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1. Patient-specific 3D in vitro modeling and fluid dynamic analysis of primary pulmonary vein stenosis

Author

Christian Devlin, Martin L. Tomov, Huang Chen, Sindhu Nama, Siraj Ali, Sunder Neelakantan, Reza Avazmohammadi, Lakshmi Prasad Dasi, Holly D. Bauser-Heaton, and Vahid Serpooshan

Subjects
3D printing, pulmonary vein stenosis (PVS), flow hemodynamics, particle image velocimetry, computational fluid dynamics, stenting, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

IntroductionPrimary pulmonary vein stenosis (PVS) is a rare congenital heart disease that proves to be a clinical challenge due to the rapidly progressive disease course and high rates of treatment complications. PVS intervention is frequently faced with in-stent restenosis and persistent disease progression despite initial venous recanalization with balloon angioplasty or stenting. Alterations in wall shear stress (WSS) have been previously associated with neointimal hyperplasia and venous stenosis underlying PVS progression. Thus, the development of patient-specific three-dimensional (3D) in vitro models is needed to further investigate the biomechanical outcomes of endovascular and surgical interventions.MethodsIn this study, deidentified computed tomography images from three patients were segmented to generate perfusable phantom models of pulmonary veins before and after catheterization. These 3D reconstructions were 3D printed using a clear resin ink and used in a benchtop experimental setup. Computational fluid dynamic (CFD) analysis was performed on models in silico utilizing Doppler echocardiography data to represent the in vivo flow conditions at the inlets. Particle image velocimetry was conducted using the benchtop perfusion setup to analyze WSS and velocity profiles and the results were compared with those predicted by the CFD model.ResultsOur findings indicated areas of undesirable alterations in WSS before and after catheterization, in comparison with the published baseline levels in the healthy in vivo tissues that may lead to regional disease progression.DiscussionThe established patient-specific 3D in vitro models and the developed in vitro–in silico platform demonstrate great promise to refine interventional approaches and mitigate complications in treating patients with primary PVS.

Published
2024
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3. 961 Tumor-infiltrating lymphocytes in tumor microenvironment assessed by artificial intelligence powered H&E image analyzer is correlated with immunomodulatory subtype of triple-negative breast cancer

Author

Chan-Young Ock, Seulki Kim, Siraj Ali, Soo Ick Cho, Seunghwan Shin, Yoojoo Lim, Heon Song, Donggeun Yoo, Taebum Lee, Mingu Kang, Chang Ho Ahn, Jimin Moon, Ken Nesmith, and Seokhwi Kim

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2023
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5. 1308 Artificial intelligence (AI)-powered immune phenotyping based on programmed death ligand 1 (PD-L1) immunohistochemistry (IHC) in triple negative breast cancer (TNBC)

Author

Chan-Young Ock, Seulki Kim, Siraj Ali, Soo Ick Cho, Gahee Park, Seunghwan Shin, Jeongun Ryu, Seonwook Park, Sangwon Shin, Taebum Lee, Juneyoung Ro, Aaron Valero, Biagio Brattoli, and Changho Ahn

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2023
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6. Comprehensive characterization of RAS mutations in colon and rectal cancers in old and young patients

Author

Ilya G. Serebriiskii, Caitlin Connelly, Garrett Frampton, Justin Newberg, Matthew Cooke, Vince Miller, Siraj Ali, Jeffrey S. Ross, Elizabeth Handorf, Sanjeevani Arora, Christopher Lieu, Erica A. Golemis, and Joshua E. Meyer

Subjects
Science
Abstract

Activating oncogenic mutations in KRAS and NRAS are common in colorectal cancer, which is a heterogenous disease. Here, the authors show that the RAS mutation spectrum is markedly different between colon and rectal cancer, and also different based on age of diagnosis and microsatellite instability.

Published
2019
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8. Improving car radiator performance by using TiO2-water nanofluid

Author

Siraj Ali Ahmed, Mehmet Ozkaymak, Adnan Sözen, Tayfun Menlik, and Abdulkarim Fahed

Subjects
Engineering (General). Civil engineering (General), TA1-2040
Abstract

The most recent developments in nanotechnology have lead to improvements in original uses of nanofluids in car motor cooling. In the present study, enhancement of car engine radiator by TiO2-water nanofluid as a coolant of car engine radiator was investigated experimentally. In order to determine the effect of TiO2-water nanofluid on radiator’s performance, experiments were performed with pure water and TiO2-water nanofluid separately and results were compared with other studies on vehicle engine system FIAT DOBLO 1.3 MJTD ENG. The main objective was to check the aspects of heat transfer of the TiO2-water nanofluid as a substitution to the customary coolant system. For this purpose, experiments were carried out using a TiO2 nanofluid with 0.1, 0.2 and 0.3% volume concentrations with flow rates of 0.097 and 0.68 m3/h in laminar floe region, where Reynolds number ranged from 560 to 1650. Our results show that the friction factor decreases when Reynolds number and the volume concentration are increased. Moreover, TiO2-water nanofluid with 0.2% concentration can enhance the effectiveness of car radiator by 47% as compared to 0.1 and 0.3% concentrations and pure water as a coolant. Finally, the average heat transfer coefficient was directly affected by the increase in Reynolds number and volume concentration fraction of the nanofluid. Keywords: Car radiator, Nanofluids, Performance, Reynolds number, TiO2-water

Published
2018
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9. Next-generation sequencing of idiopathic multicentric and unicentric Castleman disease and follicular dendritic cell sarcomas

Author

Alexandra Nagy, Aparna Bhaduri, Nahid Shahmarvand, Jahanbanoo Shahryari, James L. Zehnder, Roger A. Warnke, Tariq Mughal, Siraj Ali, and Robert S. Ohgami

Subjects
Specialties of internal medicine, RC581-951
Abstract

Abstract: Castleman disease (CD) is a rare lymphoproliferative disorder subclassified as unicentric CD (UCD) or multicentric CD (MCD) based on clinical features and the distribution of enlarged lymph nodes with characteristic histopathology. MCD can be further subtyped based on human herpes virus 8 (HHV8) infection into HHV8-associated MCD, HHV8−/idiopathic MCD (iMCD), and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin change (POEMS)–associated MCD. In a subset of cases of UCD, an associated follicular dendritic cell sarcoma (FDCS) may be seen. Although numerous reports of the clinical and histologic features of UCD, MCD, and FDCS exist, an understanding of the genetic and epigenetic landscape of these rare diseases is lacking. Given this paucity of knowledge, we analyzed 15 cases of UCD and 3 cases of iMCD by targeted next-generation sequencing (NGS; 405 genes) and 3 cases of FDCS associated with UCD hyaline vascular variant (UCD-HVV) by whole-exome sequencing. Common amplifications of ETS1, PTPN6, and TGFBR2 were seen in 1 iMCD and 1 UCD case; the iMCD case also had a somatic DNMT3A L295Q mutation. This iMCD patient also showed clinicopathologic features consistent with a specific subtype known as Castleman-Kojima disease (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly [TAFRO] clinical subtype). Additionally, 1 case of UCD-HVV showed amplification of the cluster of histone genes on chromosome 6p. FDCS associated with UCD-HVV showed mutations and copy number changes in known oncogenes, tumor suppressors, and chromatin structural-remodeling proteins.

Published
2018
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10. Checkpoint inhibitor is active against large cell neuroendocrine carcinoma with high tumor mutation burden

Author

Victoria E. Wang, Anatoly Urisman, Lee Albacker, Siraj Ali, Vincent Miller, Rahul Aggarwal, and David Jablons

Subjects
Large cell neuroendocrine tumor, Pembrolizumab, PD-L1, Tumor mutation burden, Immunotherapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Large cell neuroendocrine tumor (LCNEC) of the lung is a rare and aggressive tumor similar to small cell lung cancer (SCLC). Thus, it is often treated similarly to SCLC in the front-line setting with a platinum doublet. However, treatment for patients beyond the first line remains undefined. Case presentation We report the case of a patient with stage IB LCNEC (PD-L1 negative but positive for PD-L1 amplification and tumor mutation burden high) who progressed after adjuvant chemotherapy after surgery and subsequent therapy with an antibody drug conjugate targeting a neuroendocrine-specific cell surface marker but achieved a significant and durable response with pembrolizumab, a humanized IgG4 monoclonal anti-PD-1 antibody. Conclusions Immunotherapy with checkpoint inhibitors is an effective treatment option for patients with metastatic LCNEC, even if PD-L1 expression is negative.

Published
2017
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11. Multiple configurations of EGFR exon 20 resistance mutations after first- and third-generation EGFR TKI treatment affect treatment options in NSCLC.

Author

Michael E Goldberg, Meagan Montesion, Lauren Young, James Suh, Joel Greenbowe, Mark Kennedy, Giuseppe Giaccone, Wallace L Akerley, Afshin Dowlati, Benjamin C Creelan, James K Hicks, Paul J Hesketh, Karen L Kelly, Jonathan W Riess, Vincent A Miller, Philip J Stephens, Garrett M Frampton, Siraj Ali, Jeffrey P Gregg, and Lee A Albacker

Subjects
Medicine, Science
Abstract

After sequential treatment with first- and third-generation EGFR tyrosine kinase inhibitors (TKIs), EGFR-mutant non-small cell lung cancers frequently harbor multiple resistance mutations in exon 20 of EGFR including T790M, mediating resistance to first-generation TKIs, and at codons 792, 796, or 797 mediating resistance to third-generation TKIs. However, whether these resistance mutations are in cis or trans has therapeutic implications for patients. We analyzed a cohort of 29 patients with NSCLC harboring EGFR mutations at codons 792, 796, or 797 to establish the configuration of these mutations. We performed hybrid capture-based, next-generation sequencing on formalin-fixed paraffin-embedded biopsy tissue or liquid biopsy. 27 samples had both a T790M mutation and a mutation at codons 792, 796, or 797. In all of these cases, the mutations were found in the cis configuration; the trans configuration was not observed. Two patients' samples harbored a mutation at codon 797 but no T790M mutation. In these two cases, longitudinal analysis showed earlier biopsies harbored EGFR T790M, which was undetectable following osimertinib treatment. Treatment of one these patients with both first- and third-generation EGFR TKIs resulted in a mixed response. Here we describe multiple configurations of EGFR T790M and third-generation TKI resistance mutations at codons 792, 796, and 797. These mutations are most commonly found in cis, which confers resistance to all current EGFR TKIs. We also describe two patients that exhibited T790M loss with acquisition of a mutation at codon 797. In addition, one of these patients, with an EGFR C797S in a lung biopsy was subsequently found to have EGFR C797N in a later biopsy of pleural fluid, highlighting the dynamic multiclonal nature of advanced NSCLC.

Published
2018
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13. WEDM Characteristics of Stir-Cast Al-TiB2 Metal Matrix Composites.

Author

Khan, Siraj Ali, Poria, Suswagata, and Sahoo, Prasanta

Subjects
*ENERGY dispersive X-ray spectroscopy, *ALUMINUM composites, *SCANNING electron microscopes, *SURFACE roughness, *MICROSCOPY, *METALLIC composites
Abstract

This article presents an experimental investigation of the WEDM (Wire Electrical Discharge Machining) performance of Al-TiB2 composites fabricated using ultrasonic vibration-assisted stir casting and containing four different weight percentages (1%, 2.5%, 4%, and 5.5%) of TiB2 particles. Key machining parameters, namely pulse-on time, wire feed rate, and pulse-off time, are varied at three levels suitable for machining aluminium base material while minimizing wire breakage. Cutting speed, material removal rate, and kerf width are observed individually for each selected level of these process parameters. Surface features are assessed using SEM (Scanning Electron Microscope), EDAX (Energy Dispersive X-ray Spectroscopy), 3D optical surface profilometer, and optical microscopy. Notably, the roughness values are lower in the 4% and 5.5% TiB2 composites compared to the base matrix. This reduction in roughness is due to the protective role of the particles, which shield the surface from melting during the WEDM process. Melting and re-welding phenomena were observed throughout the machining process. It is observed that higher pulse-on time generates harsh sparks, leading to rougher surfaces that include melted zones and pits. The WEDM operations performed on the 5.5 wt% reinforced composite surface result in a significant reduction in roughness, decreasing from around 5 µm to approximately 2.7 µm. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Machining Characteristics of Stir-Cast Al-TiB2 Composites in Dry Turning.

Author

Khan, Siraj Ali, Poria, Suswagata, and Sahoo, Prasanta

Subjects
*METALLIC composites, *MACHINING, *CUTTING force, *CRACK propagation (Fracture mechanics)
Abstract

Metal matrix composites (MMCs) are new-age materials because of their elevated strength-to-weight ratio and enhanced mechanical as well as tribological performances. However, machining of MMCs is always challenging because of the presence of hard ceramic particles which are abrasive in nature. The ultrasonic vibration-assisted stir-cast method is employed to fabricate Al-TiB2 composite with four different wt% of TiB2 particles. Turning operation on CNC turning center is performed to study the machining behavior of composites. Cutting forces, power consumption, surface quality of the machined surface, and rate of material removal are measured for varying reinforcement wt%, cutting speed, feed rate, and depth of cut. Chip morphologies and composition are studied to identify the mechanism of its formation. Results depict that at lower depth of cut, feed rate, and cutting speed, machining of composites is easier than base alloy. This may be attributed to more crack propagations throughout the particle–matrix interface, ease of pullout of particles, and brittle transformation due to localized deformation. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Supplementary Table S4 from Cell-Cycle Reprogramming for PI3K Inhibition Overrides a Relapse-Specific C481S BTK Mutation Revealed by Longitudinal Functional Genomics in Mantle Cell Lymphoma

Author

Selina Chen-Kiang, John P. Leonard, Christopher E. Mason, Olivier Elemento, Scott Ely, Betty Chang, Amy Johnson, Siraj Ali, Ken Eng, Priyanka Vijay, Susan Mathew, Pedro Blecua, Jeff Sharman, Xiangao Huang, Peter Martin, Maurizio Di Liberto, and David Chiron

Abstract

Significant non-synonymous damaging SNVs detected in CDS by targeted exome sequencing in Pt 2 relapse sample.

Published
2023

17. Supplementary Figure S1 from Cell-Cycle Reprogramming for PI3K Inhibition Overrides a Relapse-Specific C481S BTK Mutation Revealed by Longitudinal Functional Genomics in Mantle Cell Lymphoma

Author

Selina Chen-Kiang, John P. Leonard, Christopher E. Mason, Olivier Elemento, Scott Ely, Betty Chang, Amy Johnson, Siraj Ali, Ken Eng, Priyanka Vijay, Susan Mathew, Pedro Blecua, Jeff Sharman, Xiangao Huang, Peter Martin, Maurizio Di Liberto, and David Chiron

Abstract

Figure S1. MCL cell lines are differentially sensitive to killing and cell cycle control by ibrutinib.

Published
2023

18. Data from A High Frequency of Activating Extracellular Domain ERBB2 (HER2) Mutation in Micropapillary Urothelial Carcinoma

Author

Philip J. Stephens, Vincent A. Miller, Matthew Hawryluk, Doron Lipson, Roman Yelensky, Sean R. Downing, Kristina Brennan, John A. Curran, Rachel Erlich, Garrett Frampton, Elaine LaBrecque, Geneva Young, Michelle Nahas, Siraj Ali, Gary Palmer, Jie He, Amy Donahue, Geoff A. Otto, Timothy A. Jennings, Christine E. Sheehan, Tipu Nazeer, Rami N. Al-Rohil, Laurie M. Gay, Kai Wang, and Jeffrey S. Ross

Abstract

Purpose: Micropapillary urothelial carcinoma (MPUC) is a rare and aggressive form of bladder cancer. We conducted genomic analyses [next-generation sequencing (NGS)] of MPUC and non-micropapillary urothelial bladder carcinomas (non-MPUC) to characterize the genomic landscape and identify targeted treatment options.Experimental Design: DNA was extracted from 40 μm of formalin-fixed paraffin-embedded sections from 15 MPUC and 64 non-MPUC tumors. Sequencing (NGS) was performed on hybridization-captured, adaptor ligation–based libraries to high coverage for 3,230 exons of 182 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. The results were evaluated for all classes of genomic alteration.Results: Mutations in the extracellular domain of ERBB2 were identified in 6 of 15 (40%) of MPUC: S310F (four cases), S310Y (one case), and R157W (one case). All six cases of MPUC with ERBB2 mutation were negative for ERBB2 amplification and Erbb2 overexpression. In contrast, 6 of 64 (9.4%) non-MPUC harbored an ERBB2 alteration, including base substitution (three cases), amplification (two cases), and gene fusion (one case), which is higher than the 2 of 159 (1.3%) protein-changing ERBB2 mutations reported for urinary tract cancer in COSMIC. The enrichment of ERBB2 alterations in MPUC compared with non-MPUC is significant both between this series (P < 0.0084) and for all types of urinary tract cancer in COSMIC (P < 0.001).Conclusions: NGS of MPUC revealed a high incidence of mutation in the extracellular domain of ERBB2, a gene for which there are five approved targeted therapies. NGS can identify genomic alteration, which inform treatment options for the majority of MPUC patients. Clin Cancer Res; 20(1); 68–75. ©2013 AACR.

Published
2023

20. Supplementary Figures S1-S10 from Genomic Profiling of a Large Set of Diverse Pediatric Cancers Identifies Known and Novel Mutations across Tumor Spectra

Author

Doron Lipson, Jack F. Shern, Trevor J. Pugh, Soheil Meshinchi, John M. Maris, Katherine A. Janeway, Philip J. Stephens, Vincent A. Miller, Blair Glanville, Alexis Germain, Vinny Faso, Hilary Davies, Joana Buxhaku, Jeffrey S. Ross, Rachel L. Erlich, Laurie Gay, Siraj Ali, Daniel Spritz, Samantha Morley, James X. Sun, Garrett M. Frampton, James Suh, Shakti Ramkissoon, Jo-Anne Vergilio, Julia Elvin, Jie He, Mark Bailey, and Juliann Chmielecki

Abstract

Long tail distribution of the top 50 altered genes in pediatric sarcoma (S1); Long tail distribution of the top 50 altered genes in pediatric extracranial embryonal tumors (S2); Long tail distribution of the top 50 altered genes in pediatric brain tumors (S3); Long tail distribution of the top 50 altered genes in pediatric heme malignancies (S4); Long tail distribution of the top 50 altered genes in pediatric carcinomas (S5); Long tail distribution of the top 50 altered genes in pediatric gonadal tumors (S6); Known fusions identified in the pediatric cohort (S7); Tileplots showing the pattern of co-occurring alterations with novel MLL3 mutations (S8); Tileplot showing the pattern of co-occurring alterations with a novel PRSS1 mutation (S9); Tileplot showing the pattern of co-occurring alterations with novel DKC1 deletions (S10).

Published
2023

22. Supplementary Tables S1-S7 from Genomic Profiling of a Large Set of Diverse Pediatric Cancers Identifies Known and Novel Mutations across Tumor Spectra

Author

Doron Lipson, Jack F. Shern, Trevor J. Pugh, Soheil Meshinchi, John M. Maris, Katherine A. Janeway, Philip J. Stephens, Vincent A. Miller, Blair Glanville, Alexis Germain, Vinny Faso, Hilary Davies, Joana Buxhaku, Jeffrey S. Ross, Rachel L. Erlich, Laurie Gay, Siraj Ali, Daniel Spritz, Samantha Morley, James X. Sun, Garrett M. Frampton, James Suh, Shakti Ramkissoon, Jo-Anne Vergilio, Julia Elvin, Jie He, Mark Bailey, and Juliann Chmielecki

Abstract

Gene lists for Version 1 of the FoundationOne Assay (S1); Gene lists for Version 2 of the FoundationOne Assay (S2); Gene lists for Version 3 of the FoundationOne Assay (S3); Gene lists for Version 4 of the FoundationOne Assay (S4); Gene lists for Version 5 of the FoundationOne Assay (S5); Distribution of samples across different FoundationOne assays (S6); Filtered variants of unknown significance (S7).

Published
2023

23. Supplementary Figure Legends from On-target Resistance to the Mutant-Selective EGFR Inhibitor Osimertinib Can Develop in an Allele-Specific Manner Dependent on the Original EGFR-Activating Mutation

Author

Christine M. Lovly, Jens Meiler, Alexa B. Schrock, Lyudmila Bazhenova, Siraj Ali, Vincent A. Miller, Jeffrey S. Ross, Jarrod A. Smith, Zhenfang Du, Vincent Huang, Huan Qiao, Yingjun Yan, David Westover, Yun-Kai Zhang, and Benjamin P. Brown

Abstract

Supplementary Figure Legends

Published
2023

25. Data from On-target Resistance to the Mutant-Selective EGFR Inhibitor Osimertinib Can Develop in an Allele-Specific Manner Dependent on the Original EGFR-Activating Mutation

Author

Christine M. Lovly, Jens Meiler, Alexa B. Schrock, Lyudmila Bazhenova, Siraj Ali, Vincent A. Miller, Jeffrey S. Ross, Jarrod A. Smith, Zhenfang Du, Vincent Huang, Huan Qiao, Yingjun Yan, David Westover, Yun-Kai Zhang, and Benjamin P. Brown

Abstract

Purpose:The third-generation EGFR inhibitor, osimertinib, is the first mutant-selective inhibitor that has received regulatory approval for the treatment of patients with EGFR-mutant lung cancer. Despite the development of highly selective third-generation inhibitors, acquired resistance remains a significant clinical challenge. Recently, we and others have identified a novel osimertinib resistance mutation, G724S, which was not predicted in in vitro screens. Here, we investigate how G724S confers resistance to osimertinib.Experimental Design: We combine structure-based predictive modeling of G724S in combination with the 2 most common EGFR-activating mutations, exon 19 deletion (Ex19Del) and L858R, with in vitro drug-response models and patient genomic profiling.Results:Our simulations suggest that the G724S mutation selectively reduces osimertinib-binding affinity in the context of Ex19Del. Consistent with our simulations, cell lines transduced with Ex19Del/G724S demonstrate resistance to osimertinib, whereas cells transduced with L858R/G724S are sensitive to osimertinib. Subsequent clinical genomic profiling data further suggest G724S occurs with Ex19Del but not L858R. Furthermore, we demonstrate that Ex19Del/G724S retains sensitivity to afatinib, but not to erlotinib, suggesting a possible therapy for patients at the time of disease relapse.Conclusions:Altogether, these data suggest that G724S is an allele-specific resistance mutation emerging in the context of Ex19Del but not L858R. Our results fundamentally reframe the problem of targeted therapy resistance from one focused on the “drug–resistance mutation” pair to one focused on the “activating mutation–drug–resistance mutation” trio. This has broad implications across clinical oncology.

Published
2023

28. Supplementary Figure 1 from A High Frequency of Activating Extracellular Domain ERBB2 (HER2) Mutation in Micropapillary Urothelial Carcinoma

Author

Philip J. Stephens, Vincent A. Miller, Matthew Hawryluk, Doron Lipson, Roman Yelensky, Sean R. Downing, Kristina Brennan, John A. Curran, Rachel Erlich, Garrett Frampton, Elaine LaBrecque, Geneva Young, Michelle Nahas, Siraj Ali, Gary Palmer, Jie He, Amy Donahue, Geoff A. Otto, Timothy A. Jennings, Christine E. Sheehan, Tipu Nazeer, Rami N. Al-Rohil, Laurie M. Gay, Kai Wang, and Jeffrey S. Ross

Abstract

PDF file - 65K, Supplementary Figure 1. Tile Plot of Genomic Alterations in 64Cases on Non-micropapillary Urothelial Carcinoma.

Published
2023

29. Supplementary Data from Relapsed Classic E-Cadherin (CDH1)–Mutated Invasive Lobular Breast Cancer Shows a High Frequency of HER2 (ERBB2) Gene Mutations

Author

Philip J. Stephens, Vincent A. Miller, Gary Palmer, Doron Lipson, Roman Yelensky, Siraj Ali, John A. Curran, Jie He, James Sun, Sean R. Downing, Geoff Otto, Ann B. Boguniewicz, Christine E. Sheehan, Kai Wang, and Jeffrey S. Ross

Abstract

Supplementary Data from Relapsed Classic E-Cadherin (CDH1)–Mutated Invasive Lobular Breast Cancer Shows a High Frequency of HER2 (ERBB2) Gene Mutations

Published
2023

30. Data from Relapsed Classic E-Cadherin (CDH1)–Mutated Invasive Lobular Breast Cancer Shows a High Frequency of HER2 (ERBB2) Gene Mutations

Author

Philip J. Stephens, Vincent A. Miller, Gary Palmer, Doron Lipson, Roman Yelensky, Siraj Ali, John A. Curran, Jie He, James Sun, Sean R. Downing, Geoff Otto, Ann B. Boguniewicz, Christine E. Sheehan, Kai Wang, and Jeffrey S. Ross

Abstract

Purpose: We queried whether comprehensive genomic profiling using a next-generation sequencing–based assay could identify novel and unanticipated targets of therapy for patients with relapsed invasive lobular carcinoma (ILC).Experimental Design: DNA sequencing (Illumina HiSeq 2000) was conducted for 3,320 exons of 182 cancer-related genes and 37 introns of 14 genes frequently rearranged in cancer on indexed, adaptor-ligated, hybridization-captured libraries using DNA isolated from formalin-fixed paraffin-embedded sections from 22 histologically verified ILC.Results: A total of 75 genomic alterations were identified with an average of 3.4 alterations per tumor (range, 1–6), of which 35 were actionable for an average of 1.59 actionable alterations per patient (range, 0–3). Nineteen of 22 (86%) of the ILC samples harbored at least one actionable alteration. Six (27%) cases featured alterations in ERRB2 including 4 (18%) with ERBB2 mutation, 1 (5%) with an ERBB2 gene fusion, and 1 (5%) with an ERBB2 copy number gain (amplification). The enrichment of ERBB2 mutations/fusion in CDH1-mutated ILC (5 of 22, 23%) compared with the 5 ERBB2 mutations in a series of 286 non-CDH1-mutated breast cancers from which the ILC cases were obtained (5 of 286, 2%) was significant (P = 0.0006).Conclusions: Comprehensive genomic profiling of relapsed CDH1-mutated ILC revealed actionable genomic alterations in 86% of cases, featured a high incidence of ERBB2 alterations, and can reveal actionable alterations that can inform treatment decisions for patients with ILC. Clin Cancer Res; 19(10); 2668–76. ©2013 AACR.

Published
2023

31. Supplementary Table 1 from A High Frequency of Activating Extracellular Domain ERBB2 (HER2) Mutation in Micropapillary Urothelial Carcinoma

Author

Philip J. Stephens, Vincent A. Miller, Matthew Hawryluk, Doron Lipson, Roman Yelensky, Sean R. Downing, Kristina Brennan, John A. Curran, Rachel Erlich, Garrett Frampton, Elaine LaBrecque, Geneva Young, Michelle Nahas, Siraj Ali, Gary Palmer, Jie He, Amy Donahue, Geoff A. Otto, Timothy A. Jennings, Christine E. Sheehan, Tipu Nazeer, Rami N. Al-Rohil, Laurie M. Gay, Kai Wang, and Jeffrey S. Ross

Abstract

PDF file - 207K, Supplementary Table Genomic Alterations in 64 Cases of Relapsed/Metastatic Non-Micropapillary Urothelial Carcinoma of the Bladder.

Published
2023

32. Data from Genomic Profiling of a Large Set of Diverse Pediatric Cancers Identifies Known and Novel Mutations across Tumor Spectra

Author

Doron Lipson, Jack F. Shern, Trevor J. Pugh, Soheil Meshinchi, John M. Maris, Katherine A. Janeway, Philip J. Stephens, Vincent A. Miller, Blair Glanville, Alexis Germain, Vinny Faso, Hilary Davies, Joana Buxhaku, Jeffrey S. Ross, Rachel L. Erlich, Laurie Gay, Siraj Ali, Daniel Spritz, Samantha Morley, James X. Sun, Garrett M. Frampton, James Suh, Shakti Ramkissoon, Jo-Anne Vergilio, Julia Elvin, Jie He, Mark Bailey, and Juliann Chmielecki

Abstract

Pediatric cancers are generally characterized by low mutational burden and few recurrently mutated genes. Recent studies suggest that genomic alterations may help guide treatment decisions and clinical trial selection. Here, we describe genomic profiles from 1,215 pediatric tumors representing sarcomas, extracranial embryonal tumors, brain tumors, hematologic malignancies, carcinomas, and gonadal tumors. Comparable published datasets identified similar frequencies of clinically relevant alterations, validating this dataset as biologically relevant. We identified novel ALK fusions in a neuroblastoma (BEND5–ALK) and an astrocytoma (PPP1CB–ALK), novel BRAF fusions in an astrocytoma (BCAS1–BRAF) and a ganglioglioma (TMEM106B–BRAF), and a novel PAX3–GLI2 fusion in a rhabdomyosarcoma. Previously characterized ALK, NTRK1, and PAX3 fusions were observed in unexpected malignancies, challenging the "disease-specific" alterations paradigm. Finally, we identified recurrent variants of unknown significance in MLL3 and PRSS1 predicted to have functional impact. Data from these 1,215 tumors are publicly available for discovery and validation. Cancer Res; 77(2); 509–19. ©2017 AACR.

Published
2023

34. Machining Characteristics of Stir-Cast Al-TiB2Composites in Dry Turning

Author

Khan, Siraj Ali, Poria, Suswagata, and Sahoo, Prasanta

Abstract

Metal matrix composites (MMCs) are new-age materials because of their elevated strength-to-weight ratio and enhanced mechanical as well as tribological performances. However, machining of MMCs is always challenging because of the presence of hard ceramic particles which are abrasive in nature. The ultrasonic vibration-assisted stir-cast method is employed to fabricate Al-TiB2composite with four different wt% of TiB2particles. Turning operation on CNC turning center is performed to study the machining behavior of composites. Cutting forces, power consumption, surface quality of the machined surface, and rate of material removal are measured for varying reinforcement wt%, cutting speed, feed rate, and depth of cut. Chip morphologies and composition are studied to identify the mechanism of its formation. Results depict that at lower depth of cut, feed rate, and cutting speed, machining of composites is easier than base alloy. This may be attributed to more crack propagations throughout the particle–matrix interface, ease of pullout of particles, and brittle transformation due to localized deformation.

Published
2024
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35. Health related quality of life and associated factors among children living in previous leprosarium and nonleprosarium areas of Eastern Ethiopia

Author

Assefa Desalew, Siraj Aliyi Adem, Fitsum Weldegebreal, Getachew Kabew Mekonnen, Temam Beshir Raru, Ukash Umer, Mulualem Keneni, and Kedir Urgesa

Subjects
Health related quality of life, Children, Previous leprosy settlements, Non-leprosy settlements, Eastern Ethiopia, Medicine, Science
Abstract

Abstract Children and their families living in leprosarium areas may have a lower quality of life than the general population. However, there is limited evidence on health-related quality of life and its associated factors among children living in previous leprosarium settlement areas. Hence, this study aimed to compare the health-related quality of life among children living in previous leprosarium and non-leprosarium settlement areas in eastern Ethiopia. A community-based comparative cross-sectional study was conducted among 515 randomly selected children aged 8 to 18 years living in the Amir Nur and Babile districts from January to February 30, 2024. Data were collected through interviews with children and parents using the Pediatric Quality of Life Inventory Version 4. The data were analyzed using STATA version 14. Simple and multiple linear regression was employed to identify associations between independent and outcome variables. The overall mean health-related quality of life scores were 73.98 ± 18.47 and 77.67 ± 14.72 in the child self-reports (P = 0.01) and 55.78 ± 12.03 and 55.61 ± 8.50 (P = 0.85) in the parent proxy reports in the previous leprosarium and nonleprosarium settlement areas, respectively. In multiple linear regression, child education (β = 14.69; 95% CI: 8.69, 20.69), the absence of neglected and tropical diseases (β = 4.02; 95% CI: 0.66, 7.37), and child face washing habits (β = 5.54, 95% CI: 2.14, 8.95) increase health-related quality of life. However, a previous history of neglected and tropical diseases (β = -8.54; 95% CI: -12.93, -4.15) and the absence of hand washing facilities (β = -8.57; 95% CI, -15.22, -1.92) decrease the mean health-related quality of life. Based on child self-reports, one in four children from previous leprosarium areas had poor health-related quality of life compared to children living in none leprosarium areas. Children’s educational status, their daily habits of washing their face, not having neglected, and tropical diseases had improved health-related quality of life. To improve health-related quality of life, stakeholders should pay attention to and work on the early detection and treatment of neglected and tropical diseases, child education, and proper sanitation practices in the leprosarium community.

Published
2024
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37. Clinicopathologic Features and Response to Therapy of

Author

Alexander, Drilon, Michael, Duruisseaux, Ji-Youn, Han, Masaoki, Ito, Christina, Falcon, Soo-Ryum, Yang, Yonina R, Murciano-Goroff, Haiquan, Chen, Morihito, Okada, Miguel Angel, Molina, Marie, Wislez, Philippe, Brun, Clarisse, Dupont, Eva, Branden, Giulio, Rossi, Alexa, Schrock, Siraj, Ali, Valérie, Gounant, Fanny, Magne, Torsten Gerriet, Blum, Alison M, Schram, Isabelle, Monnet, Jin-Yuan, Shih, Joshua, Sabari, Maurice, Pérol, Viola W, Zhu, Misako, Nagasaka, Robert, Doebele, D Ross, Camidge, Maria, Arcila, Sai-Hong Ignatius, Ou, Denis, Moro-Sibilot, Rafael, Rosell, Lucia Anna, Muscarella, Stephen V, Liu, and Jacques, Cadranel

Subjects
Adult, Aged, 80 and over, Male, Asia, Lung Neoplasms, Oncogene Proteins, Fusion, Neuregulin-1, ORIGINAL REPORTS, Middle Aged, Prognosis, United States, Europe, Survival Rate, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Humans, Female, Immunotherapy, Registries, Aged, Follow-Up Studies, Retrospective Studies
Abstract

PURPOSE: Although NRG1 fusions are oncogenic drivers across multiple tumor types including lung cancers, these are difficult to study because of their rarity. The global eNRGy1 registry was thus established to characterize NRG1 fusion–positive lung cancers in the largest and most diverse series to date. METHODS: From June 2018 to February 2020, a consortium of 22 centers from nine countries in Europe, Asia, and the United States contributed data from patients with pathologically confirmed NRG1 fusion–positive lung cancers. Profiling included DNA-based and/or RNA-based next-generation sequencing and fluorescence in situ hybridization. Anonymized clinical, pathologic, molecular, and response (RECIST v1.1) data were centrally curated and analyzed. RESULTS: Although the typified never smoking (57%), mucinous adenocarcinoma (57%), and nonmetastatic (71%) phenotype predominated in 110 patients with NRG1 fusion–positive lung cancer, further diversity, including in smoking history (43%) and histology (43% nonmucinous and 6% nonadenocarcinoma), was elucidated. RNA-based testing identified most fusions (74%). Molecularly, six (of 18) novel 5′ partners, 20 unique epidermal growth factor domain–inclusive chimeric events, and heterogeneous 5′/3′ breakpoints were found. Platinum-doublet and taxane-based (post–platinum-doublet) chemotherapy achieved low objective response rates (ORRs 13% and 14%, respectively) and modest progression-free survival medians (PFS 5.8 and 4.0 months, respectively). Consistent with a low programmed death ligand-1 expressing (28%) and low tumor mutational burden (median: 0.9 mutations/megabase) immunophenotype, the activity of chemoimmunotherapy and single-agent immunotherapy was poor (ORR 0%/PFS 3.3 months and ORR 20%/PFS 3.6 months, respectively). Afatinib achieved an ORR of 25%, not contingent on fusion type, and a 2.8-month median PFS. CONCLUSION: NRG1 fusion–positive lung cancers were molecularly, pathologically, and clinically more heterogeneous than previously recognized. The activity of cytotoxic, immune, and targeted therapies was disappointing. Further research examining NRG1-rearranged tumor biology is needed to develop new therapeutic strategies.

Published
2021

38. Clinical and Genomic Characteristics of Small Cell Lung Cancer in Never Smokers: Results From a Retrospective Multicenter Cohort Study

Author

Anish, Thomas, Idrees, Mian, Camille, Tlemsani, Lorinc, Pongor, Nobuyuki, Takahashi, Kathleen, Maignan, Jeremy, Snider, Gerald, Li, Garrett, Frampton, Siraj, Ali, Sehyun, Kim, Samantha, Nichols, Vinodh, Rajapakse, Udayan, Guha, Elad, Sharon, Junya, Fujimoto, Cesar A, Moran, Ignacio I, Wistuba, Jun S, Wei, Javed, Khan, Eva, Szabo, Aracelis Z, Torres, and Kenneth R, Carson

Subjects
Adult, Aged, 80 and over, Male, Lung Neoplasms, Smoking, Genomics, Middle Aged, Thoracic Oncology: Original Research, Small Cell Lung Carcinoma, respiratory tract diseases, Cohort Studies, Humans, Female, Aged, Retrospective Studies
Abstract

BACKGROUND: Small cell lung cancer (SCLC) has the strongest association with smoking among lung cancers. The characteristics of never smokers with SCLC is not known. RESEARCH QUESTION: Are the clinical characteristics, prognostic factors, survival, genomic alterations, and tumor mutational burdens of SCLC in patients who have never smoked different from those who have smoked? STUDY DESIGN AND METHODS: A retrospective multicenter cohort study of patients with clinician-confirmed SCLC was performed with the use of a longitudinal and nationally representative electronic medical records database. Smoking history was assessed through technology-enabled abstraction and confirmed for never smokers via chart review. Genomic characteristics of never smoker patients with SCLC were examined with the use of a next-generation sequencing-based gene panel and whole exome sequencing. RESULTS: One hundred of 5,632 patients (1.8%) with SCLC were never smokers. Relative to smokers, never smokers were more likely to be female (66.0% vs 52.4%; P = .009) and present with extensive stage (70.0% vs 62.2%; P = .028). Never smokers had a higher proportion of patients in age groups 35 to 49 years (7.0% vs 3.0%; P = .006) and ≥80 years (17.0% vs 8.2%; P = .006). Known risk factors for lung cancer were found in

Published
2019

39. Impacts of heat exposure on workers’ health and performance at steel plant in Turkey

Author

Siraj Ali Ahmed, Mehmet Özkaymak, and Abdel Karim Amar Fahed

Subjects
Fluid Flow and Transfer Processes, Computer Networks and Communications, Mechanical Engineering, Wet-bulb globe temperature, Metals and Alloys, Gas emissions, 010501 environmental sciences, Heat wave, 030210 environmental & occupational health, 01 natural sciences, Electronic, Optical and Magnetic Materials, Heat stress, Biomaterials, Toxicology, 03 medical and health sciences, 0302 clinical medicine, Hardware and Architecture, lcsh:TA1-2040, Steel mill, Environmental science, Heat load, lcsh:Engineering (General). Civil engineering (General), 0105 earth and related environmental sciences, Civil and Structural Engineering
Abstract

Workers of Iron and steel plants are exposed to extreme environmental heat that causes discomfort and limits their performance. This study investigates the influence of heat load on workers’ health and activity in Kardemir Steel Factory in Karabük-Turkey using several heat stress indices. Combined field measurements and questionnaires were carried out over a period from June to August 2016. A total number of 100 workers regularly working in the steel plant from five different workplaces were selected. The wet bulb globe temperature (WBGT), the physiological strain (PSI), and the heat stress (HSI) indices were calculated. Workers' productivity level was evaluated by analyzing the relationships between work capacities and different WBGT levels against work intensities’ curves and by using the predicted mean vote (PMV)-productivity model. The highest values of WBGT were recorded in August, notably within the blast furnace area and continuous casting unit with mean values of 31.32 ± 0.8 °C and 31.34 ± 0.74 °C respectively, while the maximum HSI was calculated at the rolling mills unit with a value of 137.83% ±18.45. About 86% of participants complained of thermal discomfort during summer as a result of heat waves, dirt and gas emissions. Strong correlations were found between PSI and WBGT indices with core body temperature (r = 0.725 and r = 0.721 respectively) as well as the rate of heartbeat (r = 0.648 and r = 0.517). These are considered as the most applicable indices for evaluating heat load impact on workers’ health and performance. Keywords: Heat load, Steel plant, Productivity, WBGT, HSI, PSI

Published
2018

40. Comprehensive Genomic Profiling of 282 Pediatric Low- and High-Grade Gliomas Reveals Genomic Drivers, Tumor Mutational Burden, and Hypermutation Signatures

Author

Adrienne Johnson, Eric Severson, Laurie Gay, Jo-Anne Vergilio, Julia Elvin, James Suh, Sugganth Daniel, Mandy Covert, Garrett M. Frampton, Sigmund Hsu, Glenn J. Lesser, Kimberly Stogner-Underwood, Ryan T. Mott, Sarah Z. Rush, Jennifer J. Stanke, Sonika Dahiya, James Sun, Prasanth Reddy, Zachary R. Chalmers, Rachel Erlich, Yakov Chudnovsky, David Fabrizio, Alexa B. Schrock, Siraj Ali, Vincent Miller, Philip J. Stephens, Jeffrey Ross, John R. Crawford, and Shakti H. Ramkissoon

Subjects
Male, Cancer Research, Adolescent, DNA Repair, PDGFRA, 03 medical and health sciences, 0302 clinical medicine, Glioma, PMS2, Humans, Medicine, Neuro‐Oncology, Child, Clinical sequencing, ATRX, Pediatric neuro‐oncology, POLD1, Genome, Human, business.industry, Precision medicine, High-Throughput Nucleotide Sequencing, Infant, Cancer, medicine.disease, Neoplasm Proteins, Tumor Burden, MSH6, Oncology, MSH2, Child, Preschool, 030220 oncology & carcinogenesis, Mutation, Cancer research, Female, Immunotherapy, business, 030217 neurology & neurosurgery
Abstract

This study highlights the value of comprehensive genomic profiling in the largest known cohort of pediatric glioma patients and explores the most common alterations across diagnosis and anatomic location. Tumor mutational burden and associated genetic factors that may predispose patients to developing a hypermutator phenotype are also discussed., Background. Pediatric brain tumors are the leading cause of death for children with cancer in the U.S. Incorporating next‐generation sequencing data for both pediatric low‐grade (pLGGs) and high‐grade gliomas (pHGGs) can inform diagnostic, prognostic, and therapeutic decision‐making. Materials and Methods. We performed comprehensive genomic profiling on 282 pediatric gliomas (157 pHGGs, 125 pLGGs), sequencing 315 cancer‐related genes and calculating the tumor mutational burden (TMB; mutations per megabase [Mb]). Results. In pLGGs, we detected genomic alterations (GA) in 95.2% (119/125) of tumors. BRAF was most frequently altered (48%; 60/125), and FGFR1 missense (17.6%; 22/125), NF1 loss of function (8.8%; 11/125), and TP53 (5.6%; 7/125) mutations were also detected. Rearrangements were identified in 35% of pLGGs, including KIAA1549‐BRAF, QKI‐RAF1, FGFR3‐TACC3, CEP85L‐ROS1, and GOPC‐ROS1 fusions. Among pHGGs, GA were identified in 96.8% (152/157). The genes most frequently mutated were TP53 (49%; 77/157), H3F3A (37.6%; 59/157), ATRX (24.2%; 38/157), NF1 (22.2%; 35/157), and PDGFRA (21.7%; 34/157). Interestingly, most H3F3A mutations (81.4%; 35/43) were the variant K28M. Midline tumor analysis revealed H3F3A mutations (40%; 40/100) consisted solely of the K28M variant. Pediatric high‐grade gliomas harbored oncogenic EML4‐ALK, DGKB‐ETV1, ATG7‐RAF1, and EWSR1‐PATZ1 fusions. Six percent (9/157) of pHGGs were hypermutated (TMB >20 mutations per Mb; range 43–581 mutations per Mb), harboring mutations deleterious for DNA repair in MSH6, MSH2, MLH1, PMS2, POLE, and POLD1 genes (78% of cases). Conclusion. Comprehensive genomic profiling of pediatric gliomas provides objective data that promote diagnostic accuracy and enhance clinical decision‐making. Additionally, TMB could be a biomarker to identify pediatric glioblastoma (GBM) patients who may benefit from immunotherapy. Implications for Practice. By providing objective data to support diagnostic, prognostic, and therapeutic decision‐making, comprehensive genomic profiling is necessary for advancing care for pediatric neuro‐oncology patients. This article presents the largest cohort of pediatric low‐ and high‐grade gliomas profiled by next‐generation sequencing. Reportable alterations were detected in 95% of patients, including diagnostically relevant lesions as well as novel oncogenic fusions and mutations. Additionally, tumor mutational burden (TMB) is reported, which identifies a subpopulation of hypermutated glioblastomas that harbor deleterious mutations in DNA repair genes. This provides support for TMB as a potential biomarker to identify patients who may preferentially benefit from immune checkpoint inhibitors.

Published
2017

41. PD47-09 FIRST SURVIVAL OUTCOMES AND ADDITIONAL SECONDARY ANALYSES FROM PURE-01: PEMBROLIZUMAB (PEMBRO) BEFORE RADICAL CYSTECTOMY (RC) IN MUSCLE-INVASIVE UROTHELIAL BLADDER CARCINOMA (MIBC)

Author

Andrea Necchi, Marco Bandini, Andrea Gallina, Marco Bianchi, Daniele Raggi, Antonella Messina, Jon Chung, Siraj Ali, Jeffrey Ross, Andrea Anichini, Maurizio Colecchia, Giorgio Gandaglia, Nicola Fossati, Simone Scuderi, Filippo Pederzoli, Andrea Salonia, Renzo Colombo, Alberto Briganti, and Francesco Montorsi

Subjects
medicine.medical_specialty, business.industry, Urology, medicine.medical_treatment, Muscle invasive, Phases of clinical research, Pembrolizumab, medicine.disease, Cystectomy, medicine, Clinical endpoint, Carcinoma, business, Complete response
Abstract

INTRODUCTION AND OBJECTIVES:PURE-01 is a phase 2 study of Pembro before RC in MIBC: the primary endpoint (pathologic complete response [pT0]) was met in advance (Necchi et al. JCO 2018).While the s...

Published
2019

42. MET Genomic Alterations in Head and Neck Squamous Cell Carcinoma (HNSCC): Rapid Response to Crizotinib in a Patient with HNSCC with a Novel

Author

Lisa Pei, Chu, Debra, Franck, Christine A, Parachoniak, Jeffrey P, Gregg, Michael G, Moore, D Gregory, Farwell, Shyam, Rao, Andreas M, Heilmann, Rachel L, Erlich, Jeffrey S, Ross, Vincent A, Miller, Siraj, Ali, and Jonathan W, Riess

Subjects
Male, stomatognathic diseases, Crizotinib, Squamous Cell Carcinoma of Head and Neck, Mutation, Humans, Precision Medicine Clinic: Molecular Tumor Board, Genomics, Middle Aged
Abstract

Identification of effective targeted therapies for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) remains an unmet medical need. A patient with platinum‐refractory recurrent oral cavity HNSCC underwent comprehensive genomic profiling (CGP) that identified an activating MET mutation (R1004). The patient was treated with the oral MET tyrosine kinase inhibitor crizotinib with rapid response to treatment. Based on this index case, we determined the frequency of MET alterations in 1,637 HNSCC samples, which had been analyzed with hybrid capture‐based CGP performed in the routine course of clinical care. The specimens were sequenced to a median depth of >500× for all coding exons from 182 (version 1, n = 24), 236 (version 2, n = 326), or 315 (version 3, n = 1,287) cancer‐related genes, plus select introns from 14 (version 1), 19 (version 2), or 28 (version 3) genes frequently rearranged in cancer. We identified 13 HNSCC cases (0.79%) with MET alterations (4 point mutation events and 9 focal amplification events). MET‐mutant or amplified tumors represent a small but potentially actionable molecular subset of HNSCC. KEY POINTS. This case report is believed to be the first reported pan‐cancer case of a patient harboring a MET mutation at R1004 demonstrating a clinical response to crizotinib, in addition to the first documented case of head and neck squamous cell carcinoma (HNSCC) with any MET alteration responding to crizotinib. The positive response to MET inhibition in this patient highlights the significance of comprehensive genomic profiling in advanced metastatic HNSCC to identify actionable targetable molecular alterations as current treatment options are limited.

Published
2019

43. Pattern of Living Arrangements among the Rural Elderly Muslims of West Bengal, India

Author

Sk. Siraj Ali

Subjects
education.field_of_study, 030214 geriatrics, Population, Developing country, Public institution, Backwardness, Social security, 03 medical and health sciences, 0302 clinical medicine, Geography, 030502 gerontology, Spouse, Rural area, 0305 other medical science, Socioeconomics, China, education
Abstract

Approaching 80 million in number, India has the second largest population of elderly people after China. The living arrangement of the elderly is seen as a parameter of great importance in understanding their difficulty in developing countries because of lack of public institutions and social security nets. Muslim people is more backward community for lack of education, economically weak, structure of household and so on the backwardness is more prone for those who are living in rural areas. There more studies article the living arrangement of elderly except Muslims. Therefore, keeping these backdrops in mind, the present research attempts to explore the present nature of living arrangement of the 200 Muslim elderly people from both sexes living in the villages. This study analyses the socio-economic, demographic, household characteristics to determine their living arrangement. The study exhibit those majorities (73.50%) of them were living with their spouse and present sons and only 07.50% were living alone. In view of the changing socio-economic and demographic condition there is a higher proportion of elderly Muslim living alone in the future.

Published
2016

44. A Pan-Cancer Landscape Analysis Reveals a Subset of Endometrial Stromal and Pediatric Tumors Defined by Internal Tandem Duplications of BCOR

Author

Luke T, Juckett, Doug I, Lin, Russell, Madison, Jeffrey S, Ross, Alexa B, Schrock, and Siraj, Ali

Subjects
Adult, Male, Repressor Proteins, Adolescent, Endometrial Stromal Tumors, Tandem Repeat Sequences, Neoplasms, Proto-Oncogene Proteins, Humans, Female, Middle Aged, Introns, Endometrial Neoplasms
Abstract

The Polycomb Repressive Complex 1 (PRC1) regulates epigenetic silencing and is manifestly linked to rare cancer types. The X-linked BCOR gene (BCL-6 Corepressor) is a member of the PRC1 complex and potentiates transcriptional repression through BCL6 binding of PRC1. Accumulating evidence suggests that internal tandem duplications (ITD) of BCOR are oncogenic drivers in a subset of pediatric sarcomas and rare adult tumors.We reviewed the genomic profiles of a large series of advanced cancer patients to determine the frequency and genomic spectrum of ITD of BCOR across cancer.Tissues from 140,411 unique advanced cancers were sequenced by hybrid-capture-NGS-based comprehensive genomic profiling of 186-315 genes plus introns from 14 to 28 genes commonly rearranged in cancer, as well as RNA for 265 genes for a portion of these cases.BCOR-ITDs were present in 0.024% of all cases (33/140,411). Of this dataset, sarcoma cancer types were most frequent, 63.6% (21/33), either of uterine origin 52.4% (11/21), or pediatric (nonuterine) 42.8% (9/21). The identified BCOR-ITDs occurred most frequently in exon 15, near C-terminus, 69.7% (23/33), with a mean insertion length of 31.7 codons (range 30-38). Of uterine cases, an expert gynecologic pathology central review identified all these cases as having a similar high-grade morphology consistent with endometrial stromal sarcomas (ESS), and 90% of cases having a round cell component. Of the uterine sarcoma cases harboring exon 15 BCOR-ITDs, none simultaneously carried gene fusions typically associated with ESS.BCOR-ITDs define a rare subset of pediatric sarcomas and clinically aggressive endometrial stromal sarcoma cases, as defined by NGS for the first time. Our findings help delineate the pan-cancer landscape of this alteration and suggest the need for focused investigation to delineate the pro-oncogenic function of BCOR, along with any sensitivity to targeted therapies.

Published
2018

45. Successful Treatment of Recurrent Primitive Myxoid Mesenchymal Tumor of Infancy With

Author

Stuart L, Cramer, Rong, Li, Siraj, Ali, Julie A, Bradley, Hee K, Kim, and Joseph G, Pressey

Subjects
Repressor Proteins, Treatment Outcome, Recurrence, Tandem Repeat Sequences, Gene Duplication, Proto-Oncogene Proteins, Humans, Infant, Female, Sarcoma, Combined Modality Therapy, Magnetic Resonance Imaging
Abstract

Primitive myxoid mesenchymal tumor of infancy (PMMTI) is a rare tumor with20 cases reported to date. Recently PMMTI tumors have been found to harbor

Published
2017

46. Abstract 1694: A multi-institutional, multi-tumor analysis of fine needle aspiration (FNA) cytology smear (FNAC) performance in clinical comprehensive genomic profiling

Author

Jonathan K. Killian, Dean Pavlick, Lindsay Croshier, John Truesdell, Chris Wright, Tim Brennan, Vera Banning, Lazaro Garcia, Laurie Gay, Gene Stirchak, Jo-Anne Vergilio, Christine Malboeuf, Nhu Ngo, Julia Elvin, Siraj Ali, Vince Miller, and Jeffrey S. Ross

Subjects
Cancer Research, Oncology
Abstract

Background. FNAC are generated during the FNA procedure - for example, commonly used in conjunction with endobronchial ultrasound (EBUS-FNA) as a minimally invasive tool for the diagnosis and management of non small-cell lung cancer (NSCLC) - as a histologic QC for the presence of malignant cells. Formalin-fixed core biopsies and aspirate cell blocks (FNACB) are then created for comprehensive genomic profiling (CGP). However, the routine pathology workup may render the FNACB unable to generate a CGP result, while the FNAC remain in reserve. In the current study we performed a retrospective multi-cancer, multi-institutional analysis of FNAC performance, including computed tumor purity analysis, using a regulated commercial grade CGP assay. Experimental procedures. 119 FNAC met minimum specimen cellularity (10K total cellularity) and DNA extraction (50ng) criteria for CGP. Extracted DNA from FNACS underwent hybrid-capture-based CGP for all classes of genomic alterations in 315 genes. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. A comparison set of 182 FNACB specimens underwent the same CGP assay. Individual specimen CGPs were annotated as Pass, Fail, or Qualified per computational biology standard procedures that factor in sequencing quality metrics such as mean target coverage and computational tumor purity modeling. Results. The 119 FNAC, collected at 14 different medical facilities, encompassed 44 distinct tumor disease ontologies (DO) from 17 unique anatomic biopsy sites. 105 of 119 FNACS (88%) received a passing report, 10 (8%) were qualified, and 4 (3%) failed. In the FNACB comparison group, 155 of 182 reports were pass (85%), 22 qualified (12%), and 5 failed (3%). The number of passing reports in FNACS versus FNACB was equivalent (P=0.5). The FNAC had a significantly higher mean target coverage than FNACB (703 vs 665; P= 0.04995). The average computational tumor purity metric was significantly higher in FNACS than in FNACB (57.9% vs. 45.3%; P=0.00001). Conclusions. This study provides new data from FNAC that further support their utility for clinical testing. FNAC derived from multiple medical facilities, biopsy sites, and tumor types were found to be equivalent or superior to FNACB for CGP. Finally, the relative cellular homogeneity and high tumor cell content of both FNAC and FNACB likely confirms the discohesiveness of malignant cells and enables CGP without required enrichment given that macrodissection would be challenging for these samples in a daily practice setting. Citation Format: Jonathan K. Killian, Dean Pavlick, Lindsay Croshier, John Truesdell, Chris Wright, Tim Brennan, Vera Banning, Lazaro Garcia, Laurie Gay, Gene Stirchak, Jo-Anne Vergilio, Christine Malboeuf, Nhu Ngo, Julia Elvin, Siraj Ali, Vince Miller, Jeffrey S. Ross. A multi-institutional, multi-tumor analysis of fine needle aspiration (FNA) cytology smear (FNAC) performance in clinical comprehensive genomic profiling [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 1694.

Published
2019

47. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part one

Author

Andreas Lundqvist, Vincent van Hoef, Xiaonan Zhang, Erik Wennerberg, Julie Lorent, Kristina Witt, Laia Masvidal Sanz, Shuo Liang, Shannon Murray, Ola Larsson, Rolf Kiessling, Yumeng Mao, John-William Sidhom, Catherine A. Bessell, Jonathan Havel, Jonathan Schneck, Timothy A. Chan, Eliot Sachsenmeier, David Woods, Anders Berglund, Rupal Ramakrishnan, Andressa Sodre, Jeffrey Weber, Roberta Zappasodi, Yanyun Li, Jingjing Qi, Philip Wong, Cynthia Sirard, Michael Postow, Walter Newman, Henry Koon, Vamsidhar Velcheti, Margaret K. Callahan, Jedd D. Wolchok, Taha Merghoub, Lawrence G. Lum, Minsig Choi, Archana Thakur, Abhinav Deol, Gregory Dyson, Anthony Shields, Cara Haymaker, Marc Uemura, Ravi Murthy, Marihella James, Daqing Wang, Julie Brevard, Catherine Monaghan, Suzanne Swann, James Geib, Mark Cornfeld, Srinivas Chunduru, Sudhir Agrawal, Cassian Yee, Jennifer Wargo, Sapna P. Patel, Rodabe Amaria, Hussein Tawbi, Isabella Glitza, Scott Woodman, Wen-Jen Hwu, Michael A. Davies, Patrick Hwu, Willem W. Overwijk, Chantale Bernatchez, Adi Diab, Erminia Massarelli, Neil H. Segal, Vincent Ribrag, Ignacio Melero, Tara C. Gangadhar, Walter Urba, Dirk Schadendorf, Robert L. Ferris, Roch Houot, Franck Morschhauser, Theodore Logan, Jason J. Luke, William Sharfman, Fabrice Barlesi, Patrick A. Ott, Laura Mansi, Shivaani Kummar, Gilles Salles, Cecilia Carpio, Roland Meier, Suba Krishnan, Dan McDonald, Matthew Maurer, Xuemin Gu, Jaclyn Neely, Satyendra Suryawanshi, Ronald Levy, Nikhil Khushalani, Jennifer Wu, Jinyu Zhang, Fahmin Basher, Mark Rubinstein, Mark Bucsek, Guanxi Qiao, Cameron MacDonald, Bonnie Hylander, Elizabeth Repasky, Shilpak Chatterjee, Anusara Daenthanasanmak, Paramita Chakraborty, Kyle Toth, Megan Meek, Elizabeth Garrett-Mayer, Michael Nishimura, Chrystal Paulos, Craig Beeson, Xuezhong Yu, Shikhar Mehrotra, Fei Zhao, Kathy Evans, Christine Xiao, Alisha Holtzhausen, Brent A. Hanks, Nicole Scharping, Ashley V. Menk, Rebecca Moreci, Ryan Whetstone, Rebekah Dadey, Simon Watkins, Robert Ferris, Greg M. Delgoffe, Jonathan Peled, Sean Devlin, Anna Staffas, Melissa Lumish, Kori Porosnicu Rodriguez, Katya Ahr, Miguel Perales, Sergio Giralt, Ying Taur, Eric Pamer, Marcel R. M. van den Brink, Robert Jenq, Nicola Annels, Hardev Pandha, Guy Simpson, Hugh Mostafid, Kevin Harrington, Alan Melcher, Mark Grose, Bronwyn Davies, Gough Au, Roberta Karpathy, Darren Shafren, Jacob Ricca, Dmitriy Zamarin, Luciana Batista, Florence Marliot, Angela Vasaturo, Sabrina Carpentier, Cécile Poggionovo, Véronique Frayssinet, Jacques Fieschi, Marc Van den Eynde, Franck Pagès, Jérôme Galon, Fabienne Hermitte, Sean G. Smith, Khue Nguyen, Sruthi Ravindranathan, Bhanu Koppolu, David Zaharoff, Gustavo Schvartsman, Roland Bassett, Jennifer L. McQuade, Lauren E. Haydu, Douglas Kline, Xiufen Chen, Dominick Fosco, Justin Kline, Abigail Overacre, Maria Chikina, Erin Brunazzi, Gulidanna Shayan, William Horne, Jay Kolls, Tullia C. Bruno, Creg Workman, Dario Vignali, Prasad S. Adusumilli, Ephraim A Ansa-Addo, Zihai Li, Andrew Gerry, Joseph P. Sanderson, Karen Howe, Roslin Docta, Qian Gao, Eleanor A. L. Bagg, Nicholas Tribble, Miguel Maroto, Gareth Betts, Natalie Bath, Luca Melchiori, Daniel E. Lowther, Indu Ramachandran, Gabor Kari, Samik Basu, Gwendolyn Binder-Scholl, Karen Chagin, Lini Pandite, Tom Holdich, Rafael Amado, Hua Zhang, John Glod, Donna Bernstein, Bent Jakobsen, Crystal Mackall, Ryan Wong, Jonathan D. Silk, Katherine Adams, Garth Hamilton, Alan D. Bennett, Sara Brett, Junping Jing, Adriano Quattrini, Manoj Saini, Guy Wiedermann, Joanna Brewer, MyLinh Duong, An Lu, Peter Chang, Aruna Mahendravada, Nicholas Shinners, Kevin Slawin, David M. Spencer, Aaron E. Foster, J. Henri Bayle, Cristina Bergamaschi, Sinnie Sin Man Ng, Bethany Nagy, Shawn Jensen, Xintao Hu, Candido Alicea, Bernard Fox, Barbara Felber, George Pavlakis, Jessica Chacon, Tori Yamamoto, Thomas Garrabrant, Luis Cortina, Daniel J. Powell, Marco Donia, Julie Westerlin Kjeldsen, Rikke Andersen, Marie Christine Wulff Westergaard, Valentina Bianchi, Mateusz Legut, Meriem Attaf, Garry Dolton, Barbara Szomolay, Sascha Ott, Rikke Lyngaa, Sine Reker Hadrup, Andrew Kelvin Sewell, Inge Marie Svane, Aaron Fan, Takumi Kumai, Esteban Celis, Ian Frank, Amanda Stramer, Michelle A. Blaskovich, Seth Wardell, Maria Fardis, James Bender, Michael T. Lotze, Stephanie L. Goff, Nikolaos Zacharakis, Yasmine Assadipour, Todd D. Prickett, Jared J. Gartner, Robert Somerville, Mary Black, Hui Xu, Harshini Chinnasamy, Isaac Kriley, Lily Lu, John Wunderlich, Paul F. Robbins, Steven Rosenberg, Steven A. Feldman, Kasia Trebska-McGowan, Parisa Malekzadeh, Eden Payabyab, Richard Sherry, Aishwarya Gokuldass, Charlene Kopits, Brian Rabinovich, Daniel S. Green, Olena Kamenyeva, Kathryn C. Zoon, Christina M. Annunziata, Joanne Hammill, Christopher Helsen, Craig Aarts, Jonathan Bramson, Yui Harada, Yoshikazu Yonemitsu, Kenneth Mwawasi, Galina Denisova, Rajanish Giri, Benjamin Jin, Tracy Campbell, Lindsey M. Draper, Sanja Stevanovic, Zhiya Yu, Bianca Weissbrich, Nicholas P. Restifo, Cornelia L. Trimble, Christian S. Hinrichs, Kwong Tsang, Massimo Fantini, James W. Hodge, Rika Fujii, Ingrid Fernando, Caroline Jochems, Christopher Heery, James Gulley, Patrick Soon-Shiong, Jeffrey Schlom, Weiqing Jing, Jill Gershan, Grace Blitzer, James Weber, Laura McOlash, Bryon D. Johnson, Simin Kiany, Huang Gangxiong, Eugenie S. Kleinerman, Michael Klichinsky, Marco Ruella, Olga Shestova, Saad Kenderian, Miriam Kim, John Scholler, Carl H. June, Saar Gill, Duane Moogk, Shi Zhong, Ivan Liadi, William Rittase, Victoria Fang, Janna Dougherty, Arianne Perez-Garcia, Iman Osman, Cheng Zhu, Navin Varadarajan, Alan Frey, Michelle Krogsgaard, Daniel Landi, Kristen Fousek, Malini Mukherjee, Ankita Shree, Sujith Joseph, Kevin Bielamowicz, Tiara Byrd, Nabil Ahmed, Meenakshi Hegde, Sylvia Lee, David Byrd, John Thompson, Shailender Bhatia, Scott Tykodi, Judy Delismon, Liz Chu, Siddiq Abdul-Alim, Arpy Ohanian, Anna Marie DeVito, Stanley Riddell, Kim Margolin, Isabelle Magalhaes, Jonas Mattsson, Michael Uhlin, Satoshi Nemoto, Patricio Pérez Villarroel, Ryosuke Nakagawa, James J. Mule, Adam W. Mailloux, Melinda Mata, Phuong Nguyen, Claudia Gerken, Christopher DeRenzo, Stephen Gottschalk, Mélissa Mathieu, Sandy Pelletier, John Stagg, Simon Turcotte, Nicholas Minutolo, Prannda Sharma, Andrew Tsourkas, Nadine Mockel-Tenbrinck, Daniela Mauer, Katharina Drechsel, Carola Barth, Katharina Freese, Ulrike Kolrep, Silke Schult, Mario Assenmacher, Andrew Kaiser, John Mullinax, MacLean Hall, Julie Le, Krithika Kodumudi, Erica Royster, Allison Richards, Ricardo Gonzalez, Amod Sarnaik, Shari Pilon-Thomas, Morten Nielsen, Anders Krarup-Hansen, Dorrit Hovgaard, Michael Mørk Petersen, Anand Chainsukh Loya, Niels Junker, Charlotte Rivas, Robin Parihar, Cliona M. Rooney, Haiying Qin, Sang Nguyen, Paul Su, Chad Burk, Brynn Duncan, Bong-Hyun Kim, M. Eric Kohler, Terry Fry, Arjun A. Rao, Noam Teyssier, Jacob Pfeil, Nikolaos Sgourakis, Sofie Salama, David Haussler, Sarah A. Richman, Selene Nunez-Cruz, Zack Gershenson, Zissimos Mourelatos, David Barrett, Stephan Grupp, Michael Milone, Alba Rodriguez-Garcia, Matthew K. Robinson, Gregory P. Adams, João Santos, Riikka Havunen, Mikko Siurala, Víctor Cervera-Carrascón, Suvi Parviainen, Marjukka Antilla, Akseli Hemminki, Jyothi Sethuraman, Laurelis Santiago, Jie Qing Chen, Zhimin Dai, Huizi Sha, Shu Su, Naiqing Ding, Baorui Liu, Anna Pasetto, Sarah R. Helman, Steven A. Rosenberg, Melissa Burgess, Hui Zhang, Tien Lee, Hans Klingemann, Paul Nghiem, John M. Kirkwood, John M. Rossi, Marika Sherman, Allen Xue, Yueh-wei Shen, Lynn Navale, James N. Kochenderfer, Adrian Bot, Anandaraman Veerapathran, Doris Wiener, Edmund K. Waller, Jian-Ming Li, Christopher Petersen, Bruce R. Blazar, Jingxia Li, Cynthia R. Giver, Ziming Wang, Steven K. Grossenbacher, Ian Sturgill, Robert J. Canter, William J. Murphy, Congcong Zhang, Michael C. Burger, Lukas Jennewein, Anja Waldmann, Michel Mittelbronn, Torsten Tonn, Joachim P. Steinbach, Winfried S. Wels, Jason B. Williams, Yuanyuan Zha, Thomas F. Gajewski, LaTerrica C. Williams, Giedre Krenciute, Mamta Kalra, Chrystal Louis, Gang Xin, David Schauder, Aimin Jiang, Nikhil Joshi, Weiguo Cui, Xue Zeng, Zeguo Zhao, Mohamad Hamieh, Justin Eyquem, Gertrude Gunset, Neil Bander, Michel Sadelain, David Askmyr, Milad Abolhalaj, Kristina Lundberg, Lennart Greiff, Malin Lindstedt, Helen K. Angell, Kyoung-Mee Kim, Seung-Tae Kim, Sung Kim, Alan D. Sharpe, Julia Ogden, Anna Davenport, Darren R. Hodgson, Carl Barrett, Jeeyun Lee, Elaine Kilgour, Jodi Hanson, Richard Caspell, Alexey Karulin, Paul Lehmann, Tameem Ansari, Annemarie Schiller, Srividya Sundararaman, Diana Roen, Mark Ayers, Diane Levitan, Gladys Arreaza, Fang Liu, Robin Mogg, Yung-Jue Bang, Bert O’Neil, Razvan Cristescu, Philip Friedlander, Karl Wassman, Chrisann Kyi, William Oh, Nina Bhardwaj, Svetlana Bornschlegl, Michael P. Gustafson, Dennis A. Gastineau, Ian F. Parney, Allan B. Dietz, Daniel Carvajal-Hausdorf, Nikita Mani, Kurt Schalper, David Rimm, Serena Chang, John Kurland, Christoph Matthias Ahlers, Maria Jure-Kunkel, Lewis Cohen, Holden Maecker, Holbrook Kohrt, Shuming Chen, George Crabill, Theresa Pritchard, Tracee McMiller, Drew Pardoll, Fan Pan, Suzanne Topalian, Patrick Danaher, Sarah Warren, Lucas Dennis, Andrew M. White, Leonard D’Amico, Melissa Geller, Mary L. Disis, Joseph Beechem, Kunle Odunsi, Steven Fling, Roshanak Derakhshandeh, Tonya J. Webb, Sigrid Dubois, Kevin Conlon, Bonita Bryant, Jennifer Hsu, Nancy Beltran, Jürgen Müller, Thomas Waldmann, Rebekka Duhen, Thomas Duhen, Lucas Thompson, Ryan Montler, Andrew Weinberg, Max Kates, Brandon Early, Erik Yusko, Taylor H. Schreiber, Trinity J. Bivalacqua, Jared Lunceford, Michael Nebozhyn, Erin Murphy, Andrey Loboda, David R. Kaufman, Andrew Albright, Jonathan Cheng, S. Peter Kang, Veena Shankaran, Sarina A. Piha-Paul, Jennifer Yearley, Tanguy Seiwert, Antoni Ribas, Terrill K. McClanahan, Xinwei Sher, Xiao Qiao Liu, Andrew Joe, Elizabeth Plimack, Alex Forrest-Hay, Cheryl A. Guyre, Kohei Narumiya, Marc Delcommenne, Heather A. Hirsch, Amit Deshpande, Jason Reeves, Jenny Shu, Tong Zi, Jennifer Michaelson, Debbie Law, Elizabeth Trehu, Sriram Sathyanaryanan, Brendan P. Hodkinson, Natalie A. Hutnick, Michael E. Schaffer, Michael Gormley, Tyler Hulett, Carmen Ballesteros-Merino, Christopher Dubay, Michael Afentoulis, Ashok Reddy, Larry David, Kumar Jayant, Swati Agrawal, Rajendra Agrawal, Ghayathri Jeyakumar, Seongho Kim, Heejin Kim, Cynthia Silski, Stacey Suisham, Elisabeth Heath, Ulka Vaishampayan, Natalie Vandeven, Natasja Nielsen Viller, Alison O’Connor, Hui Chen, Bolette Bossen, Eric Sievers, Robert Uger, Lisa Johnson, Hsiang-Fong Kao, Chin-Fu Hsiao, Shu-Chuan Lai, Chun-Wei Wang, Jenq-Yuh Ko, Pei-Jen Lou, Tsai-Jan Lee, Tsang-Wu Liu, Ruey-Long Hong, Staci J. Kearney, Joshua C. Black, Benjamin J. Landis, Sally Koegler, Brooke Hirsch, Roberto Gianani, Jeffrey Kim, Ming-Xiao He, Bingqing Zhang, Nan Su, Yuling Luo, Xiao-Jun Ma, Emily Park, Dae Won Kim, Domenico Copploa, Nishi Kothari, Young doo Chang, Richard Kim, Namyong Kim, Melvin Lye, Ee Wan, Hanna A. Knaus, Sofia Berglund, Hubert Hackl, Judith E. Karp, Ivana Gojo, Leo Luznik, Henoch S. Hong, Sven D. Koch, Birgit Scheel, Ulrike Gnad-Vogt, Karl-Josef Kallen, Volker Wiegand, Linus Backert, Oliver Kohlbacher, Ingmar Hoerr, Mariola Fotin-Mleczek, James M. Billingsley, Yoshinobu Koguchi, Valerie Conrad, William Miller, Iliana Gonzalez, Tomasz Poplonski, Tanisha Meeuwsen, Ana Howells-Ferreira, Rogan Rattray, Mary Campbell, Carlo Bifulco, Keith Bahjat, Brendan Curti, E-K Vetsika, G. Kallergi, Despoina Aggouraki, Z. Lyristi, P. Katsarlinos, Filippos Koinis, V. Georgoulias, Athanasios Kotsakis, Nathan T. Martin, Famke Aeffner, Logan Cerkovnik, Luke Pratte, Rebecca Kim, Joseph Krueger, Amaia Martínez-Usatorre, Camilla Jandus, Alena Donda, Laura Carretero-Iglesia, Daniel E. Speiser, Dietmar Zehn, Nathalie Rufer, Pedro Romero, Anshuman Panda, Janice Mehnert, Kim M. Hirshfield, Greg Riedlinger, Sherri Damare, Tracie Saunders, Levi Sokol, Mark Stein, Elizabeth Poplin, Lorna Rodriguez-Rodriguez, Ann Silk, Nancy Chan, Melissa Frankel, Michael Kane, Jyoti Malhotra, Joseph Aisner, Howard L. Kaufman, Siraj Ali, Jeffrey Ross, Eileen White, Gyan Bhanot, Shridar Ganesan, Anne Monette, Derek Bergeron, Amira Ben Amor, Liliane Meunier, Christine Caron, Antigoni Morou, Daniel Kaufmann, Moishe Liberman, Igor Jurisica, Anne-Marie Mes-Masson, Kamel Hamzaoui, Rejean Lapointe, Ann Mongan, Yuan-Chieh Ku, Warren Tom, Yongming Sun, Alex Pankov, Tim Looney, Janice Au-Young, Fiona Hyland, Jeff Conroy, Carl Morrison, Sean Glenn, Blake Burgher, He Ji, Mark Gardner, Angela R. Omilian, Wiam Bshara, Omilian Angela, Joseph M. Obeid, Gulsun Erdag, Mark E. Smolkin, Donna H. Deacon, James W. Patterson, Lieping Chen, Timothy N. Bullock, Craig L. Slingluff, John T. Loffredo, Raja Vuyyuru, Sophie Beyer, Vanessa M. Spires, Maxine Fox, Jon M. Ehrmann, Katrina A. Taylor, Alan J. Korman, Robert F. Graziano, David Page, Katherine Sanchez, Maritza Martel, Mariana Petaccia De Macedo, Yong Qin, Alex Reuben, Christine Spencer, Michele Guindani, Adriana Racolta, Brian Kelly, Tobin Jones, Nathan Polaske, Noah Theiss, Mark Robida, Jeffrey Meridew, Iva Habensus, Liping Zhang, Lidija Pestic-Dragovich, Lei Tang, Ryan J. Sullivan, Thomas Olencki, Thomas Hutson, Joanna Roder, Shauna Blackmon, Heinrich Roder, John Stewart, Asim Amin, Marc S. Ernstoff, Joseph I. Clark, Michael B. Atkins, Jeffrey Sosman, David F. McDermott, Harriet Kluger, Ruth Halaban, Mario Snzol, Senait Asmellash, Arni Steingrimsson, Chichung Wang, Kristin Roman, Amanda Clement, Sean Downing, Clifford Hoyt, Nathalie Harder, Guenter Schmidt, Ralf Schoenmeyer, Nicolas Brieu, Mehmet Yigitsoy, Gabriele Madonna, Gerardo Botti, Antonio Grimaldi, Paolo A. Ascierto, Ralf Huss, Maria Athelogou, Harald Hessel, Alexander Buchner, Christian Stief, Gerd Binnig, Thomas Kirchner, Shankar Sellappan, Sheeno Thyparambil, Sarit Schwartz, Fabiola Cecchi, Andrew Nguyen, Charles Vaske, Todd Hembrough, Jan Spacek, Michal Vocka, Eva Zavadova, Helena Skalova, Pavel Dundr, Lubos Petruzelka, Nicole Francis, Rau T. Tilman, Arndt Hartmann, Irena Netikova, Julia Stump, Amanda Tufman, Frank Berger, Michael Neuberger, Rudolf Hatz, Michael Lindner, Rachel E. Sanborn, John Handy, Rudolf M. Huber, Hauke Winter, Simone Reu, Cheng Sun, Weihua Xiao, Zhigang Tian, Kshitij Arora, Niyati Desai, Anupriya Kulkarni, Mihir Rajurkar, Miguel Rivera, Vikram Deshpande, David Ting, Katy Tsai, Adi Nosrati, Simone Goldinger, Omid Hamid, Alain Algazi, Paul Tumeh, Jimmy Hwang, Jacqueline Liu, Lawrence Chen, Reinhard Dummer, Michael Rosenblum, Adil Daud, Tsu-Shuen Tsao, Julia Ashworth-Sharpe, Donald Johnson, Srabani Bhaumik, Christopher Bieniarz, Joseph Couto, Michael Farrell, Mahsa Ghaffari, Antony Hubbard, Jerome Kosmeder, Cleo Lee, Erin Marner, Diana Uribe, Hongjun Zhang, Jian Zhang, Wenjun Zhang, Yifei Zhu, Larry Morrison, Takahiro Tsujikawa, Rohan N. Borkar, Vahid Azimi, Sushil Kumar, Guillaume Thibault, Motomi Mori, Edward El Rassi, Daniel R. Clayburgh, Molly F. Kulesz-Martin, Paul W. Flint, Lisa M. Coussens, Lisa Villabona, Giuseppe V. Masucci, Gary Geiss, Brian Birditt, Qian Mei, Alan Huang, Maribeth A. Eagan, Eduardo Ignacio, Nathan Elliott, Dwayne Dunaway, Jaemyeong Jung, Chris Merritt, Isaac Sprague, Philippa Webster, Yan Liang, Jessica Wenthe, Gunilla Enblad, Hannah Karlsson, Magnus Essand, Barbara Savoldo, Gianpietro Dotti, Martin Höglund, Malcolm K. Brenner, Hans Hagberg, Angelica Loskog, Matthew J. Bernett, Gregory L. Moore, Michael Hedvat, Christine Bonzon, Seung Chu, Rumana Rashid, Kendra N. Avery, Umesh Muchhal, John Desjarlais, Matthew Kraman, Katarzyna Kmiecik, Natalie Allen, Mustapha Faroudi, Carlo Zimarino, Mateusz Wydro, Jacqueline Doody, Sreesha P. Srinivasa, Nagaraja Govindappa, Praveen Reddy, Aparajita Dubey, Sankar Periyasamy, Madhukara Adekandi, Chaitali Dey, Mary Joy, Pieter Fokko van Loo, Henrike Veninga, Setareh Shamsili, Mark Throsby, Harry Dolstra, Lex Bakker, Ajjai Alva, Juergen Gschwendt, Yohann Loriot, Joaquim Bellmunt, Dai Feng, Christian Poehlein, Thomas Powles, Emmanuel S. Antonarakis, Charles G. Drake, Haiyan Wu, Johann De Bono, Rajat Bannerji, John Byrd, Gareth Gregory, Stephen Opat, Jake Shortt, Andrew J. Yee, Noopur Raje, Seth Thompson, Arun Balakumaran, Shaji Kumar, Brian I. Rini, Toni K. Choueiri, Mariangela Mariani, Laurence Albiges, John B. Haanen, James Larkin, Manuela Schmidinger, Domenico Magazzù, Alessandra di Pietro, Robert J. Motzer, Troels Holz Borch, Per Kongsted, Magnus Pedersen, Özcan Met, Karim Boudadi, Hao Wang, James Vasselli, Jan E. Baughman, Jon Wigginton, Rehab Abdallah, Ashley Ross, Jiwon Park, Steven Grossenbacher, Jesus I. Luna, Sita Withers, William Culp, Mingyi Chen, Arta Monjazeb, Michael S. Kent, Smita Chandran, David Danforth, James Yang, Christopher Klebanoff, Stephanie Goff, Biman Paria, Arvind Sabesan, Abhishek Srivastava, Udai Kammula, Jon Richards, Mark Faries, Robert H. I. Andtbacka, Luis A. Diaz, Dung T. Le, Takayuki Yoshino, Thierry André, Johanna Bendell, Minori Koshiji, Yayan Zhang, S Peter Kang, Bao Lam, Dirk Jäger, Todd M. Bauer, Judy S. Wang, Jean K. Lee, Gulam A. Manji, Ragini Kudchadkar, John S. Kauh, Shande Tang, Naomi Laing, Gerald Falchook, Edward B. Garon, Balazs Halmos, Hui Rina, Natasha Leighl, Sung Sook Lee, William Walsh, Konstanin Dragnev, Bilal Piperdi, Luis Paz-Ares Rodriguez, Nabeegha Shinwari, Ziewn Wei, Mary L Maas, Michael Deeds, Adam Armstrong, Tim Peterson, Sue Steinmetz, Thomas Herzog, Floor J. Backes, Larry Copeland, Maria Del Pilar Estevez Diz, Thomas W. Hare, Warner Huh, Byoung-Gie Kim, Kathleen M. Moore, Ana Oaknin, William Small, Krishnansu S. Tewari, Bradley J. Monk, Ashish M. Kamat, Kijoeng Nam, Maria De Santis, Robert Dreicer, Noah M. Hahn, Rodolfo Perini, Arlene Siefker-Radtke, Guru Sonpavde, Ronald de Wit, J. Alfred Witjes, Stephen Keefe, Dean Bajorin, Philippe Armand, John Kuruvilla, Craig Moskowitz, Mehdi Hamadani, Pier Luigi Zinzani, Sabine Chlosta, Nancy Bartlett, Rachel Sabado, Yvonne Saenger, Loging William, Michael Joseph Donovan, Erlinda Sacris, John Mandeli, Andres M. Salazar, John Powderly, Joshua Brody, John Nemunaitis, Leisha Emens, Amita Patnaik, Ian McCaffery, Richard Miller, Ginna Laport, Andrew L. Coveler, David C. Smith, Juneko E. Grilley-Olson, Sanjay Goel, Shyra J. Gardai, Che-Leung Law, Gary Means, Thomas Manley, Kristen A. Marrone, Gary Rosner, Valsamo Anagnostou, Joanne Riemer, Jessica Wakefield, Cynthia Zanhow, Stephen Baylin, Barbara Gitlitz, Julie Brahmer, Sabina Signoretti, Wenting Li, Charles Schloss, Jean-Marie Michot, Wei Ding, Beth Christian, Patricia Marinello, Margaret Shipp, Yana G. Najjar, null Lin, Lisa H. Butterfield, Ahmad A. Tarhini, Diwakar Davar, Hassane Zarour, Elizabeth Rush, Cindy Sander, Siqing Fu, Todd Bauer, Chris Molineaux, Mark K. Bennett, Keith W. Orford, Kyriakos P. Papadopoulos, Sukhmani K. Padda, Sumit A. Shah, A Dimitrios Colevas, Sujata Narayanan, George A. Fisher, Dana Supan, Heather A. Wakelee, Rhonda Aoki, Mark D. Pegram, Victor M. Villalobos, Jie Liu, Chris H. Takimoto, Mark Chao, Jens-Peter Volkmer, Ravindra Majeti, Irving L. Weissman, Branimir I. Sikic, Wendy Yu, Alison Conlin, Janet Ruzich, Stacy Lewis, Anupama Acheson, Kathleen Kemmer, Kelly Perlewitz, Nicole M. Moxon, Staci Mellinger, Heather McArthur, Trine Juhler-Nøttrup, Jayesh Desai, Ben Markman, Shahneen Sandhu, Hui Gan, Michael L. Friedlander, Ben Tran, Tarek Meniawy, Joanne Lundy, Duncan Colyer, Malaka Ameratunga, Christie Norris, Jason Yang, Kang Li, Lai Wang, Lusong Luo, Zhen Qin, Song Mu, Xuemei Tan, James Song, Michael Millward, Matthew H. G. Katz, Todd W. Bauer, Gauri R. Varadhachary, Nicolas Acquavella, Nipun Merchant, Gina Petroni, Osama E. Rahma, Mei Chen, Yang Song, Markus Puhlmann, Arun Khattri, Ryan Brisson, Christopher Harvey, Jatin Shah, Maria Victoria Mateos, Morio Matsumoto, Hilary Blacklock, Albert Oriol Rocafiguera, Hartmut Goldschmidt, Shinsuke Iida, Dina Ben Yehuda, Enrique Ocio, Paula Rodríguez-Otero, Sundar Jagannath, Sagar Lonial, Uma Kher, Jesus San-Miguel, Moacyr Ribeiro de Oliveira, Habte Yimer, Robert Rifkin, Fredrik Schjesvold, Razi Ghori, Anna Spreafico, Victor Lee, Roger K. C. Ngan, Ka Fai To, Myung Ju Ahn, Quan Sing Ng, Jin-Ching Lin, Ramona F. Swaby, Christine Gause, Sanatan Saraf, Anthony T. C. Chan, Elaine Lam, Nizar M. Tannir, Funda Meric-Bernstam, Matt Gross, Andy MacKinnon, Sam Whiting, Martin Voss, Evan Y. Yu, Mark R. Albertini, Erik A. Ranheim, Jacquelyn A. Hank, Cindy Zuleger, Thomas McFarland, Jennifer Collins, Erin Clements, Sharon Weber, Tracey Weigel, Heather Neuman, Greg Hartig, David Mahvi, MaryBeth Henry, Jacek Gan, Richard Yang, Lakeesha Carmichael, KyungMann Kim, Stephen D. Gillies, Paul M. Sondel, Vivek Subbiah, Lori Noffsinger, Kyle Hendricks, Marnix Bosch, Jay M. Lee, Mi-Heon Lee, Jonathan W. Goldman, Felicita E. Baratelli, Dorthe Schaue, Gerald Wang, Frances Rosen, Jane Yanagawa, Tonya C. Walser, Ying Q. Lin, Sharon Adams, Franco M. Marincola, Paul C. Tumeh, Fereidoun Abtin, Robert Suh, Karen Reckamp, William D. Wallace, Gang Zeng, David A. Elashoff, Sherven Sharma, Steven M. Dubinett, Anna C. Pavlick, Brian Gastman, Brent Hanks, Tibor Keler, Tom Davis, Laura A. Vitale, Elad Sharon, Chihiro Morishima, Martin Cheever, Christopher R. Heery, Joseph W. Kim, Elizabeth Lamping, Jennifer Marte, Sheri McMahon, Lisa Cordes, Farhad Fakhrejahani, Ravi Madan, Rachel Salazar, Maggie Zhang, Christoph Helwig, James L Gulley, Roger Li, John Amrhein, Zvi Cohen, Monique Champagne, Ashish Kamat, M. Angela Aznar, Sara Labiano, Angel Diaz-Lagares, Manel Esteller, Juan Sandoval, Susannah D. Barbee, David I. Bellovin, John C. Timmer, Nebiyu Wondyfraw, Susan Johnson, Johanna Park, Amanda Chen, Mikayel Mkrtichyan, Amir S. Razai, Kyle S. Jones, Chelsie Y. Hata, Denise Gonzalez, Quinn Deveraux, Brendan P. Eckelman, Luis Borges, Rukmini Bhardwaj, Raj K. Puri, Akiko Suzuki, Pamela Leland, Bharat H. Joshi, Todd Bartkowiak, Ashvin Jaiswal, Casey Ager, Midan Ai, Pratha Budhani, Renee Chin, David Hong, Michael Curran, William D. Hastings, Maria Pinzon-Ortiz, Masato Murakami, Jason R. Dobson, David Quinn, Joel P. Wagner, Xianhui Rong, Pamela Shaw, Ernesta Dammassa, Wei Guan, Glenn Dranoff, Alexander Cao, Ross B. Fulton, Steven Leonardo, Kathryn Fraser, Takashi O. Kangas, Nadine Ottoson, Nandita Bose, Richard D. Huhn, Jeremy Graff, Jamie Lowe, Keith Gorden, Mark Uhlik, Thomas O’Neill, Jenifer Widger, Andrea Crocker, Li-Zhen He, Jeffrey Weidlick, Karuna Sundarapandiyan, Venky Ramakrishna, James Storey, Lawrence J. Thomas, Joel Goldstein, Henry C. Marsh, Jamison Grailer, Julia Gilden, Pete Stecha, Denise Garvin, Jim Hartnett, Frank Fan, Mei Cong, Zhi-jie Jey Cheng, Marlon J. Hinner, Rachida-Siham Bel Aiba, Corinna Schlosser, Thomas Jaquin, Andrea Allersdorfer, Sven Berger, Alexander Wiedenmann, Gabriele Matschiner, Julia Schüler, Ulrich Moebius, Christine Rothe, Olwill A. Shane, Brendan Horton, Stefani Spranger, Dayson Moreira, Tomasz Adamus, Xingli Zhao, Piotr Swiderski, Sumanta Pal, Marcin Kortylewski, Alyssa Kosmides, Kevin Necochea, Kathleen M. Mahoney, Sachet A. Shukla, Nikolaos Patsoukis, Apoorvi Chaudhri, Hung Pham, Ping Hua, Xia Bu, Baogong Zhu, Nir Hacohen, Catherine J. Wu, Edward Fritsch, Vassiliki A. Boussiotis, Gordon J. Freeman, Amy E. Moran, Fanny Polesso, Lisa Lukaesko, Emelie Rådestad, Lars Egevad, Berit Sundberg, Lars Henningsohn, Victor Levitsky, William Rafelson, John L. Reagan, Loren Fast, Pottayil Sasikumar, Naremaddepalli Sudarshan, Raghuveer Ramachandra, Nagesh Gowda, Dodheri Samiulla, Talapaneni Chandrasekhar, Sreenivas Adurthi, Jiju Mani, Rashmi Nair, Amit Dhudashia, Nagaraj Gowda, Murali Ramachandra, Alexander Sankin, Benjamin Gartrell, Kerwin Cumberbatch, Hongying Huang, Joshua Stern, Mark Schoenberg, Xingxing Zang, Ryan Swanson, Michael Kornacker, Lawrence Evans, Erika Rickel, Martin Wolfson, Sandrine Valsesia-Wittmann, Tala Shekarian, François Simard, Rodrigo Nailo, Aurélie Dutour, Anne-Catherine Jallas, Christophe Caux, and Aurélien Marabelle

Subjects
Pharmacology, 0303 health sciences, Cancer Research, Side effect, business.industry, medicine.drug_class, Immunology, Phases of clinical research, Monoclonal antibody, Phase i study, Clinical trial, 03 medical and health sciences, 0302 clinical medicine, Oncology, Pharmacokinetics, 030220 oncology & carcinogenesis, Molecular Medicine, Immunology and Allergy, Medicine, In patient, Programmed death 1, business, 030304 developmental biology
Published
2016

48. Biliary cancer: Utility of next-generation sequencing for clinical management

Author

Milind, Javle, Tanios, Bekaii-Saab, Apurva, Jain, Ying, Wang, Robin Katie, Kelley, Kai, Wang, Hyunseon C, Kang, Daniel, Catenacci, Siraj, Ali, Sunil, Krishnan, Daniel, Ahn, Andrea Grace, Bocobo, Mingxin, Zuo, Ahmed, Kaseb, Vincent, Miller, Philip J, Stephens, Funda, Meric-Bernstam, Rachna, Shroff, and Jeffrey, Ross

Subjects
Cholangiocarcinoma, Male, Bile Duct Neoplasms, Mutation, High-Throughput Nucleotide Sequencing, Humans, Female, Gallbladder Neoplasms, Molecular Targeted Therapy, Middle Aged, Cyclin-Dependent Kinases, Neoplasm Proteins, Signal Transduction
Abstract

Biliary tract cancers (BTCs) typically present at an advanced stage, and systemic chemotherapy is often of limited benefit.Hybrid capture-based comprehensive genomic profiling (CGP) was performed for 412 intrahepatic cholangiocarcinomas (IHCCAs), 57 extrahepatic cholangiocarcinomas (EHCCAs), and 85 gallbladder carcinomas (GBCAs). The mutational profile was correlated with the clinical outcome of standard and experimental therapies for 321 patients. Clinical variables, detected mutations, and administered therapies were correlated with overall survival (OS) in a Cox regression model.The most frequent genetic aberrations (GAs) observed were tumor protein 53 (TP53; 27%), cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B; 27%), KRAS (22%), AT-rich interactive domain-containing protein 1A (ARID1A; 18%), and isocitrate dehydrogenase 1 (IDH1; 16%) in IHCCA; KRAS (42%), TP53 (40%), CDKN2A/B (17%), and SMAD4 (21%) in EHCCA; and TP53 (59%), CDKN2A/B (19%), ARID1A (13%), and ERBB2 (16%) in GBCA. Fibroblast growth factor receptor (FGFR; 11%) and IDH mutations (20%) were mostly limited to IHCCA but appeared to be mutually exclusive. In the IHCCA group, TP53 and KRAS mutations were associated significantly with poor OS, whereas FGFR2 mutations were associated with improved OS (P = .001), a younger age at onset, and female sex. IDH1/2 mutations were not prognostic. In a multivariate model, the effects of TP53 and FGFR GAs remained significant (P .05). Patients with FGFR GAs had superior OS with FGFR-targeted therapy versus standard regimens (P = .006). Targeted therapy in IHCCA was associated with a numerical OS improvement (P = .07).This is the largest clinically annotated data set of BTC cases with CGP and indicates the potential of CGP for improving outcomes. CGP should be strongly considered in the management of BTC patients. Cancer 2016;122:3838-3847. © 2016 American Cancer Society.

Published
2016

49. MA04.01 Non-Amplification Mutation of ERBB2 in EGFR-Mutated Lung Cancer

Author

Kyle Gowen, Balazs Halmos, Robert Hoyer, Woondong Jeong, James Suh, Julia Elvin, Jo-Anne Vergilio, Shakti Ramkissoon, Siraj Ali, Alexa Schrock, James Sun, Vincent Miller, Philip Stephens, Jeffrey Ross, and Laurie Gay

Subjects
Pulmonary and Respiratory Medicine, Oncology, business.industry, Mutation (genetic algorithm), medicine, Cancer research, Cancer, Lung cancer, medicine.disease, business
Published
2017

50. Effect of Mixing Date Palm Leaves Compost (DPLC) With Vermiculite, Perlite, Sand and Clay on Vegetative Growth of Dahlia (Dahlia pinnata), Marigold (Tagetes erecta), Zinnia (Zinnia elegans) and Cosmos (Cosmos bipinnatus) Plants

Author

Yusef Saleh Siraj Ali

Subjects
Dahlia, biology, ved/biology, ved/biology.organism_classification_rank.species, Zinnia elegans, General Medicine, Cosmos bipinnatus, biology.organism_classification, Dahlia pinnata, Zinnia, Tagetes, Cosmos (plant), Botany, Perlite
Published
2011

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