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Journal of Cancer 2024Head and neck squamous cell carcinoma (HNSC) is a dangerous cancer that represents an important threat to human health. Niclosamide is an anti-helminthic drug that has...
Head and neck squamous cell carcinoma (HNSC) is a dangerous cancer that represents an important threat to human health. Niclosamide is an anti-helminthic drug that has received FDA approval. In drug repurposing screens, niclosamide was found to inhibit proliferative activity for a range of tumor types. Its functional effects in HNSC, however, have yet to be established. MTT and colony formation assays were used to explore the impact of niclosamide on the proliferation of HNSC cells, while wound healing and Transwell assays were employed to assess migration and invasivity. Flow cytometry and Western immunoblotting were respectively used to assess cellular apoptosis and protein expression patterns. An HNSC xenograft tumor model system was used to evaluate the antitumor activity of niclosamide, and immunofluorescent staining was employed to assess cleaved Caspase3 and Ki67 expression. The ability of niclosamide to prevent metastatic progression was assessed with a model of pulmonary metastasis. These analyses revealed the ability of niclosamide to suppress HNSC cell migration, proliferation, and invasivity while promoting apoptotic death. From a mechanistic perspective, this drug suppressed Stat3 phosphorylation and β-catenin expression, while increasing cleaved Caspase3 levels in HNSC cells and reducing Bcl-2 levels. Importantly, this drug was able to suppress tumor growth and pulmonary metastasis formation, with immunofluorescent staining confirming that it reduced Ki67 levels and increased cleaved Caspase3 content. In conclusion, these analyses highlight the ability of niclosamide to inhibit HNSC cell migration and proliferative activity while provoking apoptotic death mediated via p-Stat3 and β-catenin pathway inactivation. Niclosamide thus holds promise for repurposing as a candidate drug for the more effective clinical management of HNSC.
PubMed: 38947381
DOI: 10.7150/jca.95682 -
Journal of Cancer 2024Hepatocellular carcinoma (HCC) is the main type of primary liver cancer, and its related death ranks third worldwide. The curative methods and progress prediction...
Hepatocellular carcinoma (HCC) is the main type of primary liver cancer, and its related death ranks third worldwide. The curative methods and progress prediction markers of HCC are not sufficient enough. Nevertheless, little progress has been made in the signature of mA-, mC-, mA-, mG-, and DNA methylation of HCC. We calibrated a risk gene signature model that can be used to categorize HCC patients based on univariate, multivariate, and LASSO Cox regression analysis. This gene signature classified the patients into high- and low-risk subgroups. Patients in the high-risk group showed significantly reduced overall survival (OS) compared with patients in the low-risk group. The gene set variation analysis (GSVA), immune infiltration, and immunotherapy response were analyzed. The results demonstrated that an immunosuppressive environment was exited and the high-risk group had higher sensitivity to 5-fluorouracil, cisplatin, sorafenib, tamoxifen, and epirubicin. These results indicated personalized therapy should be taken into consideration. Our findings enriched our understanding of the molecular heterogeneity, tumor microenvironment (TME), and drug susceptibility of HCC. mA-, mC-, mA-, mG-, and DNA methylation-related regulators may be promising biomarkers for future research.
PubMed: 38947378
DOI: 10.7150/jca.95730 -
Frontiers in Public Health 2024There is a paucity of studies that compare older adults' attitudes toward Euthanasia in two different terminal illnesses. Moreover, these studies did not relate to...
BACKGROUND
There is a paucity of studies that compare older adults' attitudes toward Euthanasia in two different terminal illnesses. Moreover, these studies did not relate to potentially influencing psycho-social factors. The current study aimed to examine the impact of a diverse range of variables on attitudes among older adults toward Euthanasia in two medical conditions: cancer and Parkinson's disease.
METHODS
A total of 501 individuals aged 75 and above participated in the study. Attitudes toward Euthanasia were measured using vignettes which described two conditions: an 80-year-old man with metastatic cancer and another man in an advanced stage of Parkinson's disease. The questionnaire included measures of relevant experience (with a close family member or a friend dying from a terminal illness), self-efficacy, will to live, satisfaction with life, will to prolong life, fear of death and dying, social support, and psycho-social characteristics. The data were analyzed using hierarchical linear regression models.
RESULTS
A more positive attitude toward Euthanasia was found in the case of cancer compared to Parkinson's disease. Being a woman, having more years of education, lower level of religiosity, greater fear of death and dying and higher self-efficacy contributes to more favorable attitudes toward Euthanasia in both end-of life conditions.
CONCLUSIONS
The finding that attitudes toward Euthanasia are statistically significantly more positive in the case of cancer compared to Parkinson's disease can be attributed to the greater prevalence of cancer in the population, and to the public's awareness of the suffering associated with each of these medical conditions. Beyond the important role of the socio-demographic characteristics of gender, education, and religiosity, it appears that fear of death and dying and self-efficacy are important psychological factors in explaining attitudes toward Euthanasia in both illnesses among older people. These findings shed light on older adults' attitudes toward Euthanasia in debilitating illnesses.
Topics: Humans; Male; Female; Parkinson Disease; Aged, 80 and over; Aged; Attitude to Death; Neoplasms; Euthanasia; Surveys and Questionnaires; Self Efficacy; Terminal Care
PubMed: 38947343
DOI: 10.3389/fpubh.2024.1393535 -
Frontiers in Immunology 2024The interaction between pyroptosis-a form of programmed cell death-and tumor immunity represents a burgeoning field of interest. Pyroptosis exhibits a dual role in... (Review)
Review
BACKGROUND
The interaction between pyroptosis-a form of programmed cell death-and tumor immunity represents a burgeoning field of interest. Pyroptosis exhibits a dual role in cancer: it can both promote tumor development and counteract it by activating immune responses that inhibit tumor evasion and encourage cell death. Current tumor immunotherapy strategies, notably CAR-T cell therapy and immune checkpoint inhibitors (ICIs), alongside the potential of certain traditional Chinese medicinal compounds, highlight the intricate relationship between pyroptosis and cancer immunity. As research delves deeper into pyroptosis mechanisms within tumor therapy, its application in enhancing tumor immune responses emerges as a novel research avenue.
PURPOSE
This review aims to elucidate the mechanisms underlying pyroptosis, its impact on tumor biology, and the advancements in tumor immunotherapy research.
METHODS
A comprehensive literature review was conducted across PubMed, Embase, CNKI, and Wanfang Database from the inception of the study until August 22, 2023. The search employed keywords such as "pyroptosis", "cancer", "tumor", "mechanism", "immunity", "gasdermin", "ICB", "CAR-T", "PD-1", "PD-L1", "herbal medicine", "botanical medicine", "Chinese medicine", "traditional Chinese medicine", "immunotherapy", linked by AND/OR, to capture the latest findings in pyroptosis and tumor immunotherapy.
RESULTS
Pyroptosis is governed by a complex mechanism, with the Gasdermin family playing a pivotal role. While promising for tumor immunotherapy application, research into pyroptosis's effect on tumor immunity is still evolving. Notably, certain traditional Chinese medicine ingredients have been identified as potential pyroptosis inducers, meriting further exploration.
CONCLUSION
This review consolidates current knowledge on pyroptosis's role in tumor immunotherapy. It reveals pyroptosis as a beneficial factor in the immunotherapeutic landscape, suggesting that leveraging pyroptosis for developing novel cancer treatment strategies, including those involving traditional Chinese medicine, represents a forward-looking approach in oncology.
Topics: Pyroptosis; Humans; Neoplasms; Immunotherapy; Animals; Immune Checkpoint Inhibitors; Tumor Microenvironment
PubMed: 38947336
DOI: 10.3389/fimmu.2024.1381778 -
Frontiers in Immunology 2024
Topics: Animals; Aquatic Organisms; Apoptosis
PubMed: 38947334
DOI: 10.3389/fimmu.2024.1428742 -
Frontiers in Immunology 2024Epithelioid hemangioendothelioma is a rare vascular malignancy, and currently, there is no standard treatment regimen for this disease and existing treatment options...
Epithelioid hemangioendothelioma is a rare vascular malignancy, and currently, there is no standard treatment regimen for this disease and existing treatment options have limited efficacy. In this case report, we present a patient with lung and lymph node metastases from prostate epithelioid hemangioendothelioma who achieved a significant partial response. This was accomplished through alternating nivolumab therapy with ipilimumab and liposomal doxorubicin, resulting in a progression-free-survival more than 6 months to date. The treatment was well-tolerated throughout. Our report suggests that dual immunotherapy alternating with anti-PD-1antibody plus doxorubicin may be a potential treatment modality for epithelioid hemangioendothelioma. However, larger sample studies are necessary to ascertain the effectiveness of this treatment strategy and it is essential to continue monitoring this patient to sustain progression-free survival and overall survival.
Topics: Humans; Male; Doxorubicin; Hemangioendothelioma, Epithelioid; Nivolumab; Prostatic Neoplasms; Programmed Cell Death 1 Receptor; Antineoplastic Combined Chemotherapy Protocols; Immunotherapy; Immune Checkpoint Inhibitors; Ipilimumab; Treatment Outcome; Polyethylene Glycols; Middle Aged
PubMed: 38947327
DOI: 10.3389/fimmu.2024.1384111 -
Frontiers in Immunology 2024Chronic obstructive pulmonary disease (COPD) is currently listed as the 3 leading cause of death in the United States. Accumulating data shows the association between...
INTRODUCTION
Chronic obstructive pulmonary disease (COPD) is currently listed as the 3 leading cause of death in the United States. Accumulating data shows the association between COPD occurrence and the usage of electronic nicotine delivery systems (ENDS) in patients. However, the underlying pathogenesis mechanisms of COPD have not been fully understood.
METHODS
In the current study, bENaC-overexpressing mice (bENaC mice) were subjected to whole-body ENDS exposure. COPD related features including emphysema, mucus accumulation, inflammation and fibrosis are examined by tissue staining, FACS analysis, cytokine measurement. Cell death and ferroptosis of alveolar epithelial cells were further evaluated by multiple assays including staining, FACS analysis and lipidomics.
RESULTS
ENDS-exposed mice displayed enhanced emphysema and mucus accumulation, suggesting that ENDS exposure promotes COPD features. ENDS exposure also increased immune cell number infiltration in bronchoalveolar lavage and levels of multiple COPD-related cytokines in the lungs, including CCL2, IL-4, IL-13, IL-10, M-CSF, and TNF-α. Moreover, we observed increased fibrosis in ENDS-exposed mice, as evidenced by elevated collagen deposition and a-SMA+ myofibroblast accumulation. By investigating possible mechanisms for how ENDS promoted COPD, we demonstrated that ENDS exposure induced cell death of alveolar epithelial cells, evidenced by TUNEL staining and Annexin V/PI FACS analysis. Furthermore, we identified that ENDS exposure caused lipid dysregulations, including TAGs (9 species) and phospholipids (34 species). As most of these lipid species are highly associated with ferroptosis, we confirmed ENDS also enhanced ferroptosis marker CD71 in both type I and type II alveolar epithelial cells.
DISCUSSION
Overall, our data revealed that ENDS exposure exacerbates features of COPD in bENaC mice including emphysema, mucus accumulation, abnormal lung inflammation, and fibrosis, which involves the effect of COPD development by inducing ferroptosis in the lung.
Topics: Animals; Ferroptosis; Pulmonary Disease, Chronic Obstructive; Mice; Nicotine; E-Cigarette Vapor; Disease Models, Animal; Cytokines; Mice, Inbred C57BL; Electronic Nicotine Delivery Systems; Male; Mice, Transgenic
PubMed: 38947318
DOI: 10.3389/fimmu.2024.1429946 -
World Journal of Gastroenterology Jun 2024Posthepatectomy liver failure (PHLF) is one of the most important causes of death following liver resection. Heparin, an established anticoagulant, can protect liver...
BACKGROUND
Posthepatectomy liver failure (PHLF) is one of the most important causes of death following liver resection. Heparin, an established anticoagulant, can protect liver function through a number of mechanisms, and thus, prevent liver failure.
AIM
To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy.
METHODS
The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) v1. 4 pinpointed patients who had undergone hepatectomy for liver cancer, subdividing them into two cohorts: Those who were injected with heparin and those who were not. The statistical evaluations used were unpaired -tests, Mann-Whitney tests, chi-square tests, and Fisher's exact tests to assess the effect of heparin administration on PHLF, duration of intensive care unit (ICU) stay, need for mechanical ventilation, use of continuous renal replacement therapy (CRRT), incidence of hypoxemia, development of acute kidney injury, and ICU mortality. Logistic regression was utilized to analyze the factors related to PHLF, with propensity score matching (PSM) aiming to balance the preoperative disparities between the two groups.
RESULTS
In this study, 1388 patients who underwent liver cancer hepatectomy were analyzed. PSM yielded 213 matched pairs from the heparin-treated and control groups. Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples. Further analysis in the matched cohorts confirmed a significant association, with heparin reducing the risk of PHLF (odds ratio: 0.518; 95% confidence interval: 0.295-0.910; = 0.022). Additionally, heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations, diminished requirements for respiratory support and CRRT, and lower incidences of hypoxemia and ICU mortality.
CONCLUSION
Liver failure is an important hazard following hepatic surgery. During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure. This indicates that heparin may provide a hopeful option for controlling PHLF.
Topics: Humans; Hepatectomy; Heparin; Male; Female; Middle Aged; Liver Failure; Liver Neoplasms; Aged; Anticoagulants; Treatment Outcome; Postoperative Complications; Retrospective Studies; Length of Stay; Risk Factors; Intensive Care Units; Propensity Score
PubMed: 38947296
DOI: 10.3748/wjg.v30.i22.2881 -
World Journal of Gastroenterology Jun 2024Coronavirus disease 2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily impacts the respiratory... (Review)
Review
Coronavirus disease 2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome, multiple organ failure, and death. Despite extensive studies on the pathogenicity of SARS-CoV-2, its impact on the hepatobiliary system remains unclear. While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels, the exact source of this damage is not fully understood. Proposed mechanisms for injury include direct cytotoxicity, collateral damage from inflammation, drug-induced liver injury, and ischemia/hypoxia. However, evidence often relies on blood tests with liver enzyme abnormalities. In this comprehensive review, we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients, drawing from liver biopsies, complete autopsies, and liver analyses. We present evidence of the direct impact of SARS-CoV-2 on the liver, substantiated by observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes, including mitochondrial swelling, endoplasmic reticulum dilatation, and hepatocyte apoptosis. Additionally, we describe the diverse liver pathology observed during COVID-19 infection, encompassing necrosis, steatosis, cholestasis, and lobular inflammation. We also discuss the emergence of long-term complications, notably COVID-19-related secondary sclerosing cholangitis. Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.
Topics: Humans; COVID-19; Liver; SARS-CoV-2; Liver Diseases; Hepatocytes
PubMed: 38947288
DOI: 10.3748/wjg.v30.i22.2866 -
Global Heart 2024The objective of this study is to conduct a temporal analysis of rheumatic heart disease (RHD) disease burden trends over a 30-year period (1991 to 2021), focusing on...
BACKGROUND
The objective of this study is to conduct a temporal analysis of rheumatic heart disease (RHD) disease burden trends over a 30-year period (1991 to 2021), focusing on prevalence, deaths, and disability-adjusted life years (DALYs) in the South Asia (SA).
METHODS
In this ecological study, we analyzed data regarding burden of RHD from the Global Burden of Diseases (GBD) study spanning the years 1991 to 2021 for the SA Region. Estimates of the number RHD-related prevalence, deaths, and DALYs along with age-standardized rates (ASR) per 100,000 population and 95% uncertainty intervals (UI) were evaluated.
RESULTS
The overall prevalent cases of RHD in the 2021 were 54785.1 × 10 (43328.4 × 10 to 67605.5 × 10), out of which 14378.8 × 10 (11206.9 × 10 to 18056.9 × 10) were from SA. The ASR of point prevalence showed upward trend between 1991 and 2021, at global level and for SA with an average annual percentage change (AAPC) of 0.40 (0.39 to 0.40) and 0.12 (0.11 to 0.13), respectively. The overall number of RHD-related deaths in the 2021 were 373.3 × 10 (324.1 × 10 to 444.8 × 10), out of which 215 × 10 (176.9 × 10 to 287.8 × 10) were from SA, representing 57.6% of the global deaths. The ASR of deaths also showed downward trend between 1991 and 2021, at global level and for SA with an AAPC of -2.66 (-2.70 to -2.63) and -2.07 (-2.14 to -2.00), respectively. The ASR of DALYs showed downward trend between 1990 and 2019, at global level and for South Asian region with an AAPC of -2.47 (-2.49 to -2.44) and -2.22 (-2.27 to -2.17), respectively.
CONCLUSION
The rising age-standardized prevalence of RHD remains a global concern, especially in South Asia which contribute to over 50% of global RHD-related deaths. Encouragingly, declining trends in RHD-related deaths and DALYs hint at progress in RHD management and treatment on both a global and regional scale.
Topics: Humans; Rheumatic Heart Disease; Global Burden of Disease; Male; Female; Prevalence; Adult; Middle Aged; Asia; Cost of Illness; Disability-Adjusted Life Years; Quality-Adjusted Life Years; Retrospective Studies; Asia, Southern
PubMed: 38947253
DOI: 10.5334/gh.1336