International Agency For Research Research Articles

Gastric cancer actionable genomic alterations across diverse populations worldwide and pharmacogenomics strategies based on precision oncology

Introduction: Gastric cancer is one of the most prevalent types of cancer worldwide. The World Health Organization (WHO), the International Agency for Research on Cancer (IARC), and the Global Cancer Statistics (GLOBOCAN) reported an age standardized global incidence rate of 9.2 per 100,000 individuals for gastric cancer in 2022, with a mortality rate of 6.1. Despite considerable progress in precision oncology through the efforts of international consortia, understanding the genomic features and their influence on the effectiveness of anti-cancer treatments across diverse ethnic groups remains essential.Methods: Our study aimed to address this need by conducting integrated in silico analyses to identify actionable genomic alterations in gastric cancer driver genes, assess their impact using deleteriousness scores, and determine allele frequencies across nine global populations: European Finnish, European non-Finnish, Latino, East Asian, South Asian, African, Middle Eastern, Ashkenazi Jewish, and Amish. Furthermore, our goal was to prioritize targeted therapeutic strategies based on pharmacogenomics clinical guidelines, in silico drug prescriptions, and clinical trial data.Results: Our comprehensive analysis examined 275,634 variants within 60 gastric cancer driver genes from 730,947 exome sequences and 76,215 whole-genome sequences from unrelated individuals, identifying 13,542 annotated and predicted oncogenic variants. We prioritized the most prevalent and deleterious oncogenic variants for subsequent pharmacogenomics testing. Additionally, we discovered actionable genomic alterations in the ARID1A, ATM, BCOR, ERBB2, ERBB3, CDKN2A, KIT, PIK3CA, PTEN, NTRK3, TP53, and CDKN2A genes that could enhance the efficacy of anti-cancer therapies, as suggested by in silico drug prescription analyses, reviews of current pharmacogenomics clinical guidelines, and evaluations of phase III and IV clinical trials targeting gastric cancer driver proteins.Discussion: These findings underline the urgency of consolidating efforts to devise effective prevention measures, invest in genomic profiling for underrepresented populations, and ensure the inclusion of ethnic minorities in future clinical trials and cancer research in developed countries.

Abstract PO3-25-02: Circadian Rhythm Disruption Accelerates Aggressive Mammary Tumorigenesis by Altering Tumor Microenvironment

Abstract \Breast cancer is the most common cancer in women worldwide, leading to over 650,000 deaths worldwide. The circadian rhythm is a 24-hour biological rhythm that controls most cellular, hormonal, and behavioral processes in living organisms, which is why perturbation of these rhythms is linked to several devastating diseases such as cardiovascular diseases, diabetes, and cancer. In the mammary gland, circadian clocks regulate the rhythmic expression of numerous genes. Circadian rhythm disruption (CRD), which has been termed a "carcinogen" by the International Agency for Research in Cancer, is caused by different factors, one of them being shift work. Several epidemiological studies have revealed that women who work night shifts are predisposed to breast cancer. The aim of this study is to investigate the effect of circadian rhythm disruption on aggressive mammary tumorigenesis. To do this, we used genetically engineered mouse models of mammary tumors (HER2-tumor and triple-negative breast tumor, or TNBC). Chronic jetlag, which mimics shift work in mice and is known to cause CRD, was introduced in one group of mice by perturbing the normal light and dark cycles with an 8-hour advance every three days. Wheel-running, which is represented by an actogram, was used to confirm the circadian disruption in the CRD mice. CRD was found to accelerate tumor initiation with a significant increase in weight in the CRD group of mice. CRD enhanced tumor burden significantly compared to LD mice. Our results also showed high metastatic foci in the lungs of CRD mice compared to LD mice. A flow cytometry study showed a higher cancer stem cell population in CRD tumors. Mammosphere assays with tumor-derived cells showed that CRD increased the number and size of the mammospheres compared to the control tumors. The tumor cells were analyzed using single-cell RNA sequencing, which showed that CRD alters the tumor microenvironment by developing more immunosuppressive and "cold" tumors. The tumor-derived organoids (tumoroid) showed resistance to chemotherapeutics. Finally, bioinformatics analysis using single-cell RNA seq data from human breast tumors (TNBC, ER/PR, and HER2) showed that the malignant cells in TNBC tumors had a significantly higher circadian rhythm disrupted score (CRD score) compared to ER/PR tumors. Taken together, our data showed how circadian rhythm disruption affects TNBC tumorigenesis and drug response by altering the tumor microenvironment. Citation Format: Olajumoke Ogunlusi, Mrinmoy Sarkar, Tristan Nguyen, Devon Boland, James Cai, Arhit Chakrabarti, Bani Mallick, Alex Keene, Tapasree Roy Sarkar. Circadian Rhythm Disruption Accelerates Aggressive Mammary Tumorigenesis by Altering Tumor Microenvironment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-25-02.

Canadian colorectal cancer screening programs: How do they measure up using the International Agency for Research on Cancer criteria for organized screening?

Abstract Background Canada has one of the highest incidences of colorectal cancer (CRC) worldwide. CRC screening improves CRC outcomes and is cost-effective. This study compares Canadian CRC screening programs using essential elements of an organized screening program outlined by the International Agency for Research on Cancer (IARC). Methods We collaborated with the Cancer Screening in 5 continents (CanScreen5) program, an initiative of IARC. Standardized data collection forms were sent to representatives of provincial and territorial CRC screening programs. Twenty-five questions were selected to reflect IARC’s essential elements of an organized screening program. We performed a qualitative analysis of Canada’s CRC screening programs and compared programs within Canada and internationally. Results CRC screening programs exist in 10 provinces and 2 territories. None of the programs in Canada met all the essential criteria of an organized screening program outlined by IARC. Three programs do not send invitations to participate in screening. Among those that do, 4 programs do not include a stool test kit in the invitations. While all provinces met the essential elements for leadership, governance, finance, and access to essential services, there was more heterogeneity in the domains of service delivery as well as information systems and quality assurance. Conclusions There is considerable heterogeneity in the design of CRC screening programs in Canada and worldwide. Programs should strive to meet all the essential IARC criteria for organized screening if local resources allow, such as issuing invitations and implementing systems to track and compare outcomes to maximize screening program quality, effectiveness, and impact.

Ppb-level unsymmetrical dimethylhydrazine detection based on In2O3 hollow microspheres with Nd doping

As one of main high-energy fuels for rocket launching, unsymmetrical dimethylhydrazine (UDMH) and its decomposition products do harm to environment and human health. It is significant to develop a device to monitor its leakage. In this work, a UDMH gas sensor based on In2O3 hollow microspheres with Nd dopant was fabricated. The pure, 1.0mol%, 3.0mol% and 5.0mol% Nd doped In2O3 were synthesized via one-step solvothermal method. Among them, 3.0% Nd-In2O3 based sensor exhibits the highest response toward UDMH vapor. Its response value to 100 ppm UDMH is 183.3 at optimal working temperature of 250°C, 6.8 times higher than that of pure In2O3 (26.8). Besides high response to UDMH, the 3% Nd-In2O3 based sensor represents excellent selectivity, rapid response speed (2s) and ultra-low theoretical LOD to UDMH (0.28 ppb). The improved gas sensing performance via Nd doping could be attributed to the enhanced specific surface area, increased concentration of adsorbed oxygen and improved adsorption capacity for UDMH molecular on the surface. The excellent sensing performance of Nd doped In2O3 hollow microspheres makes it a promising candidate for real-time UDMH detection. Environmental ImplicationUnsymmetrical dimethylhydrazine (1,1-dimethylhydrazine, UDMH) is a colorless, highly toxic compound. It has been classified as 2B human carcinogen by the International Agency for Research on Cancer (IARC). The National Institute for Occupational Safety and Health (SLOSH) also regulates the UDMH concentration limitation of 0.06 ppm in workplace. Therefore, it is urgent to fabricate a device for detecting the UDMH leakage timely during its storage and transport. In our work, Nd doped In2O3 hollow microspheres based chemiresistive gas sensor for the monitoring of UDMH was developed, which will promote the practical applications for gas sensor.

Protective Effects of Melatonin against Carcinogen-Induced Oxidative Damage in the Thyroid.

Melatonin, primarily synthesized in the pineal gland, plays a crucial role in regulating circadian rhythms and possesses significant antioxidative properties. By neutralizing free radicals and reducing oxidative stress, melatonin emerges as a promising agent for the prevention and therapy of many different disorders, including cancer. This paper reviews the relationship between the thyroid gland and melatonin, presenting experimental evidence on the protective effects of this indoleamine against oxidative damage to macromolecules in thyroid tissue caused by documented carcinogens (as classified by the International Agency for Research on Cancer, IARC) or caused by potential carcinogens. Furthermore, the possible influence on cancer therapy in humans and the overall well-being of cancer patients are discussed. The article highlights melatonin's essential role in maintaining thyroid health and its contribution to management strategies in patients with thyroid cancer and other thyroid diseases.

FACTORS INFLUENCING THE BEHAVIOR OF CONDUCTING BREAST SELF-EXAMINATION ON WOMEN OF CHILDBEARING AGE IN THE BANDUNG HEALTH CENTER AREA SERANG REGENCY IN 2023

Global Buren of Cancer data shows data on cancer patients in the world as many as 19.3 million cases. The highest number is in breast cancer patients totaling 2.261 million cases (Globocan, 2020). Data from the International Agency for Research on Cancer (IARC) in 2020, the number of new cases of breast cancer has increased and become the highest incidence of cancer in women, namely breast cancer with 665,339 new cases and 131,252 deaths from breast cancer worldwide (Globocan, 2020). The low desire of women to do BSE examination can be influenced by internal and external factors. Internal factors include knowledge, attitudes and family history of cancer. As for external factors, namely sources of information and parental support. This type of research is quantitative research with a research design using a cross sectional approach. The purpose of this study is to determine the factors that influence the behavior of conducting breast self-examination in women of childbearing age in the Bandung Health Center area, Serang Regency in 2023. By using the total sampling technique, the determination of the sample obtained was as many as 120 mothers who met the inclusion criteria. Chi Square test results show a significant relationship between knowledge, education, the role of health workers, and information media with breast self-examination behavior (P−value 0.000).

The State of Oncology Care in Russia: Localization Structure Features, Quality of Recording, and Survival of Cancer Patients in the Major Age Groups of the Population (population study). Part 6

Malignant neoplasms are considered among the most serious and prevalent diseases in many countries worldwide. In the course of our research, we conducted a review where we synthesized findings from five scientific articles providing detailed descriptions of age-related patterns of prevalence, structure, and survival among oncology patients. The final population-based study presents a culmination of all identified characteristics of this process, particularly regarding the role of age in the characteristics of prevalence and survival of cancer patients, which holds significant importance. The study utilized data from the International Agency for Research on Cancer (IARC), handbooks from the P. A. Herzen MNIOI and the N. N. Petrov National Medical Research Center of Oncology, as well as data from population-based cancer registries databases from the Saint Petersburg and Northwestern Federal District of Russia. Data processing was conducted using licensed software MS Excel 2013–2016 and STATISTICA 6.1. Modified Eurocare software, alongside mathematical, bibliographic, and statistical methods, was employed for survival calculations. The population-based study allowed for a detailed examination of the dynamics of age-specific indicators of morbidity, mortality, quality of initial patient management for MN, and survival rates of MN patients, consolidating vast datasets from across Russia and the Northwestern Federal District of Russia. All gathered and analyzed data indicate an enhancement in the quality of initial patient management for MN, a reduction in mortality rates, and an increase in survival rates.

Global burden of bladder cancer mortality in 2020 and 2040 according to GLOBOCAN estimates

IntroductionIn 2020, bladder cancer (BC) was the seventh most prevalent cancer in the world, with 5-year prevalence of more than 1.7 million cases. Due to the main risk factors—smoking and chemical exposures—associated with BC, it is considered a largely preventable and avoidable cancer. An overview of BC mortality can allow an insight not only into the prevalence of global risk factors, but also into the varying efficiency of healthcare systems worldwide. For this purpose, this study analyzes the national mortality estimates for 2020 and projected future trends up to 2040.Materials and methodsAge-standardized mortality rates per 100,000 person-years of BC for 185 countries by sex were obtained from the GLOBOCAN 2020 database, operated by the International Agency for Research on Cancer (IARC). Mortality rates were stratified according to sex and Human Development Index (HDI). BC deaths were projected up to 2040 on the basis of demographic changes, alongside different scenarios of annually increasing, stable or decreasing mortality rates from the baseline year of 2020.ResultsIn 2020, nearly three times more men died from BC than women, with more than 210,000 deaths in both sexes combined, worldwide. Regardless of gender, more than half of the total BC deaths were from countries with a very high HDI. According to our projections, while the number of deaths for men can only increase up to 54% (from 159 to around 163–245 thousand), for women it is projected to increase two- to three-fold (from 50 to around 119–176 thousand) by 2040. The burden of BC mortality in countries with a very high HDI versus high HDI appears to converge by 2040 for both sexes.ConclusionOpposite mortality trends by gender highlight the urgent need for immediate interventions to expand anti-tobacco strategies, especially for women. The implementation of more strict occupational health and safety regulations could also prevent exposures associated with BC. Improving the ability to detect BC earlier and access to treatment can have a significant positive impact on reducing mortality rates, minimizing economic costs, and enhancing the quality of life for patients.

The Risk of Oral Cancer and the High Consumption of Thermally Processed Meat Containing Mutagenic and Carcinogenic Compounds.

The International Agency for Research on Cancer has classified the consumption of heat-processed meat as a direct human carcinogen and the consumption of red meat as a probable carcinogen. Mutagenic and carcinogenic compounds present in meat dishes include, among others, polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HAAs). These compounds can cause the development of gastrointestinal cancer. Oral cancer is one of the world's research priorities due to the ever-increasing incidence rate. However, the effect of diet on oral cancer is still a poorly recognized issue. The aim of this study was to assess the relationship between the risk of oral cancer and dietary ingredients with a particular emphasis on red meat and thermally processed meat. This study was conducted among patients with oral cancer in 2022 and 2023. The shortened standardized Food Frequency Questionnaire (FFQ) and a multivariate regression statistical analysis were used. The high consumption of red meat in general and thermally processed meat, especially smoked, fried, roasted and boiled, increases the risk of oral cavity cancer. Limiting the consumption of meat products and modifying the methods of preparing meat dishes may reduce exposure to carcinogenic compounds from the diet and thus reduce the risk of developing oral cancer.

Abstract LB143: Environmental assessment of alcohol-related policies and practices at US cancer organizations

Abstract In 1998, the International Agency for Research on Cancer (IARC) declared that the consumption of alcoholic beverages was a class I carcinogen to humans; the designation was reaffirmed in 2007 and 2010. Despite this, approximately 4% of new cancer cases worldwide in 2020 were attributable to alcohol intake. Growing evidence indicates that alcohol use increases the risk of cancers of the upper aerodigestive tract (oral cavity, pharynx, esophagus, and larynx) and lower digestive tract (colon, rectum, and liver). Over half of the 6.3 million cases of these cancers are considered preventable, underscoring notable gaps regarding alcohol consumption and cancer prevention. Despite (1) the longstanding designation of alcohol as an established carcinogen, (2) an increasing and consistent body of data noting alcohol as a leading contributor to the global cancer burden, and (3) the publication of policy statements by authoritative sources, it is unclear whether cancer-focused institutions are aware of these facts or are acting on these data (i.e., implementing evidence-based policies and practices to limit alcohol-related cancer risks for their employees, guests, or the public). Driven by these data and shortfalls, we developed a 22-item survey to inquire about cancer organizations' interpretation of current literature, existing policies, decision-making processes, inclination to act, and perceived responsibility to lead in the realms of public education and policy implementation to mitigate alcohol-related cancer risks in the public’s interest. The survey will be sent to over 100 leading U.S. cancer organizations, including NCI-designated- and other major cancer centers, cancer-oriented professional organizations, and cancer-research organizations. It underwent rigorous testing for clarity, brevity, and expected response time, also drawing upon the expertise of five survey-science professionals. The study is under institutional review board (IRB) review, and we anticipate the survey’s distribution in the first quarter of the calendar year 2024. We expect to share the survey instrument and results during the meeting. Citation Format: Meghan Si, Stephanie Martch, Sanjay Shete, Ernest Hawk. Environmental assessment of alcohol-related policies and practices at US cancer organizations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB143.

Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.

This article presents global cancer statistics by world region for the year 2022 based on updated estimates from the International Agency for Research on Cancer (IARC). There were close to 20 million new cases of cancer in the year 2022 (including nonmelanoma skin cancers [NMSCs]) alongside 9.7 million deaths from cancer (including NMSC). The estimates suggest that approximately one in five men or women develop cancer in a lifetime, whereas around one in nine men and one in 12 women die from it. Lung cancer was the most frequently diagnosed cancer in 2022, responsible for almost 2.5 million new cases, or one in eight cancers worldwide (12.4% of all cancers globally), followed by cancers of the female breast (11.6%), colorectum (9.6%), prostate (7.3%), and stomach (4.9%). Lung cancer was also the leading cause of cancer death, with an estimated 1.8 million deaths (18.7%), followed by colorectal (9.3%), liver (7.8%), female breast (6.9%), and stomach (6.8%) cancers. Breast cancer and lung cancer were the most frequent cancers in women and men, respectively (both cases and deaths). Incidence rates (including NMSC) varied from four-fold to five-fold across world regions, from over 500 in Australia/New Zealand (507.9 per 100,000) to under 100 in Western Africa (97.1 per 100,000) among men, and from over 400 in Australia/New Zealand (410.5 per 100,000) to close to 100 in South-Central Asia (103.3 per 100,000) among women. The authors examine the geographic variability across 20 world regions for the 10 leading cancer types, discussing recent trends, the underlying determinants, and the prospects for global cancer prevention and control. With demographics-based predictions indicating that the number of new cases of cancer will reach 35 million by 2050, investments in prevention, including the targeting of key risk factors for cancer (including smoking, overweight and obesity, and infection), could avert millions of future cancer diagnoses and save many lives worldwide, bringing huge economic as well as societal dividends to countries over the forthcoming decades.

The influence of cation exchange on the possible mechanism of erionite toxicity: A synchrotron-based micro-X-ray fluorescence study on THP-1-derived macrophages exposed to erionite-Na

Fibrous erionite is the only zeolite classified as Group 1 carcinogen by the International Agency for Research on Cancer (IARC). Carcinogenesis induced by erionite is thought to involve several factors as biopersistence, the iron role and cation exchange processes. To better understand these mechanisms, a detailed investigation at the micro scale was performed, collecting elemental information on iron and cation release and their distribution in biological systems by synchrotron micro-X-ray fluorescence mapping (SR-micro-XRF) and synchrotron micro-X-ray absorption spectroscopy (SR-micro-XANES) at the TwinMic beamline (Elettra synchrotron) and at the ID21 beamline of the European Synchrotron Radiation Facility (ESRF). By microscopy and chemical mapping, highly detailed maps of the chemical and morphological interaction of biological systems with fibres could be produced. In detail, THP-1 cell line derived macrophages, used as in vitro model, were analysed during erionite-Na phagocytosis at different time intervals, after single dose exposure. For comparison, cellular fluorescent probes were also used to evaluate the intracellular free sodium and calcium concentrations. Synchrotron analyses visualised the spatial distribution of both fibre and mineral particle associated metals during the phagocytosis, describing the mechanism of internalisation of erionite-Na and its accessory mineral phases. The intracellular distribution of metals and other cations was mapped to evaluate metal release, speciation changes and/or cation exchange during phagocytosis. The fluorescent probes complemented microchemical data clarifying, and confirming, the cation distribution observed in the SR-micro-XRF maps. The significant cytoplasmic calcium decrease, and the concomitant sodium increase, after the fibre phagocytosis seemed due to activation of plasma membrane cations exchangers triggered by the internalisation while, surprisingly, the ion-exchange capacity of erionite-Na could play a minor role in the disruption of the two cations intracellular homeostasis. These results help to elucidate the role of cations in the toxicity of erionite-treated THP-1 macrophages and add knowledge to its carcinogenicity process.

EPIDEMIOLOGICAL ANALYSIS OF MORBIDITY AND MORTALITY FROM CANCER
 OF THE UTERINE BODY OF THE POPULATION OF ALMATY IN 2012-2022

Relevance: Cancer of the uterine body (CUB) is one of the most common types of malignant neoplasms and ranks 6th among the most
 frequently diagnosed cancers in women in the world. Despite the improvement of treatment methods, the incidence and mortality from CUB
 remain high. According to forecasts by the International Agency for Research on Cancer, by 2040, the incidence of CUB is expected to increase
 by more than 50%. Therefore, studying the epidemiological features of CUB is important for developing prevention and treatment strategies.
 The study aimed to analyze the morbidity and mortality from CUB in the female population of Almaty in 2012-2022.
 Methods: The material for the study was data from the information system «Electronic Register of Inpatient Patients» on newly
 identified cases and those registered at the dispensary with a histologically confirmed diagnosis of CUB «Malignant neoplasm of the
 uterine body» (From 54 to ICD-10) of the population of Almaty for the period from 2012 to 2022. Epidemiological indicators were calculated
 per 100,000 female population. The absolute growth, growth rate, and visibility indicators were calculated to analyze changes in intensive
 indicators over time. The database was formed, and the results were statistically processed using Microsoft Excel and the SPSS Statistics
 26 statistical package.Results: There was an increase in the crude incidence of CUB in the female population of Almaty in 2012-2022 by 3.14 times. The incidence
 of CUB increased with age, where the peak incidence was noted in the age group of 60-64 years (58.9±8.68 cases per 100,000 female population
 95% CI = 39.5-78.2). Mortality from CUB decreased from 13.5 cases in 2012 to 1.3 cases per 100,000 female population in 2022 (10.4 times).
 Conclusion: The conducted epidemiological analysis showed the need for further detailed study of the risk factors contributing to the
 occurrence of CUB and improvement of the activities of health services, starting from the primary health care level.

Nitrosyl-heme and heme iron intake from processed meats and risk of colorectal cancer in the EPIC-Spain cohort.

The International Agency for Research on Cancer classified processed meats (PMs) as "carcinogenic" and red meat as "probably carcinogenic" for humans. The possible relationship between colorectal cancer (CRC) risk and the mechanisms involved in the carcinogenesis of PMs have not been established yet. Nitrosyl-heme and heme iron have been proposed as potential-related compounds. The aim of this study was to determine the association between nitrosyl-heme and heme iron intake and CRC risk among participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain study. This prospective study included 38,262 men and women from the EPIC-Spain study. Food consumption was assessed using diet history and composition tables, with heme iron and nitrosyl-heme intake calculated from estimated PM item intakes and laboratory analyses. HR estimates were obtained by proportional hazard models, stratified by age at recruitment and study centre and adjusted for sex, total energy intake, education, smoking, body mass index, waist size, physical activity, lifetime alcohol, fibre, calcium and familiar CRC history. During a mean follow-up of 16.7years, 577 participants were diagnosed with CRC. We found no overall association between nitrosyl-heme (HRT3vsT1: 0.98 (95%IC: 0.79-1.21)) or heme iron intakes (HRT3vsT1: 0.88 (95%IC: 0.70-1.10)) with CRC risk, nor according to tumour subtypes. Our study found no evidence supporting a link between nitrosyl-heme or heme iron intake and CRC risk in Spanish subjects. As research on nitrosyl-heme is preliminary, more heterogeneous studies are necessary to provide more convincing evidence on their role in CRC carcinogenesis.

TiO2 Nanocomposite Coatings and Inactivation of Carbapenemase-Producing Klebsiella Pneumoniae Biofilm-Opportunities and Challenges.

The worldwide increase of multidrug-resistant Gram-negative bacteria is a global threat. The emergence and global spread of Klebsiella pneumoniae carbapenemase- (KPC-) producing Klebsiella pneumoniae represent a particular concern. This pathogen has increased resistance and abilities to persist in human reservoirs, in hospital environments, on medical devices, and to generate biofilms. Mortality related to this microorganism is high among immunosuppressed oncological patients and those with multiple hospitalizations and an extended stay in intensive care. There is a severe threat posed by the ability of biofilms to grow and resist antibiotics. Various nanotechnology-based strategies have been studied and developed to prevent and combat serious health problems caused by biofilm infections. The aim of this review was to evaluate the implications of nanotechnology in eradicating biofilms with KPC-producing Klebsiella pneumoniae, one of the bacteria most frequently associated with nosocomial infections in intensive care units, including in our department, and to highlight studies presenting the potential applicability of TiO2 nanocomposite materials in hospital practice. We also described the frequency of the presence of bacterial biofilms on medical surfaces, devices, and equipment. TiO2 nanocomposite coatings are one of the best long-term options for antimicrobial efficacy due to their biocompatibility, stability, corrosion resistance, and low cost; they find their applicability in hospital practice due to their critical antimicrobial role for surfaces and orthopedic and dental implants. The International Agency for Research on Cancer has recently classified titanium dioxide nanoparticles (TiO2 NPs) as possibly carcinogenic. Currently, there is an interest in the ecological, non-toxic synthesis of TiO2 nanoparticles via biological methods. Biogenic, non-toxic nanoparticles have remarkable properties due to their biocompatibility, stability, and size. Few studies have mentioned the use of nanoparticle-coated surfaces as antibiofilm agents. A literature review was performed to identify publications related to KPC-producing Klebsiella pneumoniae biofilms and antimicrobial TiO2 photocatalytic nanocomposite coatings. There are few reviews on the antibacterial and antibiofilm applications of TiO2 photocatalytic nanocomposite coatings. TiO2 nanoparticles demonstrated marked antibiofilm activity, but being nano in size, these nanoparticles can penetrate cell membranes and may initiate cellular toxicity and genotoxicity. Biogenic TiO2 nanoparticles obtained via green, ecological technology have less applicability but are actively investigated.

Human Cytomegalovirus Oncoprotection across Diverse Populations, Tumor Histologies, and Age Groups: The Relevance for Prospective Vaccinal Therapy.

The oncogenicity of the human cytomegalovirus (CMV) is currently being widely debated. Most recently, mounting clinical evidence suggests an anti-cancer effect via CMV-induced T cell-mediated tumor destruction. However, the data were mostly obtained from single-center studies and in vitro experiments. Broad geographic coverage is required to offer a global perspective. Our study examined the correlation between country-specific CMV seroprevalence (across 73 countries) and the age-standardized incidence rate (of 34 invasive tumors). The populations studied were stratified according to decadal age periods as the immunologic effects of CMV seropositivity may depend upon age at initial infection. The International Agency for Research on Cancer of the World Health Organization (IARC WHO) database was used. The multivariate linear regression analysis revealed a worldwide inverse correlation between CMV seroprevalence and the incidences of 62.8% tumors. Notably, this inverse link persists for all cancers combined (Spearman's ρ = -0.732, p < 0.001; β = -0.482, p < 0.001, adjusted R2 = 0.737). An antithetical and significant correlation was also observed in particular age groups for the vast majority of tumors. Our results corroborate the conclusions of previous studies and indicate that this oncopreventive phenomenon holds true on a global scale. It applies to a wide spectrum of cancer histologies, additionally supporting the idea of a common underlying mechanism-CMV-stimulated T cell tumor targeting. Although these results further advance the notion of CMV-based therapies, in-depth investigation of host-virus interactions is still warranted.

Abstract 4872: Elevated colorectal cancer incidence among American Indian/Alaska Native persons in Alaska compared to other populations worldwide

Abstract Background: Colorectal cancer (CRC) is a leading cancer worldwide. Incidence varies greatly by country and racial group. We present recent CRC incidence and mortality rates among American Indian/Alaska Native (AI/AN) persons in Alaska and compare them to rates among other racial groups in Alaska and AI/AN persons in other regions of the United States, and to published CRC incidence rate estimates for other countries around the world. Methods: To calculate CRC incidence in the United States, we used U.S. Cancer Statistics data, which includes cancer registry data from the Centers for Disease Control and Prevention’s (CDC) National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program. Cancer data for AI/AN persons in Alaska came from the Alaska Cancer Registry as well as the Alaska Native Tumor Registry. Death data came from the CDC’s National Death Index, which was linked with the Indian Health Service patient registry database to address race misclassification in AI/AN populations, to create the United States Cancer Statistics American Indian and Alaska Native Mortality Database. This database was used to calculate CRC mortality rates for AI/AN persons in this study. Rates were age-adjusted using the World Health Organization’s World Standard Population (2000-2025), so that rates for AI/AN persons in the United States could be more comparable to rates that have been estimated for countries around the world. Estimates of worldwide CRC incidence came from the International Agency for Research on Cancer Global Cancer Observatory GLOBOCAN 2020 database. Results: AI/AN persons in Alaska (males and females combined) had the highest CRC incidence rate (58.4 per 100,000 people) in the year 2020, when compared to AI/AN persons in every other region of the United States. Within Alaska, AI/AN persons had a higher CRC incidence rate than persons of any other racial group. When compared with published CRC incidence rates worldwide, the rate for AI/AN persons in Alaska was higher than the rates reported for any country in the world in 2020. The country with the highest recorded CRC incidence rate in 2020 was Hungary (45.3 per 100,000 people). AI/AN persons in Alaska also had the highest CRC mortality rate (27.1 per 100,000 people) in 2020. Worldwide, the country with the highest recorded CRC mortality rate in 2020 was Slovakia (21.0 per 100,000 people). Conclusions: This review of CRC incidence and mortality rates from populations in the US and worldwide showed that AI/AN persons in Alaska had the highest documented incidence and mortality rates of CRC in the world in 2020. Health systems serving AI/AN persons in Alaska could implement policies and interventions that support colorectal cancer screening, to reduce the burden of this preventable disease. Citation Format: Donald Haverkamp, Diana Redwood, Elena Roik, Stephen Vindigni. Elevated colorectal cancer incidence among American Indian/Alaska Native persons in Alaska compared to other populations worldwide [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4872.

The association between organised colorectal cancer screening strategies and reduction of its related mortality: a systematic review and meta-analysis

BackgroundTo assess the long-term association between organised colorectal cancer (CRC) screening strategies and CRC-relate mortality.MethodsWe systematically reviewed studies on organised CRC screening through PubMed, Ovid Medline, Embase and Cochrane from the inception. We retrieved characteristics of organised CRC screening from included literature and matched mortality (over 50 years) of those areas from the International Agency for Research on Cancer in May 2023. The variations of mortality were reported via the age-standardised mortality ratio. A random-effects model was used to synthesis results.ResultsWe summarised 58 organised CRC screening programmes and recorded > 2.7 million CRC-related deaths from 22 countries where rollout screening programmes were performed. The CRC screening strategy with faecal tests (guaiac faecal occult blood test (gFOBT) or faecal immunochemical tests (FIT)) or colonoscopy as the primary screening offer was associated with a 41.8% reduction in mortality, which was higher than those offered gFOBT (4.4%), FIT (16.7%), gFOBT or FIT (16.2%), and faecal tests (gFOBT or FIT) or flexible sigmoidoscopy (16.7%) as primary screening test. The longer duration of screening was associated with a higher reduction in the pooled age-standardised mortality ratio. In particular, the pooled age-standardised mortality ratio became non-significant when the screening of FIT was implemented for less than 5 years.ConclusionsA CRC screening programme running for > 5 years was associated with a reduction of CRC-related mortality. Countries with a heavy burden of CRC should implement sustainable, organised screening providing a choice between faecal tests and colonoscopy as a preferred primary test.

Exposure to cobalt metal (without tungsten carbide) and some cobalt compounds: a literature review

Cobalt is a natural metallic element with extensive applications across multiple industries, and a critical metal for lithium-ion battery production. Cobalt's only known biological function is its role as a metal component of vitamin B12. Other cobalt compounds have been described as toxic to the environment and the human body following excessive exposure. The International Agency for Research on Cancer (IARC) has classified cobalt, including cobalt metal and soluble cobalt(II) salts, as Group 2A, meaning it is probably carcinogenic to humans. This review aims to present a comprehensive overview of historical and current sources of cobalt in diverse exposure settings, along with its various intake routes. An extensive literature search was conducted between September 2021 and January 2022, analysing over 300 publications. The primary goal of these studies was to identify cobalt sources, intake routes, and exposure pathways. Workers may be exposed to various cobalt compounds and metal powders primarily through inhalation, but exposure can also occur via skin contact or ingestion. For the general population, food typically arises as the predominant source of cobalt exposure. Furthermore, exposure may occur through ambient air, tobacco smoke, and medical implants.

A magnetic graphene oxide and UiO-66 based homogeneous dual recognition electrochemical aptasensor for accurate and sensitive detection of aflatoxin B1

Aflatoxin (AFs) contamination is one of the serious food safety issues. Aflatoxin B1 (AFB1) is the most common and toxic aflatoxin, which has been classified as a class 1 carcinogen by the International Agency for Research on Cancer (IARC). It is extremely destructive to liver tissue. Developing a convenient and sensitive detection technique is essential. In this paper, we developed a homogeneous dual recognition strategy based electrochemical aptasensor for accurate and sensitive detection of aflatoxin B1 (AFB1) based on the magnetic graphene oxide (MGO) and UiO-66. The MGO was synthesized for the recognition and magnetic separation of AFB1 from complex samples. UiO-66/ferrocenecarboxylic acid (Fc)/aptamer composites were constructed as both recognition and signal probes. The probes would specifically capture AFB1 enriched by MGO, which enables dual recognition in homogeneous solution, thus further improving the accuracy of AFB1 detection. The electrochemical aptasensor for AFB1 had a linear range from 0.005 to 500 ng mL−1. Additionally, the limit of detection was 1 pg mL−1. It shows a favorable potential for both sensitive and accurate detection of AFB1 in real samples.