Higher Cancer Mortality Research Articles

Breast cancer survival in women living with HIV.

Sub-Saharan Africa, with about 10% of the world's population, accounts for nearly 70% of the global burden of HIV infection.1 Women in the region, especially young women, carry more than their share of that burden. In 2020, adolescent girls and young women (aged 15–24 years) accounted for 10% of the population, but 25% of HIV infections. In addition, although African countries have lower incidence rates of breast cancer than European and North American countries do, they have disproportionately high breast cancer mortality rates.

Korean Surgical Practice Guideline for Pancreatic Cancer 2022: A summary of evidence-based surgical approaches

Pancreatic cancer is the eighth most common cancer and the fifth most common cause of cancer-related deaths in Korea. Despite the increasing incidence and high mortality rate of pancreatic cancer, there are no appropriate surgical practice guidelines for the current domestic medical situation. To enable standardization of management and facilitate improvements in surgical outcome, a total of 10 pancreatic surgical experts who are members of Korean Association of Hepato-Biliary-Pancreatic Surgery have developed new recommendations that integrate the most up-to-date, evidence-based research findings and expert opinions. This is an English version of the Korean Surgical Practice Guideline for Pancreatic Cancer 2022. This guideline includes 13 surgical questions and 15 statements. Due to the lack of high-level evidence, strong recommendation is almost impossible. However, we believe that this guideline will help surgeons understand the current status of evidence and suggest what to investigate further to establish more solid recommendations in the future.

Abstract P3-14-05: Racial/ethnic disparities in cancer mortality after a second breast cancer

Abstract Background: Eighteen percent of breast cancer survivors will develop a second cancer within 25 years of diagnosis, of which breast cancer is the most common type. We have previously reported a higher cancer mortality among survivors who had a second cancer compared to a first cancer. In this study, we examined whether the increased cancer mortality from a second breast cancer differs by race/ethnicity. Method: A prospective cohort study was conducted among breast cancer survivors who developed a second breast cancer using data collected from the Surveillance, Epidemiology, and End Results (SEER) 18 database between 2000 and 2016. Hazard ratio (HR) and 95% confidence interval (CI) for cancer mortality after second breast cancer were estimated from Cox proportional hazard regression, comparing Non-Hispanic Black (NHB), Non-Hispanic American Indian/Alaska Native (NHAIAN), Non-Hispanic Asian/Pacific Islander (NHAPI), and Hispanic women to Non-Hispanic White (NHW) women. Models were adjusted for age at diagnosis, year of diagnosis, tumor stage, tumor grade, estrogen receptor (ER) status, and treatments (surgery, radiotherapy, and chemotherapy) of the second breast cancer. Analyses were also stratified by second cancer ER status, tumor stage, age at diagnosis (<50, 50-75, and ≥75 years), and time since first breast cancer diagnosis (≤5 and >5 years). In a subgroup of women diagnosed of second cancer after 2010 (N=8,224), we also conducted the analysis stratified by breast cancer molecular subtype [luminal A, triple-negative, and human epidermal growth factor receptor 2 (HER2)-positive]. Results: There were 14,392 breast cancer survivors diagnosed with a second breast cancer, including 9,928 NHW, 1,975 NHB, 70 NHAIAN, 988 NHAPI, and 1,431 Hispanic during the study period. The median age at diagnosis of the second cancer ranged from 57 to 66 years and the median follow-up time from diagnosis to cancer death ranged from 52 to 62 months across racial and ethnic groups. Cancer mortality was increased among NHB (HR: 1.28, 95%CI: 1.15-1.43) and Hispanic survivors (HR: 1.17, 95%CI: 1.03-1.33) compared to NHW. There was no increased cancer mortality among NHAIAN (HR: 1.07, 95%CI: 0.61-1.90) and NHAPI survivors (HR: 0.94, 95%CI: 0.80-1.12). The increased cancer mortality in NHB was observed irrespective of second cancer ER status, tumor stage, age at diagnosis, and time since first breast cancer diagnosis. Increased cancer mortality in NHB was also observed for luminal A (HR: 1.26, 95%CI: 1.11-1.44) and triple-negative subtypes (HR: 1.42, 95%CI: 1.10-1.83), but not for HER2-positive (HR: 1.19, 95%CI: 0.88-1.60) disease. For Hispanic patients, increased cancer mortality was observed in women with ER-positive disease, regional stage disease, cancer diagnosed <50 years of age, and cancer developed after 5 years. Conclusion: Racial/ethnic disparities in cancer mortality are present even among NHB and Hispanic breast cancer survivors who developed a second breast cancer. Studies are needed to understand the drivers of these disparities and to test preventive strategies to mitigate them. Citation Format: Zhengyi Deng, Miranda R Jones, Mei-Cheng Wang, Kala Visvanathan. Racial/ethnic disparities in cancer mortality after a second breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-14-05.

DGKA interacts with SRC/FAK to promote the metastasis of non-small cell lung cancer

Metastasis is responsible for the high mortality rate of lung cancer, but its underlying molecular mechanisms are poorly understood. Here, we demonstrated that the expression of diacylglycerol kinase alpha (DGKA) was elevated in the metastatic lesions of non-small cell lung cancer (NSCLC) and correlated with poor survival. Mechanistic studies revealed a direct physical interaction as well as a mutual regulation among DGKA, proto-oncogene tyrosine-protein kinase Src (SRC), and focal adhesion kinase 1 (FAK) proteins. The C-terminal domain of DGKA was responsible for the SRC SH3 domain binding, while the catalytic domain of DGKA interacted with the FREM domain of FAK. DGKA phosphorylated the SRC protein at Tyr416 and the FAK protein at Tyr397 to form and activate the DGKA/SRC/FAK complex, thus initiating the downstream WNT/β-catenin and VEGF signaling pathways, promoting epithelial-mesenchymal transition (EMT) and angiogenesis, and resulting in the metastasis of NSCLC. DGKA knockdown inhibited the invasive phenotype of NSCLC cells in vitro. Pharmacologic ablation of DGKA inhibited the metastasis of NSCLC cells in vivo, and this was reversed by the overexpression of DGKA. These results suggested that DGKA was a potential prognostic biomarker as well as a promising therapeutic target for NSCLC, especially when there was lymphatic or distant metastasis.

Plasma Angiopoietin-Like Protein 2 Levels and Mortality Risk Among Younger-Old Japanese People: A Population-Based Case-Cohort Study.

Aging is an important medical and social problem. Excessive angiopoietin-like protein (ANGPTL)-2 signaling causes chronic tissue inflammation, promoting development and progression of aging-related diseases. Moreover, circulating ANGPTL2 levels reportedly predict the risk of some aging-related diseases and subsequent death. However, there are, as yet, no reports of whether circulating ANGPTL2 levels predict vital prognosis in younger-old, community-dwelling populations. This study investigated associations between plasma ANGPTL2 levels and all-cause and specific-cause mortality in this population. The case-cohort study was abstracted from an ongoing, age-specific prospective cohort study: the New Integrated Suburban Seniority Investigation Project. This project enrolled 3 073 participants aged 64 years at the beginning of the investigation from 1996 through 2005. A subcohort of 714 randomly sampled participants plus 387 cases representing deceased participants followed through 2015 underwent survival analysis. Plasma ANGPTL2 concentrations were positively associated with >80% and 100% higher risk of all-cause mortality and cancer mortality, respectively, after adjustment for gender, smoking, alcohol consumption, walking time, sleep duration, caloric intake, medical status, disease history, BMI, and triglyceride, creatinine, uric acid, and high sensitivity C-reactive protein levels. A more robust association between ANGPTL2 levels and all-cause and cancer mortality was seen in participants with either frailties or with lifestyles of heavier drinking or current smoking. Elevated plasma ANGPTL2 levels are associated with high all-cause and cancer mortality in a community-dwelling sample of younger-old adults. These findings expand our knowledge of human aging and associated diseases.

CYTOTOXIC ACTIVITY OF NEW AZOLOAZINES IN THE STUDY OF HUMAN BREAST CANCER MCF-7 133 CELL CULTURE

The work presents the results of study the cytotoxic activity of new azoloazine derivatives to establish the potential its possibility of use as antitumor agents, including for chemotherapy of metastatic breast cancer. The relevance of the work is due to the wide spread of oncological diseases and high cancer mortality, which dictates the need to constantly obtain cell lines and improve cultivation protocols for testing new antitumor drugs and obtaining new information about the chemistry of cancer. The culturing MCF-7 cells and determining cytotoxicity in a methyltetrazolium test are base methods used in this study. Comparative cytotoxicity was carried out by determining the concentration causing 50 % cell death for 11 azolotriazine derivatives taken at concentrations from 0.25 to 10.0 pM/L. Epirubicin, widely used in breast cancer chemotherapy, we used as a comparison drug. As a result, it was found that not all substances have toxic properties, despite the similar chemical structure and mechanism of action on the cell. The least toxic substances 10 and 11, in which, at the maximum studied concentration of 10 |uM/L, cell survival was 86 and 75 %, respectively. The most toxic compounds against MCF-7 cells are substances 4 and 9 derivatives of with cytotoxicity indicators higher, respectively, by 11.0 and 3.1 highly compared to Epirubicin. The obtained data can be used as a basis for the selection of substances 4 and 9 for further study of their properties on cell models and laboratory animals as substances with potential anticancer activity.

Abstract PO-006: Building a new clinical trial diversity alliance to transform our ability to reach understudied and underserved patients

Abstract Not all segments of the population have benefited equally from advances in science and medicine. Distinct populations continue to be understudied in science, underrepresented in research, and underserved by medicine. Multiple complex factors, including the lack of diverse representation in research, are contributing to disparate health outcomes. For instance, among both men and women, Black patients have the highest cancer death rates. Without intervention, future medical innovations will not broadly benefit all patients and society. Genentech, a member of the Roche Group, believes data representative of real-world patient populations is required to optimize clinical outcomes for all patients. To make meaningful progress toward this goal, we created a system-level strategy. Last year, we began building a network of clinical trial sites to advance the representation of diverse patient populations in the company's oncology clinical trials, test recruitment and retention approaches, and establish best practices that can be leveraged across the industry to help achieve health equity for people with cancer. The first step in identifying potential partners for this alliance was to develop site criteria. We considered numerous attributes including: operational capabilities and performance in enrolling underrepresented patient populations, D&I reputation and community involvement with these patient populations, attitude and commitment to inclusive research, and scientific reputation. We used both internal and external data sources to stratify sites based on two key attributes. First, we compared sites' historical enrollment of Black, Latinx and other underrepresented patients in oncology trials. Second, we evaluated the size of the Black and Latinx populations within the catchment area of sites. Included in the data analysis were about 20,000 potential oncology sites. Within those sites that had a large number of underrepresented patient populations, we used enrollment and experience with Genentech oncology trials to further refine our search. We refined our list based on study teams' experience with site capability to conduct phase I-IV trials. We then conducted in-depth site interviews to identify those sites that were aligned with our mission and were making significant efforts to reach patients of color. After the interview process was completed, four inaugural sites were selected for the launch of the Advancing Inclusive Research Site Alliance. Each of the centers will focus on enabling historically underrepresented patient groups to participate in Genentech's oncology trials and work collaboratively to share key learnings and explore innovative ways of increasing clinical trial access for every patient who might benefit. The AIR Site Alliance plans to expand to more research centers and broaden its focus into additional disease areas in the future. Together, we will work to enrich science, eliminate disparity in outcomes and provide equitable access to innovative therapies for all patients. Citation Format: Ruma Bhagat, Meghan McKenzie, Melissa Gonzales, Gerren Wilson, Nicole Richie, Quita Highsmith. Building a new clinical trial diversity alliance to transform our ability to reach understudied and underserved patients [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-006.

Abstract PO-268: Investigating patient barriers to low-dose computed tomography lung cancer screenings among the African American population

Abstract Background Lung cancer remains the leading cause of cancer death in the United States. Lung cancer screening (LCS) with Low-Dose Computerized Tomography (LDCT) has been found to reduce lung cancer mortality up to 26% and all-cause mortality by 7%. Yet, uptake of LCS is less than 4% among those eligible. African Americans (AAs) have the highest cancer mortality rate and are also more likely to die of lung cancer compared to whites. Furthermore, little research has been done to understand this groups in terms of their knowledge, awareness, and perceptions related to LCS, and the potential barriers or facilitators to LCS. Guided by the Health Believe Models, this study aims to examine the demographic, behavioral, and psychosocial profiles related to LCS in AAs, and identify the predictors to the uptake of LCS with LDCT. Methods We have recruited 200 AA patients eligible for LDCT for a case-control cohort (100 AAs who have completed a LDCT screening and 100 who did not) through the electric medical record of a safety-net hospital. We are currently conducting online and telephone surveys to collect information on participants' personal and family history, health literacy, beliefs, psychosocial factors, patient-provider relationship, knowledge of lung cancer, perception of screening and potential care cost, transportation barriers, and racial discrimination. Results We will conduct descriptive analysis of the sociodemographic characteristics and the modifiable lifestyle behaviors of the participants separately for those who completed LDCT and those who did not. We will then conduct bivariate analysis (chi-square and t-test) to compare various psychosocial and health-related factors by LDCT completion status. Finally, we will conduct binary logistic regression to examine the association between the predictors and LDCT completion. Conclusion The findings of this study will provide critical empirical evidence on the psychosocial facilitators and barriers to LDCT uptake among AAs, a vulnerable and medically underserved population. The facilitators and barriers identified in this study will be used to design both clinic-based and community-based behavioral intervention studies to promote LDCT uptake among eligible AAs. Citation Format: Alexander Nguyen, Lin Zhu, Ra'Ann Merceir, Grace X Ma, Cherie P Erkmen. Investigating patient barriers to low-dose computed tomography lung cancer screenings among the African American population [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-268.

Abstract PO-169: Impacts of neighborhood characteristics and surgical treatment disparities on overall mortality in stage I renal cell carcinoma patients

Abstract Background Racial/ethnic minority groups in the United States have high kidney cancer mortality rates. Disparities in treatments may contribute to higher mortality in racial/ethnic minority groups, but the relationship between treatment disparities and kidney cancer mortality is not well understood. In this study, we assessed if there are differences in surgical treatments across racial/ethnic groups and surgical treatments influence disparities in overall mortality. Methods Stage I renal cell carcinoma patients who were diagnosed between 2004 and 2016 from National Cancer Database were included. Logistic regression was performed to assess associations between race/ethnicity and treatment patterns adjusting for neighborhood socioeconomic (SES) and other factors. Cox regression analysis was performed to assess associations between race/ethnicity and overall mortality. Results A total of 238,141 patients were included in the analysis. Compared to non-Hispanic Whites, American Indians/Alaska Natives, and non-Hispanic Blacks (NHBs) were more likely not to receive surgical care even after adjusting for neighborhood SES (OR 1.85, 95% CI: 1.28-2.70 and OR 1.32 95% CI: 1.20-1.45 respectively). Although all racial/ethnic groups had significantly increased odds of undergoing radical nephrectomy rather than partial nephrectomy,. NHBs had the greatest odds of receiving radical rather than partial nephrectomy (OR 1.38, 95% CI: 1.33-1.44).. The associations were slightly attenuated after including healthcare access and neighborhood SESNHBs had an elevated risk of overall mortality, while Asian Americans and Hispanic Americans had reduced risk. Including surgical treatment, health access and neighborhood factors slightly attenuated the association for NHBs, but the associations between race/ethnicity and overall mortality remained significant. Analysis was performed stratifying samples based on surgical treatment to further assess effects of surgical treatment disparities on associations between race/ethnicity and overall mortality. NHBs who had surgical treatment had increased risk of mortality (HR 1.11, 95% CI:1.06-1.17).. Among patients who underwent nephrectomy, NHBs who underwent radical nephrectomy had increased risk of mortality (HR 1.15, 95% CI: 1.08-1.23), but not NHBs who underwent partial nephrectomy (HR 0.92, 95% CI:0.84-1.02). Conclusion Racial/ethnic minority patients were more likely not to receive surgical treatment. When they do, they are likely to have less optimal surgical treatment (radical rather than partial nephrectomy). Surgical treatment disparities account for high kidney cancer mortality in NHBs. Citation Format: Alejandro Cruz, Faith Dickerson, Kathryn R. Pulling, Kyle Garcia, Francine C. Gachupin, Chiu-Hsieh Hsu, Juan Chipollini, Benjamin R. Lee, Ken Batai. Impacts of neighborhood characteristics and surgical treatment disparities on overall mortality in stage I renal cell carcinoma patients [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-169.

LncRNA AC098934 promotes proliferation and invasion in lung adenocarcinoma cells by combining METTL3 and m6A modifications.

Background: Long non-coding RNA (lncRNA) regulates the tumorigenesis as well as the development of lung adenocarcinoma (LUAD), which is one of the high-mortality cancers. We explored the influence of lncRNA AC098934 on the malignant biological behavior of LUAD and potential underlying molecular mechanisms.Methods: The expression level of AC098934 in either the LUAD or the normal tissues was identified in the TCGA database. Two AC098934 knockdown siRNAs were infected into cells of LUAD, including A549 as well as H1299 cells, using the lentivirus. Real-time Quantitative polymerase chain reaction (QPCR) helped to determine the knockdown efficiency of AC098934. CCK-8, cell cloning, wound healing combined with transwell assays tested the role of AC098934 in the cell proliferation, migration as well as the invasion. Tumor formation experiment in nude mice subcutaneously confirmed the promoting effect of AC098934 in vivo. In addition, combinations of METTL3 and AC098934, as well as m6A and AC098934 were identified through the RIP assay.Results: Compared to the normal tissues, AC098934 was more highly expressed in LUAD tissues. After AC098934 was knocked down by siRNA, the proliferation, invasion, migration as well as tumorigenesis abilities of both A549 and H1299 cells were reduced. Mechanistically, AC098934 could bind to the m6A antibody and METTL3 protein. METTL3 overexpression promoted the m6A modification on AC098934, thereby increasing the interaction of m6A modification.Conclusion: The highly expressed lncRNA AC098934 in LUAD facilitates the cell proliferation as well as invasion either in vitro or in vivo. METTL3 binds, furthermore, modulates the m6A modification of AC098934. Our research revealed a new molecular mechanism, through which AC098934 promoted the malignant behavior of LUAD tumors under the m6A modification induced by METTL3. This indicates that AC098934 is possible to be a promising biomarker as well as a therapeutic target for the patients with LUAD.

Through the Lens: Youth Experiences with Cancer in Rural Appalachian Kentucky Using Photovoice.

Rural Appalachian Kentucky experiences disproportionately high cancer incidence and mortality rates. This cancer burden is due to social determinants of health and cultural factors prominent in the region. The firsthand experiences of community members—especially young people—can highlight these factors and identify areas for improvement. The purpose of this study was to encourage Appalachian Kentucky youth to consider determinants of cancer and visualize the effects that cancer has on their families or communities by asking them to take photographs of cancer-related objects around them. Content analysis was performed on 238 photographs submitted by 25 students, and photographs were organized into themes, subthemes, and subtopics. The six themes that emerged were risk factors and exposures, marketing, awareness and support, health care, experiences, and metaphorical representations. Many of the submitted photographs aligned with cultural, environmental and/or situational factors prevalent in Appalachian Kentucky. Of the submitted photographs, 54 were displayed as an installment in two Kentucky art galleries. Viewer comments at the exhibitions demonstrated that young community members can educate and motivate change in those around them. Ultimately, this project demonstrates that young community members can recognize cancer-related issues around them and connect personal experiences back to the larger Appalachian Kentucky cancer disparity while also having an impact on other community members.

Falcarindiol Stimulates Apoptotic and Autophagic Cell Death to Attenuate Cell Proliferation, Cell Division, and Metastasis through the PI3K/AKT/mTOR/p70S6K Pathway in Human Oral Squamous Cell Carcinomas.

Human oral squamous cell carcinomas (OSCCs) have high cancer mortality and a 5-year survival rate lower than that of most other carcinomas. New therapeutic strategies are required for the treatment and prevention against OSCCs. An approach to cancer therapy using plant-derived natural compounds has been actively in progress as a trend. Falcarindiol (FALC), or its isolated form Ostericum koreanum Kitagawa (O. koreanum), is present in many food and dietary plants, especially in carrots, and this compound has a variety of beneficial effects. However, biological activity of FALC has not been reported in OSCCs yet. This study aimed to demonstrate the antitumor effects of FALC against OSCCs, YD-10B cells. In this study, FALC was selected as a result of screening for compounds isolated from various natural products in YD-10B cells. FALC suppressed cell growth, and FALC-induced apoptotic cell death was mainly accompanied by the dephosphorylation of PI3K, AKT, mTOR, and p70S6K. The apoptotic cell death was also associated with autophagy as evidenced by the expression of Beclin-1, the conversion of LC3-II, and the formation of autophagosome. FALC-induced autophagy was accompanied by MAPKs including ERK1/2 and p38. Furthermore, FALC caused the antimetastatic effects by inhibiting the migration and invasion of YD-10B cells. Taken together, the findings suggest the potential value of FALC as a novel candidate for therapeutic strategy against OSCCs.

Malignant neoplasms in HIV patients in Russia: the story over a 20-year period

According to the official statistics, by the beginning of 2021, the overall number of registered HIV cases in Russia exceeded 1.1 million. For about 100 000 new HIV-infected patients have been registered annually in Russia recent years. Russia occupies one of the leading places in the incidence of HIV infection, and the growth rate of new HIV cases is not decreasing. HIV-infected patients have higher incidence of malignant neoplasms (MN) in comparison with the overall population and have the highest cancer mortality rates. The problem of HIV-associated malignancies is at the junction of two socially significant issues, and this situation especially taking into account in Russian Federation. The problems of diagnosis and treatment of MN are becoming topical, and it is extremely important to study HIV-associated malignancies epidemiology in the Russian Federation. This will help to create effective algorithms for organizing dispensary observation for HIV infected people, will help to early diagnosis of the disease, timely initiation of treatment and, as a result, will help to achieve the best oncological results.

Role of Nurses in the Prevention and Early Detection of Oral Cavity and Pharynx Cancers

Purpose: The incidence of oral cavity and pharynx cancer is rising in the United States and South Dakota (SD) (2009-2018). In 2018, it was estimated that 396,937 of Americans were living with oral cavity and pharynx cancer. The 5-year relative survival rate for oral cancer is 66.2%, which is less than the survival rates for breast, colorectum, and prostate cancers. Tobacco and alcohol use and human papillomavirus (HPV16) exposure are some of the risk factors for oral cancer. Overall rural populations have higher cancer mortality than no rural population due to higher poverty, lower access to health services, and cigarette use. The purpose of this study is to investigate the prevalence of the oral cancer risk factors (e.g., cigarette smoking), HPV vaccination rates, and to identify the spatial distribution of social and environmental factors (e.g., social vulnerability, dental care access) in SD. Finally, this article discusses how nurses can contribute to oral cancer prevention and early detection. Methods: This descriptive study used data from multiple data sources (e.g., SD Department of Health, HRSA, County Health Rankings). Maps were created using ArcGIS. Findings: From the 66 SD counties, nearly 17% presented high-level shortage scores and were also highly socially vulnerable. HPV vaccination among youth was higher than the national average. Studies showed that improving nurse’s knowledge by training on oral cancer is needed and this may increase nurses’ practice in oral cancer prevention and control. Conclusions: Primary care professionals like nurse practitioners can assist in early detection of oral cancer and promote awareness of signs and main risk factors in rural areas. As part of the total patient care, nurses hold a vital role in prevention and early detection of oral cancer. These efforts with referral to oral cancer screening are vital for decreasing oral cancers morbidity and mortality rates primarily. Keywords: Rural health, Nurses, oral cancer, dentalcare access, Geographic Information Systems DOI: https://doi.org/10.14574/ojrnhc.v21i2.692

Low thyroid hormone receptor alpha-2 (THR\u03b1-2) tumor expression is associated with unfavorable tumor characteristics and high breast cancer mortality

BackgroundThe active thyroid hormone triiodothyronine (T3) has been found to have an estrogen-like effect on breast cancer cells. Thyroid hormone receptor alpha-2 (THRα-2) acts as an antagonist for triiodothyronine (T3) signaling, and a low expression has been associated with unfavorable tumor characteristics and a higher mortality in breast cancer. However, the evidence are not conclusive. The present study evaluates tumor-specific THRα-2 expression in invasive breast cancers and its association with tumor characteristics and long-term mortality in a large population.MethodThe Malmö Diet and Cancer Study (MDCS), a population-based cohort in Sweden that included 17,035 women from 1991 to 1996, was used. Women diagnosed with breast cancer during 1991–2010 were eligible for inclusion. A tissue micro array was constructed from stored tumor material and stained for THRα-2 using immunohistochemistry. Tumors from 654 patients were scored regarding the intensity and the fraction of cells stained, then dichotomized into low or high expression. Date and cause of death were collected up until 2018-12-31. Tumor- and patient characteristics were available from the MDCS. Missing data was imputed using chained equations. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for low vs high expression of THRα-2 related to specific tumor factors. Mortality was evaluated with Kaplan–Meier curves and Cox regression, rendering hazard ratios (HRs). Analyses were also stratified for estrogen receptor (ER) status.ResultsWe found strong evidence of an association between low THRα-2 and unfavorable tumor characteristics, including estrogen receptor negativity: OR 4.04 (95% CI 2.28–7.15) and tumor size > 20–50 mm: OR 2.20 (95% CI 1.39–3.49). We found evidence of increased breast cancer-specific mortality for women with low THRα-2, HR 1.38 (95% CI 0.96–1.99), which remained after adjusting for age at diagnosis, HR 1.48 (95% CI 1.03–2.14), but not after adjusting for relevant prognostic factors, HR 0.98 (95% CI 0.66–1.45). THRα-2 expression in ER-negative tumors had an inverse correlation with overall mortality, HR 0.27 (95% CI 0.11–0.65).ConclusionLow tumor-specific THRα-2 expression was in this study associated with prognostically unfavorable tumor characteristics and a higher mortality in breast cancer, but not independent from other prognostic factors.

An Electrochemical Aptasensor for the Detection of HER2 as a Breast Cancer Biomarker Based on Gold Nanoparticles-Aptamer Bioconjugates

Inaccurate diagnoses contributes to the high mortality rate of breast cancer. Human epidermal growth factor receptor 2 (HER2) is overexpressed in breast cancer tumors at around 20–30%. This study aims to develop an electrochemical biosensor for HER2 based on a gold nanoparticle-aptamer bioconjugate (AuNP@HER2 aptamer) and investigate the interaction between DNA aptamer and HER2 using computational methods. The bioconjugate was synthesized using maleimide and polyethylene glycol as a linker. The –NH2 group of cysteamine that modified the gold electrode can form a covalent bond with the bioconjugate maleimide. The interaction of the bioconjugated aptamer with HER2 was measured electrochemically based on the [Fe(CN)6]3−/4− redox system. The limit of detection, the linear range of HER2, precision, and accuracy in this study were 1.52 ng mL–1, 0.01 to 15.0 ng mL–1, 0.1298, and 94.06%, respectively. The structure of the DNA aptamer was modeled using mFold, Assemble2, and Chimera, with the interaction between the DNA aptamer and HER2 explored by NPDock. The modeling of the aptamer with HER2 showed that electrostatic interactions dominated the attractive forces. The resulting interaction pattern can be used as a template to improve the binding energy of the aptamer, thus providing insight into the development of aptamer-based biosensors.

Malignant neoplasms associated with HIV infection. Problems and solutions (problem outline)

HIV infection refers to socially significant diseases. As a result of the wide coverage of effective antiretroviral therapy for people living with HIV, the rates of AIDS-related mortality have significantly decreased. At the same time, there was a noticeable increase in morbidity and mortality from other non-AIDS-related diseases, not the last place in this list is occupied by malignant neoplasms. A decrease in the frequency of AIDS-associated tumors and an increase in the proportion of AIDS-unassociated tumors are significant changes in the structure of malignant neoplasms. There is a complex relationship between HIV-induced immune suppression, chronic antigenic stimulation and concomitant oncogenic viral infections, which increases the risk of developing malignant tumors in these patients. People living with HIV have higher rates of cancer mortality associated with both the lack of adequate antitumor therapy, complications of treatment, and the existence of a direct relationship between immunosuppression and tumor progression. This article analyzes the problems that arise in the treatment of oncological HIV-infected patients, and offers specific practical steps to solve complex interdisciplinary problems.

Barriers and facilitators to accessing cancer care for people with significant mental health difficulties: A qualitative review and narrative synthesis.

Inequities in cancer care contribute to higher rates of cancer mortality for individuals with significant mental health difficulties (SMHD) compared to the general population. The aim of the current systematic review was to identify, appraise and synthesise qualitative evidence of patient and clinician/system barriers and facilitators to cancer screening and treatment for individuals with SMHD. We conducted a systematic search across three electronic databases in May 2020 and we carried out a second search across five electronic databases in January 2021. A narrative synthesis was conducted across eligible studies. We identified the same six studies from both searches, with 133 individuals with SMHD and experiences of cancer care and 102 healthcare professionals. Key barriers to cancer care were related to patients' uncontrolled psychiatric symptoms and the adverse impact of their symptoms on engaging with cancer care; clinician barrier-attitudes included stigmatising attitudes from clinicians and other staff towards individuals with SMHD and systems barrier-fragmentation included the fragmentation of mental health and cancer care delivery. Key patient facilitators to accessing cancer care and completing cancer treatment included being connected with mental health services and controlled psychiatric symptoms. Stronger collaboration among healthcare professionals working across different sectors in addition to the development of a patient navigator role were identified as key facilitators to enhance patient care. Innovative approaches are needed to decrease mental health stigma, foster collaboration across disciplines, and facilitate the integration of timely mental health and cancer care for individuals with SMHD to address the mortality gap.

Development of an Autophagy-Based and Stemness-Correlated Prognostic Model for Hepatocellular Carcinoma Using Bulk and Single-Cell RNA-Sequencing.

Accumulating evidence has proved that autophagy serves as a tumor promoter in formed malignancies, and the autophagy-related prognostic signatures have been constructed as clinical tools to predict prognosis in many high-mortality cancers. Autophagy-related genes have participated in the development and metastasis of hepatocellular carcinoma (HCC), but the understanding of their prognostic value is limited. Thereafter, LIMMA and survival analysis were conducted in both ICGC and TCGA databases and a total of 10 hub autophagy-related genes, namely, NPC1, CDKN2A, RPTOR, SPHK1, HGS, BIRC5, SPNS1, BAK1, ATIC, and MAPK3, were collected. Then, GO, KEGG, correlation, consensus, and PCA analyses were utilized to reveal their potential targeted role in HCC treatment. Single-cell RNA-seq of cancer stem cells also indicated that there was a positive correlation between these genes and stemness. In parallel, we applied univariate, LASSO, and multivariate regression analyses to study the autophagy-related genes and finally proposed that ATIC and BIRC5 were the valuable prognostic indicators of HCC. The signature based on ATIC and BIRC5 exhibited moderate power for predicting the survival of HCC in the ICGC cohort, and its efficacy was further validated in the TCGA cohort. Taken together, we suggested that 10 aforementioned hub genes are promising therapeutic targets of HCC and the ATIC/BIRC5 prognostic signature is a practical prognostic indicator for HCC patients.

Obesity during childhood is associated with higher cancer mortality rate during adulthood: the i3C Consortium

BackgroundIn high-income countries, cancer is the leading cause of death among middle-aged adults. Prospective data on the effects of childhood risk exposures on subsequent cancer mortality are scarce.MethodsWe examined whether childhood body mass index (BMI), blood pressure, glucose and lipid levels were associated with adult cancer mortality, using data from 21,012 children enrolled aged 3–19 years in seven prospective cohort studies from the U.S., Australia, and Finland that have followed participants from childhood into adulthood. Cancer mortality (cancer as a primary or secondary cause of death) was captured using registries.Results354 cancer deaths occurred over the follow-up. In age-, sex, and cohort-adjusted analyses, childhood BMI (Hazard ratio [HR], 1.13; 95% confidence interval [CI] 1.03–1.24 per 1-SD increase) and childhood glucose (HR 1.22; 95%CI 1.01–1.47 per 1-SD increase), were associated with subsequent cancer mortality. In a multivariable analysis adjusted for age, sex, cohort, and childhood measures of fasting glucose, total cholesterol, triglycerides, and systolic blood pressure, childhood BMI remained as an independent predictor of subsequent cancer mortality (HR, 1.24; 95%CI, 1.03–1.49). The association of childhood BMI and subsequent cancer mortality persisted after adjustment for adulthood BMI (HR for childhood BMI, 1.35; 95%CI 1.12–1.63).ConclusionsHigher childhood BMI was independently associated with increased overall cancer mortality.