Cancer Death Research Articles

Endothelin-1 receptor blockade impairs invasion patterns in engineered 3D high-grade serous ovarian cancer tumoroids.

High-grade serous ovarian cancer (HG-SOC), accounting for 70-80% of ovarian cancer deaths, is characterized by a widespread and rapid metastatic nature, influenced by diverse cell types, cell-cell interactions, and acellular components of the tumor microenvironment (TME). Within this tumor type, autocrine and paracrine activation of the endothelin-1 receptors (ET-1R), expressed in tumor cells and stromal components, drives metastatic progression. The lack of three-dimensional models that faithfully recapitulate the unique HG-SOC TME has been the bottleneck in performing drug screening for personalized medicine. Herein, we developed HG-SOC tumoroids by engineering a dense central artificial cancer mass (ACM) containing HG-SOC cells, nested within a compressed hydrogel recapitulating the stromal compartment comprising type I collagen, laminin, fibronectin, and stromal cells (fibroblasts and endothelial cells). ET-1-stimulated HG-SOC cells in the tumoroids showed an altered migration pattern and formed cellular aggregates, mimicking micrometastases that invaded the stroma. Compared to control cells, ET-1-stimulated tumoroids showed a higher number of invasive bodies, which were reduced by treatment with the dual ET-1 receptor (ET-1R) antagonist macitentan. In addition, ET-1 increased the size of the invading aggregates compared to control cells. This study establishes an experimental 3D multicellular model eligible for mechanical research, investigating the impact of matrix stiffness and TME interactions, which will aid drug screening to guide therapeutic decisions in HG-SOC patients.

Burden of major cancers in China attributable to modifiable risk factors: Predictions from 2012 to 2035.

The cancer burden continues to escalate in China. This study was designed to quantify the burden of deaths attributable to modifiable risk factors for major cancers in China from 2012 to 2035, and to provide evidence-based recommendations for cancer management. Using nationally representative data on risk factors and cancer mortality, a comparative risk assessment approach was employed to calculate the temporal trend of population-attributable fractions (PAFs) for 15 modifiable risk factors associated with major cancers in China. The PAF for modifiable risk factors decreased from 64.5% (95% uncertainty interval [UI]: 46.2%-75.3%) in 2012 to 59.3% (95% UI: 40.6%-71.2%) in 2035. Attributable deaths increased from 1,309,990 (95% UI: 938,217-1,529,170) in 2012 to 1,313,418 (95% UI: 898,411-1,577,189) in 2035, while attributable disability-adjusted life years (DALYs) rose from 28,488,120 (95% UI: 20,471,859-33,308,237) to 33,017,705 (95% UI: 22,730,814-39,564,735). Between 2012 and 2035, the top three risk factors contributing to cancer burden shifted from smoking, insufficient fruit intake and particulate matter <2.5 μm in diameter (PM2.5) exposure to smoking, physical inactivity, and inadequate fruit intake. Controlling modifiable risk factors at recommended levels by 2020 could have prevented around 890,000 deaths and 2.2 million DALYs by 2035. The proportion of cancer burden due to modifiable risk factors is projected to decrease, but the absolute number continues to rise. Adhering to an optimal lifestyle could prevent ~40% of cancer deaths by 2035. Key modifiable risk factors including smoking, physical inactivity, and insufficient intake of fruits require high attention.

Global Disparities of Cancer and Its Projected Burden in 2050.

Cancer prevention and care efforts have been challenged by the COVID-19 pandemic and armed conflicts, resulting in a decline in the global Human Development Index (HDI), particularly in low- and middle-income countries. These challenges and subsequent shifts in health care priorities underscore the need to continuously monitor cancer outcome disparities and statistics globally to ensure delivery of equitable and optimal cancer prevention and care in uncertain times. To measure the global burden of 36 cancers in 2022 by sex, age, and geographic location and to project future trends by 2050. This cross-sectional study used population-based data from 2022 in 185 countries and territories were obtained from the Global Cancer Observatory database. Data extraction and analysis were carried out in April 2024. Counts, rates, prevalence, mortality to incidence ratios (MIRs), and demography-based projections were used to characterize current and future cancer burden. This population-based study included 36 cancer types from 185 countries and territories. By 2050, 35.3 million cancer cases worldwide are expected, a 76.6% increase from the 2022 estimate of 20 million. Similarly, 18.5 million cancer deaths are projected by 2050, an 89.7% increase from the 2022 estimate of 9.7 million. Cancer cases and deaths are projected to nearly triple in low-HDI countries by 2050, compared to a moderate increase in very high-HDI countries (142.1% vs 41.7% for cancer cases and 146.1% vs 56.8% for cancer deaths). Males had a higher incidence and greater number of deaths in 2022 than females, with this disparity projected to widen by up to 16.0% in 2050. In 2022, the MIR for all cancers was 46.6%, with higher MIRs observed for pancreatic cancer (89.4%), among males (51.7%), among those aged 75 years or older (64.3%), in low-HDI countries (69.9%), and in the African region (67.2%). In this cross-sectional study based on data from 2022, cancer disparities were evident across HDI, geographic regions, age, and sex, with further widening projected by 2050. These findings suggest that strengthening access to and quality of health care, including universal health insurance coverage, is key to providing evidence-based cancer prevention, diagnostics, and care.

TMEM206 Contributes to Cancer Hallmark Functions in Colorectal Cancer Cells and Is Regulated by p53 in a p21-Dependent Manner

Acid-induced ion flux plays a role in pathologies where tissue acidification is prevalent, including cancer. In 2019, TMEM206 was identified as the molecular component of acid-induced chloride flux. Localizing to the plasma membrane, TMEM206 contributes to cellular processes like acid-induced cell death. Since over 50% of human cancers carry loss of function mutations in the p53 gene, we aimed to analyze how TMEM206 is regulated by p53 and its role in cancer hallmark function and acid-induced cell death in HCT116 colorectal cancer (CRC) cells. We generated p53-deficient HCT116 cells and assessed TMEM206-mediated Cl− currents and transcriptional regulation using the patch-clamp and a dual-luciferase reporter assay, respectively. To investigate the contribution of TMEM206 to cancer hallmark functions, we performed migration and metabolic activity assays. The role of TMEM206 in p53-mediated acid-induced cell death was assessed with cell death assays. The TMEM206 mRNA level was significantly elevated in human primary CRC tumors. TMEM206 knockout increased acid-induced cell death and reduced proliferation and migration, indicating a role for TMEM206 in these cancer hallmark functions. Furthermore, we observed increased TMEM206 mRNA levels and currents in HCT116 p53 knockout cells. This phenotype can be rescued by transient overexpression of p53 but not by overexpression of dysfunctional p53. In addition, our data suggest that TMEM206 may mediate cancer hallmark functions within p53-associated pathways. TMEM206 promoter activity is not altered by p53 overexpression. Conversely, knockout of p21, a major target gene of p53, increased TMEM206-mediated currents, suggesting expression control of TMEM206 by p21 downstream signaling. Our results show that in colorectal cancer cells, TMEM206 expression is elevated, contributes to cancer hallmark functions, and its regulation is dependent on p53 through a p21-dependent mechanism.

Targeting SLITRK4 Restrains Proliferation and Liver Metastasis in Colorectal Cancer via Regulating PI3K/AKT/NFκB Pathway and Tumor-Associated Macrophage.

Liver metastasis is the major cause of death in colorectal cancer (CRC) due to the lack of effective treatment. To explore novel drivers of CRC liver metastasis, the transcriptomes of primary paracancerous, colorectal tumors and metastases from human patients are profiled. It is found that SLIT- and NTRK-like family member 4 (SLITRK4) is the top upregulated gene in liver metastases and is associated with worse overall survival of CRC patients. Multiple in vitro and in vivo models suggested SLITRK4 promoted CRC tumorigenesis, invasion, migration, and angiogenesis, and inhibition of it restrained CRC tumor growth and liver metastasis with a more profound effect on the tumor microenvironment (TME). Mechanistically, SLITRK4 overexpression significantly activated the PI3K/AKT/NFκB pathway, regulated extracellular matrix organization, and multiple cytokines expression. Furthermore, the results from coculture models and single-cell RNA sequencing analyses suggested SLITRK4 promoted tumor-associated macrophages (TAMs) infiltration and polarization. In addition, macrophage depletion significantly inhibited SLITRK4-induced liver metastasis in CRC. Finally, pharmacological inhibition of SLITRK4 by using lipid-polymer hybrid nanoparticles (NPs) for systemic siRNA delivery can effectively inhibit CRC liver metastasis. Taken together, these results pinpoint that SLITRK4 regulates CRC tumorigenesis and liver metastasis, and siRNA delivering NPs agents validate the therapeutic potential of targeting SLITRK4 in CRC.

Delayed and Concurrent Stereotactic Radiosurgery in Immunotherapy-Naïve Melanoma Brain Metastases

Melanoma remains a formidable challenge in oncology, causing the majority of skin cancer deaths in the United States, with brain metastases contributing substantially to this mortality. This paper reviews the current therapeutic strategies for melanoma brain metastases, with a focus on delayed and concurrent stereotactic radiosurgery (SRS). While surgery and traditional chemotherapy offer limited efficacy, recent advances in immunotherapy, particularly immune checkpoint inhibitors (ICIs), have played a major role in the advancement and improved efficacy of the treatment of cancers, including brain metastases. Recent studies indicate that monotherapy with ICIs may lead to a higher median overall survival compared to historical benchmarks, potentially allowing patients to delay radiosurgery. Other studies have found that combining SRS with ICIs demonstrates promise, with results indicating improved intracranial control. Ongoing clinical trials explore novel combinations of immunotherapies and radiotherapies, aiming to optimize treatment outcomes while minimizing adverse effects. As treatment options expand, future studies will be necessary to understand the interplay between therapies and their optimal sequencing to improve patient outcomes.

US Cancer Mortality Trends Among Asian and Pacific Islander Populations.

Cancer is the leading cause of death among Asian American individuals and the second leading cause of death among Native Hawaiian and Pacific Islander people. To evaluate longitudinal cancer mortality trends from 1999 to 2020 among Asian American and Pacific Islander populations in the US by demographic characteristics. This cross-sectional study used the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database to obtain age-adjusted cancer death rates among Asian American and Pacific Islander individuals of all ages between January 1, 1999, and December 31, 2020. Data were analyzed from January 12 to March 19, 2024. Age, sex, cancer type, and US census regions. Trends and average annual percent changes (AAPCs) in age-adjusted cancer-specific mortality (CSM) rates for non-Hispanic Asian American and Pacific Islander populations were estimated by cancer type, age, sex, and region using Joinpoint regression. Between 1999 and 2020, 305 386 Asian American and Pacific Islander individuals (median [IQR] age, 69.5 [58.5-79.2] years; 51.1% male) died of cancer in the US. Overall, the CSM rate decreased by 1.5% annually. Men experienced a greater CSM rate decrease (AAPC, -1.8%; 95% CI, -2.2% to -1.3%) compared with women (AAPC, -1.1%; 95% CI: -1.2% to -1.0%). For women, death rates decreased for most cancer types but increased for uterine (AAPC, 2.5%; 95% CI, 2.0%-3.0%) and brain and central nervous system (AAPC, 1.4%; 95% CI: 0.7%-2.1%) cancers. Colorectal cancer mortality rates increased among men aged 45 to 54 years (AAPC, 1.3%; 95% CI, 0.5%-2.1%). Liver and intrahepatic bile duct cancer mortality increased for both men and women in all US census regions, uterine cancer mortality increased in all regions for women, and pancreatic cancer mortality increased in the Midwest for both men and women. Although these findings show an overall decrease in CSM among Asian American and Pacific Islander populations, specific cancer types exhibited increased mortality rates, with further disparities by sex and age. Targeted, culturally adapted clinical and public health interventions are needed to narrow disparities in cancer mortality.

Extracellular Vesicles from Lung Adenocarcinoma Cells Induce Activation of Different Cancer-Associated Fibroblast Subtypes

Background: Lung cancer, including the major subtype lung adenocarcinoma (LUAD), is the leading cause of cancer deaths worldwide, largely due to metastasis. Improving survival rates requires new treatment strategies and a deeper understanding of the mechanisms that drive tumor progression within the tumor microenvironment (TME). This study investigated the impact of extracellular vesicles (EVs) derived from LUAD cells on lung fibroblasts. Methods: EVs were isolated from LUAD cell lines via ultracentrifugation and characterized using nanoparticle tracking analysis and Western blotting. Lung fibroblasts were treated with PBS, TGFβ, or EVs, and their activation was assessed through protein (Western blotting) and RNA analyses (RNA seq and RT-qPCR). Results: The results confirmed the TGFβ induced activation and showed that LUAD EVs could also activate fibroblasts, increasing cancer-associated fibroblast (CAF) markers. While EV-induced CAF activation displayed unique features, like an increase in proliferation-related genes, the EV and TGFβ treatments also shared some differentially expressed genes. The EV groups induced a higher expression of ECM remodeling and EMT-associated genes, but some of those genes were also upregulated in the TGFβ group. Mesenchymal genes POSTN and SPOCK1 were significantly upregulated in TGFβ- and EV-treated fibroblasts. Their secretion as proteins from the TGFβ- and EV-induced CAFs was not significant, confirmed through ELISA. Conclusions: These findings suggest that LUAD EVs play a role in CAF activation through both shared and distinct pathways compared to canonical TGFβ activation, potentially identifying novel gene expressions involved in CAF activation. Additionally, optimal protein secretion conditions of confirmed CAF-upregulated genes need to be established to determine their contribution to the TME.

Epac activation reduces trans-endothelial migration of undifferentiated neuroblastoma cells and cellular differentiation with a CDK inhibitor further enhances Epac effect.

Neuroblastoma (NB) is the most common solid extracranial neoplasm found in children and is derived from primitive sympathoadrenal neural precursor. The disease accounts for 15% of all cancer deaths in children. The mortality rate is high in patients presenting with a metastatic tumour even with extensive treatments. This signifies the need for further research towards the development of new additional therapies that can combat not only tumour growth but metastasis, especially amongst the high-risk groups. During metastasis, primary tumour cells become migratory and travel towards a capillary within the tumour. They then degrade the matrix surrounding the pericytes and endothelial cells traversing the endothelial barrier twice to establish a secondary. This led to the hypothesis that modulation of the endothelial cell junctional stability could have an influence on tumour metastasis. To test this hypothesis, agents that modulate endothelial permeability on NB cell line migration and invasion were assessed in vitro in a tissue culture model. The cAMP agonist and its antagonists were found to have no obvious effect on both SK-N-BE2C and SK-N-AS migration, invasion and proliferation. Next, NB cells were cocultured with HDMEC cells and live cell imaging was used to assess the effect of an Epac agonist on trans-endothelial cell migration of NB cells. Epac1 agonist remarkably reduced the trans-endothelial migration of both SK-N-BE2C and SK-N-AS cells. These results demonstrate that an Epac1 agonist may perhaps serve as an adjuvant to currently existing therapies for the high-risk NB patients.

Co-Colorectal cancer stem cells employ the FADS1/DDA axis to evade NK cell-mediated immunosuppression after co-cultured with NK cells under hypoxia

Colorectal cancer (CRC) ranks as China’s second most common cancer and fifth top cancer death cause. The study highlights the role of Natural Killer (NK) cells in targeting cancer stem cells (CSCs) that evade immune responses in CRC. Colorectal cancer stem cells (CCSCs) were stem from HT-29 cells and co-cultured with NK cells under normoxic or hypoxic conditions. The impact of this co-culture was evaluated using CCK8 assays for NK cell viability, ELISA for cytokine level changes, and flow cytometry for assessing NK cell apoptosis and activation. Comprehensive metabolomic and transcriptomic analyses were also performed to identify key genes and metabolites involved in the interaction between CCSCs and NK cells Co-culture of CCSCs with NK cells under hypoxia reduced NK cytotoxicity, increased NK apoptosis, and altered cytokine secretion by decreasing IFN-γ and TNF-α levels while increasing IL-6. Transcriptomic and metabolomic analysis identified 4 genes (FADS1, ALDH3A2, GCSH, MTCL1) and 3 metabolites (glyoxylic acid, spermine, DDA) as significant. Interfering with FADS1 counteracted the suppression of IFN-γ and TNF-α induced by CSC cells. Curiously, this inhibition caused by si-FADS1 could be neutralized by the addition of exogenous DDA. Co-culturing with NK cells notably increased spermine levels. Exogenous spermine resulted in a significant reduction in HT-29 cell death rates at 32 µM, 64 µM, and 128 µM, compared to NK cells without spermine. Our research explored CCSCs employed the FADS1/DDA axis to evade NK cell-mediated immunosuppression after co-cultured with NK cells under hypoxia.

Metformin (The Miracle Drug) Kinetics in Different Diseases such as Cancer

: Metformin, a miracle drug that was introduced a century ago, could be considered for various aspects of diseases such as diabetes (type 1 and 2), cancer prevention or chemotherapy, metabolic and neurodegenerative disease. It is well known that the frequency of cancer is higher in patients with type 2 diabetes mellitus. This review aims to provide updated information regarding clinical pharmacokinetics and the mechanism of action of Metformin in different diseases such as cancer. Diabetes type 1 is another chronic autoimmune disease detected usually in early childhood due to immune-mediated devastation of insulin-producing pancreatic beta-cells. Because of the lack of effective therapeutic approaches, its prevalence is increasing. Regarding cancer, an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths were reported in 2020 worldwide. By 50-60% bioavailability, the main route of metformin excretion is through urine. Its mechanism of action is based on 1) initiation of adenosine monophosphate-activated kinase, 2) block proinflammatory paths in perivascular adipose tissue, 3) decrease in monocyte-to-macrophage differentiation in vascular tissues, and 4) improvement in endothelial function. Metformin induces adenosine monophosphate-activated protein kinase signaling and suppresses gluconeogenesis. Antitumor properties of Metformin include a decrease in reactive oxygen species generation and inducing autophagy. In addition to glucose-lowering effects, Metformin has moderate anti-inflammatory and antioxidative effects. It could improve lipid profile and reduce overweight individuals' body mass and arterial blood pressure. In type 1 diabetes, Metformin reduces the requirement for daily insulin and improves glycemia. Its long-term use decreases cardiovascular events. In addition to inhibiting the synthesis of lipids via a reduction in oxidative stress, Metformin inhibits inflammation and increases energy metabolism. Finally, by reducing micro- and macro-vascular consequences, mortality-related diabetes and cancer decline by metformin administration. Therefore, in addition to diabetes, Metformin could reduce the proliferation of cancer cells and the possibility of malignancies in different types of cancer.

PAR1 Is a Candidate Target for the Treatment of Peritoneal Dissemination in Gastric Cancer.

Peritoneal dissemination (PD) is a frequent cause of death in gastric cancer (GC), and there is evidence of an association between protease-activated receptor-1 (PAR1) and the development of PD. This study hypothesized that PD in GC might be influenced by PAR1. The cytotoxic effect of paclitaxel (PTX) on PAR1-transfected MKN45 (MKN45/PAR1) cells was analyzed using the MTT assay, and IC50 values were determined. In female athymic nude mice, MKN45/PAR1 cells were suspended in 0.05 ml phosphate-buffered saline (PBS) medium and inoculated into the stomach mid-wall. In each group, intraperitoneal injections of PBS, PTX, SCH79797 (PAR1-antagonist), or PTX plus SCH79797 were administered on days 8, 15, and 22 following tumor inoculation. At 56 days after tumor inoculation, mice were examined for both abdominal tumor nodule status and size and weight of the tumors. The IC50 of PTX for MKN45/PAR1 cells was 0.0697 μM and that of SCH79797 was 0.0145 μM. Mean survival of the MKN45/PAR1 mice in the PBS group was 28.75 days, whereas survival times for the mice treated with SCH79797, PTX, or a combination of PTX and SCH79797 were 31.2, 49.2, and 48.5 days, respectively. Tumor weight was smaller in the group receiving PTX and SCH79797 intraperitoneally compared with that in the PBS group (1,086±127.2 mg vs. 33.2±19.9 mg; p<0.001). The PAR1 antagonist was found to inhibit PD in a PAR1-expressing GC cell line. PAR1 may serve as a promising therapeutic target for managing PD in gastric cancer, as it plays a crucial role in its progression.

Association of age at diagnosis of type 2 diabetes mellitus with the risks of the morbidity of cardiovascular disease, cancer and all-cause mortality: Evidence from a real-world study with a large population-based cohort study.

To investigate the impact of diagnosis age of type 2 diabetes mellitus (T2DM) on subsequent adverse outcomes within the Chinese population. 549,959 eligible T2DM patients were included from Ningbo and Jinhua city in Zhejiang province, China. Standardized ratio was used to evaluate the risks of coronary heart disease (CHD), stroke, cancer and all-cause death in different T2DM diagnosis age groups. For all adverse outcomes, higher excess risks were observed in the youngest age group (30-39) than in the oldest age group (≥80) with T2DM. The standardized incidence ratios (SIR) were 5.93 (95 % CI: 3.46, 10.14) for CHD, 5.45 (95 % CI: 3.72, 7.99) for stroke and 1.85 (95 % CI: 1.38, 2.49) for cancer in the youngest age group, and were 1.32 (95 % CI: 1.08, 1.60) for CHD, 1.25 (95 % CI: 1.08, 1.44) for stroke, and 0.78 (95 % CI: 0.56, 1.09) for cancer, respectively, in the oldest age group. The standardized mortality ratios (SMR) for all-cause death were 3.15 (1.69, 5.84) vs. 1.12 (0.88,1.43). These excess risks decreased with increasing diagnosis age (all P value < 0.001). Consistent results were observed when individuals were stratified by sex or further excluded with the time from T2DM diagnosis to endpoints less than 1 or 2 years. The earlier the diagnosis of T2DM, the higher the risk for subsequent adverse outcomes. It is imperative to enhance the management and monitoring of early-onset patients during follow-up.

High percentage of cancers potentially preventable: Better strategies, such as education, policy, and community-level interventions, are needed to reduce modifiable risk factors associated with cancer incidence and death.

High percentage of cancers potentially preventable: Better strategies, such as education, policy, and community-level interventions, are needed to reduce modifiable risk factors associated with cancer incidence and death.

Geospatial Hot Spots and Cold Spots in US Cancer Disparities and Associated Risk Factors, 2004-2008 to 2014-2018.

Despite declining cancer death rates in the US, cancer remains the second deadliest disease and disparities persist. Although research has focused on identifying risk factors for cancer deaths and associated disparities, few studies have examined how these relationships vary over time and space. The primary objective of this study was to identify cancer mortality hot spots and cold spots - areas where cancer death rates decreased less than or more than neighboring areas over time. A secondary objective was to identify risk factors of cancer mortality hot spots and cold spots. We analyzed county-level cancer death rates from 2004 through 2008 and 2014 through 2018, exploring disparities in changes over time for socioeconomic and demographic variables. We used hot spot analysis to identify areas with larger decreases (cold spots) and smaller decreases (hot spots) in cancer death rates and random forest machine learning analysis to assess the relative importance of risk factors associated with hot spots and cold spots. We mapped spatial clustering areas. Geospatial analysis showed hot spots predominantly in the Plains states and Midwest and cold spots in the Southeast, Northeast, 2 Mountain West states (Utah and Idaho), and a portion of Texas. Factors with the strongest influence on hot spots and cold spots were unemployment, preventable hospital stays, mammography screening, and high school education. Geospatial disparities in changes in cancer death rates point out the critical role of access to care, socioeconomic position, and health behaviors in persistent cancer mortality disparities. Study results provide insights for interventions and policies that focus on addressing health care access and social determinants of health.

Transcriptomics profiling of the non-small cell lung cancer microenvironment across disease stages reveals dual immune cell-type behaviors

BackgroundLung cancer is the leading cause of cancer death worldwide, with poor survival despite recent therapeutic advances. A better understanding of the complexity of the tumor microenvironment is needed to improve patients’ outcome.MethodsWe applied a computational immunology approach (involving immune cell proportion estimation by deconvolution, transcription factor activity inference, pathways and immune scores estimations) in order to characterize bulk transcriptomics of 62 primary lung adenocarcinoma (LUAD) samples from patients across disease stages. Focusing specifically on early stage samples, we validated our findings using an independent LUAD cohort with 70 bulk RNAseq and 15 scRNAseq datasets and on TCGA datasets.ResultsThrough our methodology and feature integration pipeline, we identified groups of immune cells related to disease stage as well as potential immune response or evasion and survival. More specifically, we reported a duality in the behavior of immune cells, notably natural killer (NK) cells, which was shown to be associated with survival and could be relevant for immune response or evasion. These distinct NK cell populations were further characterized using scRNAseq data, showing potential differences in their cytotoxic activity.ConclusionThe dual profile of several immune cells, most notably T-cell populations, have been discussed in the context of diseases such as cancer. Here, we report the duality of NK cells which should be taken into account in conjunction with other immune cell populations and behaviors in predicting prognosis, immune response or evasion.

Optimizing cervical cancer classification using transfer learning with deep gaussian processes and support vector machines

BackgroundCervical cancer is the fourth most frequent cancer in women worldwide. Even though cervical cancer deaths have decreased significantly in Western countries, low and middle-income countries account for nearly 90% of cervical cancer deaths. While Western countries are leveraging the powers of artificial intelligence (AI) in the health sector, most countries in sub-Saharan Africa are still lagging. In Uganda, cytologists manually analyze Pap smear images for the detection of cervical cancer, a process that is highly subjective, slow, and tedious. Machine learning (ML) algorithms have been used in the automated classification of cervical cancer. However, most of the MLs have overfitting limitations which limits their deployment, especially in the health sector where accurate predictions are needed.MethodsIn this study, we propose two kernel-based algorithms for automated detection of cervical cancer. These algorithms are (1) an optimized support vector machine (SVM), and (2) a deep Gaussian Process (DGP) model. The SVM model proposed uses an optimized radial basis kernel while the DGP model uses a hybrid kernel of periodic and local periodic kernel.ResultsExperimental results revealed accuracy of 100% and 99.48% for an optimized SVM model and DGP model respectively. Results on precision, recall, and F1 score were also reported.ConclusionsThe proposed models performed well on cervical cancer detection and classification, and therefore suitable for deployment. We plan to deploy our proposed models in a mobile application-based tool. The limitation of the study was the lack of access to high-performance computational resources.

Association of prophylactic low-dose aspirin use with all-cause and cause-specific mortality in cancer patients

The long-term use of aspirin for preventing cardiovascular disease has been recommended for decades. However, there is currently uncertainty regarding the long-term effects of aspirin use on the risk of all-cause, cardiovascular, and cancer mortality in cancer patients. The aim of this work was to analyze the connection between the prophylactic use of low-dose aspirin and the risk of all-cause death, cardiovascular death, and carcinoma death in carcinoma patients in the United States. A cohort study was conducted using National Health and Nutrition Examination Survey (NHANES) data (2011–2012, 2013–2014, 2015–2016, and 2017–2018) and associated mortality data. The 95% confidence intervals (CIs) and hazard ratios (HRs) between non-aspirin use and prophylactic low-dose aspirin use and the risk of death were measured via Cox proportional hazard regression models. A total of 1819 participants were included in the present research, of whom 945 were nonaspirin users and 874 were prophylactic aspirin users. Compared with non-aspirin users, prophylactic low-dose aspirin users had a decreased risk of all-cause death (HR = 0.647, 95% CI = 0.489–0.857). There was no statistically significant difference in the risk of cardiovascular death (HR = 0.623, 95% CI = 0.362–1.074) or cancer death (HR = 0.709, 95% CI = 0.410–1.226). Prophylactic use of low-dose aspirin may lower all-cause mortality in individuals with cancer but does not have a substantial effect on cardiovascular risk or cancer-specific mortality in this patient population.

Impact of Nordihydroguaiaretic Acid on Proliferation, Energy Metabolism, and Chemosensitization in Non-Small-Cell Lung Cancer (NSCLC) Cell Lines

Lung cancer (LC) is the leading cause of cancer death worldwide. LC can be classified into small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC), with the last subtype accounting for approximately 85% of all diagnosed lung cancer cases. Despite the existence of different types of treatment for this disease, the development of resistance to therapies and tumor recurrence in patients have maintained the need to find new therapeutic options to combat this pathology, where natural products stand out as an attractive source for this search. Nordihydroguaiaretic acid (NDGA) is the main metabolite extracted from the Larrea tridentata plant and has been shown to have different biological activities, including anticancer activity. In this study, H1975, H1299, and A549 cell lines were treated with NDGA, and its effect on cell viability, proliferation, and metabolism was evaluated using a resazurin reduction assay, incorporation of BrdU, and ki-67 gene expression and glucose uptake measurement, respectively. In addition, the combination of NDGA with clinical chemotherapeutics was investigated using an MTT assay and Combenefit software (version 2.02). The results showed that NDGA decreases the viability and proliferation of NSCLC cells and differentially modulates the expression of genes associated with different metabolic pathways. For example, the LDH gene expression decreased in all cell lines analyzed. However, GLUT3 gene expression increased after 24 h of treatment. The expression of the HIF-1 gene decreased early in the H1299 and A549 cell lines. In addition, the combination of NDGA with three chemotherapeutics (carboplatin, gemcitabine, and taxol) shows a synergic pattern in the decrease of cell viability on the H1299 cell line. In summary, this research provides new evidence about the role of NDGA in lung cancer. Interestingly, using NDGA to enhance the anticancer activity of antitumoral drugs could be an improved therapeutic resource against lung cancer.

Awareness and attitude towards human papillomavirus vaccination for cervical cancer prevention among college students in South Kerala

Background: Carcinoma cervix is the second most common cancer among women, and the most common cause of cancer deaths in developed countries, but the awareness regarding it’s prevention by HPV vaccine is limited. This study targets to identify the awareness of cervical cancer and HPV vaccine among the college students. Methods: An observational cross-sectional study was conducted among 963 college students of Kollam district of South Kerala, using a semi-structured questionnaire. Results: Among the study subjects, only 48.6% had previously heard about HPV vaccine, 85.6% knew HPV causes cervical cancer, 80.2% recommends HPV vaccine to their siblings and peers. Medical students had better awareness, practice of HPV vaccination was less among medical and non-medical students; 11.6% medical students and 4.9% non- medical students had taken HPV vaccination. Conclusions: Even though awareness regarding cervical cancer is present, to increase the practice of HPV vaccination, proper health education regarding HPV vaccination is of prime importance among college students.