Katherine Van Research Articles

Abstract 6: Applying Next-Generation Sequencing to Improve Pediatric Cancer Diagnosis in Mexico

Abstract Purpose: In Mexico, cancer is the second leading cause of mortality among children between 4 to 15 years old. The overall cure rates remain below 50%, compared to >90% in the United States. This discrepancy is in part explained by the limited access to methods for accurate diagnosis and identification of appropriate therapies in Mexico. Only 48% of large hospitals across Mexico report having the capacity to perform some of the complex testing necessary for subclassification of pediatric cancers. Pan-cancer next generation sequencing (NGS) panels are not available in Mexico. We developed a strategy to perform clinical NGS in pediatric cancer patients in Mexico for identification of single nucleotide variants, copy number changes, and fusion events that are useful for risk stratification and adjusted therapy. Methods: We established collaborative agreements between UCSF and the National Institute for Genomic Medicine (INMEGEN) in Mexico City. We developed a pediatric cancer focused panel (IMOP) encompassing 200 genes and created a cloud-based bioinformatic and analysis pipeline for remote data interpretation. We established concordance by comparing the sequencing results of clinical cases obtained with the validated UCSF500 panel and the IMOP panel. Results: The results of 8 clinical samples previously sequenced using the clinically validated UCSF500 panel were compared to results obtained using the IMOP panel. Clinically relevant SNVs and fusions were successfully detected by the IMOP panel at similar variant allelic frequencies. The IMOP panel was shipped to INMEGEN where two samples with prior sequencing results were successfully sequenced. Re-sequencing of the 8 clinical samples to establish concordance at INMEGEN is pending. Conclusion: Our ongoing pilot proof-of-concept study shows feasibility of a strategy to implement clinical NGS testing in a middle-income country. We hypothesize that implementation of centralized NGS for pediatric cancers at INMEGEN will improve diagnostic accuracy. Moving forward, we plan to complete the clinical validation of the IMOP panel for routine sequencing of pediatric cancer patients. We will use the RE-AIM implementation science framework to assess the effectiveness of the assay in refining clinical diagnosis and treatment planning for pediatric cancer cases in Mexico. Citation Format: Roberto Ruiz-Cordero, Ela Alcantara, Ana Quintanar-Alfaro, Carlos A Espinoza-Mendez, Katherine Van Loon, Lindsay Breithaupt, Jorge Melendez Zajgla, Alejandro Sweet-Cordero. Applying Next-Generation Sequencing to Improve Pediatric Cancer Diagnosis in Mexico [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 6.

Invited Commentary: Role of the Radiologist in Pregnancy-associated Cancer.

Invited Commentary: Role of the Radiologist in Pregnancy-associated Cancer.

Abstract 42: Patient-Provider Communication in the Setting of Advanced Cancer: Experience and Views from Rwanda

Abstract Purpose: Caring for patients with advanced cancer involves complex patient-provider communication (PPC), including disclosure of diagnosis, discussion of prognosis, decision-making about treatment, delivery of bad news, and transitions in goals of care. Values and norms that influence PPC differ across diverse cultural and socioeconomic contexts. We aimed to characterize PPC experiences and preferences among patients and providers at Butaro Hospital in Rwanda, understand facilitators and barriers to high quality PPC, and collect suggestions for improvement. Methods: We conducted semi-structured interviews with a purposive sample of 11 oncology providers and 11 adult patients with advanced cancer. Interviews were recorded, transcribed, translated to English, coded using software, and analyzed using framework thematic analysis. Results: Participants reported both strengths and opportunities for improvement in PPC at Butaro. Strengths include routine explanation of diagnosis, treatment plan, and potential side effects, aided by a consent form and a dedicated counselor. Patients reported that PPC focuses on symptoms and treatment plan discussion, but is limited in truth telling about prognosis, especially when goals of care transition from curative to palliative. Facilitators to quality PPC include multidisciplinary team commitment, patient trust toward providers, provider communication style, and strong resilience in distressing clinical situations. While patients perceived power imbalance between patients and providers as the main barrier to PPC, providers cited inadequate time due to work overload, discomfort facing sad situations, and unfavorable physical environment as main barriers. Suggestions to improve PPC include training providers in communication skills, patient and family education and empowerment, more time and private spaces, and standardizing approaches to harmonize PPC. Conclusion: PPC at Butaro works well though there is room for improvement. Understanding how cultural norms and values regarding poor prognoses influence patient and provider communication preferences can inform strategies to improve PPC and ensure patient-centered care in Rwanda and similar settings. Citation Format: Pacifique Uwamahoro, Hubert Tuyishime, Vincent Cubaka, Egide Mpanumusingo, Anita Ho, Katherine Van Loon, Rebecca J. DeBoer. Patient-Provider Communication in the Setting of Advanced Cancer: Experience and Views from Rwanda [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 42.

Abstract 57: Experiences and Beliefs Regarding Shared Decision-Making About Treatment of Incurable Cancer in Tanzania

Abstract Purpose: Treatment decision-making in the setting of advanced cancer is often complex and culturally embedded. Potential benefits of treatment must be weighed against toxicities, economic burden, and social consequences. The standard of shared decision-making (SDM) between doctor and patient, rooted in the Western principle of patient autonomy, may not be readily transferable to other cultural and socioeconomic contexts, where different values and considerations may take precedence. This study aims to characterize the decision-making experiences and beliefs of stakeholders at Ocean Road Cancer Institute (ORCI) in Tanzania in order to inform communication guidelines and improvement strategies. Methods: We conducted semi-structured interviews with a purposive sample of oncologists and nurses (n=13) and patients with advanced cancer (n=11) at ORCI. A diagram depicting paternalistic, informed, and shared approaches to decision-making was referenced during interviews. Interviews were recorded, transcribed verbatim, translated to English, coded using MAXQDA software, and analyzed using framework thematic analysis. Results: Patients and providers reported heterogeneous decision-making experiences and preferences, with a trend toward greater patient engagement in recent years. Providers believed SDM is especially important when treatment goals are palliative and when out-of-pocket costs are significant, but favored paternalistic decision-making in the context of curative treatment and lower patient health literacy. Patients generally placed greater importance on providers' communication style and the quality of clinical care than engagement in SDM. Several participants perceived SDM to increase patient adherence to treatment. Barriers and facilitators of SDM were identified at the patient, provider, and healthcare system levels. Community misperceptions about cancer treatment was commonly cited as a barrier. Practical suggestions included communication skills training for providers, implementation of a clinical tool for decision-making, and increased patient and public education about cancer treatment. Conclusion: Understanding the nuanced views regarding SDM is important for development of culturally informed communication guidelines, tools, and training. Citation Format: Megan Casey, Raymond Athanas, Nazima Dharsee, Anna Jazza, Kalunde Julius, Francis Semwaza, Beatrice Mushi, Emilie Kadhim, Katherine Van Loon, Anita Ho, Rebecca Deboer. Experiences and Beliefs Regarding Shared Decision-Making About Treatment of Incurable Cancer in Tanzania [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 57.

Abstract A18: Feasibility and acceptability of the Survivor Choices for Eating and Drinking (SUCCEED) digital health dietary intervention after colorectal cancer (CRC): A randomized pilot trial

Abstract Background: Dietary factors after CRC are associated with risk of recurrence and death. Our objective was to develop a digital health intervention to help individuals with CRC adopt healthy dietary habits. Methods: We conducted an unblinded 12-week (wk) pilot randomized trial to determine the feasibility and acceptability of a web-based dietary intervention with text messaging among individuals with CRC at the University of California, San Francisco. Eligible patients (pts) had colon or rectal adenocarcinoma, were not receiving chemotherapy, were disease-free or had stable disease, were able to speak and read English, and had a mobile phone. We excluded pts meeting ≥4 of the 6 target dietary behaviors. Pts were randomized 1:1 to intervention or control. All pts received print materials on diet after CRC. Pts in the intervention group received 12 wks of access to a website and daily text messaging that recommended ≥5 servings (serv)/day (d) of vegetables, ≥3 serv/d of whole grains, ≥2 serv/wk of fish, ≤2 alcoholic drinks/d for men and ≤1 alcoholic drinks/d for women, and no processed meat or sugar-sweetened beverages. Pts were encouraged to use the website to track intake of target dietary factors. Primary outcomes included feasibility (enrollment, time spent on website, text message response rate) and acceptability (self-administered online questionnaire). Secondarily, we estimated the effect of the intervention on diet using 4-d diet records, body size, blood pressure, and fasting C-reactive protein, hemoglobin A1c, glucose, cholesterol, and triglycerides using linear regression. Results: We screened 94 pts for eligibility; 75 were eligible and we randomized 50 to intervention (25) or control (25) between April 2017-May 2018. Over the course of the 12-wk study, the intervention arm accessed the website on a median of 2 d [interquartile range (IQR): 1-9 d] and spent a median of 28 min on the site (IQR: 4-51 min). Pts responded to a median of 15/21 text messages that asked for a reply (IQR: 8-20). 22/25 intervention pts completed the feedback survey; 82% were satisfied or very satisfied with the text messages. When asked to rate the quality of the website on a scale from 0-100, the median rating was 72 (IQR: 55-83). Diet records were available at baseline and 12 wks for 23 control and 22 intervention pts. Comparing baseline and 12 wks, intervention pts increased intake of whole grains (0.7 serv/d to 1.6 serv/d) and fatty fish (0 serv/d to 0.4 serv/d); controls did not change intake of whole grains (0.7 and 0.6 serv/d) or fatty fish (0.1 and 0 serv/d). We did not observe changes in either arm for other dietary factors, body size, blood pressure, or circulating markers. Conclusion: Individuals with CRC participating in a digital health dietary intervention engaged with text messaging more than a study website. The intervention led to changes in certain dietary behaviors. Additional work is needed to find strategies to increase engagement and modify other dietary factors. Trial Registration: NCT02965521 Funding: 5K07CA197077. Citation Format: Erin L. Van Blarigan, Stacey A. Kenfield, June M. Chan, Alan Paciorek, Li Zhang, Hilary Chan, Marissa Savoie, Andrea Grace Bocobo, Louis X. Wong, Angela Laffan, Katherine Van Loon, Chloe Atreya, Anthony Riberi, Olivier Riberi, Christine Miaskowski, Yoshimi Fukuoka, Jeffrey A. Meyerhardt, Alan P. Venook. Feasibility and acceptability of the Survivor Choices for Eating and Drinking (SUCCEED) digital health dietary intervention after colorectal cancer (CRC): A randomized pilot trial [abstract]. In: Proceedings of the AACR Special Conference on Modernizing Population Sciences in the Digital Age; 2019 Feb 19-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(9 Suppl):Abstract nr A18.

Abstract D111: Incidence and survival patterns of gastroenteropancreatic neuroendocrine neoplasms in California

Abstract Background. Neuroendocrine neoplasms (NEN) are a heterogeneous group of rare tumors. There is a paucity of epidemiologic data regarding risk factors. We aimed to characterize the burden of NEN in California with its diverse racial/ethnic populations. Methods Using California Cancer Registry, we identified all newly diagnosed NEN from gastroenteropancreatic (GEP) sites 1992-2015. Annual age-adjusted incidence rates (AIR) per 100,000 person-years were compared, and average annual percent change (APC) in rates were compared according to sex, race-ethnicity (non-Hispanic (NH) white, NH black, Asian/Pacific Islander, American Indian, Hispanic), primary tumor site (stomach, small intestine, colon or rectum, appendix, pancreas), stage, and type of county of residence (urban, suburban, rural) using incidence rate ratios (IRR). Overall survival from diagnosis to death by any cause was estimated by Kaplan-Meier method and compared using log-rank tests. Results There were 23,983 GEP NEN incident cases and 9,910 deaths 1992-2015. All AIRs increased over the 24 years, with the greatest increase in Hispanics with pancreatic NEN (APC 8.9). Rates for the period 2011-2015 varied according to primary tumor site: colorectal (AIR 1.41); small intestinal (AIR 0.97); pancreatic (AIR 0.92); stomach (AIR 0.44); and appendiceal (AIR 0.36). Comparing rates by populations the greatest disparities were for NH blacks vs. Asians with small intestinal NEN (IRR 7.01 95% confidence interval (CI) [5.37-9.21]) or appendiceal NEN (IRR 3.74 95% CI [2.34-6.08]), for NH whites vs. Asians with small intestinal NEN (IRR 4.34 95% CI [3.44-5.53]) or appendiceal NEN (IRR 5.10 95% CI [3.54-7.59]), for NH blacks vs. NH whites with colorectal NEN (IRR 2.59 95% CI [2.27-2.94]), and for NH whites vs. Hispanics with appendiceal NEN (IRR 2.54 95% CI [2.08-3.12]). Statistically significantly longer survival estimates were observed in women (median 13.1 years) vs. men (11.6 years), and in Asians/Pacific Islanders (20.7 years) and Hispanics (16.7 years) vs. NH blacks (12.3 years) and NH whites (9.6 years). No significant survival differences were detected across county types. Survival estimates were significantly different across primary tumor sites: colorectal (median 19.9 years); appendiceal (16.0 years); small intestinal (10.1 years); stomach (9.7 years); and pancreatic (4.4 years). Conclusions Incidence rates of GEP NEN in California steadily increase from 1992 through 2015 for all populations. Recent AIRs for particular race-ethnicities and primary tumor sites are more than double others, exposing large disparities. Survival estimates differ significantly by primary tumor site, sex, race-ethnicity, and stage, but not by county. These findings show some higher incidence rates and longer survival than in previously published estimates nationwide and add information about GEP NEN in Hispanic and Asian/Pacific Islander populations in California. Additional research is needed to clarify reasons for the disparities. Citation Format: Alan Paciorek, Brandon Shih, Meg McKinley, Iona Cheng, Li Zhang, Claire Mulvey, Ann Griffin, Eric Nakakura, Quan-Yang Duh, Insoo Suh, Katherine Van Loon, Emily Bergsland. Incidence and survival patterns of gastroenteropancreatic neuroendocrine neoplasms in California [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D111.

Abstract A108: Differences in incidence by sex and race/ethnicity of adrenocortical carcinomas and malignant pheochromocytomas and paragangliomas in California

Abstract Background: Malignant pheochromocytomas (PHEO), paragangliomas (PGL), and adrenocortical carcinomas (ACC) are rare endocrine malignancies with limited data regarding risk factors. To further elucidate their epidemiology, we sought to characterize the burden of malignant PHEO, PGL, and ACC in California. Methods: Using the population-based California Cancer Registry, we identified all new diagnoses of malignant PHEO, PGL, and ACC in California from 1992-2016 (ICD-O-3 codes 8700/3, 8680/3, and 8393/3). We calculated age-adjusted incidence rates (AIR) standardized to the 2000 United States census. We compared AIRs by sex, race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, and Asian/Pacific Islander), and county of residence (categorized as urban versus suburban/rural) using SEER*Stat and generated IR ratios (IRR). Results: Between 1992-2016, there were 261 incident cases of malignant PHEO, 271 of malignant PGL, and 866 of ACC in California. Overall AIR per 100,000 person-years were 0.03 for PHEO, 0.03 for PGL, and 0.10 for ACC. Incidence differed by both sex and race/ethnicity. Men had a higher incidence of PGL than women (IRR 1.49, 95% confidence interval [CI] 1.13-1.98; p<0.05) and tended towards higher incidence of PHEO (IRR 1.24, 95% CI 0.97-1.60; p=0.09), while men had a lower incidence of ACC than women (IRR 0.80, 95% CI 0.69-0.92; p<0.05). Compared with non-Hispanic White Californians, non-Hispanic Black Californians had higher PHEO incidence (IRR 1.65, 95% CI 1.05-2.51; p<0.05), whereas PGL incidence was lower for Hispanic (IRR 0.60, 95% CI 0.41-0.87; p<0.05) and Asian/Pacific Islander Californians (IRR 0.60, 95% CI 0.35-0.97; p<0.05). Compared with non-Hispanic White Californians, ACC incidence was lower in non-Hispanic Black (IRR 0.58, 95% CI 0.40-0.82; p<0.05), Hispanic (IRR 0.65, 95% CI 0.54-0.78; p<0.05), and Asian/Pacific Islander Californians (IRR 0.60, 95% CI 0.46-0.76; p<0.05). There were no differences in IRRs according to county of residence for either PHEO, PGL, or ACC. Conclusions: Malignant PHEO, PGL, and ACC remain rare cancers in California, with disease-specific differences in IRR’s by sex and race/ethnicity but not by urban versus suburban/rural county of residence. We report novel findings of a higher incidence of malignant PHEO in non-Hispanic Black Californians and a lower incidence of malignant PGL in Hispanic and Asian/Pacific Islander Californians. We also confirm higher incidence of ACC in women and non-Hispanic White Californians. Additional research is needed to clarify whether these differences reflect disparities in access to care. Citation Format: Claire K. Mulvey, Alan Paciorek, Brandon Shih, Meg McKinley, Dawn Pearson, Iona Cheng, Li Zhang, Ann Griffin, Quan-Yang Duh, Sanziana Roman, Julie Ann Sosa, Insoo Suh, Chienying Liu, Katherine Van Loon, Emily Bergsland. Differences in incidence by sex and race/ethnicity of adrenocortical carcinomas and malignant pheochromocytomas and paragangliomas in California [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A108.

Abstract B06: Investigating the microbial etiology of Tanzanian esophageal squamous cell carcinoma

Abstract Background: Esophageal cancer is a leading cause of cancer-associated deaths worldwide. Notably, there is a disproportionately high incidence of esophageal squamous cell carcinoma (ESCC) throughout the eastern corridor of Africa. One possible explanation for the unique geographic distribution of ESCC may be the human microbiome, which has been shown to influence other gastrointestinal (GI) cancers, including gastric and colorectal cancer (CRC). Methods: To address this question, we conducted RNA sequencing (RNAseq) and whole-genome sequencing (WGS) of samples from 61 Tanzanian ESCC patients. We used the computational microbial identification and classification software PathSeq to conduct a microbial abundance analysis of these samples. Next, we implemented linear discriminant analysis with LEfSe to determine which, if any, microbial taxa are enriched in the ESCC tumors of Tanzanian patients relative to ESCC samples from North America patients available through The Cancer Genome Atlas (TCGA). Results: Analysis of these RNAseq and WGS data reveals an extremely high abundance of Fusobacterium, Prevotella, and Streptococcus in the tumors of a subset of these patients. Based on the WGS data in particular, 14, 45, and 27 of the 61 ESCC samples maintain at least 10% relative abundance of Fusobacterium, Prevotella, and Streptococcus, respectively. The RNAseq data are consistent and reveal that as much as 75% of all bacterially derived reads in these samples are from these genera. Furthermore, LEfSe analysis suggest that these bacteria are significantly enriched in Tanzanian ESCC samples compared to North American ESCC samples. Discussion: These data suggest that the microbiome may be involved in ESCC incidence in Tanzania. Fusobacterium, Prevotella, and Streptococcus are notable for their association with CRC and are correlated with distinct clinical and molecular CRC characteristics. Members of these bacterial genera have been observed to modulate the carcinogenesis of GI cancers in a variety of ways, including through the selective stimulation or inhibition of various classes of immune cells. Furthermore, species within these genera have been observed invasively within cancerous GI tissues. Current studies are under way to visualize these microorganisms in tumor tissue, to characterize their association with molecular subtypes of ESCC, and to understand the relationship between tumor-associated bacteria and bacteria in the oral microbiome of ESCC patients in Tanzania. Citation Format: Jason Nomburg, Susan Bullman, Eric Collisson, Beatrice Mushi, Msiba Seleka, Charlie Vaske, Yulia Newton, Amie Radenbuagh, Larry Akoko, James A. DeCaprio, Matthew Meyerson, Elia J. Mmbaga, Katherine Van Loon. Investigating the microbial etiology of Tanzanian esophageal squamous cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr B06.

Social work and social welfare: A human rights foundation Katherine van Wormer and Rosemary J Link

Social work and social welfare: A human rights foundation <i>Katherine van Wormer and Rosemary J Link</i>

Abstract 2522: RNA rescue somatic mutations and RNA editing in esophageal cancer

Abstract The detection of somatic single nucleotide variants is a crucial component to the characterization of the cancer genome. Traditional mutation calling algorithms have focused on comparing the normal and tumor DNA from the same individual. For projects like The Cancer Genome Atlas (TCGA), it became routine to also sequence the tumor RNA. Our computational method, RADIA (RNA and DNA Integrated Analysis), combines the patient-matched normal and tumor DNA with the tumor RNA to detect somatic mutations. The inclusion of the RNA increases the power to detect somatic mutations, especially at low DNA allelic frequencies or when tumor purity is low. By integrating an individual’s DNA and RNA, we are able to detect mutations that would otherwise be missed by traditional algorithms that examine only the DNA. Mutations with high support in the RNA and low support in the DNA are termed RNA Rescue mutations. RNA editing is a post-transcriptional modification of pre-mRNA that has recently been identified as an additional epigenetic mechanism relevant to cancer development and progression. Using patient-matched normal and tumor DNA along with tumor RNA, we are able to identify RNA editing events across the entire transcriptome. There exists a remarkable geographic variability observed in incidence rates for Esophageal Cancer where more than 80% of cases and deaths occur in developing countries. There is an urgent demand to address the unmet clinical needs for these regions. Mutation of the tumor suppressor gene TP53 is the most frequent genetic alteration in both Esophageal Squamous Cell Cancer (ESCC) and Esophageal Adenocarcinoma (EAC). In a previous study of 59 tumors in Malawi a high proportion of tumors without TP53 mutations was reported. Here, we apply RADIA to a cohort of 61 tumors from Tanzania, and identify RNA Rescue Mutations that were previously missed by DNA mutation callers in significantly mutated genes such as TP53, CDK6, NOTCH1, VEGFA, KMT2D. RNA Editing events in the 3’UTR regions of genes are very common, especially when Alu elements are present, and are known to deregulate microRNA mediated gene regulation. MDM2 is a key oncogene in the p53 pathway with elevated gene expression in many tumor types and is known to be transcriptionally repressed by microRNAs. Here we detect transcriptome-wide RNA Editing events, and identify RNA Editing events in the seed regions of microRNA target sites of genes such as MDM2. We will also show how RNA Editing of certain genes are significantly associated with an RNA-Seq clustering solution. These genes show significantly differential expression between RNA-Seq clusters, indicating that these editing events have a functional impact on the genes they affect. We will further investigate these functional effects and downstream implications on the molecular characterization of the RNA-Seq subtypes. Citation Format: Amie J. Radenbaugh, J Zachary Sanborn, Yulia Newton, Charlie Vaske, Katherine Van Loon, Eric Collisson. RNA rescue somatic mutations and RNA editing in esophageal 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 2522.

Admiration and Awe: Morisco Buildings and Identity Negotiations in Early Modern Spanish Historiography by Antonio Urquízar-Herrera

Reviewed by: Admiration and Awe: Morisco Buildings and Identity Negotiations in Early Modern Spanish Historiography by Antonio Urquízar-Herrera Katherine Van Liere Antonio Urquízar-Herrera. Admiration and Awe: Morisco Buildings and Identity Negotiations in Early Modern Spanish Historiography OXFORD UP, 2017. 305 PP. CHRISTIAN SPAIN HAS LONG BEEN AMBIVALENT about its Muslim heritage. After the 1492 defeat of the last Muslim polity on the Peninsula, two conflicting impulses could be found in Spanish Christian culture. On the one hand, an official historiography, rooted in medieval chroniclers and expanded by Renaissance humanist writers, treated the seven centuries of Muslim rule and Christian–Muslim coexistence on the Peninsula as a cultural, political, and religious aberration and rejoiced that the Catholic monarchs' victory over Muslim Granada had ended the contaminating effects of Arab and Muslim culture, especially, though not only, in religious life. Aided by the humanist tradition that celebrated and often magnified classical origins, the received narrative in Habsburg Spain told of a Roman and Christian Hispania, rudely but temporarily interrupted by the violent Arab invasion. This written history was enhanced by a host of "miraculous finds" of artificial Christian relics from the pre-Muslim era that have been much studied of late. On the other hand, a persistent tradition of maurophilia in Christian Spain kept alive positive memories of Morisco culture, albeit in circumscribed contexts. Maurophilia's best-known incarnation is the literary tradition, stretching from medieval romanceros to Cervantes and beyond, that celebrated good-hearted and chivalrous Moors; this has been studied extensively by literary scholars since Marcelino Menéndez y Pelayo in the nineteenth century. Barbara Fuchs's Exotic Nation: Maurophilia and the Construction of Early Modern Spain (U of Pennsylvania P, 2009) highlighted a much more tangible dimension of maurophilia: a "moorish habitus" that survived in architecture, clothing, and everyday practices such as cuisine and horsemanship. Fuchs characterized this enduring embrace of morisco culture as a largely nonliterary phenomenon and one at odds with the official stance of the Catholic Church. She contrasted the fondness for mudéjar architecture and domesticity, seen especially among the laity and the nobility, with the [End Page 179] "official histories" written by ultraorthodox Spanish clergy who she alleges wrote Muslim history and Morisco culture out of the Spanish national story altogether. Citing passages from the chronicler Hernando de Pulgar and the Jesuit historian Juan de Mariana about the ephemerality of monuments, she suggested that most historians ignored the physical vestiges of the Muslim past in favor of idealized narratives of an eternally Christian Spain. Antonio Urquízar-Herrera's Admiration and Awe demonstrates the falsity of any simplistic picture of maurophilia and maurophobia as representing different segments of the Christian Spanish population. Urquízar-Herrera's main subject is the attitudes of Spain's sixteenth-century humanist historians, many of whom were churchmen, toward the physical remains of al-Andalus. He documents exhaustively that these authors wrote a good deal about the architectural remains of al-Andalus, often professing admiration for them, as exemplified by the book's title, a comment on the great mosque of Cordoba made by Ambrosio de Morales in his Antiquities of the Cities of Spain (1575). But the attitude of these antiquarians, chorographers, and civic historians was also fraught with "contradictions and complexities" (218), which UrquízarHerrera carefully examines in his ten chapters. In part 1, Urquízar-Herrera begins, appropriately, with three chapters of medieval background, both architectural and historiographical. He highlights the prevalence of the theme of "Spain's ruination" in medieval chroniclers, which ensured that "the notion of Islamic destructiveness was a good as etched into the DNA of sixteenth- and seventeenth-century historiographical thought in Spain" (35). In this near-ubiquitous paradigm, Muslims were violent conquerors who, with savagery comparable to the Visigoths before them, had vindictively destroyed buildings—perhaps even for the explicit purpose of destroying sites of historical memory. This justified the treatment of conquered Muslim palaces and mosques in one of two ways: either complete destruction as vestiges of unworthy culture that was best forgotten, or preservation as "symbolic war trophies" that could be converted to Christian use while reminding viewers of the Christian victory over Islam. Throughout...

Abstract B39: A pilot study to establish procedures for DNA and RNA isolation from African esophageal tumor specimens

Abstract Objective: We propose to utilize tumor biospecimens from patients with esophageal squamous cell carcinoma (ESCC) to identify possible genetic, molecular, and infectious determinants of this high-incidence disease in East Africa. However, laboratory technologies in East Africa are not available to support DNA and RNA extraction and genome and transcriptome sequencing from patient specimens. In preparation for establishment of a biorepository for African ESCC specimens, we compared different fixation and preservation media for transportability over long distances and success in preserving the genetic integrity and expression profiles of ESCC. Methods: Patients with a suspected diagnosis of ESCC at Muhimbili National Hospital in Dar es Salaam, Tanzania were identified and consented prior to endoscopic evaluations. For patients with endoscopic findings consistent with ESCC, tumor biopsies were obtained and stored using two different fixation and preservation media: PAXgene® Tissue Container (n=2) and RNAlater® (n=2). All specimens were shipped at room temperature from Dar es Salaam to San Francisco. DNA and RNA quantity was measured by nanodrop method and DNA was further confirmed by picogreen method, yielding measures of total DNA and RNA acquired (ug). DNA quality was measured as percent of total DNA degradation to between 200-1000 bp. RNA quality measure was determined by bioanalyzer output measure RNA Integrity Number (RIN). Results: Specimens for our first 10 patients were analyzed. Average transit time of biopsy specimens in preservative at room temperature was 6.2 days (range 3.5-9.0). Tumor specimens preserved with PAXgene® yielded a mean of 7.7 ug total DNA and 8.6 ug total RNA. Tumor specimens preserved with RNAlater® yielded a mean 1.4 ug of DNA and 8.2 ug of RNA. DNA degradation products were 0% of total with PAXgene® versus 6% of total with RNAlater®. Specimens preserved with PAXgene® yielded a mean RIN of 4, while RNAlater® yielded a mean RIN of 9. DNA and RNA quality were not associated with length of time at room temperature, up to a maximum of 9 days. Conclusion: Tissue preserved using the PAXgene® Tissue Container yielded higher DNA quantity and quality than tissue preserved in RNAlater®. RNA quantity was comparable for both mediums, but RNAlater® resulted in superior RNA quality versus PAXgene®. Both mediums allowed for flexible transport of specimens at room temperature and merit further inquiry into their potential as cost-effective methods to facilitate molecular analyses for geographically isolated diseases in Africa. Based upon our pilot data, each medium offers unique advantages. Our expanded study will continue to utilize both mediums to optimize isolation of both DNA and RNA. We will plan to present data for an enriched sample size. Funding source: National Institutes of Health, National Cancer Institute Cancer Center Administrative Supplement to Promote Cancer Prevention and Control Research in Low and Middle Income Countries, A119617, [CA-0082629]. Citation Format: Beatrice Paul Mushi, John Greer, Charles William Cahalane, II, Msiba Selekwa, Ali Mwanga, Larry Akoko, Elia Mmbaga, Eric Collisson, Katherine Van Loon. A pilot study to establish procedures for DNA and RNA isolation from African esophageal tumor specimens [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B39.

A Case-Control Study to Evaluate the Etiology of Esophageal Cancer in Tanzania

Abstract 75 Objective: East Africa has been previously reported as a geographic area with a disproportionately high incidence of squamous cell esophageal cancer (EC). In the setting of an apparent geographic cluster, we sought to identify specific etiologic factors contributing to the high incidence of EC in Tanzania (TZ). Methods: We performed a case-control study to examine possible associations between EC and selected environmental, dietary, and lifestyle factors. Newly diagnosed EC cases were recruited at Muhimbili National Hospital and Ocean Road Cancer Institute during 2014-2015. Hospital controls were identified from patients with non-malignant conditions and matched 1:1 for gender and age ±10 years. The study team conducted in-person interviews. A matched case-control analysis used McNemar’s test with a Mantel-Haenszel estimate for odds ratios (OR). Results: 375 cases and 375 controls were enrolled. 71% of cases and controls were male. Median age was 58 years (range 30-91) for cases and 55 years (range 31-88) for controls. Among cases with a confirmed pathologic diagnosis, squamous cell carcinoma was the most common histology (85%). Liquor consumption (OR 1.84, 95% CI: 1.05-3.22, p=0.04), burning firewood (OR 2.66, 95% CI: 1.88-3.76, p&lt;0.001), use of kerosene (OR 3.29, 95% CI: 2.36-4.59, p&lt;0.001), and use of surface water as a primary source of drinking water (OR 2.3, 95% CI: 1.41-3.76, p=0.001) were associated with increased risk of EC. Running water, gas, and electric utilities in the household were protective. Conclusion: Alcohol consumption, firewood and kerosene use as fuel, and surface water consumption merit further investigation as potential etiologic factors contributing to high EC incidence in TZ. Future research will include conducting multivariate analysis with these and other potential risk factors and a genome-wide analysis study using DNA extracted from saliva specimens obtained from cases and controls. Funding: Research support provided by the National Cancer Institute, National Institutes of Health Contract No. HH5N261200800001E. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: Elia Mmbaga No relationship to disclose Katrina Deardorff No relationship to disclose Beatrice Mushi No relationship to disclose Li Zhang No relationship to disclose William Mgisha No relationship to disclose Aparna Parikh Employment: Genentech Stock or Other Ownership: Genentech Travel, Accommodations, Expenses: Genentech Robert A. Hiatt No relationship to disclose Julius Mwaiselage No relationship to disclose Katherine Van Loon Consulting or Advisory Role: Bayer Company: OncoPlex Diagnostics

Book Review: Sacred History: Uses of the Christian Past in the Renaissance World, edited by Katherine Van Liere, Simon Ditchfield, and Howard Louthan

Book Review: Sacred History: Uses of the Christian Past in the Renaissance World, edited by Katherine Van Liere, Simon Ditchfield, and Howard Louthan

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Review of: The Maid Narratives: Black Domestics and the White Families in the Jim Crow South, by Katherine van Wormer, David W. Jackson III, and Charletta Sudduth

Confronting oppression, restoring justice: From policy analysis to social action. 2nd edn Katherine van Wormer, Laura Kaplan and Cindy Juby

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Sacred History: Uses of the Christian Past in the Renaissance World. Edited by Katherine Van Liere, Simon Ditchfield, and Howard Louthan

Sacred History: Uses of the Christian Past in the Renaissance World. Edited by Katherine Van Liere, Simon Ditchfield, and Howard Louthan

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Sacred History: Uses of the Christian Past in the Renaissance World. Edited by Katherine Van Liere, Simon Ditchfield, and Howard Louthan. Oxford: Oxford University Press, 2012. xxiv + 339 pp. $125.00 cloth.

Sacred History: Uses of the Christian Past in the Renaissance World. Edited by KATHERINE VAN LIERE, SIMON DITCHFIELD, and HOWARD LOUTHAN.

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Sacred History. Uses of the Christian Past in the Renaissance World ed. by Katherine van Liere, Simon Ditchfield, and Howard Louthan (review)