tbuckley/cabot-search huggingface dataset:
CÁPSULA ENDOSCÓPICA EN LA HEMORRAGIA DIGESTIVA DE ORIGEN OSCURO
Authors: A Zatarain Vallés, A Martínez Sánchez, F Sánchez Ceballos, M Megía Sánchez, S Ayllón Cano, M Asteinza Daganzo, JM Esteban López-Jamar, E Rey Díaz-Rubio
Journal: Endoscopy (2015)

Introducción: Un 5% de las hemorragias digestivas se presentan en forma de hemorragia digestiva de origen oscuro (HDOO) oculta o manifiesta. La cápsula endoscópica (CE) es la técnica de elección para su diagnóstico.
Abstract P4-03-17: Tartrate-resistant acid phosphatase (TRACP) modulates breast cancer pre-metastatic niche
Authors: M-S Dai, C-C Wu, L-C Chen, C-M Chen, T-Y Chao
Journal: Cancer Research (2017)

Abstract Background: Tartrate-resistant acid phosphatase (TRACP or ACP5) is a metalloprotein enzyme that belongs to the acid phosphatase family and is mainly expressed by osteoclasts. It is a classic marker for bone resorption and osteoclast differentiation. TRACP expression is a useful serum marker for extensive bone metastasis. Recent studies have reported that TRACP promotes the invasion and distant metastasis of melanoma and breast cancer cells through the modulation of focal adhesion kinase (FAK) phosphorylation and epithelial cell migration. Therefore, TRACP has received considerable attention as a newly discovered proinvasion metastasis driver associated with different malignancies. Additionally, TRACP overexpression is indicative of the poor prognoses cancer patients and suggests that TRACP may have an important role in promoting tumor metastasis. Its detail mechanism in modulating cancer metastasis remains unknown. We have previously demonstrated the serum TRCAP 5a is a valuable marker in assessing disease activity, severity or systemic macrophage (inflammatory) burden. It has recently been found that up-regulation of TRACP promoted cancer cell invasion and lung metastasis, whereas TRACP knockdown inhibited these processes. Aims: No studies have previously addressed the question of extracellular effects of TRAP. The aim of this study was to evaluate if TRACP binds to and is endocytosed by cancer cells. We also aim to determine if extracellular TRACP affect oncogenesis or cancer progression, alter the cancer cell expressions of angiogenesis or adhesion molecules, or direct the treatment resistance or cancer prognosis. Results: Knockdown of TRACP significantly attenuated FoxM1-enhanced invasion and lung metastasis. Extracellular TRACP in culture media influenced the tumor invasion upon endocytosis. Significant increased invasion/migration was observed upon higher concentrations of TRACP. Tumor growth was significantly enhanced when the tumor xenografting previously primed with polarized M2Ø or TRACP protein, by enhanced metalloproteinase (MMP-9) and angiogenic factor (VEGF-A) expression Conclusions: TRACP or M2Ø-secreted TRACP could promote cancer growth and modulated the tissue and microenvironment and create pre-metastatic condition by cell adhesion/angiogenesis signaling alteration. TRACP-targeting strategy is plausible in breast cancer metastasis treatment. Citation Format: Dai M-S, Wu C-C, Chen L-C, Chen C-M, Chao T-Y. Tartrate-resistant acid phosphatase (TRACP) modulates breast cancer pre-metastatic niche [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-03-17.
Identifying enzalutamide resistance mechanisms in men with castration-resistant prostate cancer.
Authors: Joshi J. Alumkal, Laura Heiser, Tomasz M. Beer, Eric Jay Small, Robert Baertsch, Josh Stuart, Carly King, James Korkola, Jeremy Cetnar, Julie Nicole Graff, George Thomas, Christopher W. Ryan, Alexandria Toschi, Jack Youngren, Erin Tucker, Kristi Eilers
Journal: Journal of Clinical Oncology (2014)

TPS5104 Background: Multiple lines of evidence demonstrate that castration-resistant prostate cancers (CRPCs) remain reliant on androgens that activate the androgen receptor (AR). Treatment with the novel anti-androgen enzalutamide improves progression-free survival (PFS) and overall survival (OS) in CRPC patients (Scher 2012, Beer 2014). However, nearly 50% of patients never respond, and progression is universal. Mechanisms of enzalutamide resistance in CRPC patient tumors are largely unknown, and few treatments exist for enzalutamide-resistant CRPC. Recent work demonstrates that CRPC tumors carry countless genomic aberrations that control many hallmarks of cancer (Grasso 2012, Hanahan 2011). Based on our work (Heiser 2012), we hypothesize that these aberrations work in concert to drive enzalutamide resistance and influence specific cancer hallmarks. Methods: We are enrolling men with metastatic CRPC who are eligible to receive enzalutamide (N=65). Through a DOD Synergistic Idea Award and a West Coast Prostate Cancer Dream Team Award, we perform a CT-guided metastatic tumor biopsy prior to treatment and at the time of PSAWG2-defined disease progression (Scher 2008). We perform RNA-seq and array CGH followed by an integrative genomic analysis with the PARADIGM algorithm to identify deregulated gene networks in each tumor sample (Heiser 2012). Then, we use logistic regression and Random Forests classification analysis to determine the association of these deregulated gene networks and our outcome measures. The primary endpoint is: Identify molecular features/pathways associated with enzalutamide response (>50% PSA decline at 12 weeks). Secondary endpoints include: Identify molecular features/pathways associated with PFS, OS, objective response, and acquired enzalutamide resistance (by comparing each subject’s pre-treatment and progression biopsies). We anticipate that this trial will identify distinct subsets of CRPC patients with specific enzalutamide resistance mechanisms. Identifying these mechanisms will lead to rationally designed clinical trials of specific enzalutamide drug combinations in distinct molecular subsets of CRPC patients in the near-term.
Abstract IA10: Renal cancer tumorgrafts: A validated model to evaluate novel targeted therapies
Authors: Andrea Pavia-Jimenez, Wenfang Chen, Haley Hill, Alana Christie, Qurratulain Yousuf, Noelle Williams, Xian-Jin Xie, Payal Kapur, James Brugarolas
Journal: Clinical Cancer Research (2016)

Abstract Renal cell carcinoma (RCC) is diagnosed in over 50,000 Americans annually and in the metastatic setting remains largely incurable. The development of new drugs is hampered by the lack of suitable preclinical animal models reproducing the characteristics of human tumors. To date, we have implanted tumors from over 700 kidney cancer patients orthotopically in mice. Our models include common tumor types, such as clear cell and papillary, but also rare tumor types such as translocation carcinomas and fumarate hydratase (FH)-deficient renal tumors from HLRCC patients. We have shown that tumor fragments implanted orthotopically into NOD/SCID mice result in tumors that reproduce: (i) histology, (ii) gene expression, (iii) DNA copy number alterations and (iv) mutations. Tumorgraft (TG)-bearing mice also reproduce paraneoplastic syndromes (paraneoplastic hypercalcemia). Furthermore, TGs recapitulate the treatment responsiveness of RCC in patients. We performed pharmacokinetic studies to determine appropriate administration regimens resulting in comparable exposures. TGs responded to drugs effective against RCC in patients (sunitinib and sirolimus, which accounts for 70% of the circulating drug after temsirolimus administration) and were resistant to ineffective drugs (erlotinib). TGs provide a superb platform to evaluate promising novel therapeutics. Data will be presented on the application of our TG platform to the evaluation of a first-in-class inhibitor of arguably the most important driver of RCC, the HIF-2 transcription factor. TGs were used to assess activity, validate a putative pharmacodynamic biomarker, identify biomarkers of sensitivity, and to assess the development of resistance. By leveraging a large and diverse TG platform, preclinical drug testing may be rigorously conducted, the most promising agents may be identified, and future clinical development may be effectively informed. Citation Format: Andrea Pavia-Jimenez, Wenfang Chen, Haley Hill, Alana Christie, Qurratulain Yousuf, Noelle Williams, Xian-Jin Xie, Payal Kapur, James Brugarolas. Renal cancer tumorgrafts: A validated model to evaluate novel targeted therapies. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr IA10.
Change in the right direction for patients
Authors: Theodora Bloom
Journal: BMJ (2017)

With the NHS facing big challenges, how can its leaders ensure that changes are those that matter most to patients? How can they ensure that everybody pulls in the same direction?

Three overseas recruits to chief executive posts tell The BMJ what the NHS needs most (doi:10.1136/bmj.j1036). There is no shortage of innovative ideas, but implementing them on the wards is hard, especially when an improvement programme may take longer than the tenure of a chief executive. Bureaucracy and paperwork are …
Abstract P6-09-46: A comprehensive analysis of GNAS DNA copy number, levels of mRNA and protein expression in primary breast cancer
Authors: M Tomiguchi, Y Yamamoto, M Yamamoto-Ibusuki, L Goto-Yamaguchi, Y Fujiki, A Sueta, T Takeshita, H Iwase
Journal: Cancer Research (2017)

Abstract Background: Result of recent advances in genetics, guanine nucleotide binding protein, alpha stimulating (GNAS), transducer of signals from G-protein coupled receptors, has been noted that this factor is related with the onset and progression of tumor in various cancers. We aimed to analyze gene amplification, mRNA and protein expression of GNAS and their potential association with clinicopathological factors and prognosis in primary breast cancer. Methods: The cohort of this study included 432 primary invasive breast cancer patients treated with standard care at Kumamoto University Hospital between June 2000 and January 2011. We performed a comprehensive analysis of GNAS at the levels of gene copy number, mRNA and GNAS protein expression analyzed by qPCR, qRT-PCR and immunohistochemistry (IHC), respectively. In the IHC assessment of GNAS protein expression, an H-score&amp;lt;150 was observed in 191 patients (44.2%), who were defined as having a low protein expression level, and an H-score≥150 was observed in 241 patients (55.8%) who were defined as having a high protein expression level. Results: The median age at diagnosis was 60 (range 27-93). Three hundred fifteen (72.9%) of these were postmenopausal women. One hundred forty two patients (32.9%) had axillary lymph node metastasis. The median Ki67 labeling index was 23.6 (range 0.5-97.0). The subtypes were 321 ER+/HER2-, 24 ER+/HER2+, 34 ER-/HER2+ and 53 ER-/HER2-. Three hundred twenty one patients (75.9%) were treated with endocrine therapy and 146 patients (34.6%) chemotherapy. Most notably, a low levels of GNAS protein expression was observed in 191(44.2%) patients, and was positivity associated with Ki67 (P=0.028). Furthermore, univariate and multivariate analysis revealed that low GNAS protein expression was significantly related with poor relapse-free survival rate (Log-rank test; P=0.0013, OR:0.40, 05%CI:0.22-0.70) and breast cancer specific survival rate (Log-rank-test; P=0.041, OR:0.43, 95%CI:0.19-0.97). GNAS amplification and mRNA expression were not correlated with prognoses. Conclusion: Contrary to expectations, GNAS expression was positively related with favorable tumor characteristics. Expression levels of GNAS protein may be an independent prognostic factor for primary breast cancer. Citation Format: Tomiguchi M, Yamamoto Y, Yamamoto-Ibusuki M, Goto-Yamaguchi L, Fujiki Y, Sueta A, Takeshita T, Iwase H. A comprehensive analysis of GNAS DNA copy number, levels of mRNA and protein expression in primary breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-46.
Maternal Circulating Transthyretin Level Is Longitudinally Associated With Increased Risk of Gestational Diabetes Mellitus: It Is Not Just an Indicator of Nutritional Status
Authors: Ting Xiong, Chunrong Zhong, Xuezhen Zhou, Renjuan Chen, Mei Xiao, Yuanjue Wu, Xingwen Hu, Weiye Wang, Xiating Li, Chaoqun Liu, Guoping Xiong, Xuefeng Yang, Liping Hao, Nianhong Yang
Journal: Diabetes Care (2017)

Transthyretin (TTR) is a carrier protein that transports thyroid hormones and retinol. Conventionally, a higher serum TTR level is usually taken as a sensitive clinical indicator of better protein nutritional status (1). However, emerging evidence has given us clues that TTR may contribute to gestational diabetes mellitus (GDM) (2–5). If this is the case, our previous “good impression” of TTR might be overturned. However, few population-based studies have focused on this issue.

In this prospective cohort study, we measured serum TTR, total protein (TP), albumin (Alb), and other parameter levels in the regular antenatal liver and renal function (LRF) test at 13–20 gestational weeks in 1,914 pregnant women (aged 18–45 years) belonging to the ongoing Tongji Maternal and Child Health Cohort (TMCHC) study in China. All procedures performed in studies involving human participants were in accordance with the ethical standards of the ethics review committee of Tongji Medical College of Huazhong University of Science and Technology and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Using logistic regression, we analyzed the association between …
Challenges in clinical electrocardiography: Dual ventricular rhythm
Authors: Apurva O. Badheka, Peeyush M. Grover, Tanyanan Tanawuttiwat, Amit Badiye, George R. Marzouka, Nileshkumar J. Patel, Sandra V. Chaparro, Raul D. Mitrani
Journal: JAMA Internal Medicine (2013)
Erratum: Molecular correlates of anemia in primary myelofibrosis: a significant and independent association with U2AF1 mutations
Authors: D Barraco, Y C Elala, T L Lasho, K H Begna, N Gangat, C Finke, C A Hanson, R P Ketterling, A Pardanani, A Tefferi
Journal: Blood Cancer Journal (2016)

Molecular correlates of anemia in primary myelofibrosis: a significant and independent association with U2AF1 mutations
Met heterogeneity evaluation by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in nonsquamous non-small cell lung cancer (nsNSCLC).
Authors: Edurne Arriola, David Casadevall, Javier Gimeno, Sergi Clave, Alvaro Taus, Marta Lorenzo, Silvia Menendez, Joan Albanell, Blanca Espinet, Marta Salido
Journal: Journal of Clinical Oncology (2014)

11005 Background: Molecular selection of patients who may benefit from Met inhibitors is being based on immunohistochemistry (IHC) with no consensus in the field. We sought to evaluate the association between MET gene copy number (GCN) and protein expression in NSCLC samples. Moreover, we wanted to analyze the heterogeneity within the same tumor specimen and its implications in Met evaluation. Methods: First, surgical cases from patients with nsNSCLC were included in a tissue microarray (TMA) representing 2 distinct morphologic areas of the tumor (2 consecutive sections). Second, biopsies from newly diagnosed patients were analyzed. Met expression was assessed by IHC (Ventana) using H-scores and MetMAb criteria and MET GCN by FISH (MET and CEP7 probes from Vysis). Association between GCN and protein expression and their correlation with clinico-pathologic and molecular information (KRAS, EGFR) was investigated. Additionally, heterogeneity of METGCN and protein expression within different tumor cores and within consecutive sections was assessed. Results: One hundred and twenty-seven samples (120 patients) were analyzed. Ninety percent were adenocarcinomas, 35% grade 3, 19% KRAS and 11% EGFR mutant. Median age was 66 years, 70% males, and 53% current smokers. Median Met H-score was 140 and according to MetMAb criteria, 48% were Met high. High Met expression was associated with advanced stage (p=0.001). No association was observed with KRAS/EGFR mutations. MET amplification was observed in 8 cases (6.3%). No association was observed between MET GCN and protein expression. Met IHC score was high (H-score 400) in amplified cases with MET/CEP7 ratio >2, but not in those with MET GCN>5. For Met IHC, intraclass correlation coefficient (ICC) was 0.8 between consecutive tumor sections and 0.4 between different tumor cores. For METFISH, ICC was 0.5 and 0.7, respectively. For amplified cases, 4 out of 12 cores were negative by FISH. Conclusions: The definition of Met positivity in the clinical setting is challenging, due to tumor heterogeneity. Met IHC does not accurately identify Met driven tumors. More precise criteria are needed for defining “Met dependence”.
Azacitadine and Low-Dose Gemtuzumab Ozogamicin for the Treatment of Poor-Risk Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS), Including Relapsed, Refractory Disease.
Authors: Laura C Michaelis, Danielle Shafer, Kevin Barton, Tulio Rodriguez, Scott Smith, Patrick Stiff, Sucha Nand
Journal: Blood (2009)
Abstract P6-07-20: Allele-specific PCR assay for estrogen receptor (ESR1) mutation detection
Authors: CM Litterst, HB Tran, S Chien, X Chen, W Wen, A Begovich
Journal: Cancer Research (2017)

Abstract Seventy percent of breast cancers are estrogen receptor (ER) positive and, while the majority of these patients initially respond to hormone therapy, approximately 20-30% will become therapy refractory. Recent data suggest activating-mutations in the estrogen receptor gene (ESR1) ligand binding domain (LBD), which are acquired during anti-estrogen treatment and rarely found in primary untreated ER+ breast cancer, are associated with resistance. Some researchers propose that ESR1 mutations are a prognostic and predictive marker, but more studies are needed to assess the clinical utility of the ESR1 mutations. However, current ESR1 mutation detection methods, that is, next generation sequencing and digital PCR, are very labor-intensive, lengthy, and expensive and require special training. To aid research on the diagnostic potential of ESR1 mutations, we developed a prototype allele-specific qPCR assay for the detection of 18 recurrent mutations in the ESR1 LBD. The test is suitable for DNA obtained from FFPE tissue as well cfDNA from plasma. It is sensitive, yet simple, robust and results can be obtained in less than 8 hours. Herein, we demonstrate the analytical performance of our ESR1 mutation detection assay using contrived samples. We are also planning to test clinical FFPET and plasma samples in the future. Citation Format: Litterst CM, Tran HB, Chien S, Chen X, Wen W, Begovich A. Allele-specific PCR assay for estrogen receptor (ESR1) mutation detection [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-07-20.
Real World Experience of Clinical Profile and Outcomes of Autoimmune Hemolytic Anemia: Single Centre Experience
Authors: Ram V Nampoothiri, Uday Yanamandra, Alka Khadwal, Gaurav Prakash, Deepesh P. Lad, Prashant Sharma, Fen Saj, Reena Das, Neelam Varma, Pankaj Malhotra, Subhash Varma
Journal: Blood (2016)
Effective treatment of triple-negative breast cancer with targeted cytotoxic somatostatin analogue AN-162 (AEZS-124)
Authors: S. Seitz, A. V. Schally, S. Gluck, F. Rick, L. Szalontay, F. Hohla, A. Papadia, F. Köster, O. Ortmann, S. Buchholz
Journal: Journal of Clinical Oncology (2009)

619 Background: Triple negative breast cancers (TNBC) represent a distinct subtype of breast cancer being negative to ER, PR and HER2 and are associated with poor prognosis. Limited systemic treatment options exist for TNBC. TNBC cells express somatostatin receptors (SSTR). Therefore, to investigate preclinical characteristics of TNBC we used a novel targeted cytotoxic somatostatin analogue AN-162 containing doxorubicin (DOX) which binds to the subtypes 2, 3 and 5 of SSTR. Methods: The expression of SSTR in HCC 1806 human TNBC cell line was detected by RT-PCR. Cytotoxic effect of AN-162 in vitro was visualized by ethidium bromide staining fluorescence microscopy. Internalization of AN-162 into HCC 1806 cells was tested by 125 Iodide-labeled AN-162 uptake assays and the presence of DOX in the nucleus was measured by fluorescence assays after separating the nucleus from the cytoplasm. For in vivo experiments, HCC 1806 TNBC cells were xenografted subcutaneously into nude mice which were then randomized into four groups receiving AN-162, DOX, an unconjugated mixture of DOX and somatostatin analogue RC-160 at the same equimolar dose of 2.5 μmol/kg (1.45 mg/kg Dox equivalent) i.v. (q7d 4x) and vehicle solution control. Results: HCC 1806 TNBC cell line was positive for the expression of all five SSTR receptor subtypes. Ethidum bromide staining of cells treated with 2.5 μM of AN-162 for 30 min demonstrated cell death after 24h by fluorescence microscopy. Uptake assays with AN-162 showed specific internalization of AN-162 into the cells mediated through the sstrs. After treatment of the cells with 2.5 μM AN-162 for 10 or 30 min, DOX could be detected in the nucleus by fluorescence assays. In vivo, AN-162 significantly (p&lt;0.05) inhibited tumor growth of HCC 1806 xenografts compared to Control, DOX and the unconjugated mixture of DOX+RC-160 from day 14 and the inhibition remained significant until the end of the study on day 35. Conclusions: Our results indicate that treatment with targeted cytotoxic somatostatin analogue AN-162 produces a greater inhibition of tumor growth than DOX alone in somatostatin receptor positive TNBC. Our findings support the concept of targeted chemotherapy based on cytotoxic peptide analogues for the treatment of breast cancer and other cancers. No significant financial relationships to disclose.