bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract LB182: Vaccination by liposomes and synthetic short peptide eradicated HPV-associated tumor
Authors: He Xuedan , Zhou Shiqi , Quinn Breandan , Jahagirdar Dushyant , Ortega Joaquin , Abrams Scott I. , Lovell Jonathan F.
Published: July 2021

Human papilloma virus (HPV)-16 is associated with cervical cancers and induces expression of the E6 and E7 oncogenes. 6 major histocompatibility complex (MHC) class I (MHC-I) epitopes were predicted to be immunogenic by sequencing a murine cell line that expresses E6/E7. A liposomal vaccine made of cobalt-porphyrin-phospholipid (CoPoP) and synthetic 9-mer epitopes appended with 3 histidine residues, resulting in rapid formation of stable peptide-liposome particles. Immunization with these predicted 6 peptides led to protection from tumor challenge on mice. Of the 6 peptides screened, only the previously identified E749-57 epitope has anti-tumor efficacy. The peptide-liposome particles that formed upon mixing E7HHH49-57 with CoPoP liposomes were stable in serum and avidly taken up by immune cells in vitro and rapidly released in lysosome. As a prophylactic vaccine, liposomal E7HHH49-57 vaccine protected mice from tumor challenge and re-challenge. As a therapeutic vaccine, immunization with the synthetic short peptide at a dose of 100 ng protected mice when admixed with CoPoP liposomes, whereas 200-fold higher peptide doses were ineffective with the Poly(I:C) adjuvant. CoPoP induced strong infiltrating CD8+ T response within the tumor microenvironment with improved functional profile. Vaccine monotherapy using nanogram dosing of the E7HHH49-57 peptide admixed with CoPoP reversed the growth of large established tumors, permanently eradicating subcutaneous tumors upwards of 100 mm3, and also completely eradicated lung tumors in a metastasis model.

Citation Format: Xuedan He, Shiqi Zhou, Breandan Quinn, Dushyant Jahagirdar, Joaquin Ortega, Scott I. Abrams, Jonathan F. Lovell. Vaccination by liposomes and synthetic short peptide eradicated HPV-associated tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB182.
Abstract LB206: Simultaneous single cell profiling of open chromatin and gene expression in B cell lymphoma highlights tumor-specific regulatory networks
Authors: Maheshwari Shamoni , Wang Li , Gopalan Vijay , Shuga Joe , Chatterjee Sharmila , Belhocine Kamila
Published: July 2021

Profiling multiple analytes from a single cell enables additional dimensions to characterize tumor biology. Simultaneous measurement of epigenetic information and gene expression in single cells provides a clearer readout of the links between regulatory elements and target genes, allowing a more mechanistic interpretation of cell clusters and better cell type distinctions based on a cell's history and its future potential.

Here, we describe simultaneous measurement of gene expression and chromatin accessibility from thousands of single nuclei using the Chromium Single Cell Multiome ATAC + Gene Expression. We leverage a microfluidic platform to generate paired barcoded gene expression and ATAC-seq libraries, linking transcriptomic and open chromatin information at the single cell level. Using this method, we jointly profiled gene expression and chromatin accessibility from over 10,000 immune cells from healthy human PBMCs and over 14,000 cells from a human B cell lymphoma sample.

In healthy immune cells, we leveraged chromatin information to better parse distinct cell states within a gene expression-defined cell type, showing that the addition of ATAC profiling to gene expression improves resolution of cell type specification.

In B cell lymphoma, we used known markers of malignancy to segregate tumor B cells from normal B cells. We constructed regulatory networks in both cell states using the observed transcription factor motif enrichment in open chromatin regions combined with gene expression from the same cells. Comparing regulatory networks in healthy vs. tumor B cells highlighted the presence of unique regulatory networks in tumor B cells. Notably, the PAX5 tumor regulator was observed only in tumor B cells, and its impacts on the regulation of many downstream genes was characterized. Building this regulatory network analysis was only made possible through the joint profiling of open chromatin and gene expression at the single cell level. Our data demonstrate the power of simultaneous profiling of both epigenomic and transcriptomic data in characterizing cells in cancer state and extracting functional information from tumor samples.

Citation Format: Shamoni Maheshwari, Li Wang, Vijay Gopalan, Joe Shuga, Sharmila Chatterjee, Kamila Belhocine. Simultaneous single cell profiling of open chromatin and gene expression in B cell lymphoma highlights tumor-specific regulatory networks [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB206.
Abstract LB207: Glutamine transporter SLC38A3 promotes breast cancer migration via GSK3beta/beta-catenin/EMT pathway
Authors: Tan Zheqiong , Tressler Caitlin M. , Sonkar Kanchan , Glunde Kristine
Published: July 2021

Breast cancer is one of the most commonly diagnosed cancers and the leading cause of cancer-related death among women. Triple negative breast cancer (TNBC) is a subtype of breast cancer characterized by the absence of estrogen receptor, progesterone receptor and HER2 expression. TNBC shows a high capacity for early metastasis and leads to worse clinical outcomes than other breast cancer subtypes due to the lack of specific therapeutic targets. We are looking to develop cancer-specific therapeutic targets for TNBC. Many types of cancer cells including TNBC cells rely on glutamine as carbon and nitrogen source to fuel unchecked growth. We screened for key genes in regulating glutamine metabolism in a panel of breast cancer cell lines. This screen identified the mRNA and protein levels of solute carrier family 38 member 3 (SLC38A3), a glutamine transporter, to be upregulated in human breast cancer cell lines, especially in TNBC cell lines. The TCGA breast cancer patient database also showed that SLC38A3 mRNA is overexpressed in invasive ductal breast carcinoma tissues, and it is even higher in TNBC relative to other breast cancer subtypes. To test the biological role of SLC38A3 protein in TNBC cells, we performed loss-of-function experiments in multiple TNBC cell lines. Silencing of SLC38A3 decreased cellular glutamate, glutamine and alanine levels. Silencing of SLC38A3 also activated apoptosis, and suppressed cell viability, migration and invasion in several TNBC cell lines. Interestingly, silencing of SLC38A3 increased the activity of glycogen synthase kinase 3-β (GSK3β) which promoted the degradation of β-catenin, leading to the decrease of the mRNA levels of epithelial-to-mesenchymal-transition (EMT)-associated transcription factors in TNBC cell lines. In summary, we showed that SLC38A3 is overexpressed in TNBC and promotes breast cancer migration and invasion via GSK3β/β-catenin/EMT pathway, which could be a novel therapeutic target for breast cancer.

Citation Format: Zheqiong Tan, Caitlin M. Tressler, Kanchan Sonkar, Kristine Glunde. Glutamine transporter SLC38A3 promotes breast cancer migration via GSK3beta/beta-catenin/EMT pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB207.
Abstract LB211: Epstein-Barr virus BART lncRNAs induce IKZF3/Aiolos to maintain EBV latency and promote tumorigenicity in nasopharyngeal carcinoma
Authors: HE Songtao , Liu Jiayan , Chen Honglin
Published: July 2021

Epstein-Barr virus (EBV) infection is one of the main causative factors of nasopharyngeal carcinoma (NPC), which is prevalent in southern China and some Southeast Asian countries. EBV infection in NPC cells is characteristically type II latency, where very few viral proteins (EBNA1, LMP1 and LMP2A) but high levels of noncoding RNAs (especially BARTs: BamHI-A rightward transcripts) are expressed. Our previous study found that BART lncRNAs modulate transcription of IKZF3, which encodes Aiolos, through epigenetic pathways in NPC cells. However, the biological significance functional mechanism of IKZF3/Aiolos are not yet clearly defined. We now further show that IKZF3/Aiolos expression levels are associated with copy numbers of EBV episomes in the EBV-harboring NPC cell line, NPC43, and specifically correlate to the level of lnc-BARTs, as demonstrated using CRISPR systems. Transcriptomic analysis of IKZF3-knockout C666-1 NPC cells revealed that 17 EBV-encoded microRNAs and 53 lytic genes were significantly downregulated or upregulated (FDR p value <0.05 and posterior fold changes >1.5). Immunoblot testing showed that the EBV lytic reactivator Zta and antigen BMRF1 are upregulated following knockout of IKZF3 in C666-1 cells, suggesting involvement of IKZF3/Aiolos in maintaining EBV latency in NPC. Gene ontology and KEGG (Kyoto Encyclopaedia of Genes and Genomes) analysis of IKZF3-knockout C666-1 cells found that most of the host genes with differential expression that are enriched in Epstein-Barr virus infection are associated with apoptosis, focal adhesion, cancer cell growth and mammary neoplasm (p value <0.01). In addition, a soft agar assay demonstrated that oncogenic transformation of C666-1 cells was attenuated after knocking down expression of lnc-BARTs, knocking out IKZF3, or treatment with the IKZF3 inhibitor lenalidomide. Immunoprecipitation (IP) testing showed that Aiolos interacted with core elements (HDAC1 and MTA2) of the Mi-2/NuRD (nucleosome remodelling deacetylase) complex in NPC cells. Our findings suggest that Aiolos may recruit Mi-2/NuRD complexes for deacetylation of histone lysine residues bordering promoter regions of EBV lytic genes and host tumour suppressor genes, leading to inhibition of reactivation of EBV lytic infection, thereby preventing apoptosis of NPC cells.

Citation Format: Songtao HE, Jiayan Liu, Honglin Chen. Epstein-Barr virus BART lncRNAs induce IKZF3/Aiolos to maintain EBV latency and promote tumorigenicity in nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB211.
Abstract LB224: The potential effect of chronically increased endotoxin levels on breast carcinoma progression in obese patients.
Authors: Meirovitz Amichay , Nahmias Daniela , Hermano Esther , Maimon Ofra , Peretz Tamar , Elkin Michael
Published: July 2021

Obesity serves as a risk factor for estrogen-dependent postmenopausal breast cancer (BC). While the exact association occurring between these two disease states remains unknown, obesity-associated inflammation is thought to be the most likely contributing factor. In addition, obesity has been correlated to changes in gut microbiota composition and a subsequent chronic increase in bacterial endotoxin (lipopolysaccharide [LPS] - canonic ligand of toll-like receptor 4 [TLR4]) blood levels. It was recently shown that BC cells intrinsically express TLR4 and such expression has been associated with decreased patient survival as well as increased tumor growth. We hypothesized that obesity-associated endotoxemia may contribute to BC progression by utilizing TLR-dependent mechanisms and exerting cancer-promoting effects directly (on carcinoma cells) and indirectly (triggering abnormal activation of macrophages). Utilizing a chronic metabolic endotoxemia and breast cancer murine model as well as in vitro experimental systems, we found that continuous exposure to low concentrations of LPS not only promotes BC progression in vivo but stimulates BC cell growth in culture through the activation of key breast cancer-promoting signaling pathways (Stat3, Akt, ERK1/2). Obesity has reached epidemic proportions globally, where elucidation of the molecular mechanisms underlying breast tumor-promoting action of obesity has become of vital importance. Improving the understanding of such mechanisms has the potential to reveal improved efficacious therapy regimens and prevention strategies in a rapidly growing population of obese, breast cancer patients.

Citation Format: Amichay Meirovitz, Daniela Nahmias, Esther Hermano, Ofra Maimon, Tamar Peretz, Michael Elkin. The potential effect of chronically increased endotoxin levels on breast carcinoma progression in obese patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB224.
Abstract LB230: Inactivation of the CFTR gene in duodena of mice exposed to hexavalent chromium (Cr(VI)) in drinking water supports its tumor-suppressor status and implies its role in Cr(VI)-induced carcinogenesis of the small intestines
Authors: Mezencev Roman , Auerbach Scott S.
Published: July 2021

Hexavalent chromium [Cr (VI)] compounds are used in metallurgical, chemical and refractory industries. Their carcinogenicity has been supported by a number of epidemiological and animal studies; however, their carcinogenic mode of action is still incompletely understood. To identify mechanisms involved in cancer development from toxicologically relevant exposures to Cr(VI), we analyzed gene expression data from duodena of mice exposed for 7 or 90 days to Cr(VI) in drinking water at concentrations 0.3-520 mg/L. This analysis included identification of upstream regulatory molecules that are likely responsible for the observed gene expression changes, and identification of annotated gene expression data from public repositories that correlate with gene expression changes in duodena of Cr(VI)-exposed mice. We identified the CFTR gene among top scoring upstream regulators, including at low exposure levels that, for the given timepoints, did not induce observable tissue damage. Furthermore, the expression data from duodena of Cr(VI)-exposed mice displayed a positive correlation with other datasets in public repositories associated with the inactive CFTR gene, of which the top scoring were datasets for ilea and duodena of Cftr-knockout mice. Our results support the tumor-suppressor role of the CFTR gene, which was previously suggested for intestinal carcinogenesis in humans and mice. Furthermore, our findings indicate, for the first time, the role of CFTR inactivation in chemical carcinogenesis and expand the range of plausible mechanisms that may be operative in Cr(VI)-mediated carcinogenesis of intestinal and possibly other tissues. Disclaimer: The views expressed are those of the authors and do not necessarily represent the views or policies of the US EPA.

Citation Format: Roman Mezencev, Scott S. Auerbach. Inactivation of the CFTR gene in duodena of mice exposed to hexavalent chromium (Cr(VI)) in drinking water supports its tumor-suppressor status and implies its role in Cr(VI)-induced carcinogenesis of the small intestines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB230.
Abstract PL06-03: Exploiting genome instability for new cancer therapies: PARP inhibitors and beyond
Authors: Jackson Stephen P.
Published: July 2021

As DNA is frequently subject to a wide array of molecularly distinct forms of damage, life has evolved multiple DNA repair and associated processes, collectively termed the DNA-damage response (DDR). The importance of DNA repair and other DDR mechanisms is underlined by their deregulation or loss causing cancer and various human genetic disorders. Work in my laboratory aims to decipher DDR mechanisms, particularly those triggered by DNA double-strand breaks. In my talk, I will begin by briefly summarising past work by me and my collaborators that led to the world's first registered DDR enzyme inhibitor drug - the PARP inhibitor olaparib/Lynparza. I will then describe some of our recent work using CRISPR-Cas9 genetic screens to discover new DDR factors/regulators, identify potential new avenues for anti-cancer therapy, and help us understand how cancer cells can evolve resistance to DNA-damaging chemotherapies, PARP inhibitors or other DDR enzyme inhibitors.

Citation Format: Stephen P. Jackson. Exploiting genome instability for new cancer therapies: PARP inhibitors and beyond [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr PL06-03.
Abstract SY02-02: Understanding evolution of metastatic disease in renal cancer and melanoma
Authors: Turajlic Samra
Published: July 2021

While our knowledge of the evolutionary features of primary tumors has grown exponentially over the last few years our understanding of evolution of metastases is more limited and many open questions remain, regarding the timing of metastatic dissemination, the acquisition of metastatic competence and the underpinning of the variety of metastatic phenotypes observed in the clinic from latent metastases to solitary and oligo-metastases to widespread metastases. We have leveraged unique translational protocols that allow interrogation of tumor evolution from the earliest stages of diseases to death to address some of these questions. In the context of renal cell cancers we show that the mode of evolution at the primary tumor site determines the tempo and distribution of systemic metastases; that the features that distinguish metastasis-competent clones included genome instability and aneuploidy; and that metastatic competence often emerges in the centre of the primary tumor. In the context of melanoma we observe a wide spectrum of metastatic seeding that includes organ-specific metastatic clones, monophyletic and polyphyletic seeding and polyclonal mixing at metastatic sites. We observe progressive increase in aneuploidy and occurrence of whole genome doubling as melanoma metastases progress and resist treatment suggesting this as a a mechanism of immune-evasion and treatment resistance.

Citation Format: Samra Turajlic. Understanding evolution of metastatic disease in renal cancer and melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr SY02-02.
Abstract SY06-02: Optically activated nanomedicines: Photochemical activation as a priming and imaging tool in pancreatic cancer
Authors: Hasan Tayyaba
Published: July 2021

Optical activation of materials leads to thermal, photochemical and radiative processes which can be captured for response-based therapeutic design. The ability to use light as a reagent to provide free radical and activated oxygen-mediated cytotoxicity, combined with a control of conventional drug release, allows for the fabrication of light-controllable intelligent multiagent nanoconstructs that attack multiple pathways making nanomedicines more effective against cancer. This optically activated approach allows for a mechanistically diverse and spatiotemporally controlled strategy to tumor destruction. The molecules used for light activation have, in addition to therapeutic capabilities, finite fluorescence, creating an imaging handle and providing a built-in Theranostic process. Strategies for syntheses and applications of these nanoagents in biology and medicine will be discussed.

Citation Format: Tayyaba Hasan. Optically activated nanomedicines: Photochemical activation as a priming and imaging tool in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr SY06-02.
Abstract SY24-01: Spatiotemporal definitions of immune archetypes across cancer types
Authors: Krummel Matthew F.
Published: July 2021

Cancers display significant heterogeneity with respect to tissue of origin, driver mutations and other features of the surrounding tissue. It is likely that persistent tumors differentially engage inherent patterns-here "Archetypes"-of the immune system, to both benefit from the tumor immune microenvironment (TIME) and to disengage tumor-targeting. To discover dominant immune system archetypes across diverse cancer types, we processed in an unbiased way 364 individual tumors across 12 cancer indications using standardized protocols. Computational clustering of flow cytometry and transcriptomic data obtained on cell sub compartments uncovered archetypes that exist across indications and are durable to increased granularity in higher dimensions. Immune composition-based archetypes differentiate tumors based upon the distribution of large unrelated collections of immune and tumor gene-expression patterns. Archetypes discovered this way also tie closely to well-established classifications of tumor biology. The resultant Immunoprofiler Initiative (IPI) resource provides a template for understanding cancer immunity as a collection of dominant patterns of immune infiltration and provides a rational path forward to study cancer immunity and learn how to modulate these patterns to improve therapy.

Citation Format: Matthew F. Krummel. Spatiotemporal definitions of immune archetypes across cancer types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr SY24-01.
Abstract SY31-01: Remodeling of the cell surface proteome in cancer
Authors: Wells James A.
Published: July 2021

The cell surface proteome (surfaceome) is the primary hub for cells to communicate with the outside world, and are major targets for immunotherapy. Oncogenes are known to cause huge changes in cells (see Figure 1). Our group has applied state-of-the-art proteomics methods to quantitatively compare the surfaceomes of oncogene transformed (KRAS, HER2, EGFR, BRAF, MEK, AKT and MYC) versus isogenic controls (1-3). Oncogenes lead to large and bi-directional remodeling of the surfaceomes of isogenic cell lines that can be exploited for target ID. Each oncogene has a unique signature that depends on cell line, but broadly similar across cell lines. Differences among related oncogenes converge when viewed at functional level by Geneset analysis. Proliferative oncogenes (EGFR, HER2, KRAS, BRAF, MEK) remodel the surfaceome primarily through MAPK pathway. MYC is much more unique, especially in the large changes induced in solute carrier proteins. We have also recently developed a technology to identify proteolytic cut sites in membrane proteins (4) which also show bi-direction remodeling. We show proteolysis is an orthogonal remodeling event, and the union with expression data offers new neo-epitope markers for immunotherapy.

References

1. Martinko A.J., Truillet C., Julien O., Diaz J.E., Horlbeck, M.A., Whiteley G., Blonder J., Weissman J.S., Bandyopadhyay S., Evans M.J., Wells J.A. (2018) "Targeting RAS Driven Human Cancer Cells with Antibodies to Upregulated and Essential Cell-Surface Proteins." eLife. 2018;7:e31098

2. Leung, K. K., Wilson, G. M., Kirkemo, L. L., Riley, N. M., Coon, J. J., & Wells, J. A. (2020). Broad and thematic remodeling of the surfaceome and glycoproteome on isogenic cells transformed with driving proliferative oncogenes. PNAS 117 (14), 7764-7775.

3. Chen, W., Mou, K. Y., Solomon, P., Aggarwal, R., Leung, K. K., & Wells, J. A. (2021). Large remodeling of the Myc-induced cell surface proteome in B cells and prostate cells creates new opportunities for immunotherapy. PNAS, 118(4), 1-11.

4. Weeks, A. M., Byrnes, J. R., Lui, I., & Wells, J. A. (2021). Mapping proteolytic neo-N termini at the surface of living cells. PNAS, 2020.02.23.961904.

Citation Format: James A. Wells. Remodeling of the cell surface proteome in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr SY31-01.
Abstract 108: The Relationship Between Cervical Cancer and Women Living with Disabilities in Kentucky
Authors: Akakpo Carolyn
Published: July 2021

Purpose: Despite many national interventions, cervical cancer (CC) rates persist, and in Kentucky (KY), CC incidence rates are on the rise. Additionally, women with disabilities are medically underserved and face more barriers to secondary prevention and healthcare access, have more known risks, and experience more health disparities than women without disabilities. Given that 1 in 4 persons live with a disability in the USA, the purpose of this observational, cross-sectional, quantitative study was to explore the relationship between CC and women with disabilities as evidenced by reproductive cancer discharges from inpatient hospital (IHD) and outpatient services databases (OSD) so as to compare population-specific differences from social determinants of health framework.

Methods: Data from the Kentucky Cabinet for Health and Family Services for 2015 to 2018 were analyzed using MLR. In total, the sample included 584 women with disabilities and 32,773 women without disabilities living in KY. Results: The IHD data analysis found that county of residence (p =.014) and insurance payer (p = .000) were statistically significant and that women on public insurance were 9.6 times as likely to be diagnosed with CC.

Results: of the OSD data analysis found that place of residence (p = .000) and age group (p = .000) were statistically significant and that women aged 40-44 were 9.5 and 2.9 times as likely to have breast cancer and CC respectively.

Conclusion: This study's findings call for; greater attention to strengthening public health surveillance and infrastructure affording visibility of women with disabilities who are underserved, increased proportion of breast and cervical cancer screening at an early age, and increase health access interventions for low resource settings.

Citation Format: Carolyn Akakpo. The Relationship Between Cervical Cancer and Women Living with Disabilities in Kentucky [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 108.
Abstract 113: Burden of Risk Factors for Cervical Cancer among Women Living In East Africa: Analysis of the Latest Demographic Health Surveys Conducted between 2014 And 2017
Authors: Abila Derrick , Ainembabazi Provia , Wasukira Sulaiman , Wabinga Henry
Published: July 2021

Purpose: In East Africa, cervical cancer is a leading cause of morbidity and mortality amongst women diagnosed with cancer in East Africa. We aimed to describe the burden of risk factors for cervical cancer among women of reproductive age in five East African countries to inform the design of interventions to the reduce exposure of women to them.

Methods: For each country, using STATA13 and sampling weights, we analysed Demographic and Health Survey (DHS) datasets conducted between 2014 and 2017 in Burundi, Kenya, Rwanda, Tanzania, and Uganda. The surveys followed a two-stage cluster random sampling procedure. We included women aged 15 to 49 years and considered six risk factors (tobacco use, body mass index, age at first sexual intercourse, age at first birth, number of children and hormonal contraceptive use). Poisson regression was used to determine the demographics associated with the number of risk factors a woman had.

Results: From 93,616 women from the countries, each country had more than half younger than 30 years of age with majority living in rural areas. Pooled proportion of women with at least one risk factor was 89% (95% Confidence interval, CI 87% - 91%). Living in a rural area in Burundi (Adjusted Incidence Rate Ration, aIRR 0.94; 95% CI: 0.9–0.99; p = 0.019) and Rwanda [aIRR 0.92; 95% CI: 0.88 - 0.96; p < 0.001] was associated with a lower number of risk factors among women compared with living in an urban area. In all the countries, women with complete secondary education were associated with the lowest number of risk factors for cervical cancer compared with those living in urban areas.

Conclusion: Our study revealed a high burden of risk factors for cervical cancer in East Africa with a high proportion of women having at least one risk factor.

Citation Format: Derrick Abila, Provia Ainembabazi, Sulaiman Wasukira, Henry Wabinga. Burden of Risk Factors for Cervical Cancer among Women Living In East Africa: Analysis of the Latest Demographic Health Surveys Conducted between 2014 And 2017 [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 113.
Abstract 114: Funders and Collaborators of Cancer Research in Kenya, 2007-2017: A Bibliometric Analysis
Authors: Vargas Jasmin , Joseph Anyona , Maina Martha , Karagu Alfred , Cira Mishka , Lu Ya-Ling , Livinski Alicia
Published: July 2021

Purpose: It is well established that cancer research is essential to the development and implementation of effective control strategies and interventions. In Kenya, cancer is the third leading cause of death. Country specific research conducted by both local and international investigators has the potential to shape a national plan which addresses local needs across the cancer care continuum. This analysis aims to provide information about the trends in research collaborations, funding and outputs from 2007-2017 types of research collaborations, institutional and individual research collaborations, the types of cancer in order to understand gaps and opportunities to strengthen Kenya-led cancer research capacity.

Methods: This analysis included 243 studies from a previously published phase 1 scoping review of oncology research conducted in Kenya from 2007-2017. The citation metadata was drawn from Pubmed and manually standardized in Microsoft Excel. Using Sci2, a series of bibliometric network analyses were conducted to identify funding patterns, collaborations between authors and institutions, and the types of cancer research conducted in Kenya. Gephi and Excel provided descriptive analyses and graphs of the network. The analyses are categorized into three themes: article production, collaboration, and research topics. These findings were contextualized by study co-authors from Kenya and the US.

Results: The bibliometric analysis described which agencies are funding cancer research in Kenya, which authors and institutions are collaborating with whom, and the cancer research areas most published on in this dataset. The publication trend from 2007-2017 was highlighted, emphasizing the historical development and enabling important recognition of researchers and funders in advancing medical oncology in Kenya.

Conclusion: This study identifies future areas for collaborations between investigators in similar sub-fields and cancer research funding priorities for the nation. The findings provide a bigger picture that will guide policymakers on developing evidence-based decision-making, planning to strengthen future research capacity, and funding.

Citation Format: Jasmin Vargas, Anyona Joseph, Martha Maina, Alfred Karagu, Mishka Cira, Ya-Ling Lu, Alicia Livinski. Funders and Collaborators of Cancer Research in Kenya, 2007-2017: A Bibliometric Analysis [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 114.
Abstract 13: High-Throughput, Non-Invasive Raman Spectroscopy of Anticancer Nanomedicine for Liver Cancer Therapeutic Intervention
Authors: Poojari Radhika , Bhujbal Mithila , Hole Arti , Chilakapati Murali Krishna
Published: July 2021

Purpose: Liver cancer remains one of the most difficult to treat, heterogeneous forms of cancer with poor prognosis. Available current therapies face many limitations. Raman spectroscopy is a promising platform for clinical drug development and surgical interventions for improved patient outcomes. Herein, we present a new insight with a rapid, non-destructive, non-invasive Raman spectroscopy modality based molecular signatures unique to anticancer nanomedicine signifying distinct stratification in liver cancer treated tissues of SCID mice.

Methods: The therapeutic intervention was investigated using a high-throughput Raman spectroscopy in ex vivo liver tissues treated with combinatorials; targeted and non-targeted polymeric nanocomplexes encapsulated microtubule inhibitors against metastatic liver cancer in SCID mice. Principal Component Analysis (PCA), Linear Discriminate Analysis (LDA) for multivariate data analysis, and cross validation method was used to extrapolate the high throughput Raman based treatment efficiency study in ex vivo liver tissues.

Results: Raman spectral signatures obtained by Raman spectroscopy of liver tissue samples of healthy normal liver versus liver cancer cohorts exhibited complete discrimination of healthy ones from the affected diseased counterparts with high accuracy classification. This could be useful as a liver cancer diagnosis tool. Peculiar Raman profiles with distinct stratification of targeted anticancer nanomedicine combinatorials treated cohort were observed. Interestingly, apoptotic lipid bodies and amide I was the prominent features revealed in anticancer nanomedicine combinatorials treatment cohorts.

Conclusion: Our approach is a significant advancement for unique Raman molecular signatures-based targeted anticancer nanomedicine combinatorials therapeutic intervention for liver cancer in tissues. Clinical translation of this proposed modality would define Raman based rapid, high-throughput platform for the clinical drug development and monitoring against liver cancer remains warranted.

Citation Format: Radhika Poojari, Mithila Bhujbal, Arti Hole, Murali Krishna Chilakapati. High-Throughput, Non-Invasive Raman Spectroscopy of Anticancer Nanomedicine for Liver Cancer Therapeutic Intervention [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 13.
Abstract 19: Geospatial Analysis and Impact of Targeted Development of Breast Cancer Care in The Gambia: A Cross-Sectional Study
Authors: Lopez-Verdugo Fidel , Mali Meghan , Moustafa Moustafa , Nellermoe Jonathan , Sorensen Justin , Bittaye Mustapha , Njie Ramou , Singhateh Yankuba , Goldsmith Alison , Mohammed Nuredin I. , Price Raymond R. , Sutherland Edward , Sanyang Ousman
Published: July 2021

Purpose: To characterize the capacity of healthcare facilities to provide breast cancer care in The Gambia and calculate the proportion of the population with access to services.

Methods: A facility-based service assessment tool was administered to all healthcare facilities in The Gambia. Proximity of service availability and population analysis were assessed using GPS coordinates and LandScan population density raster. Distance thresholds of 10km, 25km, and 45km were established to determine access to screening services, pathologic diagnosis, and surgical management, respectively. An additional population analysis was performed to observe the potential impact of targeted resource development.

Results: All 102 healthcare facilities were included. Breast cancer screening was mainly performed through clinical breast examination and was available in 52 facilities. Seven facilities provided pathologic diagnosis and surgical management of breast cancer. The proportion of the Gambian population with access to screening, pathologic diagnosis and surgical management was 72%, 57%, and 62%, respectively. Patients living on the eastern side of the country have to travel up to 35 km for screening services and up to 300 km for pathologic diagnosis and surgical management. Widespread implementation of clinical breast examination for screening, and targeted expansion of diagnostic and surgical resources in two hospitals would increase the covered population to 95%, 67%, and 84%. This would decrease the maximum distance to access breast cancer care to 15 km for screening and 90 km for diagnosis and surgical management.

Conclusion: Almost half of the Gambian population do not have access to pathologic diagnosis and surgical management of breast cancer within a reasonable travel distance, and all facilities offering these services are located in the capital city. Mapping and population analysis can identify key areas of need. This approach allows targeted development of resources to significantly increase access to breast cancer care in a low resource setting.

Citation Format: Fidel Lopez-Verdugo, Meghan Mali, Moustafa Moustafa, Jonathan Nellermoe, Justin Sorensen, Mustapha Bittaye, Ramou Njie, Yankuba Singhateh, Alison Goldsmith, Nuredin I. Mohammed, Raymond R. Price, Edward Sutherland, Ousman Sanyang. Geospatial Analysis and Impact of Targeted Development of Breast Cancer Care in The Gambia: A Cross-Sectional Study [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 19.
Abstract 21: Mapping Breast Cancer Resource Availability Across Ghana's Eastern Region
Authors: Moustafa Moustafa , Mali Meghan , Lopez-Verdugo Fidel , Sanyang Ousman , Ayensu-Danquah Grace , Sorensen Justin , Nellermoe Jonathan , Manortey Stephen , Goldsmith Alison , Ofei Irina , Biritwurm-Nyarko Alberta , Price Raymond , Sutherland Edward
Published: July 2021

Purpose: Improve allocation of breast cancer resources across Ghana's Eastern Region by systematically assessing and mapping breast cancer screening, diagnosis, and treatment capacity.

Methods: A survey to assess breast cancer care capacity was developed and administered to hospitals in the Eastern Region of Ghana. Hospitals were stratified based on their available services. All facilities were mapped using GPS coordinates to demonstrate the location and distance between key services using thresholds of 10, 25, and 45km for screening, diagnostic, and surgical treatment capacity respectively.

Results: Thirty-three (out of 34) hospitals in the Eastern Region were surveyed: 27 (82%) hospitals provide basic screening services (clinical diagnosis with clinical breast exam), 11 (33%) provide pathologic diagnosis, and 3 (9%) provide those services in addition to basic surgical care. A total of 53% of the population lives within a 10km travel distance of screening services, 64% within 25km of diagnostic services, and 78% within 45km of surgical treatment. Ninety-four percent of facilities have a general practitioner; 55% have a radiology technician; 39% employ a surgeon. Oncology specialists, and pathology personnel are only available in 1 facility across the Eastern Region. Limited chemotherapy is available at 2 hospitals, endocrine therapy at 1 hospital, and radiotherapy is not available.

Conclusion: No hospitals are able to provide the full spectrum of care outlined by the Basic NCCN Framework Guidelines, which are intended for use in low resource settings. Although 82% of hospitals provide screening, only half the population lives within reasonable distance of these services. Few hospitals offer diagnosis and surgical treatment services. This geospatial analysis suggests two priorities in order to cost-effectively expand breast cancer services: increase the quantity of screening hospitals in targeted locations, and enhance treatment services at hospitals already providing diagnosis and surgery.

Citation Format: Moustafa Moustafa, Meghan Mali, Fidel Lopez-Verdugo, Ousman Sanyang, Grace Ayensu-Danquah, Justin Sorensen, Jonathan Nellermoe, Stephen Manortey, Alison Goldsmith, Irina Ofei, Alberta Biritwurm-Nyarko, Raymond Price, Edward Sutherland. Mapping Breast Cancer Resource Availability Across Ghana's Eastern Region [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 21.
Abstract 23: Oncology Nurse Mentor, a Model to Offer Training and Continued Mentorship to General Nurses in Low Resource Setting
Authors: Wambasi David , Achieng Emmah , Were Pamela
Published: July 2021

Purpose: The GLOBOCAN report for 2018 estimated 47,887 new cases of cancer annually with a mortality of 32, 987 in Kenya. Low income countries face a growing burden of cancer and a shortage of specialized Oncology nurses to meet the need. Partnerships between centers with specialised oncology nurses and counties that are setting up oncology units can be a bridge to improve access to remote sites in LMIC countries.

Methods: The International Cancer Institute (ICI) partnered with four counties Meru, Makueni, Sori and Taita Taveta to set up oncology centers in remote areas. Unspecialised nurses interested in oncology care were selected from the four counties and were offered short courses in oncology. Oncology nurses then travel to the sites on a three weekly basis for further on job training and mentorship. Continuous medical education is done on all aspects of nursing oncology management including assessment of patients, care of the patients, screening and chemotherapy.

Results: When the program started the oncology nurses from Eldoret travelled to the sites every three weeks but gradually this was reduced and phone and tele consults encouraged. Distance from Eldoret to the four sites is Meru (168 Miles), Makueni (228 Miles), Sori lakeside (99 Miles) and Taita Taveta (353 Miles). Two sites are now independent and run on their own on a daily basis. Eight nurses have been trained and mentored.

Conclusion: Capacity building through on job training and mentorship by the specialised Oncology nurses to general nurses has demonstrated improved access to oncology care in low resource settings over a shorter duration of time.

Citation Format: David Wambasi, Emmah Achieng, Pamela Were. Oncology Nurse Mentor, a Model to Offer Training and Continued Mentorship to General Nurses in Low Resource Setting [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 23.
Abstract 31: Impact of the COVID-19 Pandemic on Cancer Registry Operations in the Caribbean
Authors: Quesnel-Crooks Sarah , Hanisch Rachel , Soerjomataram Isabelle , Edwards Brenda , White Arica , Kohler Betsy , Chao Ann , Mery Les , Andall-Brereton Glennis
Published: July 2021

Purpose: Cancer registration is an integral part of national disease surveillance, and actions must be taken to maintain operation of such essential systems, even during concurrent public health emergencies. This abstract summaries the impact of the COVID-19 pandemic on operations of population-based cancer registries (PBCRs) in the Caribbean.

Methods: In May 2020, the International Agency for Research on Cancer (IARC) issued a worldwide survey to members of the International Association of Cancer Registries (IACR) to assess the impact of the COVID-19 pandemic on PBCRs. In November, the IARC Caribbean Hub renewed this call for responses from IACR members plus additional Caribbean PBCRs. The experience of ten of thirteen registries contacted is presented.

Results: Survey responses were received from PBCRs in the Bahamas, Barbados, Bermuda, Cuba, Dominican Republic, Guyana, Jamaica, Martinique, Puerto Rico, and Trinidad and Tobago. Five (50%) registries reported that the COVID-19 pandemic negatively affected operations. These same registries reported a reduction in data collection capacity ranging from 28% to 100%. Reasons for data collection disruptions included an inability to fully access physical data sources and a reduced capacity or inability to receive cancer notifications and files. Where data collection was impacted, all registries expected missing cancer cases to be registered later in the next 12-15 months. Remote working was one strategy implemented by unaffected registries. One (10%) registry reported an impact on registry financing, and two (20.0%) reported that staffing was affected.

Conclusions: Half of responding Caribbean registries reported having been negatively affected by the COVID-19 pandemic, particularly regarding data collection. Improved access to physical data sources for registration activities could mitigate continuing operational challenges in the current pandemic. Accelerating the development of electronic records and direct source abstraction via remote electronic access could support continuous operation of cancer registries amidst future emergencies or operational disruptions.

Citation Format: Sarah Quesnel-Crooks, Rachel Hanisch, Isabelle Soerjomataram, Brenda Edwards, Arica White, Betsy Kohler, Ann Chao, Les Mery, Glennis Andall-Brereton. Impact of the COVID-19 Pandemic on Cancer Registry Operations in the Caribbean [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 31.