ABSTRACT
Primary hepatic liposarcoma is an extremely rare malignant tumour derived from adipocytes and is part of the group of mesenchymal tumours. We present the case of a 43-year-old Hispanic male patient with a pleomorphic hepatic liposarcoma and absence of MDM2 gene amplification. Two years and six months after surgery, the patient is asymptomatic. The present case is the first report of this entity with positive immunohistochemical testing for p16, p53, S100, vimentin and absence of MDM2 gene amplification. (AU)
El liposarcoma hepático primario es un tumor maligno extremadamente raro, derivado de adipocitos, y forma parte del grupo de tumores mesenquimales. Presentamos el caso de un paciente masculino de 43 años con diagnóstico de liposarcoma hepático pleomorfo con ausencia de amplificación del gen MDM2. Dos años y 6 meses después de la cirugía el paciente se encuentra asintomático. El presente caso es el primer informe de esta entidad con estudio inmunohistoquímico positivo para p16, p53, S100, vimentina y ausencia de amplificación del gen MDM2. (AU)
Subject(s)
Humans , Male , Adult , Liposarcoma , Neoplasms , Adipocytes , Mesenchymal Stem Cells , VimentinABSTRACT
El tumor fibroso calcificante (TFC) es una inusual lesión benigna de origen mesenquimal que puede presentar características similares a otros tumores más comunes. El caso involucra a una mujer de 36 años con un tumor en el yeyuno proximal, inicialmente sospechoso de ser un tumor del estroma gastrointestinal (GIST). Se realiza una resección quirúrgica, revelando un nódulo bien delimitado en el borde antimesentérico con características microscópicas típicas de TFC. Las células tumorales presentaban positividad para CD34 y negatividad para demás marcadores, diferenciándolo de otras neoplasias. El TFC puede confundirse con tumores más comunes debido a su apariencia, pero un diagnóstico preciso respaldado por inmunohistoquímica es esencial. La extirpación quirúrgica completa suele ser curativa. (AU)
Calcifying fibrous tumor (CFT) is a rare benign lesion of mesenchymal origin that may present similar characteristics to other more common tumors. We present the case of a 36-year-old woman with a tumor in the proximal jejunum, initially suspected to be a gastrointestinal stromal tumor (GIST). Surgical resection was performed, revealing a well-demarcated nodule at the anti-mesenteric border with microscopic features typical of a calcifying fibrous tumor. The tumor cells were positive for CD34 and negative for other markers, differentiating it from other neoplasms. Calcifying fibrous tumors can be confused with more common tumors because of its appearance, but an accurate diagnosis supported by immunohistochemistry is essential. Complete surgical excision is usually curative. (AU)
Subject(s)
Humans , Animals , Neoplasms , Mesenchymal Stem Cells , Immunohistochemistry , Pancreatic Ducts , Wounds and InjuriesABSTRACT
[ABSTRACT]. This report provides a summary of childhood cancer and the efforts made in the Dominican Republic to address child and adolescent cancer in line with the World Health Organization’s Global Initiative for Childhood Cancer. Information was obtained by review of recent local and international literature on pediatric oncology. As a result of the Global Initiative, a meeting was held by the Council of Ministers of Health of Central America to support the development of national pediatric cancer plans for each country. The objectives of these plans are to improve overall survival and quality of care for children with cancer through early detection, diagnosis, and treatment. In the Dominican Republic, several steps have been taken in the past 5 years to enhance diagnosis and care of children with cancer. For example, the National Committee of Childhood Cancer, headed by the Ministry of Public Health and including relevant stakeholders, was established to develop the national childhood cancer plan. In addition, a campaign was launched to raise awareness of childhood cancer, and the first early detection manual and public policy on child and adolescent cancer were published. A government initiative has been working to improve the hospital infrastructure and expand the pediatric cancer center, and a national course on early detection of pediatric cancers has been held. In 2023, the National Strategic Childhood Cancer Plan 2023–2030 was launched in the Dominican Republic. The plan will help policy-makers, implementers, researchers, and advocates enhance diagnosis and care of children with cancer.
[RESUMEN]. En este informe se presenta un resumen del cáncer infantil y las medidas adoptadas por República Dominicana para abordar el cáncer en la población infantil y adolescente en consonancia con la Iniciativa Mundial contra el Cáncer Infantil de la Organización Mundial de la Salud. La información se obtuvo mediante el análisis de las publicaciones nacionales e internacionales recientes sobre oncología pediátrica. Como resultado de la Iniciativa Mundial, el Consejo de Ministros de Salud de Centroamérica celebró una reunión para brindar apoyo a la elaboración de planes nacionales sobre el cáncer infantil para cada país. Los objetivos de estos planes son mejorar la supervivencia general y la calidad de la atención que se presta a la población infantil con cáncer mediante la detección temprana, el diagnóstico y el tratamiento. En los últimos cinco años, República Dominicana ha adoptado varias medidas para mejorar el diagnóstico y la atención prestada a la población infantil con cáncer. Así, por ejemplo, se creó el Comité Nacional de Cáncer Infantil, encabezado por el Ministerio de Salud e integrado por las partes interesadas pertinentes, para elaborar el plan nacional sobre el cáncer infantil. Además, se puso en marcha una campaña de sensibilización sobre el cáncer infantil y se publicaron el primer manual de detección precoz y la primera política pública sobre el cáncer en la población infantil y adolescente. Mediante una iniciativa gubernamental se ha buscado mejorar la infraestructura hospitalaria y ampliar el centro de atención a pacientes oncológicos pediátricos, al tiempo que se ha impartido un curso nacional sobre detección precoz del cáncer infantil. En el 2023, República Dominicana puso en marcha el Plan Estratégico Nacional sobre Cáncer Infantil 2023-2030. Este plan será útil a los responsables de la formulación de políticas, las personas encargadas de su ejecución, los investigadores y los promotores para mejorar el diagnóstico y la atención prestada a la población infantil con cáncer.
[RESUMO]. Este relatório fornece um resumo sobre o câncer infantil e os esforços da República Dominicana para enfrentar a doença em crianças e adolescentes, em consonância com a Iniciativa Global para o Câncer Infantil da Organização Mundial da Saúde. As informações foram obtidas por meio de uma revisão da literatura local e internacional recente sobre oncologia pediátrica. Em consequência da Iniciativa Global, o Conselho de Ministros da Saúde da América Central se reuniu para apoiar a elaboração de planos nacionais de câncer pediátrico para cada país. Os objetivos desses planos são melhorar a sobrevida global e a qualidade da atenção a crianças com câncer por meio de detecção, diagnóstico e tratamento precoces. Na República Dominicana, várias medidas foram tomadas nos últimos cinco anos para melhorar o diagnóstico e a atenção a crianças com câncer. Por exemplo, o Comitê Nacional de Câncer Infantil, que é chefiado pelo Ministério da Saúde e inclui as partes interessadas pertinentes, foi criado para elaborar o plano nacional de câncer infantil. Foi lançada uma campanha de conscientização sobre o câncer infantil no país. Além disso, foram publica- dos o primeiro manual de detecção precoce e a política pública de câncer infantojuvenil. Uma iniciativa do governo vem trabalhando para melhorar a infraestrutura hospitalar e ampliar o centro de câncer pediátrico e ministrou um curso nacional sobre a detecção precoce de cânceres pediátricos. Em 2023, foi lançado o Plano Estratégico Nacional de Câncer Infantil 2023–2030 na República Dominicana. O plano ajudará formuladores de políticas, implementadores, pesquisadores e defensores da causa a aprimorar o diagnóstico e a atenção a crianças com câncer.
Subject(s)
Neoplasms , Child , Adolescent , Public Policy , Quality of Health Care , Dominican Republic , Neoplasms , Child , Adolescent , Public Policy , Quality of Health Care , Dominican Republic , Child , Quality of Health CareABSTRACT
Procure receitas saudáveis e saborosas. Manter um peso corporal saudável é essencial na prevenção da obesidade e do câncer
Subject(s)
Diet, Healthy , Ideal Body Weight , Menu Planning , NeoplasmsABSTRACT
DNA methylation is an essential epigenetic chromatin modification, and its maintenance in mammals requires the protein UHRF1. It is yet unclear if UHRF1 functions solely by stimulating DNA methylation maintenance by DNMT1, or if it has important additional functions. Using degron alleles, we show that UHRF1 depletion causes a much greater loss of DNA methylation than DNMT1 depletion. This is not caused by passive demethylation as UHRF1-depleted cells proliferate more slowly than DNMT1-depleted cells. Instead, bioinformatics, proteomics and genetics experiments establish that UHRF1, besides activating DNMT1, interacts with DNMT3A and DNMT3B and promotes their activity. In addition, we show that UHRF1 antagonizes active DNA demethylation by TET2. Therefore, UHRF1 has non-canonical roles that contribute importantly to DNA methylation homeostasis; these findings have practical implications for epigenetics in health and disease.
Subject(s)
DNA Methylation , Neoplasms , Humans , CCAAT-Enhancer-Binding Proteins/genetics , CCAAT-Enhancer-Binding Proteins/metabolism , Chromatin , DNA (Cytosine-5-)-Methyltransferase 1/genetics , DNA (Cytosine-5-)-Methyltransferase 1/metabolism , Neoplasms/genetics , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolismABSTRACT
Significance: Quantitative phase imaging (QPI) offers a label-free approach to non-invasively characterize cellular processes by exploiting their refractive index based intrinsic contrast. QPI captures this contrast by translating refractive index associated phase shifts into intensity-based quantifiable data with nanoscale sensitivity. It holds significant potential for advancing precision cancer medicine by providing quantitative characterization of the biophysical properties of cells and tissue in their natural states. Aim: This perspective aims to discuss the potential of QPI to increase our understanding of cancer development and its response to therapeutics. It also explores new developments in QPI methods towards advancing personalized cancer therapy and early detection. Approach: We begin by detailing the technical advancements of QPI, examining its implementations across transmission and reflection geometries and phase retrieval methods, both interferometric and non-interferometric. The focus then shifts to QPI's applications in cancer research, including dynamic cell mass imaging for drug response assessment, cancer risk stratification, and in-vivo tissue imaging. Results: QPI has emerged as a crucial tool in precision cancer medicine, offering insights into tumor biology and treatment efficacy. Its sensitivity to detecting nanoscale changes holds promise for enhancing cancer diagnostics, risk assessment, and prognostication. The future of QPI is envisioned in its integration with artificial intelligence, morpho-dynamics, and spatial biology, broadening its impact in cancer research. Conclusions: QPI presents significant potential in advancing precision cancer medicine and redefining our approach to cancer diagnosis, monitoring, and treatment. Future directions include harnessing high-throughput dynamic imaging, 3D QPI for realistic tumor models, and combining artificial intelligence with multi-omics data to extend QPI's capabilities. As a result, QPI stands at the forefront of cancer research and clinical application in cancer care.
Subject(s)
Neoplasms , 60704 , Humans , Artificial Intelligence , Neoplasms/diagnostic imagingABSTRACT
Antigen-specific T cell receptor-engineered T cell (TCR-T) based immunotherapy has proven to be an effective method to combat cancer. In recent years, cross-talk between the innate and adaptive immune systems may be requisite to optimize sustained antigen-specific immunity, and the stimulator of interferon genes (STING) is a promising therapeutic target for cancer immunotherapy. The level of expression or presentation of antigen in tumor cells affects the recognition and killing of tumor cells by TCR-T. This study aimed at investigating the potential of innate immune stimulation of T cells and engineered T cells to enhance immunotherapy for low-expression antigen cancer cells. We systematically investigated the function and mechanism of cross-talk between STING agonist diABZI and adaptive immune systems. We established NY-ESO-1 full knockout Mel526 cells for this research and found that diABZI activated STING media and TCR signaling pathways. In addition, the results of flow cytometry showed that antigens presentation from cancer cells induced by STING agonist diABZI also improved the affinity of TCR-T cells function against tumor cells in vitro and in vivo. Our findings revealed that diABZI enhanced the immunotherapy efficacy of TCR-T by activating STING media and TCR signaling pathways, improving interferon-γ expression, and increasing antigens presentation of tumor cells. This indicates that STING agonist could be used as a strategy to promote TCR-T cancer immunotherapy.
Subject(s)
Neoplasms , T-Lymphocytes , Antigen Presentation , Antibodies , Flow Cytometry , Receptors, Antigen, T-Cell , Neoplasms/therapyABSTRACT
Breast cancer remains one of the most intractable diseases, especially the malignant form of metastasis, with which the cancer cells are hard to track and eliminate. Herein, the common known carbohydrate polymer chitosan (CS) was innovatively used as a shelter for the potent tumor-killing agent. The designed nanoparticles (NPs) not only enhance the solubility of hydrophobic paclitaxel (PTX), but also provide a "hide" effect for cytotoxic PTX in physiological condition. Moreover, coupled with the photothermal (PTT) properties of MoS2, results in a potent chemo/PTT platform. The MoS2@PTX-CS-K237 NPs have a uniform size (135 ± 17 nm), potent photothermal properties (η = 31.5 %), and environment-responsive (low pH, hypoxia) and near infrared (NIR) laser irradiation-triggered PTX release. Through a series of in vitro and in vivo experiments, the MoS2@PTX-CS-K237 showed high affinity and specificity for breast cancer cells, impressive tumor killing capacity, as well as the effective inhibitory effect of metastasis. Benefit from the unique optical properties of MoS2, this multifunctional nanomedicine also exhibited favorable thermal/PA/CT multimodality imaging effect on tumor-bearing mice. The system developed in this work represents the advanced design concept of hierarchical stimulus responsive drug release, and merits further investigation as a potential nanotheranostic platform for clinical translation.
Subject(s)
Chitosan , Neoplasms , Animals , Mice , Molybdenum , Nanomedicine , Paclitaxel/pharmacology , Paclitaxel/therapeutic use , Multimodal ImagingABSTRACT
The 15th annual Frontiers in Cancer Science (FCS) conference gathered scientific experts who shared the latest research converging upon several themes of cancer biology. These themes included the dysregulation of metabolism, cell death, and other signaling processes in cancer cells; using patient "omics" datasets and single-cell and spatial approaches to investigate heterogeneity, understand therapy resistance, and identify targets; innovative strategies for inhibiting tumors, including rational drug combinations and improved drug delivery mechanisms; and advances in models that can facilitate screening for cancer vulnerabilities and drug testing. We hope the insights from this meeting will stimulate further progress in the field.
Subject(s)
Neoplasms , Research , Humans , Cell Death , Drug Delivery Systems , Neoplasms/therapyABSTRACT
The role of the microbiome in immunotherapy has recently garnered substantial attention, with molecular studies and clinical trials providing emerging evidence on the pivotal influence of the microbiota in enhancing therapeutic outcomes via immune response modulation. However, the impact of microbial communities can considerably vary across individuals and different immunotherapeutic approaches, posing prominent challenges in harnessing their potential. In this comprehensive review, we outline the current research applications in tumor immunotherapy and delve into the possible mechanisms through which immune function is influenced by microbial communities in various body sites, encompassing those in the gut, extraintestinal barrier, and intratumoral environment. Furthermore, we discuss the effects of diverse microbiome-based strategies, including probiotics, prebiotics, fecal microbiota transplantation, and the targeted modulation of specific microbial taxa, and antibiotic treatments on cancer immunotherapy. All these strategies potentially have a profound impact on immunotherapy and pave the way for personalized therapeutic approaches and predictive biomarkers.
Subject(s)
Microbiota , Neoplasms , Probiotics , Humans , Immunotherapy , Probiotics/therapeutic use , Neoplasms/therapyABSTRACT
Cholesterol is crucial for cell survival and growth, and dysregulation of cholesterol homeostasis has been linked to the development of cancer. The tumor microenvironment (TME) facilitates tumor cell survival and growth, and crosstalk between cholesterol metabolism and the TME contributes to tumorigenesis and tumor progression. Targeting cholesterol metabolism has demonstrated significant antitumor effects in preclinical and clinical studies. In this review, we discuss the regulatory mechanisms of cholesterol homeostasis and the impact of its dysregulation on the hallmarks of cancer. We also describe how cholesterol metabolism reprograms the TME across seven specialized microenvironments. Furthermore, we discuss the potential of targeting cholesterol metabolism as a therapeutic strategy for tumors. This approach not only exerts antitumor effects in monotherapy and combination therapy but also mitigates the adverse effects associated with conventional tumor therapy. Finally, we outline the unresolved questions and suggest potential avenues for future investigations on cholesterol metabolism in relation to cancer.
Subject(s)
Neoplasms , Humans , Carcinogenesis , Combined Modality Therapy , Cell Survival , Cell Transformation, Neoplastic , Tumor MicroenvironmentABSTRACT
Cancer immunotherapy has emerged as a novel therapeutic approach against tumors, with immune checkpoint inhibitors (ICIs) making significant clinical practice. The traditional ICIs, PD-1 and PD-L1, augment the cytotoxic function of T cells through the inhibition of tumor immune evasion pathways, ultimately leading to the initiation of an antitumor immune response. However, the clinical implementation of ICIs encounters obstacles stemming from the existence of an immunosuppressive tumor microenvironment and inadequate infiltration of CD8+T cells. Considerable attention has been directed towards advancing immunogenic cell death (ICD) as a potential solution to counteract tumor cell infiltration and the immunosuppressive tumor microenvironment. This approach holds promise in transforming "cold" tumors into "hot" tumors that exhibit responsiveness to antitumor. By combining ICD with ICIs, a synergistic immune response against tumors can be achieved. However, the combination of ICD inducers and PD-1/PD-L1 inhibitors is hindered by issues such as poor targeting and uncontrolled drug release. An advantageous solution presented by stimulus-responsive nanocarrier is integrating the physicochemical properties of ICD inducers and PD-1/PD-L1 inhibitors, facilitating precise delivery to specific tissues for optimal combination therapy. Moreover, these nanocarriers leverage the distinct features of the tumor microenvironment to accomplish controlled drug release and regulate the kinetics of drug delivery. This article aims to investigate the advancement of stimulus-responsive co-delivery nanocarriers utilizing ICD and PD-1/PD-L1 inhibitors. Special focus is dedicated to exploring the advantages and recent advancements of this system in enabling the combination of ICIs and ICD inducers. The molecular mechanisms of ICD and ICIs are concisely summarized. In conclusion, we examine the potential research prospects and challenges that could greatly enhance immunotherapeutic approaches for cancer treatment.
Subject(s)
Immune Checkpoint Inhibitors , Neoplasms , Programmed Cell Death 1 Receptor , Immunotherapy , Drug Delivery Systems , CD8-Positive T-Lymphocytes , Neoplasms/drug therapyABSTRACT
Cancer-associated fibroblasts (CAF) are the most abundant stromal cells in the tumor microenvironment (TME), especially in solid tumors. It has been confirmed that it can not only interact with tumor cells to promote cancer progression and metastasis, but also affect the infiltration and function of immune cells to induce chemotherapy and immunotherapy resistance. So, targeting CAF has been considered an important method in cancer treatment. The rapid development of nanotechnology provides a good perspective to improve the efficiency of targeting CAF. At present, more and more researches have focused on the application of nanoparticles (NPs) in targeting CAF. These studies explored the effects of different types of NPs on CAF and the multifunctional nanomedicines that can eliminate CAF are able to enhance the EPR effect which facilitate the anti-tumor effect of themselves. There also exist amounts of studies focusing on using NPs to inhibit the activation and function of CAF to improve the therapeutic efficacy. The application of NPs targeting CAF needs to be based on an understanding of CAF biology. Therefore, in this review, we first summarized the latest progress of CAF biology, then discussed the types of CAF-targeting NPs and the main strategies in the current. The aim is to elucidate the application of NPs in targeting CAF and provide new insights for engineering nanomedicine to enhance immune response in cancer treatment.
Subject(s)
Cancer-Associated Fibroblasts , Nanoparticles , Neoplasms , Immunotherapy , Nanomedicine , Nanotechnology , Neoplasms/drug therapyABSTRACT
Serving as a pivotal immunotherapeutic approach against tumors, anti-PD-1/PD-L1 therapy amplifies the immune cells' capability to eliminate tumors by obstructing the interaction between PD-1 and PD-L1. Research indicates that immune checkpoint inhibitors are effective when a patient's gut harbors unique beneficial bacteria. As such, it has further been revealed that the gut microbiome influences tumor development and the efficacy of cancer treatments, with metabolites produced by the microbiome playing a regulatory role in the antitumor efficacy of Immune checkpoint inhibitors(ICBs). This article discusses the mechanism of anti-PD-1 immunotherapy and the role of intestinal flora in immune regulation. This review focuses on the modulation of intestinal flora in the context of PD-1 immunotherapy, which may offer a new avenue for combination therapy in tumor immunotherapy.
Subject(s)
Gastrointestinal Microbiome , Neoplasms , Humans , Programmed Cell Death 1 Receptor , B7-H1 Antigen , Immune Checkpoint Inhibitors/therapeutic use , Ligands , Immunotherapy , Neoplasms/therapyABSTRACT
A lanthanide complex based on europium (Eu) and chelidamic acid was synthesized (Eu-CHE) and characterized. The complex Eu-CHE exhibited intense luminescence at 615 nm under excitation at 300 nm and was further investigated for highly sensitive turn-off detection of l-kynurenine (l-kyn), a cancer biomarker. The probe detected l-kyn linearly from 6 nM to 0.2 µM with a limit of detection and limit of quantification of 1.37 and 4.57 nM, respectively. The probe was investigated for selectivity towards l-kyn among co-existing amino acids and further extended for detecting l-kyn from human serum and urine samples. A low-cost paper strip-based sensing platform was also developed for the visual detection of l-kyn.
Subject(s)
Lanthanoid Series Elements , Neoplasms , Humans , Kynurenine , Biomarkers, Tumor , Neoplasms/diagnosis , Amino Acids , EuropiumABSTRACT
PURPOSE: Visitor restriction policies to prevent the spread of COVID-19 among patients and clinicians were widespread during the pandemic, resulting in the exclusion of caregivers at key points of cancer care and treatment decision-making. The aim of this study was to explore how visitor restrictions impacted cancer treatment decision-making and care from patient and physician perspectives. METHODS: Sixty-seven interviews, including 48 cancer patients and 19 cancer and palliative care physicians from four academic cancer centers in the USA between August 2020 and July 2021. RESULTS: Visitor restrictions that prevented caregivers from participating in clinic appointments and perioperative hospital care created challenges in cancer care that spanned three domains: practical, social, and informational. We identified eight themes that characterized challenges within the three domains across all three groups, and that these challenges had negative emotional and psychological consequences for both groups. Physicians perceived that patients' negative experiences due to lack of support through the physical presence of caregivers may have worsened patient outcomes. CONCLUSIONS: Our data demonstrate the tripartite structure of the therapeutic relationship in cancer care with caregivers providing critical support in the decision-making and care process to both patients and physicians. Caregiver absences led to practical, psychosocial, and informational burdens on both groups, and likely increased the risk of burnout among physicians. Our findings suggest that the quality of cancer care can be enhanced by engaging caregivers and promoting their physical presence during clinical encounters.
Subject(s)
COVID-19 , Neoplasms , Humans , COVID-19/prevention & control , Pandemics/prevention & control , Arm , Hospitals , Caregivers/psychology , Neoplasms/therapy , Neoplasms/psychology , Qualitative ResearchABSTRACT
BACKGROUND: This study explored the association of cardiovascular disease (CVD) with cancer mortality risk in individuals with or without a history of cancer, to better understand the interplay between CVD and cancer outcomes. METHODS: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018, a retrospective cohort analysis was conducted. This analysis accounted for the survey's complex design to ensure national representativeness. The association of CVD with cancer mortality was assessed through multivariable Cox proportional hazards models. RESULTS: The present study included 59,653 participants, of whom 54,095 did not have cancer and 5558 had a history of cancer. In individuals without cancer, heart failure (HF) was associated with an increased risk of mortality from cancer (HR, 1.36; 95% CI, 1.09-1.69; P = 0.005). In participants with cancer, HF correlated with a higher risk of mortality from cancer (HR, 1.76; 95% CI, 1.32-2.34; P < 0.001). Diabetes (DM), hypertension (HBP) and coronary heart disease (CHD) were not significantly associated with an increased risk of mortality from cancer. Significant differences were observed in the interaction between cancer and CHD (HR, 0.68; 95% CI, 0.53-0.87; P = 0.002). For cancer and HBP, a similar trend was noted (HR, 0.75; 95% CI, 0.62-0.91; P = 0.003). No significant differences were found in interactions between HF, DM and cancer. CONCLUSIONS: HF was associated with an increased risk of mortality from cancer, regardless of cancer history, while HBP, CHD and DM showed no significant association. These findings underscore the importance of understanding the mechanisms behind the increased risk of cancer mortality following HF.
Subject(s)
Cardiovascular Diseases , Coronary Disease , Heart Failure , Neoplasms , Humans , Nutrition Surveys , Retrospective Studies , Risk Factors , Cohort Studies , Heart Failure/epidemiology , Heart Failure/etiology , Coronary Disease/complicationsABSTRACT
BACKGROUND: Limited evidence exists on the population attributable fraction (PAF) of cancer cases and deaths in Latin America. In Peru several studies have been published regarding the PAF of various risk factors and their associated diseases. The objective of this study was to estimate the fraction of cancer cases and deaths attributable to potentially modifiable risk factors in Peru in 2018, before the COVID-19 pandemic in the population of 15 years old and older. METHODS: An ecological study was conducted using the prevalence of exposure of the Peruvian population to modifiable risk factors for cancer, the relative risk associated with each factor, and the number of cancer cases and deaths in 2018 as inputs. We used the Parkin formula with a Montecarlo statistical simulation model to calculate the PAF and confidence intervals. The number of new cancer cases and deaths attributed to each risk factor was determined by multiplying the number of cases and deaths in each gender by the PAF of each risk factor. FINDINGS: In Peru, 38.5% of new cases (34.5% in men and 42% in women) and 43.4% of cancer-related deaths (43.4% in men and 43.4% in women) were attributable to modifiable risk factors. The number of cancers attributable was 25,308 (10,439 in men and 14,869 in women) and the number of deaths attributable to cancer was 14,839 (6,953 in men and 7,886 in women). The predominant modifiable risk factors contributing to the highest number of cases and deaths were HPV infection (4,563 cases, 2,409 deaths), current tobacco use (3,348 cases, 2,180 deaths), and helicobacter pylori infection (2,677 cases, 1,873 deaths). Among the risk factors, oncogenic infections constituted the group with the highest PAF (16.6% for cases, 19.2% for deaths) followed by other unhealthy lifestyle factors (14.2% for cases, 16.7% for deaths), tobacco (7.2% for cases, 7.2% for deaths) and ultraviolet radiation (0.5% for cases, 0.3% for deaths). CONCLUSIONS: Prior to the COVID-19 pandemic, 38.5% of cancer cases and 43.4% of cancer-related deaths in Peru were linked to modifiable risk factors in the population of 15 years old and older. Most preventable cancer cases and deaths were related to oncogenic infections, primarily caused by HPV and helicobacter pylori, followed by tobacco and obesity.
Subject(s)
COVID-19 , Helicobacter Infections , Helicobacter pylori , Neoplasms , Papillomavirus Infections , Male , Humans , Female , Adolescent , Peru/epidemiology , Ultraviolet Rays , Helicobacter Infections/complications , Pandemics , Risk Factors , Neoplasms/epidemiology , Neoplasms/etiology , COVID-19/epidemiology , COVID-19/complications , Papillomavirus Infections/complications , Papillomavirus Infections/epidemiologyABSTRACT
BACKGROUND: Aneuploidy, an abnormal number of chromosomes within a cell, is a hallmark of cancer. Patterns of aneuploidy differ across cancers, yet are similar in cancers affecting closely related tissues. The selection pressures underlying aneuploidy patterns are not fully understood, hindering our understanding of cancer development and progression. RESULTS: Here, we apply interpretable machine learning methods to study tissue-selective aneuploidy patterns. We define 20 types of features corresponding to genomic attributes of chromosome-arms, normal tissues, primary tumors, and cancer cell lines (CCLs), and use them to model gains and losses of chromosome arms in 24 cancer types. To reveal the factors that shape the tissue-specific cancer aneuploidy landscapes, we interpret the machine learning models by estimating the relative contribution of each feature to the models. While confirming known drivers of positive selection, our quantitative analysis highlights the importance of negative selection for shaping aneuploidy landscapes. This is exemplified by tumor suppressor gene density being a better predictor of gain patterns than oncogene density, and vice versa for loss patterns. We also identify the importance of tissue-selective features and demonstrate them experimentally, revealing KLF5 as an important driver for chr13q gain in colon cancer. Further supporting an important role for negative selection in shaping the aneuploidy landscapes, we find compensation by paralogs to be among the top predictors of chromosome arm loss prevalence and demonstrate this relationship for one paralog interaction. Similar factors shape aneuploidy patterns in human CCLs, demonstrating their relevance for aneuploidy research. CONCLUSIONS: Our quantitative, interpretable machine learning models improve the understanding of the genomic properties that shape cancer aneuploidy landscapes.
