tbuckley/cabot-search huggingface dataset:
Abstract 4613: Mathematical modeling of tumor growth in mouse models
Authors: Chao Zhang, Xiaoqian Jiang, Sheng Guo, Qixiang Li
Journal: Cancer Research (2019)

Abstract A variety of tumor models are used in preclinical oncology drug discovery, including patient-derived xenografts (PDXs), cell line-derived xenografts (CDXs), and syngeneic homografts. Tumors in mouse models exhibit heterogeneous growth patterns with or without drug treatment, which is further complicated by measurement errors. Mathematical modeling of tumor growth helps us better understand such patterns and analyze drug efficacy in transplanted tumor models. Many mathematical models have been proposed to describe tumor growth curves, each with certain assumptions and equations, suitable for specific situations or data sets1-5. It is yet unknown which models are best in fitting the growth curves for a large collection of mouse models. In this study, we systematically evaluated a set of mathematical models including exponential models, logistic and Gompertz model, biphasic models, dynamic carrying capacity model, and power law model on more than 50,000 tumor growth datasets collected from in vivo efficacy studies in PDXs, CDXs and syngeneic models. A set of metrics were used to evaluate the goodness of fit, including Akaike Information Criterion (AIC), root mean square error (RMSE), coefficient of determination, mean absolute relative error, etc. We also proposed a new composite metric to combine many criteria for easy selection of growth models. Our results show that tumor growth patterns are less complex under vehicle treatment, and different mathematical models have relatively small difference in modeling the growth curves. Tumor growth patterns are more diverse under drug treatment. Tumors may shrink or completely remit, though some may grow in the first days after inoculation before drug effect takes place. Still some tumors stop growing or even shrink before drug resistance develops and resume fast growing. Therefore, different mathematical models are needed to describe the different patterns. Finally, we present summary statistics to give an overall picture on the applicability of the mathematical models, and suggest statistical models for subsequent analysis for drug efficacy evaluation and biomarker discovery. Citation Format: Chao Zhang, Xiaoqian Jiang, Sheng Guo, Qixiang Li. Mathematical modeling of tumor growth in mouse models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4613.
Anal cancer outcomes and human immunodeficiency virus: a single-center experience
Authors: C. Garcia Duran, R. Rodriguez Alonso, E. Moreno-Olmedo, B. Rodriguez Alonso, M. Ortiz, T. Cano, M. Rodriguez Liñan, S. Garcia Cabezas, M. Gómez, E. Aranda
Journal: Annals of Oncology (2019)
Abstract 2603: Herbal extract SH003 suppresses tumor growth and metastasis of MDA-MB-231 breast cancer cells by inhibiting STAT3-IL-6 signaling
Authors: Yu-Jeong Choi, Myeong-Sun Kim, SooYeon Kang, Seo Yeon Lee, Ji Hye Kim, Youn Kyung Choi, Sukjoong Oh, Seong-Gyu Ko
Journal: Cancer Research (2019)

Abstract Cancer inflammation promotes cancer progression, resulting in a high risk of cancer. Here, we demonstrate that our new herbal extract, SH003, suppresses both tumor growth and metastasis of MDA-MB-231 breast cancer cells via inhibiting STAT3-IL-6 signaling path. Our new herbal formula, SH003, mixed extract from Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii Maximowicz, suppressed MDA-MB-231 tumor growth and lung metastasis in vivo and reduced the viability and metastatic abilities of MDA-MB-231 cells in vitro. Furthermore, SH003 inhibited STAT3 activation, which resulted in a reduction of IL-6 production. Therefore, we conclude that SH003 suppresses highly metastatic breast cancer growth and metastasis by inhibiting STAT3-IL-6 signaling path. Citation Format: Yu-Jeong Choi, Myeong-Sun Kim, SooYeon Kang, Seo Yeon Lee, Ji Hye Kim, Youn Kyung Choi, Sukjoong Oh, Seong-Gyu Ko. Herbal extract SH003 suppresses tumor growth and metastasis of MDA-MB-231 breast cancer cells by inhibiting STAT3-IL-6 signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2603.
Abstract 2169: Doxorubicin conjugation to reovirus enhances tumor cell-directed oncolysis
Authors: Jameson T. Berry, Bernardo A. Mainou
Journal: Cancer Research (2019)

Abstract Breast cancer remains the most diagnosed type of cancer and second leading cause of cancer-related deaths in women in the United States. Triple-negative breast cancer (TNBC) constitutes 10-20% of breast cancer cases. TNBCs are characterized by lack of estrogen (ER) and progesterone (PR) receptors and growth factor receptor HER2/Neu on the cell surface. Therapies that target ER, PR, or HER2 are thus ineffective against TNBC. TNBC is primarily treated with cytotoxic chemotherapy or radiation therapy, which can cause significant damage to healthy cells and tissue. Therefore, there is need for therapies that selectively kill TNBC cells with reduced off-tumor effects. The concept of oncolytic virotherapy has existed since the early 1900s. However, oncolytic viruses have limited efficacy as single agents. Mammalian orthoreovirus (reovirus) is a non-enveloped, segmented double-stranded RNA virus with tropism for transformed cells. Reovirus is in Phase I - III clinical trials to test its oncolytic efficacy against a variety of cancers. Success has been limited and few trials have tested reovirus against breast cancer. In a high-throughput screen of small molecule inhibitors, we identified the topoisomerase II inhibitor doxorubicin hydrochloride (dox) as an enhancer of reovirus infectivity in the TNBC cell line MDA-MB-231. To better control dox delivery and enhance reovirus oncolytic potential, we chemically conjugated dox to reovirus virions (reo-dox). While reo-dox attachment to MDA-MB-231 cells is slightly impaired, viral replication is largely unaffected. Infection of MDA-MB-231 cells with reo-dox resulted in increased cytopathicity and faster induction of cell death than virus alone. MDA-MB-231 cells infected with reo-dox, but not virus alone, induced DNA double-strand breaks and activation of DNA damage response. Together, our findings show that reo-dox exhibits superior toxicity in TNBC cells than virus alone. Future studies will define the mechanism of enhanced cytopathicity of reo-dox and oncolytic efficacy of dox-conjugated reovirus in vivo. Delivery of small molecule inhibitors via conjugation to reovirus particles may provide an effective new method to directly target and kill cancer cells while minimizing toxicity to healthy cells and tissues. Citation Format: Jameson T. Berry, Bernardo A. Mainou. Doxorubicin conjugation to reovirus enhances tumor cell-directed oncolysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2169.
Genome study of PDGFRA D842V mutant GIST using next generation sequencing approach.
Authors: Maria A. Pantaleo, Annalisa Astolfi, Milena Urbini, Valentina Indio, Margherita Nannini, Maristella Saponara, Cristian Lolli, Maria Caterina Pallotti, Anna Mandrioli, Lidia Gatto, Guido Biasco
Journal: Journal of Clinical Oncology (2013)

10540 Background: Mutations of the receptors KIT and PDGFRA in GIST are the oncogenetic events of disease as well as the targets of molecular therapies. Within the PDGFRA mutations, the D842V mutation in exon 18 confers in vitro and in vivo resistance to imatinib. Next generation sequencing techniques may completely dissect all the possible somatic mutations and genomic rearrangements in order to identify novel therapeutic targets in this patients population. Methods: Five patients with gastric GIST were analyased (3 M, 2 F; mean age 65,5 years, range 51-77). The tumor dimension ranged between 3 and 15 cm, MI &lt; 2 and 8 /50 HPF. No metastases were present in all cases. The KIT and PDGFRA anlysis showed a D842V mutation in exon 18 of PDGFRA in all cases. Whole transcriptome sequencing was performed with Illumina HiScanSQ platform with a paired-end strategy (75x2). After performing quality controls, the short reads were mapped with Tophat-Botie pipeline against the human reference genome (HG19). The variations, such as Single nucleotide variants (SNVs) and InDels, were called by SNVMix2 (a software suited for SNVs discovery in tumor samples) implementing an accurate filtering procedures developed in our laboratory. Two predictors of mutations effect at protein level (SNPs&amp;GO and Provean) were employed in order to prioritize the emerging variation. Results: An average of 206 coding non-synonymous variants were highlighted in the five GIST samples, of which ~ 30% were predicted as deleterious with at least one predictor. In addition to PDGFRA D842V mutation, in all five patients were found mutations on different receptor tyrosine kinases, such as FGFR4 and DDR2. Moreover three out of five patients harboured mutations on members of the MDR/TAP subfamily that are involved in multidrug resistance, in particular on ABCB1, ABCB4 and on ABCB6 genes. Other mutations were found on the hedgehog and MAPK signaling pathway and on SNF/SWI chromatin remodeling complex. Conclusions: New molecular events have been identified in PDGFRA D842V mutant GIST. These data should be validated in larger series and the role of these mutations as therapeutic targets should be further investigated.
Understanding and Improving Palliative Care and Care Near the End of Life
Authors: Gordon D. Rubenfeld, Stephan D. Fihn, Frederick P. Rivara
Journal: JAMA Network Open (2019)

Luai Al Rabadi, MD; Michael LeBlanc, PhD; Taylor Bucy, BS; Lee M. Ellis, MD; Dawn L. Hershman, MD, MS; Frank L. Meyskens Jr, MD; Lynne Taylor, MD; Charles D. Blanke, MD
Abstract 261: Assessment of Area Duty Cycle in Manual Chest Compressions During Out-of-Hospital Cardiopulmonary Resuscitation
Authors: Sofía Ruiz de Gauna, Jesus M Ruiz, Digna M González-Otero, Mikel Leturiondo, Jose J Gutiérrez, Iker Arana, James K Russell, Mohamud Daya
Journal: Circulation (2018)

Introduction: To be compliant with resuscitation guidelines, chest compressions (CCs) should be provided at a rate between 100 and 120 min -1 and a depth between 50 and 60mm during cardiopulmonary resuscitation (CPR). However, two manual CCs coincident in rate (the inverse of duration) and depth can show very different compression waveforms (left figure: the narrower CC depicted in blue suggests a higher impulse compression/decompression pattern). We hypothesized that area duty cycle (ADC) could characterize the narrowness of manual CCs. Objective: To assess the ADC of manual CCs during out-of-hospital CPR and its relationship with rate and depth. Methods: We collected electronic recordings containing compression signals from Philips HeartStart MRx monitor-defibrillators used in 30 patients during out-of-hospital CPR. ADC was defined as the ratio between the area under the compression curve (dashed area in the right figure) and the total area of the compression cycle with maximum depth (area of the red box). For each CC, we annotated the compression duration T c , the area under the depth curve A, and the maximum compression depth D. ADC was computed as 100·A/T c ·D (%). The linear relationship of ADC with compression rate and depth was assessed. Results: A total of 66,971 CCs were annotated. Medians (5 th -95 th percentiles) for compression rate, depth and ADC were 109.9 min -1 (93.8, 133), 46.5 mm (30.1, 61.7), and 41.9% (32.1, 49.5), respectively. ADC showed a very low correlation with rate and depth, favoring ADC’s independence. For every 10 min -1 increase in rate, ADC increased 0.16%. For every 10 mm increase in depth, ADC decreased 0.5%. Conclusions: ADC metric could be used for characterizing the narrowness of manual CCs, independently of depth and rate. This finding could contribute to improve understanding of manual CPR dynamics and their influence on patient’s outcome.
Abstract 1618: Breast cancer screening in low and lower - middle income country : A program in Vietnam
Authors: Voc Tai Dang, Tu Van Dao, Thuan Van Tran, Huong Thi Tran
Journal: Cancer Research (2019)

Abstract Background: From 1980 to 2010, new breast cancer cases increased by more than 50% worldwide. Disease burden increased even more rapidly in low- and middle-income countries (LMICs), where over half of breast cancer cases now occur. In Vietnam, approximately 15229 new cases of breast cancer were diagnosed with 6103 resulted deaths in 2018. Breast cancer can be detected early by screening; however, it is not covered by medical insurance. Mammogram is currently one of the most reliable screening tools for breast cancer. Regular mammograms can help detect breast cancer early, thus allowing for early treatment Purposes: To raise public awareness on breast cancer prevention and early detection, while promoting a habitual routine of breast self - examination and breast cancer screening participation; to call on companies to include breast cancer screening on the periodic health examination for female employees. Methods: We collected data on risk factors of breast cancer. Breast Imaging-Reporting and Data System (BI-RADS fifth edition) scores from the radiology reports were utilized. The information collected from women who completed the questionnaires included: age, BMI, family history of breast cancer, personal history of breast or ovarian cancer, number of pregnancies, number of babies born, number of abortion, number of miscarriage, stillbirth, hormonal medication use (hormone replacement therapy and daily oral contraceptive), age of menarche, menopause, smoking habit, and breast self-examination results. Results: There were 10,000 Vietnamese women who were over 40 years old (over 35 years old if their mother or their sister had breast cancer) participated in this program. Rate for regular breast self-examination was 19.1%. In the 40 to 55 years-old age group, the rate was 70%, 2.2% for women aged 35-39 years (with a family history of breast cancer). Eight women were diagnosed with breast cancer, the incidence rate was 80 per 100,000 population, respectively. Conclusions: The total fee for a breast cancer screening in Viet Nam is approximately $25 ($20 for a mammogram and $5 for consultation fee). This remains one of the best solutions to detect breast cancer early and reduce the overall burden of cancer treatment costs on the already strained Vietnamese health system. Note: This abstract was not presented at the meeting. Citation Format: Voc Tai Dang, Tu Van Dao, Thuan Van Tran, Huong Thi Tran. Breast cancer screening in low and lower - middle income country : A program in Vietnam [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1618.
Abstract 2765: Exosomal miRNAs as circulating biomarkers for prediction of metastasis in stage II/III gastric cancer
Authors: Xin Liu, Kent-Man Chu
Journal: Cancer Research (2019)

Abstract Background: Metastasis is the fatal character of cancer, leading to mortality of gastric cancer. In recent years, exosomes have been reported as extracellular vesicles secreted by cells. They contain various biological molecules including miRNAs from the original cells. Exosomal miRNAs are significant for pre-metastatic niche formation, as they can change the microenvironment and make it favorable for future metastasis. Therefore, the aim of this study was to identify dysregulated exosomal miRNAs as circulating biomarkers for prediction of metastasis of gastric cancer. Materials and Methods: Pre-treatment serum samples of 36 metastatic patients and 55 non-metastatic patients with stage II/III gastric cancer were collected. Exosomes were extracted and validated by western blot, transmission electron microscope and nanoparticle tracking analysis. MiRCURY LNATM miRNA miRNome PCR Array (containing 752 miRNAs) was performed in three pairs of serum exosomes. Each pair samples were with the same stage, race, gender and similar age. These three pairs of samples represented stage II, IIIA or IIIB gastric cancer, respectively. A panel of commonly dysregulated exosomal miRNAs was released from the PCR Array. Expressions of exosomal miRNAs were validated in the remaining 33 metastatic and 52 non-metastatic patients by RT-qPCR, as well as in gastric cancer cell culture medium and cell lines. Results: By comparing the expressions of exosomal miRNAs between the metastatic patients and matched non-metastatic ones, 13 upregulated and 6 downregulated miRNAs were released after normalization with miR-16-5p and miR-93-5p. Among these miRNAs, 7 of them were selected for further validation according to their fold changes, p-values and association with cancer development. MiR-379-5p and miR-410-3p were validated to be significantly upregulated in metastatic patients (P&amp;lt;0.01). Sensitivity, specificity and AUC were 67.31%, 69.70% and 0.6894 for miR-379-5p, and 65.38%, 66.67% and 0.6719 for miR-410-3p. Higher expression of serum exosomal miR-379-5p or miR-410-3p showed shorter overall survival of the patients (P&amp;lt;0.05). It was also found that miR-379-5p and miR-410-3p expressed significantly higher in gastric cancer cell culture medium comparing with gastric cancer cells. Conclusions: Exosomal miRNAs are dysregulated in the serum of metastatic gastric cancer patients before they are clinically diagnosed. Upregulation of serum exosomal miR-379-5p and/or miR-410-3p are promising circulating biomarkers for prediction of metastasis in stage II/III gastric cancer. Citation Format: Xin Liu, Kent-Man Chu. Exosomal miRNAs as circulating biomarkers for prediction of metastasis in stage II/III gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2765.
Abstract LB-099: Prostate cancer-secreted CCN3/NOV promotes osteoblast differentiation via Wnt signal pathway and miR-608 suppression
Authors: Po-Chun Chen, Chia-Chia Chao, An-Chen Chang, Chih-Hsin Tang
Journal: Cancer Research (2019)

Objective: NOV/CCN3 is a secreted protein that interacts with the extracellular matrix and thereby regulates many cellular functions, including cell division, chemotaxis, apoptosis, adhesion, motility, and ion transport. Recently, CCN3 expression have been implicated in progression of various cancer, and our previous study indicates that CCN3 increases the migration and invasion of prostate cancer (PCa) cells by regulation of ICAM-1 expression. Our research group also review the pivotal role CCN3 in bone metastasis of PCa by modulating the tumor-bone microenvironment. Moreover, evidence has highlighted the pivotal role of osteoblasts in osteoblastic bone metastasis in PCa.  Material and Methods: MC3T3-E1 osteoblast cells were incubated with conditioned media collected from PCa cells. The cell proliferation and osteogenic differentiation were evaluated by MTT assay and Alizarin red S staining. The osteogenic markers were also examined by Western blot and QPCR. Furthermore, the Wnt activation was tested by Western blot and luciferase reporter assay. Pretreatment with chemical inhibitor of Wnt was used to determine the regulatory role of Wnt in osteogenic differentiation in response to PCa CM. Finally, expression of miR-608 was investigated by QPCR and mimic miR-608 was used to certify the role of miR-608 in osteogenic differentiation in response to PCa CM.  Results: Here, we show that PCa-secreted CCN3 increases expression of osteoblastic differentiation factors including BMPs, Runx2 and Osterix. Furthermore, this effect is regulated by Wnt signal pathway or miR-608 repression. The present study supposes that PCa-secreted CCN3 can promote osteoblastic bone metastasis in PCa by activating Wnt signal and inhibition of miR-608 expression. Our present study provides an opportunity to develop CCN3 as a therapeutic target that prevents bone metastasis in PCa.   Citation Format:  Po-Chun Chen, Chia-Chia Chao, An-Chen Chang, Chih-Hsin Tang. Prostate cancer-secreted CCN3/NOV promotes osteoblast differentiation via Wnt signal pathway and miR-608 suppression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-099.
Abstract 1165: Differential expression of CD44 variants drive the progression, invasion, drug-resistance and stemness characteristics in human oral squamous cell carcinoma
Authors: Tanushree Kashyap, Siddavaram Nagini, Ajay Rana, Rajakishore Mishra
Journal: Cancer Research (2019)

Abstract Purpose: Cluster of differentiation 44 (CD44) is a cell-surface glycoprotein and plays role in the progression and severity of oral squamous cell carcinoma (OSCC). Here we report differential function of CD44 variants in OSCC progression. Materials and methods: The expression of CD44 standard (CD44s) and variants (CD44v4, CD44v6); the activation of signaling pathways (MAPK, PI3K); the cell viability; and the MMP-9/-2 activity were assessed using RT-PCR, immunohistochemistry, Western blotting, MTT assay and gelatin zymography. These experiments were carried out using fresh human OSCC tissue specimens, including adjacent normal, noninvasive (N0), invasive tumor samples (N1-3) and chemo-radiation resistant tumor samples (RCRT). We also used OSCC cell lines, including parental (SCC9/SCC4) and Cisplatin-resistant (CisR-SCC9/-SCC4) to confirm our observation with human tissues. Knock down of CD44 variants or inactivation of MAPK/PI3K pathways was achieved for in vitro analysis in OSCC cells. Summary: Differential expressions of CD44 variants (v4and v6) were associated with overall oral cancer aggressiveness. CD44v4 expression was positively correlated with the activation of MAPK pathway causing chemoresistance. Conversely, CD44v6 expression and activation of PI3K-Akt caused invasiveness of OSCC. Finally, an overlapping role of two major signal transduction pathways such as MAPK and PI3K, that impinge on the variants/ isoforms expressions of a single gene i.e. CD44 that leads to the OSCC aggressiveness. Conclusion: Collectively, these results established that CD44 variants (v4and v6) expression driven by MAPK/PI3K are associated with the overall progression, drug-resistance, invasion, and stemness characteristics leading to the aggressiveness of OSCC. Hence targeting these pathways may be exploited for treating OSCC. Keywords: OSCC, CD44s, CD44v4/6, MAPK, PI3K, Notch, Chemoresistance, Invasion/migration, stemness, aggressiveness of OSCC. Note: This abstract was not presented at the meeting. Citation Format: Tanushree Kashyap, Siddavaram Nagini, Ajay Rana, Rajakishore Mishra. Differential expression of CD44 variants drive the progression, invasion, drug-resistance and stemness characteristics in human oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1165.
Widefield OCT-Angiography and Fluorescein Angiography Assessments of Nonperfusion in Diabetic Retinopathy and Edema Treated with Anti–Vascular Endothelial Growth Factor
Authors: Aude Couturier, Pierre-Antoine Rey, Ali Erginay, Carlo Lavia, Sophie Bonnin, Bénédicte Dupas, Alain Gaudric, Ramin Tadayoni
Journal: Ophthalmology (2019)