tbuckley/cabot-search huggingface dataset:
Albinism in Tanzania: the struggle to survive
Authors: Elizabeth Emsley
Journal: BMJ (2013)

Witchdoctor-led violence against people with albinism has left them fearing for their lives and lacking adequate healthcare People with albinism have often had to fight stigma attached to their condition, many having to deal with name calling and social exclusion. However, in some parts of the world, those living with albinism face more extreme danger. In some areas of East Africa, particularly Tanzania—which has a high prevalence of albinism—there has been a belief, perpetuated by witchdoctors, that the body parts of people with albinism bring luck.1 People with albinism in Tanzania have experienced kidnap, dismemberment, murder, and their graves have been robbed2 because of attempts by witchdoctors to procure their body parts. The social isolation of people with albinism in Tanzania puts them in further danger because it has meant that they have not been adequately screened and protected from skin cancer, from which they are at particular risk. Albinism is a collection of inherited disorders characterised by little or none of the skin pigment, melanin (box 1).3These conditions are generally rare, but some parts of sub-Saharan Africa have a prevalence of albinism much higher than average. Albinism has a global prevalence of 1 in 17 000 to 1 in 20 000. However, in South Africa, for instance, the prevalence is about 1 in 4000.4 #### What is albinism?
Abstract P5-03-13: ERVMER34 sensitizes the response of HER2 positive breast cancer to neoadjuvant therapy
Authors: Y Chi, W Ji, B Xiu, Q Zhang, J Wu
Journal: Cancer Research (2019)

Abstract Although anti-HER2/neu antibody therapy combined with chemotherapy has achieved an outstanding effect, many patients with HER2-positive breast cancer still succumb due to therapeutic resistance. Understanding the mechanisms of therapeutic resistance is of vital importance. In this study, core needle biopsy tissue from HER2-positive patients was collected before neoadjuvant chemotherapy. Differentially expressed RNAs between pCR and non-pCR group have been identified through RNA-seq. Here we found that ERVMER34, an endogenous retroviral envelope protein was significantly inhibited in non-pCR group compared to pCR group. High ERVMER34 expression was associated with good overall survival both in TCGA database and our own patients cohort. Further study showed that ERVMER34 could be glycosylated and secreted to cell supernatant. The IC50 of paclitaxel and trastuzumab in HER2 positive breast cancer cells was decreased by ectopic overexpression of ERVMER34. Furthermore, RNA-seq, FACS assay and western blot revealed that ERVMER34 could promote cell apoptosis and sensitize therapy response through inhibiting mTOR pathway in HER2 positive breast cancer cells. Via mass spectrometry, TRIM21, an E3 ligase was found to interact with ERVMER34 and promoted its ubiquitination degradation. Taken together, these data suggest that ERVMER34 may severve as a novel biomarker to predict therapy response in HER2 positive breast cancer. Citation Format: Chi Y, Ji W, Xiu B, Zhang Q, Wu J. ERVMER34 sensitizes the response of HER2 positive breast cancer to neoadjuvant therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-03-13.
Abstract 2029: Identification and characterization of cancer stem cells in ovarian cancer
Authors: Gil Mor, Rui Chen, Han Hsuan Fu, Michele Montagna, Irene Visintin, Dan Silasi, Peter Schwartz, Masoud Azodi, Thomas Rutherford, Ayesha Alvero
Journal: Cancer Research (2008)

Abstract Introduction: One of the major burdens in the treatment of epithelial ovarian cancer (EOC) is the high percentage of recurrence characterized by chemoresistance. The biology underlying the tumor’s high capacity for recurrence has not been elucidated. Tumors are made of a heterogeneous cell population consisting of both cancer and non-cancer cells. New data suggest that even the cancer cell population is heterogeneous and contains a small subset of cells, the cancer stem cells (CSC), which constitute a reservoir that can self-renew and therefore maintain the tumor. CSC can divide and expand their pool and also differentiate into non-CSC, which constitute the bulk of the tumor. Contrary to CSC, the non-CSC are rapidly dividing and therefore sensitive to therapies, which target highly proliferative cells. In the present study we identified and characterized the CSC of EOC. Methods: EOC cells were isolated from malignant ovarian cancer ascities and solid tumors (n=80). Marker expression was determined using Flow Cytometry, Western Blots and Immunocytochemistry. Xenograft nude mice model was used for tumor growth by injecting cancer cells either s.c. or i.p. Isolation of CD44+ population was done using FACS. Cancer cells were maintained in culture as previously described {Kamsteeg, 2003 #358} Results: CSC were identified in EOC cells isolated form ascites and solid tumors with the following characteristics: 1) cellular markers: CD44+, MyD88+, constitutive NFκB activity and cytokine and chemokine production, high capacity for repair, chemoresistance to conventional chemotherapies, resistance to TNFα-mediated apoptosis, capacity to form spheroids in suspension, and unique microRNA phenotype; 2) tumor formation in animals: 100% CD44+ cells formed tumors which contained 10% CD44+ and 90% CD44-negative cells. Re-injection of isolated CD44+ cells from previous engraftment was able to again recapitulate the original tumor phenotype. Isolation and in vitro treatment of CD44+ cells from fresh samples showed resistance to carboplatin and paclitaxel. In contrast, the sorted CD44-negative cell population from the same sample/patient was chemosensitive. Conclusion: Present chemotherapy modalities eliminate the bulk of the tumor but it leaves a core of cancer cells with high capacity for repair and renewal. CSC corresponds to the core of malignant cells that promotes recurrence and chemoresistance. Identification of these cells represents the first step in the development of therapeutic modalities that can eliminate not only the bulk of the tumor but its source. Prevention of recurrence will be achieved only with therapies targeting this cell population.
Printing Therapeutic Proteins in 3D using Nanoengineered Bioink to Control and Direct Cell Migration
Authors: Charles W. Peak, Kanwar Abhay Singh, Mu'ath Adlouni, Jeffrey Chen, Akhilesh K. Gaharwar
Journal: Advanced Healthcare Materials (2019)

A nanoengineered bioink loaded with therapeutic proteins is designed to direct cell function in a 3D printed construct. The bioink is developed from a hydrolytically degradable polymer and 2D synthetic nanoparticle. The synthesis of poly(ethylene glycol)-dithiothreitol (PEGDTT) via a Michael-like step growth polymerization results in acrylate terminated degradable macromer. The addition of 2D nanosilicates to PEGDTT results in formation of shear-thinning bioinks with high printability and structural fidelity. The mechanical properties, swelling kinetics, and degradation rate of 3D printed constructs can be modulated by changing the ratio of PEG:PEGDTT and nanosilicates concentration. Due to high surface area and charged characteristic of nanosilicates, protein therapeutics can be sequestered in 3D printing structure for prolong duration. Sustained release of pro-angiogenic therapeutics from 3D printed structure, promoted rapid migration of human endothelial umbilical vein cell. This approach to design biologically active inks to control and direct cell behavior can be used to engineer 3D complex tissue structure for regenerative medicine.
An alternative option?
Authors: Isobel Weinberg
Journal: BMJ (2013)

If a patient asks for your advice on using an alternative therapy, what will you tell them? Let’s flick through their evidence bases: homeopathy—shown not be better than a placebo; healing—no evidence of efficacy; chiropractic—may be effective for back pain but has harmful side effects. And so on. Edzard Ernst summarises the evidence bases (doi:10.1136/sbmj.f1604).

So, that solves the problem of what to tell your patient. Or does it? When a chronically ill patient wants to try homeopathy as a last resort, what will you say? After all, as Margaret McCartney points out in her …
Construction of lanthanide-doped upconversion nanoparticle-Uelx Europaeus Agglutinin-I bioconjugates with brightness red emission for ultrasensitive in vivo imaging of colorectal tumor
Authors: Rongrong Tian, Shuang Zhao, Guifeng Liu, Hongda Chen, Lina Ma, Hongpeng You, Chunming Liu, Zhenxin Wang
Journal: Biomaterials (2019)
Abstract P6-02-18: Hepatic complications of breast cancer
Authors: MJ Wong, H Choi
Journal: Cancer Research (2019)

Abstract Background Breast cancer is the most common malignancy and the leading cause of cancer death in women in the United States. Nearly 30% of women with metastatic breast cancer will have liver metastases, with a median survival from time of 4.23 months from time of metastatic diagnosis. Hepatic involvement of breast cancer is common and can result from metastatic tumor burden or treatment with chemotherapy or radiation. Being able to recognize and diagnose hepatic involvement of breast cancer is of utmost importance, as it has a dramatic effect on patient prognosis and management. Learning Objectives To familiarize multidisciplinary clinical team members with the radiographic presentations of hepatic complications of breast cancer in a variety of imaging modalities including computed tomography, dual-energy computed tomography, ultrasound, and MR. This will facilitate accurate and prompt diagnosis and treatment of hepatic involvement of breast cancer. Abstract Our educational pictorial essay demonstrates the typical appearance of hepatic metastases on multiple imaging modalities, as well as atypical presentations such as hyperdense, hypervascular, or hypoechoic lesions and pseudoprogression. We will show examples of hepatic metastases presenting as pseudocirrhosis, left lobar atrophy, capsular retraction, as well as sequelae of pseudocirrhosis such as malignant ascites, varices, portal vein thrombosis, and biliary obstruction. We will discuss the radiographic appearance of the liver after being treated with locoregional liver-directed techniques such as surgical resection, ablation, and chemoembolization. Importantly, we will illustrate examples of hepatic complications from systemic therapy including steatohepatitis from tamoxifen, as well as hepatic fibrosis from gemcitabine. Conclusion Clinicians must have a thorough understanding of the hepatic complications of cancer to ensure excellent diagnostic accuracy and management. References 1. Diamond JR, Finlayson CA, Borges VF. Hepatic complications of breast cancer.Lancet Oncol. 2009;10:615–621. 2. Wyld L, Gutteridge E, Pinder SE, James JJ, Chan SY, Cheung KL, Robertson JF, Evans AJ, 2003 Prognostic factors for patients with hepatic metastases from breast cancer Brit J Cancer 89: 284–290. 3. Adike A, Karlin N, Menias C, Carey EJ. Pseudocirrhosis: A case series and literature review. Case Rep Gastroenterol. 2016;10(2):381–91 4. Agarwal K, Jones DE, Burt AD, et al. Metastatic breast carcinoma presenting as acute liver failure and portal hypertension. Gastroenterol Hepatol. 2002;97:750–751. Citation Format: Wong MJ, Choi H. Hepatic complications of breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-02-18.
Abstract LB-305: Soluble CD23 levels increase following lumiliximab dosing in relapsed chronic lymphocytic leukemia patients
Authors: Sarah Harris, James Woodworth, Julie Ranuio-Kelley, Annalee Estrellado, Alessandra Cesano, Hua Mu, Shabnam Tangri
Journal: Cancer Research (2008)

Abstract Lumiliximab is an anti-CD23 monoclonal antibody under investigation for the treatment of patients with B-cell chronic lymphocytic leukemia (B-CLL). Lumiliximab binds specifically to human CD23, a glycoprotein expressed on the majority of CLL B cells. CD23 is a trimeric molecule with both membrane-bound (mCD23) and soluble (sCD23) forms. mCD23 is a 45 kD glycoprotein expressed on B cells, monocytes/macrophages, eosinophils, platelets, and dendritic cells, with increased levels observed on chronic lymphocytic leukemia (CLL) cells. Soluble CD23 is produced by the cleavage of mCD23 by endogenous proteases into various fragments, with the 25 kD fragment found in normal human serum at concentrations around 2 ng/ml. Increased levels of sCD23 are found in the serum of patients with several disease states including CLL. Data from a Phase 1 lumiliximab monotherapy trial in relapsed CLL showed that levels of sCD23 rapidly increased in the serum of some patients after dosing with lumiliximab. To confirm this phenomenon, serum sCD23 levels and their relationship with treatment response were evaluated in a Phase 1/2 study of lumiliximab in combination with fludarabine, cyclophosphamide, rituximab (FCR) in patients with relapsed CLL. The pharmacokinetic (PK) profiles of both lumiliximab and rituximab were also compared to sCD23 profiles. Methods: Thirty-one patients with relapsed CLL were enrolled to receive up to 6 cycles treatment with lumiliximab plus FCR. Lumiliximab PK, Rituxan PK and sCD23 levels were each measured in 31 patients using validated enzyme-linked immunosorbant assays. PK data was analyzed with WinNonlin. Results and Conclusions: Our analysis shows that sCD23 increases from the ng/ml range to the ug/ml range immediately after each dosing with lumiliximab/FCR, then declines throughout the remainder of the treatment cycle. The levels of sCD23 increase again with subsequent lumiliximab/FCR doses, until the there are little to no B-CLL cells remaining in the circulation. The pattern of increase parallels the PK profile of lumiliximab. The intensity of sCD23 increase varied from patient to patient, and did not appear to correlate with treatment outcome. These data demonstrate that although lumiliximab/FCR dosing increases serum levels of sCD23, there is no apparent impact on patient response. This will be evaluated further in upcoming clinical trials. The mechanism of sCD23 release is also currently being investigated.
Abstract P3-01-14: Diverse inter- and intra-patient circulating tumor cells (CTCs) phenotypic heterogeneity identified in metastatic breast cancer (MBC) cohort
Authors: Y Wang, B Hom, P Ontiveros, C Landaverde, E Roth, MK Levin, S Hippely, M Landers, R Dittamore, JA O'Shaughnessy
Journal: Cancer Research (2019)

Abstract Background: There is unmet need for biomarkers to guide the treatment selection in MBC. We described phenotypic CTC heterogeneity in metastatic castrate resistant prostate cancer(mCRPC), and showed that pts with CTC high heterogeneity have improved OS with chemotherapy, while with pts low CTC heterogeneity pts have longer OS with AR inhibitors (Scher et al. 2017 Cancer Research). Here, the same methodology was applied to evaluate the feasibility of CTC heterogeneity analysis in MBC pts. Material and methods: 92 blood samples from MBC pts were processed for HER2 CTC analysis utilizing the Epic Sciences platform. Following enumeration, multi-dimensional phenotypic characterization analysis was performed utilizing protein expression and digital pathology features. 20 features from each CTC were clustered using unsupervised approach (K-means) and the optimal number of clusters was determined using the elbow method with greater than 85% of variance taken into account. Shannon Index was used to score intra-patient CTC heterogeneity. Results: CTCs were detected in 77.2% (71/92) of the MBC pts. 1501 CTCs from 60 pts were clustered into phenotypic subtypes which are distinctively different in nuclear size, circularity, CK and HER2 intensity etc. HER2 expression was enriched in cell types that had higher CK intensity and was more circular morphologies often associated with replicative stress. A wide range of CTC phenotypic heterogeneity was observed across pts, Shannon Index scores from 0 (low heterogeneity) to 1.67 (high heterogeneity) with a median of 0.60. CTC heterogeneity was independent of CTC counts, some low count pts had heterogeneous CTC subtypes while some high count pts had homogeneous CTC subtypes. Conclusions: Diverse inter- and intra-patient phenotypic CTC heterogeneity were observed in this MBC cohort, consistent with that seen in mCRPC and other MBC cohorts (Beverly H et al, ASCO 2018). Studies linking degree and patterns of CTC heterogeneity to therapeutic outcomes are ongoing. Citation Format: Wang Y, Hom B, Ontiveros P, Landaverde C, Roth E, Levin MK, Hippely S, Landers M, Dittamore R, O'Shaughnessy JA. Diverse inter- and intra-patient circulating tumor cells (CTCs) phenotypic heterogeneity identified in metastatic breast cancer (MBC) cohort [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-01-14.
Abstract P6-14-07: Not presented
Authors: J Lai, Y Antill, G Richardson, M Vereker, S David
Journal: Cancer Research (2019)

Abstract This abstract was not presented at the conference. Citation Format: Lai J, Antill Y, Richardson G, Vereker M, David S. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-14-07.
Endoscopic choledochoduodenostomy by lumen-apposing metal stent in jaundice recurrence after transpapillary metal stent placement
Authors: Andrea Anderloni, Alessandro Fugazza, Gaia Pellegatta, Edoardo Troncone, Simona Attardo, Annalisa Cappello, Alessandro Repici
Journal: Endoscopy (2019)

Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CD) with placement of an electrocautery-enhanced lumen-apposing metal stent (EC-LAMS) has been increasingly used as an alternative treatment option in patients with distal malignant biliary obstruction and failed endoscopic retrograde cholangiopancreatography (ERCP) [1] [2] [3].
Abstract P6-12-01: Withdrawn
Authors: DL Palliyaguru, DV Chartoumpekis, JJ Skoko, SG Wendell, SR Woodcock, N Wakabayashi, Y Yagishita, S Oesterreich, GK Michalopoulos, TW Kensler
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Palliyaguru DL, Chartoumpekis DV, Skoko JJ, Wendell SG, Woodcock SR, Wakabayashi N, Yagishita Y, Oesterreich S, Michalopoulos GK, Kensler TW. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-12-01.
Abstract LB-270: Hexokinase II (HK2) regulates stemness of ovarian cancer cells
Authors: Yuxin JIANG, Michelle KY Siu, Jingjing Wang, Thomas HY Leung, Annie NY Cheung, Hextan YS Ngan, Karen KL Chan
Journal: Cancer Research (2017)

Abstract Cancer stem cells (CSCs) constitute a small proportion of tumor cells and can drive tumor growth, metastasis and recurrence. Identification of CSCs in ovarian cancer has been reported. However, the mechanisms regulating ovarian cancer CSCs remain unknown. High lactate production and low glucose oxidation, despite oxygen availability, termed as the Warburg effect, are commonly found in cancers. Hexokinase 2 (HK2) converts glucose to glucose-6-phosphate, the first committed step in the Warburg effect. HK2 regulates tumorigenesis in different cancers. Yet, roles of HK2 and its underline mechanisms in ovarian cancer remain to be explored. In this study, we investigate the clinical significance, effects and mechanisms of HK2 on cell metastasis and CSCs regulation in ovarian cancer. HK2 was found to be up-regulated in ovarian cancer patients by immunohistochemistry when compared with benign ovarian cystadenomas. Significantly higher HK2 immunoreactivity was detected in metastatic foci than their corresponding primary tumors and associated with shorter disease-free survival. Decreased lactate production, impaired cell migration and invasion were detected in HK2 knockdown A2780CP cells using lactate assay, Transwell migration and invasion assays, respectively. Oppositely, ectopic expression of HK2 increased lactate production, cell migration and invasion in SKOV3 cells. We also found ectopic expression of HK2 in SKOV3 cells promoted anchorage-independent growth by soft agar assay. Then we further investigated the effect of HK2 on CSC load of ovarian cancer. Stable knockdown of HK2 in OVCAR3 cells led to impaired capacity to grow as multi-cellular spheroids in stem-condition culture system by sphere formation. Knockdown of HK2 in OVCAR3 cells down-regulated CD117 as measured by flow cytometry, which was accompanied by decreased mRNA/protein expression of Nanog, Bmi-1 and Klf-4, genes related to ovarian CSCs. Inversely, ectopic expression of HK2 in SKOV-3 cells promoted spheroids growth and increased CD117 proportion, which was accompanied by increased Nanog, Bmi-1 and Klf-4 mRNA/protein expression. Our data suggested that HK2 was associated with ovarian cancer progression, metastasis and stemness. HK2 could be a novel prognostic marker and potential therapeutic molecular target in ovarian cancer. Citation Format: Yuxin JIANG, Michelle KY Siu, Jingjing Wang, Thomas HY Leung, Annie NY Cheung, Hextan YS Ngan, Karen KL Chan. Hexokinase II (HK2) regulates stemness of ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-270. doi:10.1158/1538-7445.AM2017-LB-270
Abstract P4-07-11: Investigating the activity of ESR1 allosteric compounds in ER+ breast cancer
Authors: A Uwimana, CL Tiong Yip, R Das, Q Cheng, E Meredith, AL Gaither
Journal: Cancer Research (2019)

Abstract Breast cancer (BCa) is the most frequently diagnosed cancer in women worldwide. Approximately 80% of breast cancer is estrogen receptor positive (ER+) with 74% demonstrating high expression of estrogen receptor alpha (). Thus, current endocrine therapies such as selective estrogen receptor degraders (i.e.- Fulvestrant) or selective estrogen receptor modulators (i.e-Tamoxifen) are involved modulation of ER signaling. However, most patients develop resistance to these drugs, and disease progression is common resulting in metastatic disease. Therefore, targeting alternative sites on the surface of has been proposed as an effective therapy to directly block its activity. In the present study, we investigated putative AF2 compounds that can bind to AF2 allosteric sites and inhibit complex formation and transcription of targetgenes. In the present study, we characterized a series of allosteric compounds using breast cancer cellular assays. MCF7 parental cells were treated with a series of putative allosteric compounds in a seven day CTG cell proliferation assay, and the compound ERX-11 was found to exhibit anti-proliferative activity. Genomic RNA was isolated after overnight treatment with ERX-11 to investigate compounds treatment on the expression of key ER pathway transcription factors via real time PCR. The degradation effect on nuclear ER and cytoplasmic ER after treatment with ERX-11 were assessed via western blots. We successfully characterized a series of putative allosteric compounds with ERX-11 being the only compound that exhibited anti-proliferative activity in both MCF7 parental and LSZ resistant cells. ERX-11 inhibited the activation of ER transcription gene and degradation of nuclear ER. These findings show promising effects of ERX-11 to block the AF2 sites on the binding domain of ERα with potential therapeutics for ER+ breast cancer. Citation Format: Uwimana A, Tiong Yip CL, Das R, Cheng Q, Meredith E, Gaither AL. Investigating the activity of ESR1 allosteric compounds in ER+ breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-07-11.