100 mg/m 2 IV given weekly for 3 weeks of each 4-week cycle. Pts who achieve CR, PR, or SD after 4 cycles may continue weekly cetuximab monotherapy until disease progression or unacceptable toxicity. The primary objectives were to estimate median progression-free survival (PFS) and the PFS rate at 6 months. Secondary objectives included response rate. Results: The study has completed accrual, with 168 pts randomized and 165 treated. Data are available for 164 pts and confirmed responses for 155 pts. Conclusions: Cetuximab combined with Cb and Pac in both dose schedules demonstrated activity and an acceptable toxicity profile in pts with NSCLC. Final PFS and overall survival data are pending. No significant financial relationships to disclose. [Table: see text]
Supercomputer Boosts Scientists' Analytical Power
Authors: Tom Reynolds
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Supercomputer Boosts Scientists' Analytical Power Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 6, 18 March 1992, Pages 385–387, https://doi.org/10.1093/jnci/84.6.385 Published: 18 March 1992
PTH-128 Small Bowel Cancer: A 20-year Single Uk Centre Experience
Authors: L Chan, G Evans
Journal: Gut (2014)

<h3>Introduction</h3> Small bowel cancer (SBC) is rare and accounts for 5% of all gastrointestional (GI) malignancies despite the small bowel forming 75% of the GI tract. <sup>[1]</sup> Typical non-specific symptoms lead to late diagnosis and poor prognosis. We aim to establish a better understanding of the natural history and genetic features of SBC. <h3>Methods</h3> A regional UK cancer registry identified local SBC patients diagnosed from January 1991 to January 2011. We retrospectively reviewed medical records collecting data on patient demographics, environmental and medical risk factors, family history, natural disease progression and immunohistochemical analysis (IHC). <h3>Results</h3> The registry identified 205 SBC patients, 58% male and 42% female, who were diagnosed at a mean age of 63 years. Patients presented with abdominal pain (23.3%, n = 60), altered bowel habit (16.7%), weight loss (15.0%), bowel obstruction (15.0%) jaundice (13.3%), anaemia (10.0%) and other (6.6%). Investigations included CT (85.7%, n = 35), MR (8.6%) and barium (11.4%) imaging; gastroscopy (37.1%) that detected 8 of 9 duodenal SBCs and were reported normal in 2 jejunal and 2 ileal SBCs, DBE (2.9%) and ERCP (2.9%) that detected 1 duodenal SBC each; emergency (8.6%) and staging laparotomy (8.6%). SBC anatomical and histological distributions are described in Table 1. Patients were diagnosed at disease stage I (11.4%, n = 35), II (22.9%), III (20.0%) and IV (45.7%). Treatment included curative surgery (66%, n = 38; 12 resections, 7 bypasses and 6 Whipple procedures and adjuvant chemotherapy (AC) in 20%) with a 60% success rate and recurrence in 16.7% within a year; palliative surgery (18.4%; 6 bypasses and AC in 66.7%) and medical palliation (15.6%). Mortality rates at 1, 2, 5 and 10 years were 74.3%, 79.8%, 91.7% and 98.2% respectively (n = 109). Environmental factors included smoking (47%, n = 53) and drinking alcohol (51.1%, n = 45). Co-morbidities included peptic ulcer disease (8.4%, n = 72), coeliac disease (4.2%), Crohn’s disease (1.4%) and ulcerative colitis (1.4%). Furthermore, 23.6% of patients (n = 89) had ≥1 other malignancies that were metachronous (83.3%), synchronous (12.5%) or both (4.2%). Family history included a 1<sup>st</sup> or 2<sup>nd</sup> degree relative with malignancy (28.2%, n = 39) or familial adenomatous polyposis (7.7%). IHC showed Lynch syndrome and adenomatous polyposis coli gene mutations in 42.1% (n = 19) and 40% (n = 10) respectively. <h3>Conclusion</h3> Our understanding of SBC is limited by its insidious course, difficult assessment and rarity coupled with multiple histological subtypes. A more comprehensive understanding of SBC and it’s genetic predisposition may allow high-risk patient stratification to earlier identify and treat SBC thus improving its poor prognosis. <h3>Reference</h3> Ross <i>et al</i>.<i> British Journal of Cancer</i> 1991;63:143–145 <h3>Disclosure of Interest</h3> None Declared.
CB-15 * NKCC1 REGULATES MIGRATION CAPACITY OF GLIOBLASTOMA TUMOR INITIATING CELLS BY MODULATING ACTIN CYTOSKELETON THROUGH SMALL RHO GTPASES
Authors: P. Schiapparelli, R. Magana-Maldonado, S. Hamilla, L. Sibener, J. C. Martinez-Gutierrez, H. Aranda-Espinoza, A. Quinones-Hinojosa
Journal: Neuro-Oncology (2014)

Glioblastoma (GBM) is a highly invasive and lethal brain tumor due to its high invasion and recurrence. The mechanisms that confer GBM cells their invasive behavior and their regulatory system have not been fully elucidated. We have shown that pharmacological inhibition and decreased expression of the electroneutral Na + -K + -Cl- cotransporter-1 (NKCC1) in GBM leads to a decreased cell migration and invasion capacity, in vitro and in vivo. We have previously reported that NKCC1 knockdown cells (NKCC1 KD) show significantly larger focal adhesions, suggesting a potential role of NKCC1 in cell adhesion. Here, we focused on the role of NKCC1 on the cytoskeleton dynamics of GBM cells. We found that glioma cells display a significant decrease on their cell spreading capacity upon NKCC1 knockdown or pharmacologic inhibition by Bumetanide (BMT) (p < 0.0001). F-actin staining showed a change in the organization of fibrillary actin of the cells, where NKCC1 KD cells displayed a ring shape actin morphology that was absent in control cells. In addition the bundled actin content was decreased by NKCC1 inhibition (GBM 612 p < 0.05; GBM 965 p < 0.001). The molecular regulation of actin dynamics can be due to the activity of RhoA acting through Cofilin, which acts as an initiator of actin polymerization. We observed that the small GTPase RhoA and Rac1 active levels decreased 40-50% in the NKCC1 KD cells. This result suggests that NKCC1 regulates cytoskeleton dynamics through multiple targets that include filament actin regulation and RhoA and Rac1 activity. Based on our results, NKCC1 modulates migration of GBM cells by at least two different mechanisms: cell volume regulation (through ion transport) and regulation of the actin cytoskeleton. Due to its essential role in cell migration and high expression in GBM, NKCC1 may serve as a specific therapeutic target to decrease GBM cell invasion.
Acute hemorrhagic colitis induced by the oral administration of oseltamivir used for influenza A treatment
Authors: Y. Nakagawa, T. Nagai, H. Okawara, H. Nakashima, A. Hisamatsu, M. Shuto, M. Yamauchi, S. Kai, S. Yokoyama, K. Murakami, T. Fujioka
Journal: Endoscopy (2011)

A 40-year-old woman with a history of bronchial asthma was diagnosed with influenza A using a rapid diagnosis kit. She began to experience abdominal pain, diarrhea, and hematochezia approximately 4 hours after a single capsule of oseltamivir had been administered. Colonoscopic findings indicated circumferential hemorrhagic colitis with longitudinal erosions in the descending colon, findings which mimicked those of ischemic colitis ([Fig. 1]). Histopathological analysis of the lesion showed the presence of mucosal hemorrhage and submucosal edema ([Fig. 2]). Stool culture showed normal flora. Discontinuation of the oseltamivir therapy was followed by an immediate improvement in the hemorrhagic colitis. The lymphocyte transformation test (LTT) yielded positive results for oseltamivir only, with negative results for the other drugs administered, which included clarithromycin and acetaminophen.
Abstract 3326: ΔNp63α is a regulator of epithelial-mesenchymal transition in human keratinocytes
Authors: Ju-Eun Oh, Zi Liu, Reuben Kim, Ki-Hyuk Shin, No-Hee Park, Mo K. Kang
Journal: Cancer Research (2012)

Abstract p63 is a p53 family protein required for morphogenesis and postnatal regeneration of epithelial tissues. Here we demonstrate that ΔNp63α, a p63 isoform lacking N-terminal transactivation domain, induces epithelial-mesenchymal transition (EMT) in primary human keratinocytes in TGF-β-dependent manner. Rapidly proliferating normal human epidermal keratinocytes (NHEK) were infected with retroviral vector expressing ΔNp63α, ΔNp63α, ΔNp63α, or empty vector, and serially subcultured until replicative senescence. No phenotypic changes were observed until the culture reached senescence. Then, cells transduced with ΔNp63α and ΔNp63α demonostrated morphological changes resembling mesenchymal cells, while ΔNp63α did not trigger such change in phenotype. Treatment with exogenous TGF-β accelerated EMT in pre-senescent ΔNp63α-transduced cells, and inhibition of TGF-β signaling reversed the EMT phenotype. Molecular markers of EMT, such as loss of E-Cadherin and cytokeratin 14 expression, were observed in cells expressing ΔNp63α but not those expressing ΔNp63α. TGF-β treatment alone led to growth arrest in control NHEK with no evidence of EMT, indicating that ΔNp63α altered the cellular response to TGF-β treatment. ΔNp63α-transduced cells acquiring EMT gained ability to be differentiated to osteo/odontogenic and adipogenic pathways, resembling mesenchymal stem cells (MSCs). Furthermore, these cells expressed enhanced levels of Nanog and Lin28, which are transcription factors associated with pluripotency. These data indicate that ΔNp63α triggered EMT in TGF-β-dependent manner, while ΔNp63α only caused morphologically changes resembling mesenchymal cells. The current study suggests that mesenchymal transition of normal skin keratinocytes might be a novel approach to generate induced MSCs (iMSCs), which may be useful for regenerative therapies. 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 3326. doi:1538-7445.AM2012-3326
The notion of incommensurability can be extended to the child's developing theories of mind as well
Authors: Szabolcs Kiss
Journal: Behavioral and Brain Sciences (2011)

Abstract In this commentary I argue that the notion of incommensurability can be extended to the child's developing theories of mind. I use Carey's concept of Quinian bootstrapping and show that this learning process can account for the acquisition of the semantics of mental terms. I suggest a distinction among three stages of acquisition and adopt the theory–theory of conceptual development.
AB0255 Delay in Diagnosis from Onset of Symptoms by More than One Year in 48% of 177 Patients with Rheumatic Diseases, Including 36% in Patients with Rheumatoid Arthritis in Australia:
Authors: K.A. Gibson, G. Luta, T. Pincus
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Delayed diagnosis is recognized in many rheumatic diseases. Early treatment is regarded as critical for optimal clinical outcomes in patients with inflammatory rheumatic diseases. We studied possible delay in diagnosis in a usual care setting in 2013 using a simple 1-page form completed by the rheumatologist. <h3>Objectives</h3> To analyze patients seen in a teaching hospital rheumatology clinic for year of onset of symptoms and year of diagnosis and onset of treatment, using a standardized form for rheumatologists (RHEUMDOC). <h3>Methods</h3> All patients seen in one setting were evaluated according to a multidimensional health assessment questionnaire (MDHAQ) completed by the patient, and by a complementary doctor form (RHEUMDOC) completed by the physician. RHEUMDOC includes entry of 3 possible rheumatic diagnoses queried for year of onset of symptoms and year of diagnosis. For this study, patients were classified into 4 groups according to diagnosis: rheumatoid arthritis (RA), osteoarthritis (OA), other inflammatory diseases (INF), and other non-inflammatory diseases (NON); differences between groups were compared using Wilcoxon rank sum tests. <h3>Results</h3> Among 177 patients seen between February and October 2013, the mean interval from year of symptom onset to year of diagnosis was 3.7 years, 1.4 years in RA, 4.9 years in OA, and 4.6 years in other INF and other NON inflammatory diseases. Among all patients, 91 (51%) had a diagnosis within one year, including 64% with RA, 36% with OA, 49% with other INF, and 50% with other NON. The delay in RA was significantly less than in OA (p=0.004), other INF (p=0.027) and all non-RA (p=0.006). Nonetheless, 28% of RA patients received a diagnosis 1-5 years, and 8% &gt;5 years, after symptom onset. <h3>Conclusions</h3> A considerable delay from onset of symptoms to definitive diagnosis remains an important problem in rheumatic diseases. Delay in diagnosis is more common in patients with diseases other than RA, but remains in more than 1/3 of RA patients. Identification of specific contributors to this delay could inform education of both patients and physicians regarding the importance of early diagnosis and treatment, and health policy resources to facilitate timely management of rheumatic diseases. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3447
137 TOXICOLOGY AND LIVER TRANSDUCTION EFFICACY EVALUATION OF A RECOMBINANT ADENO-ASSOCIATED VIRAL VECTOR IN NON HUMAN PRIMATES AS A POTENTIAL TREATMENT FOR ACUTE INTERMITTENT PORPHYRIA
Authors: A. Pañeda, E. Lopez-Franco, A. Fontanellas, C. Unzu, C. Olagüe, R. Ferrero, A. Sampedro, I. Mauleon, S. Hermening, S. Beattie, H. Petry, J. Ruiz, A. Benito, D. Davola, J. Prieto, G. Gonzalez-Aseguinolaza
Journal: Journal of Hepatology (2012)
A new method for endoscopic drainage of pancreatic necrosis through a gastrostomy site using an endosponge
Authors: Martin Fähndrich, Marcel Sandmann
Journal: Endoscopy (2014)

Pancreatic fluid collections (PFCs) with necrosis can be very challenging to manage. The two main factors that impede adequate endoscopic drainage of many complex PFCs are the presence of thick fluid and debris, and their large size. Herein, we present a novel technique to manage complex PFCs endoscopically using an endosponge.
Abstract 1392: Role of mutant p53 for anti-TGF-β therapy in isogenic basal-like breast cancer models.
Authors: Fernando P. Lugo, Shu Lin, Abhik Bandyopadhyay, Junhua Yang, Lu-Zhe Sun
Journal: Cancer Research (2013)

Abstract Breast cancer remains as one of the most common cancers worldwide accounting for 450,000 deaths. During cancer progression, transforming growth factor-β (TGF-β) signaling in tumor cells is often converted from tumor suppression to tumor promotion. However, how this oncogenic switch occurs is not well understood. Tripe-negative breast cancer (TNBC) is a breast cancer subtype, which is frequently associated with p53 mutation and lacks specific molecular targets for therapeutic intervention. TGF-β signaling has been shown to be oncogenic in TNBC models. Therefore, we tested the hypothesis that mutation of p53 may cause the oncogenic switch of TGF-β and thus serve as a biomarker for anti-TGF-β therapy. In an effort to create isogenic models resembling the transformation of normal breast epithelial cells into TNBC, oncogenic H-Ras V12, human telomerase reverse transcriptase (hTERT), and mutant p53 R175H (mP53) or vector control were sequentially introduced into untransformed human breast epithelial MCF-10A cells. These generated cell lines were orthotopically introduced into the mammary fat pads of female nude mice and tumor burden was monitored. Mice were divided into two groups receiving a TGF-β type I receptor (RI) kinase inhibitor or PBS as control. Harvested lungs were analyzed for metastasis with GFP fluorescent imaging and quantitative PCR for tumor cell specific genes. Mice inoculated with the transformed MCF-10A cells containing mp53 (10A/mp53) displayed greater tumor burden and lung metastasis incidence than the vector control counterparts. Systemic treatment with the TGF-β inhibitor resulted in a decrease in metastasis in the mice inoculated with 10A/mp53 representing disruption of TGF-β’s oncogenic role. In contrast, inhibition of TGF-β signaling in mice inoculated with 10A/pp290 vector control displayed greater lung metastasis incidence, likely due to the disruption of TGF-β tumor suppressive effects. Our results indicate that the mp53 may serve as a biomarker for the oncogenic switch of TGF-β pathway and anti-TGF-β therapy for the inhibition of TNBC-induced metastasis. Citation Format: Fernando P. Lugo, Shu Lin, Abhik Bandyopadhyay, Junhua Yang, Lu-Zhe Sun. Role of mutant p53 for anti-TGF-β therapy in isogenic basal-like breast cancer models. [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 1392. doi:10.1158/1538-7445.AM2013-1392
1340 THE INFLUENCE OF WAIST CIRCUMFERENCE ON INSULIN RESISTANCE AND NONALCOHOLIC FATTY LIVER DISEASE IN APPARENTLY HEALTHY KOREAN SUBJECTS
Authors: D.Y. Ju, Y.K. Cho, E.H. Jeong, W.S. Jeong, K.B. Bang, H.J. Kim, B.I. Kim
Journal: Journal of Hepatology (2013)
P4-10-11: Genetic and Environmental Predictors, Endogenous Hormones and Growth Factors and Risk of Estrogen Receptor-Positive Breast Cancer in Japanese Women.
Authors: N Yoshimoto, T Nishiyama, T Toyama, S Takahashi, N Shiraki, H Sugiura, Y Endo, M Iwasa, Y Fujii, H Yamashita
Journal: Cancer Research (2011)

Abstract The incidence of breast cancer in Japanese women has doubled in all age groups over the past two decades. We have recently demonstrated that this marked increase is mostly due to an increase in the estrogen receptor (ER)-positive subtype. It is necessary to establish risk factors capable of predicting the risk of ER-positive breast cancer which will enable the efficient selection of candidates for preventive chemotherapy. We analyzed genetic factors, including 14 single nucleotide polymorphisms (SNPs), environmental risk factors (body-mass index (BMI), age at menarche, pregnancy, age at first birth, breastfeeding, family history of breast cancer, age at menopause, use of hormone replacement therapy, alcohol intake and smoking), serum hormones and growth factors (estradiol, testosterone, prolactin, insulin-like growth factor 1 (IGF1) and IGF binding protein 3 (IGFBP3)) and mammographic density in 913 women with breast cancer and 278 disease-free controls. To identify important risk factors, risk prediction models for ER-positive breast cancer in both pre- and postmenopausal women were created by logistic regression analysis. In premenopausal women, 1 SNP (CYP19A1-rs10046), age, pregnancy, breastfeeding, alcohol intake, serum levels of prolactin, testosterone and IGFBP3 were considered to be risk predictors. In postmenopausal women, 1 SNP (TP53-rs1042522), age, BMI, age at menopause, serum levels of testosterone and IGF1 were identified as risk predictors. Risk factors may differ between women of different menopausal status, and inclusion of common genetic variants and serum hormone measurements as well as environmental factors might improve risk assessment models. Further validation studies will clarify appropriate risk groups for preventive chemotherapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-10-11.