tbuckley/cabot-search huggingface dataset:
Detection of circulating tumor cells (CTCs) in central venous blood (CVB) versus peripheral venous blood (PVB) in patients with metastatic cancers.
Authors: Ayhan Ulusakarya, Fei Ye, Janine Wechsler, Pasquale F Innominato, Mazen Haydar, Naoual Benali-Furet, Jean F. Morere, Georges Uzan
Journal: Journal of Clinical Oncology (2015)

e22039 Background: CTCs are considered as useful indicators of tumor aggressiveness, patient prognosis, and treatment effectiveness monitoring. Detection of CTCs in blood is difficult due to the extreme rarity of CTCs found in PVB. Peripheral veins carrying CTCs merge with intrathoracic caval veins and nearly all patients with metastatic cancer have a central venous access device. We hypothesized that the chances of detecting CTCs might be higher in the CVB versus PVB due to having a richer CTC content for anatomical reasons. This study compared CTC numbers between CVB and PVB in patients with metastatic carcinomas. Methods: Twenty-nine patients with metastatic cancers of biliary tract (5), breast (4), colon (7), duodenum (1), lung (2), ovary (2), pancreas (4), prostate (1) and stomach (3) were included in this study. The CVB and PVB samples were simultaneously collected through the central venous access device and a superficial forearm vein in each patient. Blood filtration was performed using 3-ml blood diluted with fixative buffer and subjected to ScreenCell Cyto technology. Selected cells were stained with May-Grunwald Giemsa and the number of CTCs was counted under the light microscope by two operators for whom the blood draw sites (central versus peripheral) were blinded. Results: CTCs were found in both CVB and PVB in 100% of patients. These CTCs were characterized according to the cytomorphological criteria in favor of malignancy: large nucleus size ( > 20 µm), high nucleo-cytoplasmic ratio, and irregular nucleus contour. In 28 of 29 patients the number of cells matching the above criteria was higher in CVB than PVB. An average of 2.4-fold more (241% ± 21% as mean ± SEM) CTCs were recorded in CVB as compared to PVB. Conclusions: Our study showed that CVB contains significantly more CTCs than PVB. Central veins may provide an efficient access to a higher concentration of CTCs. Our results also suggest that future research studies that include CTC enumeration should specify blood collection site given different prevalence rates found per site.
Evidence base of Mistletoe drug -interaction in Supportive- care.
Authors: Afsar imam Zaidi
Journal: Journal of Clinical Oncology (2015)

e20746 Background: Mistletoe is often used as complimentary therapy in Europe . There is an increasing need to learn more about possible interactions between CAM and anticancer drugs. Like other Herbal extracts etc. , Viscum Album extract [VAE] is used as supportive care during chemotherapy. The anti-tumor effects of VAE are well documented . However the clinical activity of VAE treatment still remains contraversal. The effect of VAE was investigated with common chemo-drugs usings different cell lines in vitro . Methods: Human leukemia cell lines K562 and KG1a were treated with Vincistrin, Mafosfamide, Idarubicine and Cisplatin. Breast cell carcinoma cell lines HCC1937 and HCC1143were treated with Doxorubicin HCl , prostate carcinoma cell line DU145, with Docetaxel and Mitoxantrone HCl and lung carcinoma cell line NCL-H460 was treated with Docetaxal and Cispaltin . Each dose of chemotherapeutic drug was combined with VAE in clinically relavent concentrations and proliferaton and apoptosis were measured. Results: VAE inhibited colony formation and did not exert any protective activity against induced inhibition of colongenicity .VAE did not inhibit chemotherapy induced cytostasis and cytotoxicity in any of experimental settings . Conclusions: The study provides evidence that VAE is capable of enhancing cytotxicity of antcancer agents in vitro. Hence no risk of safety by herb drug- interactions is to be expected from the exposition of cancer cells to chemotherapeutic drugs and VAE at the same time. The study shows moderate to high evidence and further studies are warrented for clinical trial with optimized study design and treatment conditions.
Converged Biofabrication: Simultaneous Micropatterning of Fibrous Meshes and Bioinks for the Fabrication of Living Tissue Constructs (Adv. Healthcare Mater. 7/2019)
Authors: Mylène de Ruijter, Alexandre Ribeiro, Inge Dokter, Miguel Castilho, Jos Malda
Journal: Advanced Healthcare Materials (2019)

In article number 1800418, Miguel Castilho, Jos Malda, and co-workers demonstrate how micropatterning of fibrous meshes and bioinks in a one-step approach enables more control over cell and fiber deposition. This control over both the fibrous and cellular part is promising for the fabrication of living tissue constructs. The reinforcing effect of the fibers is present. Furthermore, viability and chondrogenic differentiation of mesenchymal stromal cells are not affected by the fabrication process.
SAT-491-Assessment of liver function by 13C methacetin breath test may help to predict liver function deterioration after selective transarterial chemoembolisation of hepatocellular carcinomas
Authors: Florian Van Bömmel, Stella Wellhöner, Rhea Veelken, Florian Gerhardt, Tim-Ole Petersen, Bettina Maiwald, Steffen Strocka, Albrecht Boehlig, Thomas Berg
Journal: Journal of Hepatology (2019)
Treatment optimization and genomic outcomes in refractory severe aplastic anemia treated with eltrombopag
Authors: Thomas Winkler, Xing Fan, James Cooper, Ronan Desmond, David J. Young, Danielle M. Townsley, Phillip Scheinberg, Sophia Grasmeder, Andre Larochelle, Marie Desierto, Janet Valdez, Jennifer Lotter, Colin Wu, Ruba N. Shalhoub, Katherine R. Calvo, Neal S. Young, Cynthia E. Dunbar
Journal: Blood (2019)
THU-162-The combination of sofosbuvir and daclatasvir is well tolerated and extremely effective in treating patients with hepatitis C with severe renal impairment including hemodialysis patinets
Authors: Shahin Merat, Amir-Houshang Sharifi, Ali Akbar Shayesteh, Mohammad Minakari, Mohammad Reza Fattahi, Maryam Moini, Fatemeh Roozbeh, Fariborz Mansour-Ghanaei, Behrooz Afshar, Marjan Mokhtare, Taghi Amiriani, Masomeh Sofian, Mohammad-Hossein Somi, Shahram Agah, Iradj Maleki, Maryam Latifnia, Ahmad Hormati, Masoud Khoshnia, Masoud Sohrabi, Reza Malekzadeh
Journal: Journal of Hepatology (2019)
Abstract 16954: Utilization and Adherence to Remote Monitoring of Cardiac Implantable Electronic Devices in Pediatric Patients Comparable to Adults
Authors: Akash Patel, Kevin Davis, Allision T Connolly, Julie B Prillinger, Yelena Nabutovsky, Ronn E Tanel
Journal: Circulation (2017)

Background: High adherence to remote monitoring (RM) in adults with cardiac implantable electronic devices (CIED) contributes to improved survival and reduced healthcare utilization. Data regarding...
MicroRNA‐223 Ameliorates Nonalcoholic Steatohepatitis and Cancer by Targeting Multiple Inflammatory and Oncogenic Genes in Hepatocytes
Authors: Yong He, Seonghwan Hwang, Yan Cai, Seung‐Jin Kim, Mingjiang Xu, Dingcheng Yang, Adrien Guillot, Dechun Feng, Wonhyo Seo, Xin Hou, Bin Gao
Journal: Hepatology (2019)

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases ranging from simple steatosis to more severe forms of liver injury including nonalcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma (HCC). In humans, only 20%-40% of patients with fatty liver progress to NASH, and mice fed a high-fat diet (HFD) develop fatty liver but are resistant to NASH development. To understand how simple steatosis progresses to NASH, we examined hepatic expression of anti-inflammatory microRNA-223 (miR-223) and found that this miRNA was highly elevated in hepatocytes in HFD-fed mice and in human NASH samples. Genetic deletion of miR-223 induced a full spectrum of NAFLD in long-term HFD-fed mice including steatosis, inflammation, fibrosis, and HCC. Furthermore, microarray analyses revealed that, compared to wild-type mice, HFD-fed miR-223 knockout (miR-223KO) mice had greater hepatic expression of many inflammatory genes and cancer-related genes, including (C-X-C motif) chemokine 10 (Cxcl10) and transcriptional coactivator with PDZ-binding motif (Taz), two well-known factors that promote NASH development. In vitro experiments demonstrated that Cxcl10 and Taz are two downstream targets of miR-223 and that overexpression of miR-223 reduced their expression in cultured hepatocytes. Hepatic levels of miR-223, CXCL10, and TAZ mRNA were elevated in human NASH samples, which positively correlated with hepatic levels of several miR-223 targeted genes as well as several proinflammatory, cancer-related, and fibrogenic genes. Conclusion: HFD-fed miR-223KO mice develop a full spectrum of NAFLD, representing a clinically relevant mouse NAFLD model; miR-223 plays a key role in controlling steatosis-to-NASH progression by inhibiting hepatic Cxcl10 and Taz expression and may be a therapeutic target for the treatment of NASH.
CG '806, a Highly Potent First-in-Class Pan-FLT3/BTK Inhibitor, Targets Multiple Clusters of Kinases Operative in Diverse Subtypes of Acute Myeloid Leukemia
Authors: Hongying Zhang, Andrea Local, Khalid Benbatoul, Peter Folger, Susan Sheng, Cheng-Yu Tsai, Stephen Howell, William Rice
Journal: Blood (2017)
Assessment of toxicity and clinical outcomes with SBRT in lung metastases: A single institute experience
Authors: V. Pareek
Journal: Annals of Oncology (2019)

Background: Stereotactic body radiation therapy (SBRT) can help deliver a high biologically equivalent dose to the tumor volume in a small number of fractions with a steep dose fallout on surrounding healthy tissues. A retrospective analysis was performed on patients treated for lung oligo-metastatic disease from various histopathologies. Methods: A total of 155 patients were retrospectively assessed who were diagnosed with lung metastases in various primary malignancies. Clinical outcomes in the form of local control (LC), overall survival (OS) and progression free survival (PFS) were assessed. Toxicity was scored according to CTCAE grading. Univariate analysis was performed to correlate various prognostic factors associated with the disease and grade of toxicities associated. Patients were followed up and assessed for late toxicities as per the institution protocol. Results: The median follow up was 22 months. Colorectal carcinomas formed the major site of primary disease followed by sarcoma and renal cell carcinoma. LC at 1 and 2 years was 94 and 86% respectively. OS at 1 and 2 years was 90, 68.8% respectively. Both OS and L were impacted by the primary histopathology and also the presence of extrapulmonary disease present. PFS at 1 and 2 years was 87% and 62% respectively. Primary histopathology, presence of extrapulmonary disease and age showed a correlation with prognosis at univariate analysis. The treatment follow-up showed no significant late toxicities and Grade 3 and 4 toxicities were not seen in the cohort. Conclusions: The study suggests the role of SBRT as a treatment option for oligometastases in the lung. However, the factors mostly influencing prognosis were the presence of extra-pulmonary disease and the number of lung lesions. With lower number of metastases to treat, the outcome is found to be better. Legal entity responsible for the study: V. Pareek. Funding: Has not received any funding. Disclosure: The author has declared no conflicts of interest.
TCTAP C-043 PCI with the Rotational Atherectomy of the Stent Struts in LMCA Bifurcation
Authors: Seigo Iwane, Takahiro Sawada, Tetsuya Yamamoto, Nobuyuki Takahashi, Tomofumi Takaya, Yoshinori Yasaka
Journal: Journal of the American College of Cardiology (2019)
Gene therapy with apoptosis-associated speck-like protein, a newly described schwannoma tumor suppressor, inhibits schwannoma growth in vivo
Authors: Sherif G Ahmed, Ahmed Abdelnabi, Casey A Maguire, Mohamed Doha, Jessica E Sagers, Rebecca M Lewis, Alona Muzikansky, Marco Giovannini, Anat Stemmer-Rachamimov, Konstantina M Stankovic, Giulia Fulci, Gary J Brenner
Journal: Neuro-Oncology (2019)

Abstract Background We evaluated apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) as a schwannoma tumor suppressor and explored its utilization in a schwannoma gene therapy strategy that may be translated to clinical use. Methods ASC protein expression and mRNA level were assessed in human schwannoma by immunohistochemistry and quantitative PCR, respectively. Methylation- specific PCR was used to assess ASC promoter methylation. The effect of ASC overexpression in schwannoma cells was evaluated through ATP-based viability, lactate dehydrogenase release, and apoptosis staining. Western blotting and colorimetric assay were used to test the effect of ASC overexpression on endogenous pro-apoptotic pathways. Bioluminescence imaging, behavioral testing, and immunohistochemistry in human xenograft and murine allograft schwannoma models were used to examine the efficacy and toxicity of intratumoral injection of adeno-associated virus (AAV) vector encoding ASC. Results ASC expression was suppressed via promoter methylation in over 80% of the human schwannomas tested. ASC overexpression in schwannoma cells results in cell death and is associated with activation of endogenous caspase-9, caspase-3, and upregulation of BH3 interacting-domain death agonist. In a human xenograft schwannoma model, AAV1-mediated ASC delivery reduced tumor growth and resolved tumor-associated pain without detectable toxicity, and tumor control was associated with reduced Ki67 mitotic index and increased tumor-cell apoptosis. Efficacy of this schwannoma gene therapy strategy was confirmed in a murine schwannoma model. Conclusion We have identified ASC as a putative schwannoma tumor suppressor with high potential clinical utility for schwannoma gene therapy and generated a vector that treats schwannomas via a novel mechanism that does not overlap with current treatments.
Abstract 10876: Speckle-tracking vs. Pressure-Volume Loop Measures of Left Ventricular Systolic Function in Children: An Inter-vendor Comparison
Authors: Shahryar M Chowdhury, Ryan J Butts, Carolyn L Taylor, Karen S Chessa, Anthony M Hlavacek, Girish S Shirali, Arni Nutting, George H Baker
Journal: Circulation (2015)

Introduction: The variability in speckle-tracking echocardiography (STE) algorithms between vendors is well recognized. While some are attempting to standardize algorithms across vendors, it is currently unknown which algorithm best compares to gold-standard measures of systolic function. The objective of this study was to compare STE measures of deformation from two vendors vs. gold-standard measures of LV contractility and global ventricular efficiency in children. Methods: Children with normal loading conditions undergoing routine left heart catheterization were prospectively enrolled. Pressure-volume loops were obtained via conductance catheterization. The gold-standard measure of contractility, end-systolic elastance (Ees), was obtained via balloon occlusion of the vena cavae. Ventriculo-arterial coupling was assessed using the arterial elastance to Ees ratio (Ea/ Ees). STE was performed immediately after PVL analysis under the same anesthetic conditions. Offline STE analysis was perfomed using both QLAB v9.0 (Phillips, Andover, MA) and Cardiac Performance Analysis v3.0 (Tomtec, Hamden, CT) by a single blinded observer. The relationships between PVL and STE measures of systolic function were determined using Spearman’s correlation. Results: Of 24 patients, 18 patients were s/p heart transplant, 6 patients had a small patent ductus arteriosus or small coronary fistula. Mean age was 9.1 ± 5.6 years. The average invasive Ees was 3.04 ± 1.65 mmHg/mL. The average Ea/Ees was 0.88 ± 0.35. Correlations between invasive Ees and Ea/Ees to STE measures of deformation are reported in the Table. Conclusion: STE measures of GLS and GLSR derived from Cardiac Performance Analysis have better correlation with gold-standard measures of cardiac performance when compared to QLAB. GCS derived from both vendors has no correlation to invasive measures. Attempts to standardize STE algorithms should take these results into consideration.
Abstract 16978: Pim1: A New Dna Repair Modulator Implicated in Pulmonary Hypertension
Authors: Marie-Claude Lampron, Nolwenn Samson, Ève Tremblay, Jolyane Meloche, Roxane Paulin
Journal: Circulation (2017)

Background: Pulmonary Arterial Hypertension (PAH) is a fatal disease characterized by the narrowing of pulmonary arteries (PAs) due to vascular remodeling. It is now established that this phenotype...
Pretreating Mesenchymal Stem Cells with Cancer Conditioned‐Media or Proinflammatory Cytokines Changes the Tumor and Immune Targeting by Nanoghosts Derived from these Cells
Authors: Yael Lupu‐Haber, Tomer Bronshtein, Hagit Shalom‐Luxenburg, Domenico D'Atri, Jacopo Oieni, Limor Kaneti, Alona Shagan, Shani Hamias, Liat Amram, Galoz Kaneti, Noa Cohen Anavy, Marcelle Machluf
Journal: Advanced Healthcare Materials (2019)

Abstract Nanoghosts (NGs) are nanovesicles reconstructed from the cytoplasmic membranes of mesenchymal stem cells (MSCs). By retaining MSC membranes, the NGs retain the ability of these cells to home in on multiple tumors, laying the foundations, thereby, for the development of a targeted drug delivery platform. The susceptibility of MSCs to functional changes, following their exposure to cytokines or cancer‐derived conditioned‐media (CM), presents the opportunity to modify the NGs by conditioning their source cells. This opportunity is investigated by comparing the membrane protein composition and the tumor uptake of NGs derived from naïve MSCs (N‐NG) against conditioned NGs made from MSCs pre‐treated with conditioned‐media (CM‐NG) or with a mix of the proinflammatory cytokines TNF‐α and IL‐1β (Cyto‐NG). CM‐NGs are found to be more targeted towards immune cells than Cyto‐ or N‐NGs, while Cyto‐NGs are the most tumor‐targeted ones, with similar immune‐targeting capacity as N‐NGs but with a higher affinity towards endothelial cells. Proteomic variations were wider in the CM‐NGs, with exceptionally higher levels of ICAM‐1 compared to N‐ and Cyto‐NGs. From a translational point of view, the data show that the tumor‐targeting ability of the NGs, and possibly that of other MSC‐derived extracellular vesicles, can be enhanced by simple conditioning of their source cells.
Preliminary analysis on the RNA sequencing data of lung squamous cell carcinoma.
Authors: Lu-Lu Yang, Xuchao Zhang, Wen-Chao Gao, Yi-Long Wu
Journal: Journal of Clinical Oncology (2015)

e19126 Background: Potential specific molecular characteristics of lung squamous cell carcinoma (SCC) remain obscure and no therapy has proven to be efficient. This study was conducted to study on the transcriptional alterations of lung squamous cell carcinoma by transcriptome sequencing. Methods: We performed transcriptome sequencing on 10 frozen tumor samples from lung squamous cell carcinoma. They were all of IIIA stage and triple-negative (EGFR, KRAS, ALK). High-throughput data of transcriptome sequencing were generated on the platform of Illumina HiSeq2000. Based on the human reference genome assembly, we analysed mutations, gene fusions, and gene expressions. Results: There were 12.15/Mb SNV in these 10 samples. TP53 was the most frequent gene mutations. C:G-T:A and A:T-G:C transitions were the most frequent type of point mutations in these samples. The analysis of gene ontology on the mutated genes demonstrated the overrepresentation of items related to the energy and substance metabolism, and the mutated genes also enriched in the pathways associated with metabolism. In contrast, mutated genes from TCGA database showed no enrichment in these gene ontology items and pathways related to metabolism. A total of 132 gene fusions were identified in these samples according to TopHat. 70.5% (93/132) of gene fusions occurred in intrachromosomal rearrangements. Based on the number of reads of supported fusions, we verified 20 out of 26 gene fusions using RT-PCR and DNA sequencing. Conclusions: The items and pathways related to the energy and metabolism were enriched in these 10 SCC compared with TCGA database. In addition, these data provide an in-depth view of the profile of gene fusions in SCC and are very helpful to further identification of potential targets for therapeutic intervention.
Immunomodulatory effects of Tumor Treating Fields (TTFields) on lung cancer models
Authors: U. Weinberg, N. Kaynan, T. Voloshin Sela, S. Davidi, Y. Porat, A. Shteingauz, M. Munster, R.S. Schneiderman, C. Tempel Brami, E. Zeevi, K. Gotlib, S. Cahal, M. Giladi, E. Kirson, A. Kinzel, Y. Palti
Journal: Annals of Oncology (2019)

Background: Tumor Treating Fields (TTFields) are a clinically approved anti-mitotic treatment modality delivered via noninvasive application of low intensity, intermediate frequency, alternating electric fields. In this study, we evaluated whether TTFields-induced cell death can be perceived as immunogenic. Methods: Human and murine lung carcinoma cell lines were treated with TTFields using the inovitro system. Immunogenic cell death was evaluated by changes in the levels of calreticulin (CRT) on the surface of treated cells, phosphorylation of the translation initiation factor eIF2α, and secretion of ATP and High mobility group box 1 (HMGB1). Activation of immune cells was evaluated using co-culture of bone marrow derived dendritic cells (DCs) with TTFields treated cells. For in-vivo studies, mice orthotopically implanted with lung tumors were treated with TTFields, the immune checkpoint inhibitor anti-PD-1 or a combination of the two modalities. Tumor volume was monitored and flow cytometry analysis was performed for phenotypic characterization of infiltrating immune cells. Results: We demonstrate that cancer cells that died under TTFields application exhibited release of HMGB1, ATP secretion from cells, and ER stress leading to CRT translocation to the cell surface, all of which are cardinal signs of immunogenic cell death. TTFields treated cells promoted in vitro phagocytosis by DCs and DC maturation as well as initiation of inflammation in vivo. The combined treatment of lung tumor-bearing mice with TTFields plus the immune checkpoint inhibitor anti-PD-1 led to a significant decrease in tumor volume compared to anti-PD-1 alone or to the control group. Significant increases in CD45+ tumor infiltrating cells were observed in the TTFields plus anti-PD-1 group. These infiltrating cells demonstrated upregulation of surface PD-L1 expression. Correspondingly, cytotoxic T-cells isolated from these tumors showed higher levels of IFN-γ production relative to untreated mice. Conclusions: Our results demonstrate the potential of TTFields therapy to induce immunogenic cell death and increase the efficacy of anti PD-1 therapy by further enhancing antitumor immunity. Legal entity responsible for the study: Novocure Israel. Funding: Novocure Israel. Disclosure: U. Weinberg, T. Voloshin Sela, Y. Porat, M. Munster, R.S. Schneiderman, C. Tempel Brami, S. Cahal, M. Giladi, A. Kinzel, Y. Palti: Full time employee: Novocure Israel; Stock options, stocks: Novocure. N. Kaynan, S. Davidi, A. Shteingauz, K. Gotlib, E. Zeevi: Full time employee: Novocure Israel; Stock options: Novocure. E. Kirson: Full time employee: Novocure Israe; Stock options, stocks: Novocure; Senior leadership position: Novocure.