tbuckley/cabot-search huggingface dataset:
P247 Management Of Airway Stenosis And Bronchomalacia With Biodegradable Stents After Lung Transplantation. Single Institution Experience
Authors: S. Gelvez-Zapata, A. Wilkinson, D. Thomas, M. Pittman, J. Parmar
Journal: Thorax (2014)

<h3>Introduction</h3> Although the rate of airway stenosis following lung transplantation (LT) has reduced dramatically, it is still a significant cause of morbidity and mortality. Traditional self expanding metallic stents (SEMS) carry a high risk of bleeding and hyperplastic granulation tissue formation. Biodegradable stents (BS) present a potential alternative approach that could reduce these complications, though little is currently known about their effectiveness and safety. <h3>Methods</h3> A retrospective analysis of our institutions use of 7 BS (polidioxanone) placed in 6 patients who presented bronchial stenoses after LT between December 2011 and January 2013. 2 patients with single (1 right and 1 left) and 4 with bilateral LT. The indications for placing the stents were anastomotic bronchomalacia in 3 cases and bronchial stenoses in 4. The outcomes from these stents were compared with the last 10 patients who have SEMS. <h3>Results</h3> Re-stenoses recurred in 3 cases, after 10, 6 and 4 months respectively; 2 responded to balloon dilatation and cryotherapy but 1 patient needed repeat stenting for restenosis. Stent migration occurred in 2 cases. No bleeding was reported. One patient died of obliterative bronchiolitis. The mean increase in FEV1 following treatment was a 312ml increase. Patients required an average of 4.3 (1–9) bronchoscopies following stent insertion. Mean follow up was 12 months and mean survival 27.2 months. These results compare very favourably with a historical comparator group of the last 10 patients who received MS between 2009 and 2012 who required an average of 15.3 bronchoscopies after MS insertion and who had an overall mean drop in FEV1 of 0.59 L. SEMS have been used for a longer period of time, so follow up in this group was 30.5 months and mean survival 34.7 months (Table 1). <h3>Conclusion</h3> Our data add to the limited literature that BS can be a safe alternative to MS for airway stenosis, and may also represent a useful treatment for anastamotic bronchomalacia.
Abstract LB-393: Genotoxicity of arsenic in primary human bronchial cells
Authors: Hong Xie, Sara Martin, John Wise, Shouping Huang
Journal: Cancer Research (2012)

Abstract Arsenic originates from both geochemical and numerous anthropogenic activities including mining, combustion of fossil fuels, wood preservation, agriculture and metallurgy. Exposure of the general public to significant levels of arsenic is widespread. Arsenic is a well-documented human carcinogen. Long-term exposure to low levels of arsenic in drinking water have been linked to bladder, lung, kidney, liver, prostate, and skin cancer. Among them, lung cancer is of great public concern. However, little is known about how arsenic causes lung cancer. The purpose of this study was to determine the cytotoxicity and genotoxicity in human primary bronchial fibroblasts cells (NHBF). Our data show that arsenic induces a concentration-dependent increase in cell death after acute (24 h) or chronic (120 h) exposure. 0.1, 1 and 10 uM arsenic for 24 h induced 85, 64 and 35 percent relative survival, respectively, and induced 73, 57 and 11 percent of relative survival, respectively after 120 h treatment. 24 h exposure of 5 and 10 uM arsenic induced 15 and 32 chromosome damage compared to the control. Comet assay was used to measure the formation of DNA double strand breaks. We found that 120 h exposure induced a concentration-dependent increase in double strand breaks. Future study will focus on arsenic cytotoxicity and genotoxicity in primary bronchial epithelial cells. 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-393. doi:1538-7445.AM2012-LB-393
Abstract 2187: Protocadherin 10, a novel tumor suppressor, suppresses tumorigenesis and liver metastasis of colorectal cancer cells in mice
Authors: Tzu-Ming Jao, Ming-Hong Tsai, Wei-Ting Weng, Chia-Yun Chang, Hoi-Yan Lio, Yen-Chun Lai, Sung-Liang Yu, Ya-Chein Yang
Journal: Cancer Research (2011)

Abstract Colorectal cancer (CRC) is one of the leading causes of cancer death in the world. By loss of heterozygosity approach, we identified Protocadherin 10 (PCDH10) gene with a high frequency of allelic deletion in CRC. Furthermore, the genetic alteration was associated with presence of distant metastasis and poorer overall survival of patients. Importantly, the expression of PCDH10 mRNA was silenced or downregulated in 37 (84.1%) out of 44 colorectal tumors as compared with their paired normal mucosa. We proposed that PCDH10 might be a CRC-associated tumor suppressor gene, and then investigated the biological functions of PCDH10 in CRC cells. First of all, re-expression of PCDH10 in HCT116 cells reduced cell proliferation, migration, invasion and anchorage-independent growth in vitro. Meanwhile, stable PCDH10- expressing cells (HCT116/PCDH10) exhibited suppression of tumorigenicity and liver metastasis in xenograft tumor models. In SCID mice, HCT116/PCDH10 cells with subcutaneous injection showed reduced tumor growth, and, with intrasplenic injection, showed reduced metastatic incidence and nodules in the liver, as compared with mock control cells. Taken together, these results indicate that PCDH10 is a tumor suppressor gene associated with CRC, and its downregulation might promote tumor progression and distant metastasis. In addition, allelic loss of PCDH10 gene could serve as a molecular predictor of metastasis and poor prognosis in patients with CRC. 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 2187. doi:10.1158/1538-7445.AM2011-2187
SP0029 Auto-Immune and Auto-Inflammatory Monogenic Diseases of the Immune System. What can be Learned from their Studies?
Authors: F. Alain
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> In the recent years, multiple monogenic diseases have been described that cause auto-inflammatory and/or auto-immune diseases in association or not with vulnerability to microorganisms i.e, classic primary immunodeficiencies. I would herein review some of the genetic defects affecting checkpoints of reactivity to self, notably of the FAS apoptotic pathway that is providing a model to discuss the role of somatic mutations in the generation of auto-immune disorders. Early onset Inflammatory Bowel Disease (IBD) can also exhibit mendelian inheritance. XIAP, a molecule downstream of the NOD2 signaling pathway, when deficient can trigger severe IBD in humans and, is, together with chronic granulomatous and deficiencies in the IL-10 pathway, the strongest genetic risk factor for human IBD <h3>Disclosure of Interest</h3> None Declared
Abstract 1452: Examination of mechanisms involved in spontaneous melanoma metastasis to CNS
Authors: William Cruz, Shan Man, Maria Jaramillo, Maureen O'Connor-McCourt, Myriam Banville, Robert S. Kerbel
Journal: Cancer Research (2010)

Abstract Cerebral metastases occur in a majority of metastatic melanoma patients and are the major cause of mortality in those cases. Testing of novel therapeutic approaches has been slowed by the absence of appropriate preclinical models of spontaneous metastatic melanoma, particularly spontaneous CNS metastasis. To examine the efficacy of potentially promising treatment regimens, a highly visceral metastatic variant of the human melanoma WM239 cell line, named 6-4L, was developed and used to test the effectiveness of metronomic chemotherapy in the treatment of advanced metastatic disease. Concurrent low-dose cyclophosphomide/vinblastine led to significant disease control of mice with overt metastases in lungs, liver and lymph nodes. Among mice that survived the long-term treatment, 20% showed the presence of spontaneous brain metastases which likely emerged as a result of prolonged survival mediated by the therapy. From these, 2 cell lines (131/4-5B1 and 131/4-5B2) were generated which metastasize spontaneously to brain parenchyma. This constitutes the first model of heritable spontaneous melanoma brain metastasis by a human cell line from a subdermal transplant, without any therapeutic intervention. Characterization shows two salient functional alterations that may contribute to this phenotype 1) adhesion to brain-endothelial cells and 2) proliferation in the presence of brain-derived factors. When compared to poorly or highly metastatic cell lines (WM239A and 113/6-4L respectively), microarray analysis shows that 4-5B1/B2 cell lines have markedly different expression profiles. These cell lines show differential expression of 108 genes, thirteen of which share a common alteration for both brain-metastatic cell lines, including ednrb (endothelin receptor B) and bcl2a1 (BCL2-related protein A1), which stand out as potentially relevant. These molecules have been previously associated with increased proliferation in the presence of ENT-3; a peptide expressed in the brain, as well as resistance to TNF induced apoptosis and increased metastatic potential. Lentiviral vectors were used to induce stable upregulation of these genes in the otherwise non-brain metastatic parental 113/6-4L cell line. This upregulation mediated an increase in metastatic potential and, in the case of EDNRB, increased intracranial tumor growth. Future efforts will focus on characterizing the alterations in these cell lines, to confirm their clinical relevance and to test novel inhibitors for treating melanoma brain metastases. 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 1452.
P64 Review of CXRs Requested in the Community: Can We Improve Cancer Detection?
Authors: V Wells, A Stanton, P Osborne, W Hicks, A Beale, N Ridley
Journal: Thorax (2012)

<h3>Introduction</h3> In our trust all patients with a CXR suggestive of cancer have their CXR reviewed in the lung MDT. Following a serious incident investigation in our trust the question was raised as to whether this practise should be extended to all patients with “red flag symptoms” but not necessarily an abnormal CXR, in an attempt to improve early detection of lung cancer. <h3>Aims</h3> To determine frequency of red flag symptoms (i.e. hoarseness/haemoptysis) in patients undergoing community chest radiography To determine frequency of subsequent lung cancer diagnosis in such patients To determine if routine MDT review of such patients would improve time to lung cancer diagnosis. <h3>Method</h3> Review of community CXR request forms and images over a 1 month period (January 2010) was performed. Any CXR requested for a red flag symptom and reported as “normal”, was re-reviewed by a radiologist. Review of medical records over the succeeding 27 months to determine if there was any subsequent detection of lung cancer. <h3>Results</h3> 549 community CXR’s were requested in the review period. A random sample of 229 requests were reviewed. 8 requests included haemoptysis in clinical details and none included hoarseness. 5/8 CXR’s were reported as normal. 3/8 were reported as abnormal, with one suggestive of cancer (subsequently diagnosed) and discussed at MDT anyway. The remaining 2 patients with abnormal CXR’s had subsequent unremarkable imaging. None of the remaining 5 patients with haemoptysis and a normal CXR had any subsequent presentation with lung cancer. <h3>Conclusion</h3> The prevalence of red flag symptoms in patients being referred for community CXR’s is low. In those with red flag symptoms and a CXR that does not suggest cancer, subsequent presentation with cancer is at worst highly unlikely. The practise of routinely reviewing images of such patients in a lung cancer MDT is unlikely to improve detection rate or time to diagnosis of lung cancer.
Diffuse Hepatic FDG Activity From Nonmalignant Etiologies
Authors: Li Huo, Youjing Zheng, Fang Li
Journal: Clinical Nuclear Medicine (2015)

Diffuse increased ¹⁸F-FDG activity is commonly caused by malignant involvement. We describe here cases of diffuse, uniformly increased ¹⁸F-FDG activity due to nonmalignant illnesses in 2 patients: one had parvovirus B19 infection, whereas the other had porphyria, a heme synthesis disorder.
A case of mass-forming autoimmune pancreatitis (AIP)
Authors: Hyodo Naoko, Hyodo Takafumi
Journal: Endoscopy (2011)

A 48-year old man was hospitalized to our hospital due to an intermittent severe epigastralgia and left hypochondralgia. Contrast-enhanced (CE) CT showed two hypoperfusional lesions in the arterial phase: 40mm at the pancreatic tail and 18mm at the pancreatic head, and gradually and homogenously enhanced in the parenchymal phase. The regional lymph nodes were swollen (Maximal size was 15mm). Although the conventional US was a poor study due to gas collection, EUS could reveal two hypoechoic lesions with reticular hyperechoic inclusions, little enhanced by Levovist but enhanced in the delayed phase by Sonazoid. ERCP showed almost normal findings of the common bile duct, the main pancreatic duct and its branches, except slight compression at the tail of the main pancreatic duct. The serum IgG4 concentration was elevated: 258mg/dl (nl: 4–108). To make a differenzial diagnosis of AIP or pancreatic cancer, we performed EUS-guided fine needle aspiration (FNA) and fine needle biopsy (FNB) of the mass lesion in the pancreatic tail. The histological findings showed irregular duct features with inflammatory stroma without cancer cells, preferring mass-forming AIP. The pancreatic mass lesions were mostly disappeared after 3 months of corticosteroid therapy (initial dose 40mg), and the serum IgG4 concentration was normalized after 5 months. He is now free of any symptoms after 15 months. We experienced a case of mass-forming AIP diagnosed by EUS-guided biopsy.
1092 DISCOVERY OF NOVEL KINASE INHIBITORS FOR THE TREATMENT OF HEPATOCELLULAR CARCINOMA
Authors: S. Toffanin, L. Cabellos, H. Dong, C. Alsinet, A. Harrington, H. Cornella, R.V. Reddy, P.M. Reddy, J.M. Llovet
Journal: Journal of Hepatology (2013)
P590 RELATION OF HCV INDUCED INSULIN RESISTANCE AND HEPATOCELLULAR CARCINOMA: ROLE OF MDR1 GENE c.335T&gt;C AND c.3073A&gt;C SNPS
Authors: A.Z. Elsamanoudy, A.A. Atwa, H. Elalfy, A.H.A. Metwali
Journal: Journal of Hepatology (2014)
Abstract P4-06-10: Epigenetic silencing of glutamine synthetase (Glul) defines glutamine depletion therapy
Authors: F Cavicchioli, A Shia, K O'Leary, V Haley, TR Crook, AM Thompson, M Lackner, Nigro C Lo, P Schmid
Journal: Cancer Research (2012)

Abstract Background: Methylation-dependent transcriptional silencing of genes involved in amino acid synthesis can provide potential targets for novel synthetic lethality strategies. Glutamine synthetase (Glul) is the key enzyme in the biosynthesis of glutamine. We identified Glul as a novel gene subject to methylation-dependent transcriptional silencing in breast cancer cell lines using a combined functional screen with methylation reversal assays and methylation arrays. Methods: Methylation reversal assays were performed using 5-aza-2-deoxycytidine and/or trichostatin treatment coupled with whole genome mRNA microarrays (Illumina HT-12 v4 Expression BeadChip Kit). Expression of Glul with and without pharmacological methylation reversal with azacytidine and/or trichostatin was validated using qRT-PCR and Western Blot. Methylation of Glul was analysed using methylation microarrays (Illumina 450K Methylation BeadChip), bisulphite sequencing and pyrosequencing. Sensitivity to glutamine deprivation was assessed using an MTT assay after culturing cells in media with various glutamine concentrations or in complete absence of glutamine. We used a panel of 55 breast cancer cell lines and formalin-fixed paraffin-embedded tissue from a series of 116 stage I-III primary breast cancers with linked mature clinical outcome data that were randomly selected from the Cuneo Tissue Bank. Tissue samples were subject to histopathological review to ensure adequate representation of cancer cells. Results: Dense methylation of the CpG-island of Glul was detected in 45% of cell lines across all subtypes. Methylation of the CpG island was linked with absent or down-regulated expression of Glul in some but not all cell lines, and Glul expression could be reactivated by azacytidine and trichostatin in these cell lines. Methylation of shore areas was detected in several cell lines but was not associated with transcriptional silencing. Cells with methylation-dependent low or absent Glul expression were highly sensitive to glutamine deprivation, whereas cell lines without Glul methylation were rescued by compensatory up-regulation of Glul. Using pyrosequencing, dense methylation of the CpG island of Glul was found in 32.8% of patients, with an additional 17.2% of patients showing partial methylation. No significant association with a specific breast cancer subtype or outcome was found. Conclusions: This is the first report of methylation-dependent transcriptional silencing of Glul expression in cancer. Our data demonstrate that a significant proportion of primary breast cancers show methylation of Glul and suggest that glutamine deprivation could be a novel synthetic lethality strategy for these cancers. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-06-10.
Medicare's Vision for Delivery-System Reform — The Role of ACOs
Authors: Hoangmai H. Pham, John Pilotte, Rahul Rajkumar, Elizabeth Richter, Sean Cavanaugh, Patrick H. Conway
Journal: New England Journal of Medicine (2015)

Accountable care organizations could be central to Medicare's strategy for delivery-system reform. To further improve ACOs, the Centers for Medicare and Medicaid Services is applying the lessons it's been learning from its ACO initiatives over the past 5 years.
Abstract 4401: UCHL1 as a potential therapeutic target in uterine papillary serous carcinoma.
Authors: Suet Ying Kwan, Kwong-Kwok Wong, Rosemarie E. Schmandt, Karen H. Lu
Journal: Cancer Research (2013)

Abstract Uterine papillary serous carcinoma (UPSC) comprises less than 10% of all endometrial cancers but accounts for a disproportionately high number of deaths. Due to its rarity, few prospective studies have been conducted which focus on this aggressive subtype, and it has been difficult to establish optimal treatment strategies. With poor survival rates and high recurrence rates, the identification of novel therapeutic targets would aid in the management of UPSCs. RNAseq data from The Cancer Genome Atlas (TCGA) was analyzed using Significant Analysis of Microarrays to identify genes that were differentially expressed between 81 cases of grade 2 endometrioid endometrial carcinoma (EEC) and 41 cases of UPSC. A gene of interest was then selected based on its subcellular location, correlation with survival and normal tissue specificity. The findings were validated by immunohistochemical staining of UPSC paraffin sections. All patient samples were obtained and stored in accordance with human subject research protocols approved by the Institutional Review Board. All paraffin sections were reviewed by a pathologist. By comparing the RNAseq profiles of UPSCs and EECs, we identified 242 genes that were differentially expressed (q&amp;lt;0.005). Among these, ubiquitin C-terminal hydrolase 1 (UCHL1) showed higher expression in UPSCs compared to EECs, with an increase of over 6-fold. UCHL1 was chosen for further studies as Kaplan-Meier analysis of all endometrial cases in the TCGA database revealed that UCHL1 expression also correlated significantly with poorer disease-free survival (p&amp;lt;0.05). Preliminary immunohistochemical studies also show higher expression of UCHL1 in UPSCs than in ECCs. Interestingly, contrast analysis of TCGA data for breast cancer indicates that basal-like breast tumors also show significantly higher UCHL1 expression compared to the other breast cancer subtypes (p&amp;lt;0.005). Both basal-like breast cancer and UPSC have a high rate of p53 mutation (80% and 90%); this shared upregulation of UCHL1 suggests that a possible mechanism by which UCHL1 contributes to pathogenesis is through stabilization of mutant p53. In conclusion, our data identifies UCHL1 as a gene that is upregulated in UPSCs and is associated with poor disease-free survival. UCHL1 is a possible novel therapeutic target for the management of UPSCs. Further studies are needed to elucidate the underlying mechanisms in which it contributes to tumorigenesis. Citation Format: Suet Ying Kwan, Kwong-Kwok Wong, Rosemarie E. Schmandt, Karen H. Lu. UCHL1 as a potential therapeutic target in uterine papillary serous carcinoma. [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 4401. doi:10.1158/1538-7445.AM2013-4401
P1-01-10: Immune Suppression of Regulatory T Cells and M2 Macrophage in Breast Cancer Patients.
Authors: S Imoto, N Sakemura, H Kamma, T Nakatsura
Journal: Cancer Research (2011)

Abstract Background: Recent multi-disciplinary treatments of breast cancer (BC) could decrease the mortality rate, but successful immune therapy remains uncertain. To explore new strategy of immune therapy of BC, we are investigating about host-tumor immune response in BC patients. Materials and methods: Tumor tissue specimens and peripheral blood mononuclear cells (PBMC) were obtained from early and advanced BC patients. PBMC were also collected from healthy volunteers. Regulatory T (Treg) cells were examined by counting CD4+CD25highCD127low/−cells in PBMC with flow cytometry analysis. Immunohistochemical evaluation of tumor specimens was performed with monoclonal antibodies of HLA-ABC and DR, CD56, CD68, CD83, and CD163. The number of stained cells was analyzed using a semiquantitative ordinal scale ranging from 0 to 3 (0, +/−, ++, +++). Results: HLA-ABC and DR were stained negative in 44% and 82% of 50 BC cases. When host-tumor immune response were compared between 38 early BC cases and 12 advanced BC cases, numbers of CD68-positive cells significantly increased in peripheral tumor tissues of advanced BC cases than in those of early BC cases (92% versus 53%). CD163-positive tumor cells were also detected more frequently in advanced BC cases than in early BC cases (75% versus 16%). There were no significant differences of distribution of CD4, CD8, CD56, and CD83-positive cells in early and advanced BC cases. Treg cells in PBMC significantly increased in percentage of the population in 37 BC patients than in 21 healthy volunteers (4.2% versus 2.5% of CD4-positive cells at mean value). Interestingly, Treg cells decreased in percentage of the population in 36 postoperative BC patients. Conclusions: Our results suggest that Treg cells render BC patients under immune suppression and M2 macrophage plays an important role of tumor progression. Targeted therapy against M2 macrophage may be a promising strategy of breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-01-10.
Closure of a persistent gastric leak using a cardiac septal occluder
Authors: Vivek Kumbhari, Andrew Storm, Payal Saxena, Patrick Okolo
Journal: Endoscopy (2014)

Anastomotic leaks occur in up to 5 % of patients who undergo bariatric surgical procedures [1]. Reoperation is associated with a high morbidity, and a mortality of up to 10 % [2]. Therefore, endoscopic management should be considered in the first instance. We present a case of a gastric anastomotic leak that was successfully closed with a cardiac septal occluder device (Amplatzer; St. Jude Medical, Plymouth, Minnesota, USA).