Cancer Biology & Medicine最新文献

Objective: The burden of gastric cancer (GC) across different age groups needs updating. We determined the GC global, regional, and national burden profiles and changes in incidence for 3 sequential 5-year intervals from 2003 to 2017.

Methods: The latest incidence and mortality estimates of GC from 185 countries and regions were extracted from the GLOBOCAN 2022 database. The 5-year interval age-standardised incidence rates (ASIRs) were evaluated using cancer registry data from volumes X-XII of the Cancer Incidence in Five Continents (CI5). Correlation analysis was used to evaluate the relationship between ASIR or the age-standardised mortality rate (ASMR) and the Human Development Index (HDI).

Results: There was an estimated global 968,000 new GC cases and 660,000 deaths in 2022, with male predominance. GC ASIRs and ASMRs were 9.2 and 6.1 per 100,000 persons, respectively. East Asia had the highest burden, with 53.8% of cases and 48.2% of deaths among all geographic regions. There was a significant correlation between ASIR and HDI. Over three 5-year intervals from 2003 to 2017, the incidence of GC notably decreased in most countries but peaked at 2008-2012 in New Zealand, Turkey, and South Africa. Several countries in Europe, Oceania, and America suggest an increasingly concerning trend among younger individuals, especially females.

Conclusions: GC is a significant health issue, especially among males and in geographic regions with an HDI, such as eastern Asia. While the incidence of GC is decreasing in many countries due to prevention efforts and improved treatments, a rising trend persists among younger individuals. Comprehensive prevention strategies tailored to different age patterns are clearly needed.

Objective: This study aimed to provide a comprehensive overview of the global burden of esophageal cancer (EC) and determine the temporal trends and factors influencing changes in the global burden.

Methods: The latest incidence and mortality data for EC worldwide were obtained from GLOBALCAN 2022. The mortality and disability-adjusted life years (DALYs) rates for EC from 1990-2019 were sourced from the 2019 Global Burden of Diseases. Trends in EC mortality and DALYs attributable to 11 risk factors or clusters of risk were analyzed using the joinpoint regression model. The trends in age-related EC burden were assessed using a decomposition approach.

Results: An estimated 511,054 new cases of EC were diagnosed in 2022 with 445,391 deaths worldwide. Approximately 75% of cases and deaths occurred in Asia. Nearly 50% of global EC deaths and DALYs were attributed to tobacco use in men in 2019, while 20% were attributed to high body mass index (BMI) in women. From 1990-2019, EC deaths and DALYs attributable to almost all risk factors had declining trends, while EC deaths and DALYs attributed to high BMI in men had upward trends. The age-related EC burden exhibited an upward trend driven by population growth and aging, which contributed to 307.4 thousand deaths and 7.2 million DALYs due to EC.

Conclusions: The EC burden remains substantial worldwide. Effective tobacco and obesity control measures are critical for addressing the risk-attributable burden of EC. Population growth and aging pose challenges for EC prevention and control efforts.

Objective: Little progress has been made in recent years using first-line chemotherapy, including gemcitabine combined with nab-paclitaxel, FOLFIRINOX, and NALIRIFOX, for advanced pancreatic adenocarcinoma (APC). In addition, the optimal second-line chemotherapy regimen has not been determined. This study aimed to compare the effectiveness of different types of second-line chemotherapy for APC.

Methods: Patients with APC who received first-line treatment from January 2008 to January 2021 were considered eligible for this retrospective analysis. The primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS), respectively.

Results: Four hundred and thirty-seven and 617 patients were treated with 5-fluorouracil- and gemcitabine-based chemotherapy as first-line treatment, respectively. Demographic and clinical features, except age and liver metastasis, were comparable between the two groups (P < 0.05). The median OS was 8.8 and 7.8 months in patients who received a 5-fluorouracil- and gemcitabine-based combined regimen for first-line therapy, respectively (HR = 1.244, 95% CI = 1.090-1.419; P < 0.001). The median OS was 5.6 and 1.9 months in patients who received second-line chemotherapy and supportive care, respectively (HR = 0.766, 95% CI = 0.677-0.867; P < 0.001). The median PFS was not significantly differently between gemcitabine or 5-fluorouracil monotherapy and combination therapy.

Conclusions: A 5-fluorouracil- or gemcitabine-based combined regimen was shown to be as effective as a single 5-fluorouracil or gemcitabine regimen as second-line therapy for patients with APC.

Objective: Improvement in cancer survival over recent decades has not been accompanied by a narrowing of socioeconomic disparities. This study aimed to quantify the loss of life expectancy (LOLE) resulting from a cancer diagnosis and examine disparities in LOLE based on area-level socioeconomic status (SES).

Methods: Data were collected for all people between 50 and 89 years of age who were diagnosed with cancer, registered in the NSW Cancer Registry between 2001 and 2019, and underwent mortality follow-up evaluations until December 2020. Flexible parametric survival models were fitted to estimate the LOLE by gender and area-level SES for 12 common cancers.

Results: Of 422,680 people with cancer, 24% and 18% lived in the most and least disadvantaged areas, respectively. Patients from the most disadvantaged areas had a significantly greater average LOLE than patients from the least disadvantaged areas for cancers with high survival rates, including prostate [2.9 years (95% CI: 2.5-3.2 years) vs. 1.6 years (95% CI: 1.3-1.9 years)] and breast cancer [1.6 years (95% CI: 1.4-1.8 years) vs. 1.2 years (95% CI: 1.0-1.4 years)]. The highest average LOLE occurred in males residing in the most disadvantaged areas with pancreatic [16.5 years (95% CI: 16.1-16.8 years) vs. 16.2 years (95% CI: 15.7-16.7 years)] and liver cancer [15.5 years (95% CI: 15.0-16.0 years) vs. 14.7 years (95% CI: 14.0-15.5 years)]. Females residing in the least disadvantaged areas with thyroid cancer [0.9 years (95% CI: 0.4-1.4 years) vs. 0.6 years (95% CI: 0.2-1.0 years)] or melanoma [0.9 years (95% CI: 0.8-1.1 years) vs. 0.7 years (95% CI: 0.5-0.8 years)] had the lowest average LOLE.

Conclusions: Patients from the most disadvantaged areas had the highest LOLE with SES-based differences greatest for patients diagnosed with cancer at an early stage or cancers with higher survival rates, suggesting the need to prioritise early detection and reduce treatment-related barriers and survivorship challenges to improve life expectancy.

Pseudomyxoma peritonei (PMP) is an indolent malignant syndrome. The standard treatment for PMP is cytoreductive surgery combined with intraperitoneal hyperthermic chemotherapy (CRS + HIPEC). However, the high recurrence rate and latent clinical symptoms and signs are major obstacles to further improving clinical outcomes. Moreover, patients in advanced stages receive little benefit from CRS + HIPEC due to widespread intraperitoneal metastases. Another challenge in PMP treatment involves the progressive sclerosis of PMP cell-secreted mucus, which is often increased due to activating mutations in the gene coding for guanine nucleotide-binding protein alpha subunit (GNAS). Consequently, the development of other PMP therapies is urgently needed. Several immune-related therapies have shown promise, including the use of bacterium-derived non-specific immunogenic agents, radio-immunotherapeutic agents, and tumor cell-derived neoantigens, but a well-recognized immunotherapy has not been established. In this review the roles of GNAS mutations in the promotion of mucin secretion and disease development are discussed. In addition, the immunologic features of the PMP microenvironment and immune-associated treatments are discussed to summarize the current understanding of key features of the disease and to facilitate the development of immunotherapies.

Objective: Liver cancer is a major health concern globally and in China. This analysis investigated deaths and disability-adjusted life years (DALYs) with respect to etiologies and risk factors for liver cancer in China and worldwide.

Methods: Global and China-specific data were collected on liver cancer deaths, DALYs, and age-standardized rates (ASRs) from the Global Burden of Disease Study 2019 database. Liver cancer etiologies were classified into five groups and risk factors were categorized into three levels. Each proportion of liver cancer burden was calculated in different geographic regions. The joinpoint regression model were used to assess the trends from 1990-2019.

Results: Liver cancer accounted for 484,577 deaths worldwide in 2019 with an ASR of 5.9 per 100,000 population. China had an elevated liver cancer death ASR in 2019 and males had an ASR 1.7 times the global rate. The global ASR for DALYs peaked at 75-79 years of age but peaked earlier in China. Hepatitis B virus was the prominent etiology globally (39.5%) and in China (62.5%), followed by hepatitis C virus and alcohol consumption. In high sociodemographic index countries, non-alcoholic steatohepatitis has gained an increasing contribution as an etiologic factor. The liver cancer burden due to various etiologies has decreased globally in both genders. However, metabolic risk factors, particularly obesity, have had a growing contribution to the liver cancer burden, especially among males.

Conclusions: Despite an overall decreasing trend in the liver cancer burden in China and worldwide, there has been a rising contribution from metabolic risk factors, highlighting the importance of implementing targeted prevention and control strategies that address regional and gender disparities.

Objective: Australia has relatively high multiple myeloma (MM) incidence and mortality rates. Advancements in MM treatment over recent decades have driven improvements in MM survival in high-income countries; however, reporting in Australia is limited. We investigated temporal trends in population-wide MM survival across 3 periods of treatment advancements in New South Wales (NSW), Australia.

Methods: Individuals with an MM diagnosis in the NSW Cancer Registry between 1985 and 2015 with vital follow-up to 2020, were categorized into 3 previously defined treatment eras according to their diagnosis date (1985-1995, chemotherapy only; 1996-2007, autologous stem cell transplantation; and 2008-2015, novel agents including proteasome inhibitors and immunomodulatory drugs). Both relative survival and cause-specific survival according to Fine and Gray's competing risks cumulative incidence function were calculated by treatment era and age at diagnosis.

Results: Overall, 11,591 individuals were included in the study, with a median age of 70 years at diagnosis. Five-year relative survival improved over the 36-year (1985-2020) study period (31.0% in 1985-1995; 41.9% in 1996-2007; and 56.1% in 2008-2015). For individuals diagnosed before 70 years of age, the 5-year relative survival nearly doubled, from 36.5% in 1985-1995 to 68.5% in 2008-2015. Improvements for those > 70 years of age were less pronounced between 1985-1995 and 1996-2007; however, significant improvements were observed for those diagnosed in 2008-2015. Similar overall and age-specific patterns were observed for cause-specific survival. After adjustment for gender and age at diagnosis, treatment era was strongly associated with both relative and cause-specific survival (P < 0.0001).

Conclusions: Survival of individuals with MM is improving in Australia with treatment advances. However, older age groups continue to experience poor survival outcomes with only modest improvements over time. Given the increasing prevalence of MM in Australia, the effects of MM treatment on quality of life, particularly in older age, warrant further attention.

Gastric cancer (GC) ranks fifth in cancer incidence and fourth in cancer-related mortality worldwide. Reactive oxygen species (ROS) are highly oxidative oxygen-derived products that have crucial roles in cell signaling regulation and maintaining internal balance. ROS are closely associated with the occurrence, development, and treatment of GC. This review summarizes recent findings on the sources of ROS and the bidirectional regulatory effects on GC and discusses various treatment modalities for GC that are related to ROS induction. In addition, the regulation of ROS by natural small molecule compounds with the highest potential for development and applications in anti-GC research is summarized. The aim of the review is to accelerate the clinical application of modulating ROS levels as a therapeutic strategy for GC.

Objective: Mitochondrial fatty acid oxidation is a metabolic pathway whose dysregulation is recognized as a critical factor in various cancers, because it sustains cancer cell survival, proliferation, and metastasis. The acyl-CoA synthetase long-chain (ACSL) family is known to activate long-chain fatty acids, yet the specific role of ACSL3 in breast cancer has not been determined.

Methods: We assessed the prognostic value of ACSL3 in breast cancer by using data from tumor samples. Gain-of-function and loss-of-function assays were also conducted to determine the roles and downstream regulatory mechanisms of ACSL3 in vitro and in vivo.

Results: ACSL3 expression was notably downregulated in breast cancer tissues compared with normal tissues, and this phenotype correlated with improved survival outcomes. Functional experiments revealed that ACSL3 knockdown in breast cancer cells promoted cell proliferation, migration, and epithelial-mesenchymal transition. Mechanistically, ACSL3 was found to inhibit β-oxidation and the formation of associated byproducts, thereby suppressing malignant behavior in breast cancer. Importantly, ACSL3 was found to interact with YES proto-oncogene 1, a member of the Src family of tyrosine kinases, and to suppress its activation through phosphorylation at Tyr419. The decrease in activated YES1 consequently inhibited YAP1 nuclear colocalization and transcriptional complex formation, and the expression of its downstream genes in breast cancer cell nuclei.

Conclusions: ACSL3 suppresses breast cancer progression by impeding lipid metabolism reprogramming, and inhibiting malignant behaviors through phospho-YES1 mediated inhibition of YAP1 and its downstream pathways. These findings suggest that ACSL3 may serve as a potential biomarker and target for comprehensive therapeutic strategies for breast cancer.