tbuckley/cabot-search huggingface dataset:
The Possible Role of F-18 FDG Positron Emission Tomography in the Differential Diagnosis of Focal Pancreatic Lesions
Authors: Miklós Papós, Tamás Takács, Lajos Trón, Gyula Farkas, Edit Ambrus, Szabolcs Szakáll, János Lonovics, László Csernay, László Pávics
Journal: Clinical Nuclear Medicine (2002)

To compare the diagnostic values of different methods for the differentiation of malignant from benign pancreatic lesions.In 22 patients with focal pancreatic lesions, the carbohydrate antigen (CA) 19-9 level was measured; abdominal ultrasound (US), computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) were performed; and the value of these methods were analyzed for their use in cancer diagnosis.Malignant lesions were identified in six patients and verified by surgery or clinical follow-up. The CA 19-9 level was elevated in four of the five patients examined (sensitivity, 80%). In all six cases, US and CT revealed hypoechogenic and hypodense areas (sensitivity, 100%). In one patient, ERCP was unsuccessful but yielded true-positive results in three others (sensitivity, 60%). The sensitivity of FDG PET was 100%. Sixteen focal cases of pancreatic disease proved to be benign. The CA 19-9 level was elevated in four of them (specificity, 73%). Hypoechogenic and hypodense areas were evident on US and CT in eight patients. The specificity of CT was 50% (8 of 16 cases). The specificity of US was 47% (7 of 15 cases). The specificity of successful ERCP was 92%. Fourteen negative FDG-PET results were truly negative. In two patients, however, the PET findings proved to be falsely positive (specificity, 88%).FDG-PET is an effective tool to differentiate malignant from benign focal pancreatic lesions. In persons with focal pancreatic hypoechogenic or hypodense lesions detected by CT or US and an elevated CA 19-9 level, FDG PET should be the next step in the diagnostic strategy.
Abstract LB-81: Purification and characterization of a human urinary compound with potent anticancer activity
Authors: Tony Antakly, Ling Chen, Francine Lafaille, Emil Toma, José Menezes, Abdul-Hamid Emwas, Alan Brox
Journal: Cancer Research (2010)

Abstract Historically, the urine, considered as a blood filtrate has been recognized as a source of medicinal products and important constituents of widely used drugs. However, various molecules in human urine such as growth factors, hormones, and their metabolites have not yet been thoroughly characterized. A group of low molecular weight compounds named HIP's (HCG-like Inhibitory Proteins), was discovered in our laboratories while investigating the hormonal regulation of a skin cancer, Kaposi's sarcoma (KS). Following extraction from the urine of pregnant women, HIP was found to inhibit the growth and kill KS cancer cells by apoptosis both in vitro and in vivo. Initial results following intralesional injection with HIP, revealed a marked reduction in the number of neoplastic cells in the tumor. We are presently testing this product in clinical trials on KS patients in a double blind placebo controlled study. Preliminary results reveal HIP to be safe and well tolerated with no adverse or unexpected reactions. More recently, two other tumors types were demonstrated to be sensitive to HIP and are under further investigation. Following the use of gene microarrays and RT-PCR, the principal target genes for HIP were identified as belonging to a growth factor receptor family. Further purification and biochemical characterization is underway using proteomics and NMR spectroscopy. Overall, the present studies further establish HIP as a urinary compound with potent anti-cancer activity. 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 LB-81.
Abstract 5697: Multistage vectored nanotherapeutics of breast cancer lung metastasis
Authors: Haifa Shen
Journal: Cancer Research (2012)

Abstract Breast cancer metastasis to remote organs is the major cause of cancer death. Although significant progresses have been made on survival of patients with Stage I-III breast cancer, the situation with breast cancer metastasis is discouraging. Nanotechnology has played an important role in the fight against breast cancer in the last decade. The first nano-liposomal formulation of doxorubicin (Dox), Doxil, was FDA approved in 1994, and is currently used to treat multiple cancer types including recurrent and refractory breast cancers. More nano-formulated drugs have since been approved. These nanotherapeutics work based on the enhanced permeability and retention (EPR) effect, and still cause severe toxicity to the body, however. To overcome these defects of the first generation of nanotherapeutics, we have developed a silicon-based multistage vector (MSV) system with the aim to specifically delivery drugs to cancer tissues with the least toxicity to the normal organs. We have demonstrated highly reproducible therapeutic efficacy with this system to deliver the conventional chemotherapy drugs and siRNA oligos in nanoparticles. We have generated mouse lung metastasis models with the human breast cancer cell line MDA-MB-231 which was engineered with a luciferase gene, and used multiple doxorubicin formulations to treat the tumor mice. These included free doxorubicin (3 mg/kg weekly), Doxil (6 mg/kg biweekly), a doxorubicin prodrug (proDox, 6 mg/kg biweekly), and proDox in MSV (MSV/proDox, 6 mg/kg biweekly). Tumor growth in the lung was monitored by bioluminescence with a Xenogen IVIS200 optical in vivo imaging system. As expected, treatment with free Dox caused significant weight loss indicating drug toxicity, most likely to the heart. Tumor growth in the free Dox treatment group halted initially, but resumed two weeks later. The tumor cells in these animals might have developed resistance to Dox during the treatment. Doxil treatment also triggered weight loss initially. This correlates with reduced the cardiac side effect of the drug observed in clinic comparing to free Dox. Neither proDox nor MSV/proDox caused weight loss. Fifty percent of the untreated mice died of lung metastasis by 11 weeks. The free Dox- and proDox-treated mice extended life by 2 weeks. Half of Doxil-treated mice died by 15 weeks, when all MSV/proDox-treated mice have survived. These results indicate that we have developed a powerful system for tumor-specific delivery of therapeutic in the treatment of breast cancer metastasis. 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 5697. doi:1538-7445.AM2012-5697
OC-012 How Commonly is Oesophageal Cancer Missed at Endoscopy (A UK Primary Care Based Study)?
Authors: D Cheung, S Menon, N Trudgill
Journal: Gut (2013)

<h3>Introduction</h3> The frequency of upper gastrointestinal cancer being diagnosed following a negative oesophagogastroduodenoscopy (OGD) up to 3 years previously in selected single unit series ranges from 6.7–14%. We have examined how often oesophageal cancer (OC) is missed at OGD in a large unselected primary care cohort and associated risk factors. <h3>Methods</h3> All subjects with OC from a UK primary care database (The Health Improvement Network (THIN)) were studied. THIN covers over 6 million patients and is regionally and demographically representative of the UK population. A nested case-control study was performed with cases of 'missed OC' subjects who underwent OGD 1–5 years prior to their OC diagnosis and controls subjects who did not have OGD 1–5 years prior to their OC diagnosis. Logistic regression analysis was used to study associations with having an OGD that potentially missed OC. <h3>Results</h3> 5354 subjects with OC were identified (3561 (67%) male, mean age 71 ± 11years) and 9187 OGD were analysed. 380 subjects (237 (62%) male, mean age 72 ± 11years) had OGD 1–5 years prior to OC diagnosis (715 OGD, mean 1.9 per subject). 266 (5.0%) subjects had OGD 1–3 years and 144 (2.7%) had OGD 3–5 years prior to OC diagnosis. 180 (47.4%) of OGD which did not diagnose OC 1–5 years previously had an abnormality detected (Oesophagus – Barrett's 59 (15.5%), hiatus hernia 45, oesophagitis 16, gastro-oesophageal reflux disease 17, stricture 8, ulcer 7; Stomach – gastritis 25, ulcer 7, polyp 4; Duodenum – duodenitis 17, ulcer 8, coeliac disease 1). The 'missed OC' subjects had a total 329 primary care consultations 1 year prior to their OGD that missed OC. 'Alarm symptoms' were present at 139 consultations (38 anaemia, 1 abdominal mass, 78 dysphagia, 20 haematemesis/melaena and 6 weight loss). Subjects presenting with anaemia (OR 2.05, 95%CI 1.4–3.1, p = 0.0006), haematemesis/melaena (1.82, 1.1–3.2, p = 0.03) or dyspepsia (2.20, 1.7–2.8, p &lt; 0.05) were more likely to have had an OGD that missed OC. In contrast, subjects with dysphagia (0.74, 0.5–0.9, p = 0.04) or weight loss (0.39, 0.2–0.9, p = 0.02) were less likely to have an OGD that missed OC. Logistic regression did not find any association between age (0.7, –0.5–1.8, p = 0.3) or female gender (1.2, 0.9–1.5, p = 0.07) with OGD that failed to diagnose OC 1–5 years prior to OC diagnosis. <h3>Conclusion</h3> Missing OC at OGD was relatively uncommon in this unselected cohort with 5% of OC subjects having had an OGD 1 – 3 years prior to diagnosis that did not diagnose OC. Presenting with anaemia, haematemesis/melaena or dyspepsia were positively associated with missing OC at OGD. In contrast, subjects with dysphagia or weight loss were less likely to have OC missed at OGD. Many of the OGD which missed OC had an abnormality recorded, with Barrett's oesophagus reported in 15.5%. <h3>Disclosure of Interest</h3> None Declared
Abstract SY14-02: p53-mediated senescence impairs the apoptotic response to chemotherapy in breast cancer
Authors: Guillermina Lozano, James G. Jackson
Journal: Cancer Research (2012)

Abstract Studies on the role of p53 mutation in human breast cancer response to chemotherapy are controversial. Using MMTV-Wnt1 murine breast tumor model, we show that tumors with mutant p53 exhibited a superior clinical response compared to tumors with wild-type p53. Doxorubicin treated p53-mutant tumors failed to arrest proliferation leading to abnormal mitoses and cell death, while p53 wild-type tumors underwent arrest and senescence with expression of senescence-associated cytokines that led to autocrine/paracrine activity and mitogenic potential. Wild-type p53 could still mediate arrest and inhibit drug response even in the context of a heterozygous p53 point mutation or absence of p21. Thus, we show wild-type p53 activity hinders chemotherapy response and demonstrate the need to reassess the paradigm for p53 in cancer therapy. 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 SY14-02. doi:1538-7445.AM2012-SY14-02
PTU-119 The impact of various factors on bone loss in IBD patients treated with oral steroids
Authors: M Y Gherghab, P Sahay
Journal: Gut (2012)

<h3>Introduction</h3> Many factors can contribute to bone loss in Inflammatory bowel disease (IBD) patients treated with oral steroids. <h3>Methods</h3> To assess the prevalence and evaluate the impact of various factors on bone density in IBD patients treated with oral steroids. We conducted a retrospective study on 50 patients with ulcerative colitis (UC) and 40 patients with Crohn9s disease. BMD of lumbar spine and femoral neck were measured by axial dual-energy x-ray absorpiometry scan (DEXA) in 57 patients, and that of forearm by peripheral DEXA scan in 33 patients. <h3>Results</h3> 60% of all patients (n=55) had low BMD (8.8% were osteoporotic, 51% were osteopenic). The osteoporotics were predominantly (75%) patients with CD and were smokers. On the other hand, 63% of osteopenics had UC and 28% were smokers. Although most of males (80.7%) had low BMD (73.3% were aged &lt;50 years), only one third of females below the age of 45 years had low BMD. Only five patients had BMI &lt;19, the majority of these patients (80%) had low BMD. All of the osteoporotic CD patients had terminal ileum (TI) involvement, and nearly 60% of patients who underwent surgery for CD had low bone mineral density. Patients who had IBD for 10 years showed low BMD in 62.5%, while 54% of those with disease duration more than 10 years had low BMD. 40% of patients who were on steroid sparing agents had normal BMD. All of the osteoporotic female patients were aged &gt;45 years and were not on bone protection. <h3>Conclusion</h3> The high prevalence of bone loss in IBD patients treated with oral steroids is multifactorial. Disease type (CD), site of the disease (TI), disease severity (requiring oral steroids and surgical intervention) and low BMI seems to be the major variables and early bone protection is recommended especially in young men. <h3>Competing interests</h3> None declared.
Abstract LB-56: My journey as a breast cancer survivor, from diagnosis to advocate
Authors: Jeannette Morrow
Journal: Cancer Research (2012)

Abstract 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 LB-56. doi:1538-7445.AM2012-LB-56
Abstract 5292: Tumor accumulation and biodistribution of a thermally responsive cell cycle inhibitory polypeptide <i>in vivo</i>
Authors: Leslie Robinson, Eddie Perkins, Lacey McNally, Drazen Raucher
Journal: Cancer Research (2011)

Abstract Elastin-like Polypeptide (ELP) is a macromolecular carrier for various therapeutic peptides that has the ability to penetrate tumor vasculature which is mediated by a cell-penetrating peptide. ELP is a biopolymer consisting of pentapeptide repeats in the motif Val-Pro-Gly-Xaa-Gly where Xaa is any amino acid except proline. The polymer is soluble at normal physiological temperature but aggregates above 41° C. Peptides without carriers have very short half-lives, so ELP not only allows for longer circulation time, but its thermal properties allow the peptide to accumulate inside the tumor when heated. Bac7-ELP1-p21 is an ELP conjugate that uses Bac7 to penetrate the nucleus and p21 to inhibit the cell cycle at G1/S. This construct can be actively targeted to the tumor site using focused infrared light that heats the tumor to 41-42° C. In this study, tumor accumulation and biodistribution of fluorescently labeled Bac7-ELP1-p21 was monitored in a mouse subcutaneous xenograft model of S2013 pancreatic cancer by whole animal imaging using the IVIS® system. Luciferase transfected S2013 pancreatic cells were used to establish the tumor, allowing monitoring tumor growth by quantifying luciferase signal over a period of time. The animals were intravenously injected with Alexa750 labeled Bac7-ELP1-p21. Animals were imaged for fluorescence signal at 1, 2, 3, 4, 6, 8, 24, 48, and 72h after treatment to monitor the level of protein with respect to time. This allowed for the detection and quantification of the protein level throughout the whole body. Tumor uptake of intravenously administered Bac7-ELP1-p21 was examined in both heated and unheated tumors. Using both luminescence and fluorescence data, protein levels inside the tumor were compared to the whole body. Bac7-ELP1-p21 accumulates 3-fold more inside the heated tumor than the unheated tumor, and it is still present inside the tumor 72h after treatment. Fusing a therapeutic peptide to macromolecular carriers results in its improved pharmacokinetics and accumulation of the peptide preferentially in the tumor tissue due to passive targeting. Furthermore, this passive targeting is further improved due to externally induced hyperthermia. This approach will allow us to use lower concentrations of drug systemically and therefore reduce side effects in normal tissues. 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 5292. doi:10.1158/1538-7445.AM2011-5292
The Sex Hormones in Advanced Breast Cancer
Authors: Edward F. Lewison, Robert G. Chambers
Journal: New England Journal of Medicine (1952)

THE treatment of cancer of the breast is one of the gravest and most formidable problems confronting the medical profession at the present time. The National Cancer Institute recently estimated that the number of new cancer cases (all sites) increased 34 per cent during the ten-year period 1937 to 1947 and that of this increase only 7 per cent was due to greater longevity. There is little comfort in the knowledge that breast cancer in the female is the most common type of cancer, according to current death rates for all malignant diseases. Statistics, compiled both in this country and . . .
VALIDATION OF FAST T2-GRASE MAPPING OF THE HEART: MAGNETIC RESONANCE AND HISTOLOGICAL STUDY IN A PIG MODEL OF ISCHEMIA/REPERFUSION
Authors: Rodrigo Fernandez-Jimenez, Javier Sanchez-Gonzalez, Jaume Aguero, Carlos Galan-Arriola, Gonzalo Javier Lopez-Martin, María Del Trigo, Valentin Fuster, Borja Ibanez
Journal: Journal of the American College of Cardiology (2015)
IT-26 * IDENTIFICATION OF PSEUDO-PROGRESSION IN NEW DIAGNOSED GLIOBLASTOMA (GBM) IN A RANDOMIZED PHASE 2 OF ICT-107: MRI AND PATHOLOGY CORRELATION
Authors: S. Phuphanich, J. Yu, S. Bannykh, J.-J. Zhu
Journal: Neuro-Oncology (2014)

BACKGROUND: Previously reports of pseudo-progression in patients with brain tumor after therapeutic vaccines in pediatric and adult glioma (Pollack, JCO online on June 2, 2014 and Okada, JCO Jan 20, 2011; 29: 330-336) demonstrated that RANO criteria for tumor progression may not be adequate for immunotherapy trials. Similar observations were also seen in other checkpoint inhibitor in melanoma and NSLSC. METHODS: We identified 2 patients, who developed tumor progression by RANO criteria, underwent surgery following enrollment in a phase 2 randomized ICT-107 (an autologous vaccine consisting of patient dendritic cells pulsed with peptides from AIM-2, TRP-2, HER2/neu, IL-13Ra2, gp100, MAGE1) after radiation and Temozolomide (TMZ). RESULTS: The first case is a 69 years old Chinese male, who underwent 1st surgery of gross total resection right occipital GBM on 10/26/2011. Subsequently he received 19 cycles of TMZ and 9 vaccines/placebo. MRI from 7/2/2013 showed enhancement surrounding surgical cavity. After 2nd surgery, pathology showed only rare residual tumor cells with macrophages and positive CD 8 cells. He continued on this vaccine program and MRI showed more progression with finger-like extension into parietal lobe 4 months later. The 3rd surgery also showed extensive reactive changes with no active tumor cells. For 2nd case, a 62 years old male, who underwent first surgery on 7/11/2011 of right temporal lobe, developed 2 areas of enhancement after 6 cycles of TMZ and 7 vaccines/placebo on 4/18/2012. With 2nd surgery, pathology showed reactive gliosis without active tumor. The subject continued in this trial. CONCLUSION: Pseudo-progression was confirmed by pathology in these 2 patients at 20 and 9 months which were delayed comparing to pseudo-progression observed in patients treated with concurrent XRT/TMZ (3-6 months). Future iRANO criteria development is essential for immunotherapy trials. Accurately identifying and managing such patients is necessary to avoid premature termination of therapy.
362 THE PLATELET-DERIVED CHEMOKINE CXCL7 STIMULATES PRO-ANGIOGENIC PROPERTIES OF HEPATIC STELLATE CELLS VIA CXCR1 ACTIVATION
Authors: M.-L. Berres, I. Lettow, P. Fischer, D. Heinrichs, C. Trautwein, H.E. Wasmuth
Journal: Journal of Hepatology (2012)
SC-38 * IDENTIFICATION OF NOVEL THERAPEUTIC TARGETS FOR GLIOBLASTOMA STEM CELLS
Authors: S. Young, Y. Liang, S. Murphy, S. Guo, Z. Sheng
Journal: Neuro-Oncology (2014)

The prognosis for patients with glioblastoma (GBM) is poor. Recent evidence suggests that the cells driving GBM malignancy and possibly recurrence are GBM stem cells (GSCs), a small population of GBM cells capable of developing resistance to current therapeutics. To target GSCs, we hypothesized that specific protein kinases are essential to GSC survival. Knockdown of these essential kinases in GSCs will result in inhibition of both GSC and overall GBM tumor growth. To identify kinases essential for GSCs, we first performed a drop-out screen in U87MG human GBM cells using an shRNA library directed against human kinases. We then screened the candidate kinases in a GSC line, GS9-6/NOTCH1 + , and identified 39 kinases that are essential to GSCs. Among these, we elected to focus on casein kinase 1 epsilon (CSNK1E) and maternal embryonic leucine zipper kinase (MELK) for the following reasons: 1) multiple shRNAs targeting these kinases were revealed from our screen; 2) MELK is a known essential kinase for GSCs; 3) chemical inhibitors are available for these kinases. Further experiments revealed that knockdown of CSNK1E or MELK resulted in a significant decrease in viability in multiple GSC lines isolated from either established cell lines, such as LN229, LN18, and U251, or fresh tumor tissues, such as VTC001. To probe the mechanism by which these kinases are essential for GSCs, we measured the self-renewal and differentiation of these GSCs. We found that knockdown of MELK and CSNK1E significantly inhibited stem cell self-renewal and promoted differentiation of GS9-6/NOTCH1+ cells. Taken together, our research revealed that MELK and CSNK1E are essential to GSC survival, thereby becoming appealing drug targets. Future work will further evaluate MELK and CSNK1E as therapeutic targets by utilizing small molecule kinase inhibitors in an in vivo mouse model of GBM.
Abstract P6-05-07: Molecular Classification of Breast Cancer: Clinical Correlation and Outcome in a Venezuelan Population
Authors: G Mackarem, B Duran, L Vilchez, M Sierra, E Bracho, J. Colina
Journal: Cancer Research (2010)

Abstract Background: Gene expression analysis has defined several subtypes of breast cancer that differ in prognosis and response to therapy. Distribution of clinical, pathological features and outcome was performed among Venezuelan women diagnosed with breast cancer. The objective of this study was to evaluate clinical features and outcome. Material and Methods Of 1004 women treated at the BCTC between January 1, 2000 and April 30, 2010, 624 patients had assessable data for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER 2/neu). Molecular subtypes were defined as Luminal A (ER+, PR+, HER 2-), Luminal B (ER+, PR+, HER 2+), Basal Like (ER-, PR-, HER 2-) and HER 2/neu (ER+, PR+, HER 2+). Clinical and Pathologic features were available for all 624 patients. Follow-up (FU) for distant recurrence (D.R.) and deaths were available for 514 patients (survival and distant disease free survival). Data was compared for women younger than 50 years with those 50 and older Results Median FU was 33 months. 268 patients (43%) were 49 years or younger and 356 were 50 years (57%) or older. Discussion: Distribution of molecular subtypes in Venezuelan women is different than other ethnicities. This study also revealed that both age subgroups in the HER2/neu subtype had the worst outcome followed by patients under 50 in the Basal subtype. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-05-07.