bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from 3D-Informed Targeting of the Trop-2 Signal-Activation Site Drives Selective Cancer Vulnerability
Authors: Guerra Emanuela , Trerotola Marco , Relli Valeria , Lattanzio Rossano , Tripaldi Romina , Ceci Martina , Boujnah Khouloud , Pantalone Ludovica , Sacchetti Andrea , Havas Kristina M. , Simeone Pasquale , Travali Nicole , Querzoli Patrizia , Pedriali Massimo , Roversi Pietro , Iezzi Manuela , Tinari Nicola , Antolini Laura , Alberti Saverio
Published: June 2023

Abstract
Next-generation Trop-2–targeted therapy against advanced cancers is hampered by expression of Trop-2 in normal tissues. We discovered that Trop-2 undergoes proteolytic activation by ADAM10 in cancer cells, leading to the exposure of a previously inaccessible protein groove flanked by two N-glycosylation sites. We designed a recognition strategy for this region, to drive selective cancer vulnerability in patients. Most undiscriminating anti–Trop-2 mAbs recognize a single immunodominant epitope. Hence, we removed it by deletion mutagenesis. Cancer-specific, glycosylation-prone mAbs were selected by ELISA, bio-layer interferometry, flow cytometry, confocal microscopy for differential binding to cleaved/activated, wild-type and glycosylation site–mutagenized Trop-2. The resulting 2G10 mAb family binds Trop-2–expressing cancer cells, but not Trop-2 on normal cells. We humanized 2G10 by state-of-the-art complementarity determining region grafting/re-modeling, yielding Hu2G10. This antibody binds cancer-specific, cleaved/activated Trop-2 with Kd < 10−12 mol/L, and uncleaved/wtTrop-2 in normal cells with Kd 3.16×10−8 mol/L, thus promising an unprecedented therapeutic index in patients. In vivo, Hu2G10 ablates growth of Trop-2–expressing breast, colon, prostate cancers, but shows no evidence of systemic toxicity, paving the way for a paradigm shift in Trop-2–targeted therapy.
Data from Targeting Glutamine Metabolism with a Novel Na+/K+-ATPase Inhibitor RX108 in Hepatocellular Carcinoma
Authors: Wei Daoyan , Chen Dongmei , Mou Hongyuan , Chakraborty Sharmistha , Wei Bo , Tan Lin , Lorenzi Philip L. , Qian Xiangping , Yang Peiying
Published: June 2023

Abstract
The poor prognosis and limited therapeutic options for human hepatocellular carcinoma (HCC), the most common form of liver cancer, highlight the urgent need to identify novel therapeutic modalities. Here we describe the antitumor activity and underlying molecular mechanisms of a novel Na+/K+-ATPase inhibitor RX108 in human HCC cells and its xenograft model. RX108 dose-dependently inhibited HCC cell proliferation in vitro and tumor growth in a xenograft mouse model, and that the inhibition was associated with induction of apoptosis. Mechanistically, RX108 significantly downregulated alanine serine cysteine transporter 2 (ASCT2) protein expression and reduced glutamine and glutamate concentration in HCC cells and tumors. Additionally, RX108 exposure led to a significant decrease in cell energy metabolism in Huh7 and Hep3B cells, including decreased levels of glutathione, NADH, NADPH, and mitochondrial respiration oxygen consumption rate (OCR). Furthermore, HCC cells exhibited evidence of glutamine addiction; the antiproliferative effect of RX108 was dependent on glutamine transport. Clinically, elevated ASCT2 mRNA expression in HCCs was associated with unfavorable survival. Taken together, these findings reveal a novel approach to target glutamine metabolism through inhibiting Na+/K+-ATPase and provide a rationale for using RX108 to treat HCC in patients whose tumors express ASCT2 at high levels. RX108 is currently under clinical development.
Predicting the Abscopal Effect: Associated Tumor Histologic Subtypes and Biomarkers
Authors: Nelson Blessie Elizabeth , Adashek Jacob J. , Sheth Aakash Akshay , Subbiah Vivek
Published: June 2023

Radiotherapy is a pillar of cancer treatment, which has historically been used primarily to treat localized disease with curative intent. With the increasing role of radiotherapy for metastatic disease and rapid integration of immunotherapy into the standard of care for various cancers, it has been observed that local radiation to one malignant site can lead to shrinkage of tumors at other sites, a phenomenon termed the “abscopal effect.” Historically, there was little mechanistic elucidation as to how this phenomenon occurs. However, multiple groups have recently identified associated immuno-prognostic factors, such as high post-radiotherapy absolute lymphocyte count, neoantigens, myeloid-derived suppressor cells, and NK cells. The concomitant use of immunotherapy with radiotherapy has been documented to induce the abscopal effect. As immunotherapies continue to be incorporated into most cancer treatment approaches, understanding which patients are more likely to benefit from an abscopal effect may allow for optimization of both systemic and radiotherapeutic strategies. This review highlights the tumor histologic subtypes and biomarkers of the greatest utility for the recognition and identification of patients likely to benefit from the abscopal effect.
Abstract 18: Cervical Cancer Prevention and Control in the Pacific: A Comprehensive Systems Based Approach in Yap State, Federated States of Micronesia
Authors: Palafox Neal , Edilyong James , Reichhardt Martina
Published: June 2023

Purpose: The US Affiliated Pacific Islands, is composed of 3 US Territories (Guam, American Samoa, Commonwealth of the Northern Marianas) and 3 Sovereign Nations (Federated States of Micronesia (FSM), Republic of the Marshall Islands, Republic of Palau. The cervical cancer incidence in several of these island nations are amongst the highest globally. This project is designed to implement a sustainable comprehensive cervical cancer (CC) control program to eliminate CC in the island nations. Yap State, FSM an LMIC is a current project site.

Planning, over 7 years, was through the Cancer Council of the Pacific Islands. Funding is primarily through a CDC Prevention and Control Capacity Building Grant, and other grant funds.

To eliminate cervical cancer in Yap State, FSM through enhanced evidence based public health practices. The primary objective is to increase sustainable capacity to control cervical cancer.

Methods: This non-research project is guided by the principles of community-based participatory development/engagement (CBPE), implementation science, transdisciplinary approach, and capacity building.

The team is composed of 4 working cores, coordinated and led by an implementation core. The 4 cores are 1.) medical protocol and laboratory support 2.) community engagement and outreach 3.) data and informatics 4.) medical modeling and micro-costing. Capacity building through training and infrastructure development is a key component.

Each core works synergistically and interfaces with the Yap Community Advisory Board, which has decision making authority.

Results: Working towards cervical cancer control in a small island LMIC nation, with human resource and health infrastructure limitations, geographic challenges require flexibility and patience. The project processes involve multiple iterations, are culturally/geographically nuanced, and requires constant adjustment to national and international agency and medical regulatory bodies. Strong partnerships with health policy leaders, vaccination programs, clinicians is essential. Modelling projections to understand potential outcomes is necessary.

Conclusions: Cervical Cancer Prevention and Control in Yap State, FSM an LMIC can be done with close and trusting community engagement that is participatory and capacity building. Building strong relationships with local, national, and international programs necessary.

Citation Format: Neal Palafox, James Edilyong, Martina Reichhardt. Cervical Cancer Prevention and Control in the Pacific: A Comprehensive Systems Based Approach in Yap State, Federated States of Micronesia [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 18.
Abstract 2: A Model of Public Health Campaign on the Awareness of Alcohol Flushing and Prevention of Upper Aerodigestive Tract Cancers in East Asia
Authors: Chen Che-Hong , Mochly-Rosen Daria , Hou Su-I
Published: June 2023

Purpose: The purpose of this study is to share a model of public health campaign on the awareness of alcohol flushing and prevention of upper aerodigestive tract cancers in East Asia. East Asians suffers the highest cancer burden attributable to alcohol use with a particularly high incidences of esophageal cancer and other upper aerodigestive trac (UADT) cancers. Alcohol use and carrying the common East Asian-specific dysfunctional mutation in the aldehyde dehydrogenase (ALDH2) gene are two major and synergistic risk factors. Alcohol flushing or alcohol intolerance is the better-known manifestation of ALDH2 deficiency following alcohol consumption. Although UADT cancers are highly preventable, there is a lack of awareness and education on alcohol flushing and its associated health risks in East Asian countries and Asian communities in the U.S.

Methods: Several small-scale university-based studies have shown that alcohol flushing education and awareness could reduce alcohol consumption, indicating that a promising model for community-based public health campaign. In Taiwan, we have successfully created such a model by establishing a non-profitable advocacy group (Taiwan Alcohol Intolerance Education Society, TAIES) and collaborate with community leaders, universities, hospitals, volunteers, and government health promotion agencies to educate the public. Educational materials such as fliers, posters, animation videos, interviews were produced and disseminated widely in public exhibitions, conferences, university/community outreach events and via government websites and news/social media.

Results: An interview with a popular social media influencer reached more than 500,000 viewers within one week. A national “Taiwan No Alcohol Day” on May 9th (59 =無酒, a homophone in Chinese) was also launched to raise awareness since 2019. ‘No Alcohol Day’ received endorsements from the government and more than 150 organizations. A pilot study to incorporate ALDH2 genetic test and education in oral cancer prevention program in Taiwan has been initiated.

Conclusion: Our public health campaign model demonstrated wide reach and strong community and government support. Similar public health campaign on alcohol flushing and cancer risk should also be translated and disseminated in other East Asian countries and to the nearly 19 million Asian Americans in the U.S.

Citation Format: Che-Hong Chen, Daria Mochly-Rosen, Su-I Hou. A Model of Public Health Campaign on the Awareness of Alcohol Flushing and Prevention of Upper Aerodigestive Tract Cancers in East Asia [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 2.
Abstract 29: Detection of Protein Kinase C Isoenzymes in Patients at Risk of Schistosoma Haematobium Induced Bladder Cancer
Authors: Abdulsalam Zanna , Inuwa Adamu , Zailani Sambo Bello
Published: June 2023

Purpose: The Detection of Protein Kinase C Isoenzymes in Patients at risk of Schistosoma haematobium induced Bladder Cancer attending University of Maiduguri Teaching Hospital (UMTH) was carried out. The study comprised of fifty six (56) patients aged ten to fifty six (10-56) years with clinical features of schistosomiasis and confirmed for the presence of S .haematobium eggs in urine samples.

Methods: Twenty milliliters (20ml) of urine was centrifuged at 1000 rpm for 10 min to obtain the sediment. The supernatants were then discarded and the sediment (pellet) re-suspended for S. haematobium. A drop of the sediment were transferred to a glass slide, covered with a cover slip and examined using × 40 objective lens. The urine samples were observed for red blood cells and deposits that might contain proteins. The extraction of total urine template RNA was carried out according to Bioneer Specification and protocol; fifty six (56) of the S. haematobium samples of the patients were used. AccuPrep® Universal RNA Extraction Kit (K-3141) from Bioneer Corporation was used and one page protocol was followed for RNA Extraction. Pre- Denaturation was done for 5min at 94oC, Denaturation for 30sec at 94oC, Annealing for 30sec at 52oC, Extension for 1min at 72oC 35 cycles, Final extension for 5min at 72oC.

Results: Result was run on 2% agarose gel. The study was able to investigate and detect the putative involvement of different PKC isoforms (alpha, beta, and delta) in patient with risk of schistosoma related bladder cancer. Out of the fifty six (56) Multiplex PCR Amplification of PKC Alpha, PKC Beta and PKC Delta from cDNA of extracted RNA template of S. haematobium infected urine sample investigated, only twenty seven (27) showed detection base pairs predicted size from Lane 1-9; of which PKC Alpha (325bp) has two (2) lane; PKC Beta (490bp) has seven (7) lane; and PKC Delta (404bp) has eighteen (18) lane of predicted base pair according to the cDNA size marker, some empty-zero (0) bands lanes and Unpredicted base pair band size were also seen.

Conclusion: The major findings in the present study were the detection of PKC isoenzymes base pairs (band) which indicated the risk level of schistoma induced bladder cancer and stages of the patients using the analysis that proves Isoenzymes are detected by electrophoresis. Snail control, sanitation, avoid contacts with bullinus species and focus on early detection and diagnosis of patients infected with S. haematobium.

Citation Format: Zanna Abdulsalam, Adamu Inuwa, Sambo Bello Zailani. Detection of Protein Kinase C Isoenzymes in Patients at Risk of Schistosoma Haematobium Induced Bladder Cancer [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 29.
Abstract 46: Human Papilloma Virus Vaccination and Its Determinants Among Adolescent Girls Aged 14 Years Old in Hai District of Kilimanjaro Region in Northern Tanzania
Authors: Josephat Jojet
Published: June 2023

Purpose: Human Papilloma Virus (HPV) vaccination is a key primary prevention method against cervical cancer which is given to young girls before onset of sexual activity. In Tanzania, cervical cancer is the most frequent occurring cancer among women and is the leading cause of cancer mortality. The HPV Vaccination program was rolled-out in Tanzania in 2018 for adolescent girls aged 9-14 years old to receive two doses at a six months interval, with the annual vaccine uptake of 46.1%. In 2019, the uptake of the HPV vaccine was 64%, where as the national coverage target is 75%. This study is aimed at assessing the determinants of HPV vaccination among adolescent girls in Hai district, Kilimanjaro region, northern Tanzania.

Methods: A cross-sectional study was conducted between July and August 2020 among 14 years old girls in selected secondary schools within Hai district. Close ended questionnaire interviews were conducted to the girls on the study. Data was analysed using SPSS version 20 and odds ratio was used to assess the association between several factors and HPV vaccination.

Results: A total of 301 adolescent girls aged 14 years consented to the study. HPV vaccination uptake was 65% (196). More than three fifth (60.7%, 119) reported to have received the two required doses. Knowledge of HPV (OR = 5.68 95% CI (0.72- 44.96); p-value = 0.01) and HPV vaccine (OR = 20.11 95% CI (10.88- 37.99); p-value = 0.01) contributed significantly to HPV vaccine uptake among the adolescent girls in the study. More than one-third (34.9%, 105) of the participants were not vaccinated, main reasons adduced for not being vaccinated include lack of proper information about HPV vaccine (60.0%), fear of side effects (14%) and parental refusal (11%).

Conclusion: HPV vaccination is globally accepted as a pivotal primary prevention means against cervical cancer. Emphasizing dissemination of clear and comprehensible information to the society, especially to the adolescent girls, about HPV, cervical cancer and HPV vaccine will significantly increase HPV vaccination among the adolescent girls. Utilizing health care workers and policy makers in providing such education will facilitate its successful implementation.

Citation Format: Jojet Josephat. Human Papilloma Virus Vaccination and Its Determinants Among Adolescent Girls Aged 14 Years Old in Hai District of Kilimanjaro Region in Northern Tanzania [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 46.
Abstract 60: Low-Income is a Negative Prognostic Factor in Patients With MPNST: An NCDB Analysis
Authors: Kennard Jared , Braaten Marco , Silberstein Peter
Published: June 2023

Purpose: Malignant Peripheral Nerve Sheath Tumors (MPNST) are a form of soft tissue tumor that forms from the Schwann cell lineage. Previous studies have noted that treatment at income is generally associated with improved survival in cancer patients. Thus, the objective of this study was to investigate the influence of patient income level on overall survival for patients with MPNST.

Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with MPNST from 2004 to 2019 using the ICD-O-3 histology code 9540. Median Income Quartiles were identified as assigned by the Commission on Cancer Accreditation program and re-classified into three categorical variables: high (HI= >$46,000) middle (MI =$30,000 – $45,999) and low (LI =<$29,000). Descriptive statistics and Kaplan Meier curves were used to measure survival in these patients and Chi-square analyses were used to evaluate differences in demographics. Data was analyzed using SPSS and statistical significance was set at α = 0.05.

Results: Of the 2222 patients with MPNST queried, 2,023 met selection criteria for Kaplan-Meier analysis. Patients in the high-income bracket experienced the longest median survival (83.6 months) compared to 47 and 37 months for the median- and low-income groups, respectively. A Log-Rank test found the difference in survival by income groups to be statistically significant. A Cox Proportional Hazards Model revealed that increased income was not significantly associated with decreased hazard (death), however being in the lowest income bracket was associated with a 41% increase in the relative risk of death (HR 1.41; 95% CI 1.19-1.67). Low-income patients did not present with more advanced disease, however, they experienced a longer average delay in the onset of treatment and were significantly more likely to be uninsured and of Black or Native American) race.

Conclusion: This retrospective cohort study found that for patients with MPNST, low income was independently associated with inferior survival. These patients were more likely to be a minority race and presented with less insurance coverage. They thus experienced a longer duration between diagnosis and the initiation of therapy compared to patients with higher incomes.

Citation Format: Jared Kennard, Marco Braaten, Peter Silberstein. Low-Income is a Negative Prognostic Factor in Patients With MPNST: An NCDB Analysis [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 60.
Abstract 7: Assessment of Baseline Nutritional Status of Pediatric Cancer Patients Treated in the Pediatric Oncology Unit of Jimma University Medical Center: A Cross-Sectional Study
Authors: Gebremedhin Rediet , Abebe Melku Tsefaye
Published: June 2023

Purpose: Childhood cancer becomes a public health problem in developing countries which aggravates the burden of childhood mortality through infectious diseases and malnutrition. Even though it has been shown that malnutrition affects the clinical outcome, survivability and quality of life of cancer patients, studies are still scarce to explore the magnitude of nutritional status and its determinants among pediatric cancer patients in Ethiopia and the study area in particular. Therefore the purpose of this study was to assess the prevalence of malnutrition and its associated factor among pediatrics cancer patients.

Methods: A 1-Year retrospective study was carried out among all patients less than 15 years old admitted between May 2016 to October 2017 to the pediatric oncology unit of Jimma University Medical Center, southwest Ethiopia. Medical charts were reviewed. Sociodemographic and anthropometric measurements were taken. Data were entered into Epidata and analyzed using SPSS version 20 statistical package.

Results: A total of eighty-nine pediatrics cancer patients were admitted at Jimma University Pediatric Oncology and Hematology Unit (POHU). From this, thirty-one (34.8%) were ⇐5 years, and 65.2% were between 6 and 15 years with the mean age of 8 years. Majority, forty eight (53.9%) of pediatrics cancer patients were male. Fourty (44.9%) had hematologic malignancy, thirty six (40.4%) had solid tumors and other Malignancies were about thirty (14.6%). eleven (12.4%), nine (10.1%) were moderately and mildly wasted, respectively based on MUAC and WFH. Fourty (44.9%) of the patients were underweight based on BMI and WFA and twenty (22.5%) were stunted based on HFA. From the total of 27 SAM patients, sixteen (18.0%) were non edematous type of malnutrition, six (6.7%) were edematous types of malnutrition and five (5.6%) were Marasmic kwashakor.

Conclusion: considerable cases of malnutrition were observed among the study population. Therefore Further studies are required to examine the effect of malnutrition on patient prognosis and its effect over the various cancer medications. Strengthening the pediatric oncology unit to identify malnourished children on admission, providing nutritional supplements and identifying and treating infection that could result in malnutrition, early intervention of cancer and creating awareness about malnutrition for the parents could minimize the burden and improve survival of cancer patients.

Citation Format: Rediet Gebremedhin, Melku Tsefaye Abebe. Assessment of Baseline Nutritional Status of Pediatric Cancer Patients Treated in the Pediatric Oncology Unit of Jimma University Medical Center: A Cross-Sectional Study [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 7.
Abstract 70: Prognostic Factors in the Overall Survival of Skin Appendage Carcinoma: An NCDB Analysis
Authors: Wu Xinxin , Swedek Michelle , Silberstein Peter , Vardell Victoria
Published: June 2023

Purpose: Skin appendage carcinoma (SAC) is a malignant neoplasm arising from hair follicles or sweat glands. The incidence rates of cutaneous-type appendageal carcinomas have been increasing in the United States. The epidemiology of SAC is poorly understood due to its rarity. The National Cancer Database (NCDB) was analyzed to determine the primary sites at which SAC presents and the prognostic factors relating to overall survival.

Methods: A retrospective cohort analysis utilizing the NCDB from 2004 to 2019 included patients diagnosed with histologically confirmed SAC between 0-99 years (N=815). Demographic factors were analyzed using Pearson Chi-squared tests, and a multivariate analysis of factors in overall survival was performed via Cox Regression.

Results: The number of cases diagnosed with SAC has steadily increased from 2004 to 2019 (43 and 67, respectively). The majority of the cases analyzed were White (89.8%), male (57.5%), non-Hispanic (91.0%), located in the Atlantic regions (39.9%), insured by Medicare (55.1%), and had a median household income in the top quartile (44.9%). The mean age at diagnosis was 69.1 years (std. deviation=13.1) with an average comorbidity Charlson-Deyo Score of 0.3 (std. deviation=0.7). The most common primary site for SAC was the skin of the face (23.9%), followed by the scalp and neck (22.2%), the trunk (18.7%), and the upper limb and shoulder (14.2%). Site-specific surgical procedure of the primary site was performed in 94.6% of cases. Prognostic factors leading to better overall survival include age at diagnosis younger than 65 years of age (p<0.001; 95% CI= [1.5-3.2]), lower Charlson-Deyo scores (p<0.001), private insurance status (p<0.001; 95% CI= [0.2-0.9]), and surgery of the primary site (p<0.001; 95% CI= [<0.1-5.7]).

Conclusions: There has been an upward trend in the diagnosis of SAC since 2004, with a predilection for White, non-Hispanic, older men in the South and Middle Atlantic regions. Given the rarity of the disease, this study serves as a valuable tool for understanding the prognostic trend of SAC.

Citation Format: Xinxin Wu, Michelle Swedek, Peter Silberstein, Victoria Vardell. Prognostic Factors in the Overall Survival of Skin Appendage Carcinoma: An NCDB Analysis [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 70.
Abstract 74: Supporting African Countries in Developing Cancer Control Programmes: The Added Value of South-South Cooperation
Authors: Nobile Marianna , Ralefala Tlotlo , Lishimpi Kennedy , Mudavanhu Justice
Published: June 2023

Purpose: Advisory support to develop National Cancer Control Programmes (NCCP) is one of the services offered to Ministries of Health by the International Atomic Energy Agency’s (IAEA) Programme of Action for Cancer Therapy (PACT), the World Health Organization (WHO) and the International Agency for Research on Cancer (IARC) within the framework of the WHO-IAEA Joint Programme on Cancer Control. The aim is to assist Member States in developing evidence-based, prioritized, country-specific strategic documents and to strengthen regional coordination to tackle the raising burden of cancer.

Methods: IAEA-WHO-IARC support to develop NCCPs is provided through international experts covering the entire continuum of cancer control. The work encompasses the identification of the country’s needs and capacities through a detailed situational analysis, regular meetings with the team appointed by the Ministry of Health, and in-country workshops with national stakeholders, including civil society organizations, academia, and cancer survivors. Regional experts are involved to give a strategic direction to improve cancer prevention and control services taking into consideration common best practices and challenges.

Results: In the African region the involvement of regional experts strengthened south-south cooperation through the creation of a network of cancer control professionals that can share experiences and lessons learned, paving the way for possible partnerships to implement cancer control priorities. In countries such as Botswana, Zambia and Zimbabwe this approach facilitated the establishment of a dialogue that fostered longer-lasting mutual support for capacity building and the exchange of knowledge to advance the implementation of cancer control activities in sustainable ways.

Conclusion: The development of an NCCP is a critical first step to ensure that effective national responses are put in place to reduce the challenges posed by cancer. This leads to the implementation of priority activities through strategic partnerships, strong coordination mechanisms and resource mobilization to achieve the objective of reducing cancer incidence and mortality. A robust NCCP becomes also the foundation document to further support countries in establishing and expanding radiation medicine services through different initiatives, such as the recently launched Rays of Hope, directly contributing to fulfil the 2030 Agenda and Sustainable Development Goals.

Citation Format: Marianna Nobile, Tlotlo Ralefala, Kennedy Lishimpi, Justice Mudavanhu. Supporting African Countries in Developing Cancer Control Programmes: The Added Value of South-South Cooperation [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 74.
Abstract 77: The Cervical Cancer Treatment Gap Among Mexican Women Without Social Security From 2006-2016 After the Introduction of Public Financing for Treatment
Authors: McClellan Sean , Unger-Saldaña Karla , Espinoza-Tamez Priscilla , Suazo-Zepeda Erick , Potter Michael B. , Barquet-Muñoz Salim Abraham , Torres-Ibarra Leticia , Lamadrid-Figueroa Hector , Lajous Martín
Published: June 2023

Purpose: Women in low-and-middle income countries face persistent barriers to cervical cancer treatment. To reduce financial barriers to cervical cancer treatment, in 2005 Mexico implemented public financing for treatment for women with Seguro Popular, a government insurance program for individuals without social security.

Methods: We estimated the cervical cancer treatment gap for each year of the 11-year period following this policy change by comparing the number of cervical cancer cases with treatment financed by Seguro Popular with estimates of cervical cancer incident cases among women without social security. We used a nationwide administrative database to estimate the number of women receiving financing for treatment. To estimate the number of incident cervical cancer cases among the population without social security, we used national surveys with information on insurance affiliation and incidence estimates from the Global Burden of Disease Study.

Results: From 2006, the first complete year financing for treatment was available, until 2016, the nation-wide treatment gap remained between 0.45 (95% CI 0.43, 0.48) and 0.60 (95% CI 0.59, 0.62). There was no substantial change in the years immediately following the introduction of financing and there was a minimal downward trend over the entire study period (β = -0.012 [95% CI: -.02, -0.001]). The treatment gap was higher in states with greater marginalization.

Conclusions: These results suggest that substantial barriers to cervical treatment persisted after the introduction of public financing for treatment among women without social security. Cervical cancer control programs must be strengthened to reduce barriers to treatment, particularly in the most marginalized Mexican states.

Citation Format: Sean McClellan, Karla Unger-Saldaña, Priscilla Espinoza-Tamez, Erick Suazo-Zepeda, Michael B. Potter, Salim Abraham Barquet-Muñoz, Leticia Torres-Ibarra, Hector Lamadrid-Figueroa, Martín Lajous. The Cervical Cancer Treatment Gap Among Mexican Women Without Social Security From 2006-2016 After the Introduction of Public Financing for Treatment [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 77.
Abstract 83: The Perceived Relationship Between Nutrition and Cancer Among Breast Cancer Patients in Northern Tanzania
Authors: Barnes Garrett , Dwarampudi Sindhu , Msoka-Bright Elizabeth , Gutnik Lily
Published: June 2023

Purpose: Modifiable risk factors, including nutrition, are of particular interest in cancer research. There are limited studies establishing associations between dietary patterns and breast cancer risk. The purpose of this qualitative study is to explore the nutritional practices and perceptions of nutrition and cancer among breast cancer patients in northern Tanzania.

Methods: Participants with confirmed diagnosis of breast cancer were identified in an outpatient setting and included in a larger qualitative study regarding patient breast cancer experiences and reasons for advanced stage at time of diagnosis. Semi-structured interviews were conducted by trained interviewers and transcribed verbatim, then translated from Swahili to English. Thematic coding using a grounded theory approach was done by two independent researchers.

Results: Twenty patients (10 rural and 10 urban) participated in the interviews. The average age was 56; 11 (55%) completed primary education, 10 (50%) were unemployed, and 5 (25%) were married. Fourteen (70%) of the patients had stage 4 breast cancer, 3 (15%) had stage 3, and 3 (15%) had stage 2. Food access varied with 6 (30%) patients identifying as farmers or growing up on coffee plantations. Within this group, two-thirds mentioned pesticide use.

Cancer causes perceived by patients included animal products (n = 5, 25%), cooking oil and fried food (n = 5, 25%), toxins or chemicals in food (n = 6, 30%), alcohol use (n = 5, 25%), smoking (n = 2, 10%), and being overweight/obese (n = 1, 5%). After receiving the cancer diagnosis, 55% (n = 11) modified their diet: decreased or ceased alcohol intake (n = 4, 20%), stopped consuming soda (n = 2, 10%), prepared food by boiling instead of frying (n = 2, 10%), and increased vegetable intake (n = 3, 15%).

Conclusions: Many participants perceived cancer to be caused by dietary factors with some correctly identifying risk factors including smoking, alcohol use, and being overweight/obese. These beliefs were impactful enough to lead many to change their dietary habits after cancer diagnosis. Further research is needed to elucidate the impact of dietary habits on cancer outcomes in Sub-Saharan Africa and provide educational interventions to promote healthier lifestyles in patients.

Citation Format: Garrett Barnes, Sindhu Dwarampudi, Elizabeth Msoka-Bright, Lily Gutnik. The Perceived Relationship Between Nutrition and Cancer Among Breast Cancer Patients in Northern Tanzania [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 83.
Abstract 93: Utility of the Cytosponge for Aetiological Research in Esophageal Squamous Cell Carcinoma: Proof-of-Concept Pilot Study Using Tobacco-Specific Methylation Markers
Authors: Simba Hannah , Taludkar Fazlur Rahman , Middleton Daniel , Mmbaga Blandina , Mremi Alex , McCormack Valerie
Published: June 2023

Purpose: Esophageal cancer caused 544,076 deaths in 2020. It has two major subtypes: esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). A geographically intriguing African Esophageal Cancer Corridor has very high incidence and mortality rates for ESCC. We propose that ESCC research in this corridor might benefit from leveraging advances in tools used for the early detection of EAC, namely using the esophageal sponge cytology. The Cytosponge™ was developed by the University of Cambridge Fitzgerald-laboratory. This pill-on-a-string is an endoscopy-alternative and may form an attractive appropriate health technology in Africa. However, use of the Cytosponge™ for ESCC research in Africa is limited to the CytoSCCAPE study which demonstrated high acceptability and safety of administering the device among 102 asymptomatic adult community volunteers in Kilimanjaro, Tanzania.

Methods: In the present proof-of-concept pilot study, we investigated whether FFPE cytology blocks obtained in the CytoSCCAPE study could be used for exposure-specific methylation studies, via two objectives: (i) examine DNA yield from the cytology blocks and (ii) evaluating if the isolated DNA can be used for investigating DNA methylation-based exposure analysis. Here we performed pyrosequencing to compare DNA methylation status of established tobacco-specific methylation markers (CpG cg05575921 & a nearby CpG locus) in ever compared to never tobacco users.

Results: Among 102 participants (mean age 50 (SD 12) years, 52% female), 58% (N=58) had good DNA yield (>100 ng), 19 had poor DNA concentration (range 3-54.9ng) and 25 had low DNA concentration (range 60-104ng). In total, 49 (77%) samples passed the quantification stage out of 64 samples that were pyrosequenced. Among these 49 participants, median (IQR) cg05575921 methylation was low overall: 33% (27-44) and did not differ between the 8 ever and 41 never-tobacco users (p=0.85). Hypomethylation in tobacco consumers was not observed, in contrast to work published using blood DNA.

Conclusion: We discuss possible reasons for this inconsistency, which include low cellularity and deparaffinization of FFPE sections and provide recommendations for future Cytosponge™ studies for ESCC etiological research.

Citation Format: Hannah Simba, Fazlur Rahman Taludkar, Daniel Middleton, Blandina Mmbaga, Alex Mremi, Valerie McCormack. Utility of the Cytosponge for Aetiological Research in Esophageal Squamous Cell Carcinoma: Proof-of-Concept Pilot Study Using Tobacco-Specific Methylation Markers [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 93.
Data from ADAM Metallopeptidase Domain 12 Facilitates Colorectal Cancer Progression by Inhibiting Hippo Signaling Pathway Activity
Authors: Wang XiaoPeng , Zhu Mo , Zuo Hao , Hou Guowei , Xie Rui
Published: June 2023

Abstract
This work focused on investigating the effect of A Disintegrin And Metalloproteases 12 (ADAM12) on colorectal cancer development. ADAM12 levels within colorectal cancer samples were analyzed by using The Cancer Genome Atlas (TCGA) database. Then, altogether 55 patients with colorectal cancer were enrolled to detect ADAM12 expression. ADAM12 overexpression or knockdown was transfected into colorectal cancer cells. Thereafter, this work examined colorectal cancer cell viability through Cell Counting Kit-8 (CCK-8) and cell clone forming assays. Meanwhile, nude mice were utilized for in vivo analysis. Transwell assays were conducted for detecting migration and invasion of colorectal cancer cells. In addition, mRN and protein expression was analyzed through qRT-PCR, Western blotting (WB) together with IHC staining. As a result, ADAM12 and YAP1 expression increased among colorectal cancer cases, and it indicated the dismal prognostic outcome of patients. Furthermore, ADAM12 promoted colorectal cancer cell growth, migration, invasion along with in vivo growth. ADAM12 suppressed p-MST1/MST1, p-LATS1/LATS1 together with p-YAP1 protein levels within colorectal cancer cells. ADAM12 increased YAP1 and TAZ protein levels as well as CTGF, Cyr61, and Birc5 mRNA expression in colorectal cancer cells. YAP1 inhibitor administration counteracted ADAM12’s function in promoting colorectal cancer cell growth, migration, invasion, and increasing CTGF, Cyr61, and Birc5 expression.
Implications:
Our study indicates that ADAM12 facilitates colorectal cancer progression through suppressing Hippo pathway activity, and that ADAM12 is the candidate therapeutic target and prognostic biomarker for patients with colorectal cancer.
Data from Significance of RB Loss in Unlocking Phenotypic Plasticity in Advanced Cancers
Authors: Venkadakrishnan Varadha Balaji , Yamada Yasutaka , Weng Kenny , Idahor Osasenaga , Beltran Himisha
Published: June 2023

Abstract
Cancer cells can undergo plasticity in response to environmental stimuli or under selective therapeutic pressures that result in changes in phenotype. This complex phenomenon of phenotypic plasticity is now recognized as a hallmark of cancer. Lineage plasticity is often associated with loss of dependence on the original oncogenic driver and is facilitated, in part, by underlying genomic and epigenetic alterations. Understanding the molecular drivers of cancer plasticity is critical for the development of novel therapeutic strategies. The retinoblastoma gene RB1 (encoding RB) is the first tumor suppressor gene to be discovered and has a well-described role in cell-cycle regulation. RB is also involved in diverse cellular functions beyond cell cycle including differentiation. Here, we describe the emerging role of RB loss in unlocking cancer phenotypic plasticity and driving therapy resistance across cancer types. We highlight parallels in cancer with the noncanonical role of RB that is critical for normal development and lineage specification, and the downstream consequences of RB loss including epigenetic reprogramming and chromatin reorganization that can lead to changes in lineage program. Finally, we discuss potential therapeutic approaches geared toward RB loss cancers undergoing lineage reprogramming.
Reproductive Events and Risk of Women's Cancers: From Parturition to Prevention
Authors: Sherman Mark E. , Levi Miriam , Teras Lauren R.
Published: June 2023

Reproductive events beginning with pregnancy and ending with remodeling of the breast after cessation of breastfeeding alter breast structure and function and produce dramatic changes in systemic biology. In aggregate, these processes lower overall risk for breast, tubo-ovarian and endometrial cancers, albeit differentially by molecular subtypes of these tumors. Herein, we explore opportunities for research on protective mechanisms operative during this period of the life course, with the goal of encouraging studies to advance cancer prevention.

See related article by Getz et al., p. 353
Data from KRT17 promotes T-lymphocyte infiltration through the YTHDF2-CXCL10 axis in colorectal cancer
Authors: Liang Wenfeng , Liu Huashan , Zeng Ziwei , Liang Zhenxing , Xie Hao , Li Wenxin , Xiong Li , Liu Zhihang , Chen Mian , Jie Haiqing , Zheng Xiaobin , Huang Liang , Kang Liang
Published: June 2023

Abstract
Poor infiltration of T lymphocytes has been regarded as a crucial mechanism of tumor immune escape. Here, we demonstrate a protective role of KRT17 in colorectal cancer (CRC), where KRT17 reversed the tumor immunosuppressive microenvironment by increasing T-lymphocyte infiltration. High-throughput RNA sequencing suggested KRT17 was significantly upregulated in deficient mismatch repair (dMMR) tumors compared to proficient mismatch repair (pMMR) tumors. In a CRC cohort of 446 cases, KRT17 expression positively correlated with better clinical outcomes. Krt17 overexpression decreased xenograft tumor growth in immune-competent mice. T-cell depletion in a murine model showed that the presence of T lymphocytes was necessary for Krt17-mediated disruption of tumorigenesis. Mass spectrometry and co-immunoprecipitation assays suggested KRT17 caused YTHDF2 degradation through the ubiquitin-proteasome system. Through high-throughput RNA immunoprecipitation sequencing, we found CXCL10 was the target gene of the N6-methyladenosine (m6A) ‘reader’ YTHDF2. KRT17 synergized with anti-PD-1 for better tumor control in an immunotherapy-resistant murine model. In a cohort of patients with CRC receiving pembrolizumab, high KRT17 expression was found within the tumors of responders. Collectively, we elucidated a critical role of KRT17 in CRC to prevent immune escape. These findings present new insights into potential therapeutic strategies and effective markers of immunotherapy reactivity against pMMR tumors.
Data from KRT17 Promotes T-lymphocyte Infiltration through the YTHDF2–CXCL10 Axis in Colorectal Cancer
Authors: Liang Wenfeng , Liu Huashan , Zeng Ziwei , Liang Zhenxing , Xie Hao , Li Wenxin , Xiong Li , Liu Zhihang , Chen Mian , Jie Haiqing , Zheng Xiaobin , Huang Liang , Kang Liang
Published: June 2023

Abstract
Poor infiltration of T lymphocytes has been regarded as a crucial mechanism of tumor immune escape. Here, we demonstrate a protective role of KRT17 in colorectal cancer, where KRT17 reversed the tumor immunosuppressive microenvironment by increasing T-lymphocyte infiltration. High-throughput RNA sequencing suggested that KRT17 was significantly upregulated in deficient mismatch repair (dMMR) tumors compared with proficient mismatch repair (pMMR) tumors. In a colorectal cancer cohort of 446 cases, KRT17 expression positively correlated with better clinical outcomes. Krt17 overexpression decreased xenograft tumor growth in immune-competent mice. T-cell depletion in a murine model showed that the presence of T lymphocytes was necessary for Krt17-mediated disruption of tumorigenesis. Mass spectrometry and coimmunoprecipitation assays suggested KRT17 caused YTHDF2 degradation through the ubiquitin-proteasome system. Through high-throughput RNA immunoprecipitation sequencing, we found that CXCL10 was the target gene of the N6-methyladenosine (m6A) “reader” YTHDF2. KRT17 synergized with anti–PD-1 for better tumor control in an immunotherapy-resistant murine model. In a cohort of patients with colorectal cancer receiving pembrolizumab, high KRT17 expression was found within the tumors of responders. Collectively, we elucidated a critical role of KRT17 in colorectal cancer to prevent immune escape. These findings present new insights into potential therapeutic strategies and effective markers of immunotherapy reactivity against pMMR tumors.
THE ROLE OF THE NURSES IN CARE OF PATIENTS WITH DIGESTIVE SYSTEM DISEASES
Authors: Murdakhaychayeva O. , Lokay B. A. , Krekhovska-Lepiavko O. M.
Published: June 2023

Digestive system diseases can affect individuals of all ages and require comprehensive and specialized care. Effec­tive management of digestive system diseases requires a multidisciplinary approach, involving healthcare professionals with specialized skills and knowledge. Nurses play an integral role in this approach, working in collaboration with other healthcare professionals to provide high-quality care to patients with digestive system diseases.
ВІКОВІ Й СТАТЕВІ ОСОБЛИВОСТІ СТРУКТУРИ ФАКТОРІВ РИЗИКУ РОЗВИТКУ ХРОНІЧНОГО ОБСТРУКТИВНОГО ЗАХВОРЮВАННЯ ЛЕГЕНЬ ТА БРОНХІАЛЬНОЇ АСТМИ
Authors: Ільчишин О. В. , Рега Н. І.
Published: June 2023

У статті розглянуто фактори ризику розвитку хронічного обструктивного захворювання легень (ХОЗЛ) та бронхіальної астми (БА) у пацієнтів різних вікових груп і статей на основі аналізу вітчизняних та зарубіжних джерел. Отримані дані вказують на те, що захворюваність на ХОЗЛ прямо залежить від розповсюдженості тютюнокуріння і професійних шкідливостей, але хворобу можуть викликати й інші шкідливі чинники. Розвитку ХОЗЛ сприяють генетичні аномалії, порушення розвитку легень та прискорене старіння. Основними факторами ризику розвитку БА є чинники, які зумовлюють виникнення астми, і чинники, що сприяють розвитку її загострень. Поширеність БА на даний час недооцінено. Загалом перебіг БА в осіб старшого віку тяжчий та асоціюється з вищою коморбідністю. Саме тому своєчасне діагностування БА не лише сприяє зниженню інвалідизації та підвищенню ефективності лікування, але й допомагає уникнути додаткових фінансових витрат сім’ї і системи охорони здоров’я.