-
AJNR. American Journal of Neuroradiology Jun 2024Light-chain deposition disease (LCDD) is a rare CNS disorder characterized by the extracellular accumulation of monoclonal immunoglobulin light chains in various organs.... (Review)
Review
Light-chain deposition disease (LCDD) is a rare CNS disorder characterized by the extracellular accumulation of monoclonal immunoglobulin light chains in various organs. LCDD typically arises secondary to an underlying plasma cell dyscrasia, such as monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma. However, rare cases can occur in the absence of a demonstrable plasma cell disorder. The kidneys, liver, lungs, and heart are the most affected organs. Intracerebral LCDD, particularly without an underlying plasma cell neoplasm, represents an exceedingly uncommon entity with limited documented cases in literature. This review article explores the pathogenesis, histopathological features, and characteristic neuroimaging findings of intracerebral LCDD. We emphasize the diverse imaging presentations of this disease, which can closely resemble other neurological pathologies. Recognizing these potential mimics is crucial for avoiding misdiagnosis, especially in the absence of a known underlying plasma cell disorder. This article aims to provide a comprehensive overview from a neuroradiological perspective, facilitating the recognition and differentiation of this challenging entity.ABBREVIATIONS: LCDD, light chain deposition disease; ALD, amyloidoma.
PubMed: 38914431
DOI: 10.3174/ajnr.A8390 -
BMC Medicine Jun 2024To assess the largely undetermined separate and joint effects of sleep and liver function biomarkers on liver cancer.
BACKGROUND
To assess the largely undetermined separate and joint effects of sleep and liver function biomarkers on liver cancer.
METHODS
Data of 356,894 participants without cancer at baseline in the UK Biobank were analyzed. Sleep score was evaluated using five sleep traits (sleep duration, chronotype, insomnia, snoring, and excessive daytime sleepiness) and dichotomized into healthy or unhealthy sleep. Circulating liver function biomarkers were measured. Cox proportional hazard model was performed to investigate the independent and joint associations of sleep and liver function biomarkers with liver cancer incidence.
RESULTS
After a median follow-up time of 13.1 years, 394 cases of incident liver cancer were documented. The multivariable-adjusted hazard ratio (HR) for liver cancer was 1.46 (95% confidence interval: 1.15-1.85) associated with unhealthy sleep (vs. healthy sleep), and was 1.17 (1.15-1.20), 1.20 (1.18-1.22), 1.69 (1.47-1.93), 1.06 (1.06-1.07), 1.08 (1.07-1.09), 1.81 (1.37-2.39), or 0.29 (0.18-0.46) associated with each 10-unit increase in alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total protein (TP), or albumin (ALB), respectively. Individuals with unhealthy sleep and high (≥ median) ALT, AST, TBIL, GGT, ALP, or TP or low (< median) ALB level had the highest HR of 3.65 (2.43-5.48), 4.03 (2.69-6.03), 1.97 (1.40-2.77), 4.69 (2.98-7.37), 2.51 (1.75-3.59), 2.09 (1.51-2.89), or 2.22 (1.55-3.17) for liver cancer, respectively. Significant additive interaction of unhealthy sleep with high TP level on liver cancer was observed with relative excess risk due to an interaction of 0.80 (0.19-1.41).
CONCLUSIONS
Unhealthy sleep was associated with an increased risk of liver cancer, especially in participants with lower ALB levels or higher levels of ALT, AST, TBIL, GGT, ALP, or particularly TP.
Topics: Humans; Male; Female; Middle Aged; Liver Neoplasms; Prospective Studies; Sleep; Biomarkers; Aged; United Kingdom; Adult; Incidence; Liver Function Tests; Risk Factors; Liver
PubMed: 38915009
DOI: 10.1186/s12916-024-03440-w -
BMC Gastroenterology Jun 2024Hepatocellular carcinoma (HCC) represents a significant global health challenge with high incidence and mortality rates. T cells and natural killer (NK) cells are...
BACKGROUND
Hepatocellular carcinoma (HCC) represents a significant global health challenge with high incidence and mortality rates. T cells and natural killer (NK) cells are pivotal in this context, yet HCC can evade immune surveillance. CD161 (KLRB1), a C-type lectin receptor, modulates immune responses and is expressed on NK cells and a subset of T cells. Its relevance in HCC remains poorly understood, with conflicting findings regarding its impact on patient prognosis.
METHODS
Utilizing TCGA data and single-cell analysis, we investigated the biological functions of KLRB1 in HCC. Peripheral blood samples from 126 HCC patients were collected to assess KLRB1 expression on NK and T cells. The diagnostic performance of KLRB1 on NK and CD8 + T cells was evaluated using receiver operating characteristic curve (ROC) analysis, while its prognostic significance was assessed using Kaplan-Meier analysis and COX regression models.
RESULTS
Analysis of TCGA data revealed a significant correlation between KLRB1 expression and immune activation, particularly T cell activation. Single-cell data further demonstrated elevated KLRB1 expression in tissue-resident NK and T cells within HCC, which co-expressed markers of immune activation. Clinical data showed downregulated KLRB1 expression on NK and T cells in HCC patients compared to health individuals, with lower expression levels correlating with poorer prognosis.
CONCLUSION
KLRB1 emerges as a promising biomarker in HCC, with its downregulation on peripheral blood NK and T cells suggesting potential prognostic value. Further elucidation of KLRB1's role in HCC may pave the way for the development of targeted immunotherapies and the improvement of patient outcomes.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Killer Cells, Natural; Prognosis; Male; Female; Middle Aged; Biomarkers, Tumor; NK Cell Lectin-Like Receptor Subfamily B; CD8-Positive T-Lymphocytes; Kaplan-Meier Estimate; Aged; Single-Cell Analysis; ROC Curve; Lymphocyte Activation; Down-Regulation
PubMed: 38914941
DOI: 10.1186/s12876-024-03299-4 -
Journal of Cancer Research and Clinical... Jun 2024Tumor-associated macrophages (TAMs) play a critical role in hepatocellular carcinoma (HCC) progression and metastasis. Systematic investigation of the cross-talk between...
PURPOSE
Tumor-associated macrophages (TAMs) play a critical role in hepatocellular carcinoma (HCC) progression and metastasis. Systematic investigation of the cross-talk between TAMs and HCC may help in searching for the critical target to guard against HCC metastasis.
METHODS AND RESULTS
Herein, we found that TREM1 highly expressed in HCC tissue by analyzing the data obtain from GEO database. Interestingly, the results indicated that TREM1 was primarily expressed by monocytes. Immune infiltration studies further validated that TREM1 expression was positively related with increased infiltration of macrophages in HCC tissues. In vitro, we observed that TREM1 knockdown significantly abrogated the effect of TAMs in promoting the metastasis and epithelial-mesenchymal transition (EMT) of HCC cells. Additionally, cytokine array detection identified CCL7 as the main responsive cytokine following with TREM1 knockdown in TAMs.
CONCLUSION
Taken together, our findings strongly suggested that high expression of TREM1 was positively associated with metastasis and poor prognosis of HCC. Furthermore, TAMs expressing TREM1 contribute to EMT-based metastasis through secreting CCL7. These results provide a novel insight into the potential development of targeting the TREM1/CCL7 pathway for preventing metastatic HCC.
Topics: Humans; Liver Neoplasms; Carcinoma, Hepatocellular; Triggering Receptor Expressed on Myeloid Cells-1; Epithelial-Mesenchymal Transition; Prognosis; Tumor-Associated Macrophages; Cell Line, Tumor; Male; Female; Neoplasm Metastasis
PubMed: 38914803
DOI: 10.1007/s00432-024-05831-1 -
Journal of Cancer Research and Clinical... Jun 2024Hepatocellular carcinoma (HCC) is a critical global health concern, with existing treatments benefiting only a minority of patients. Recent findings implicate the...
PURPOSE
Hepatocellular carcinoma (HCC) is a critical global health concern, with existing treatments benefiting only a minority of patients. Recent findings implicate the chemokine ligand 17 (CCL17) and its receptor CCR4 as pivotal players in the tumor microenvironment (TME) of various cancers. This investigation aims to delineate the roles of CCL17 and CCR4 in modulating the tumor's immune landscape, assessing their potential as therapeutic interventions and prognostic markers in HCC.
METHODS
873 HCC patients post-radical surgery from 2008 to 2012 at Zhongshan Hospital, Fudan University were retrospectively examined. These individuals were stratified into a training cohort (n = 354) and a validation cohort (n = 519). Through immunohistochemical analysis on HCC tissue arrays, the expressions of CCL17, CCR4, CD73, CD47, HHLA2, and PD-L1 were quantified. Survival metrics were analyzed using the Cox model, and a prognostic nomogram was devised via R software.
RESULTS
The investigation confirmed the presence of CCL17 and CCR4 within the cancerous and stromal compartments of HCC tissues, associating their heightened expression with adverse clinical markers and survival outcomes. Notably, the interplay between CD73 and CCR4 expression in tumor stroma highlighted a novel cellular entity, CCR4 + CD73 + stromal cells, impacting overall and relapse-free survival. A prognostic nomogram amalgamating these immunological markers and clinical variables was established, offering refined prognostic insights and aiding in the management of HCC. The findings suggest that reduced CCR4 and CCR4 + CD73 + cell prevalence may forecast improved outcomes post-TACE.
CONCLUSION
This comprehensive evaluation of CCR4, CCL17, and associated markers introduces a nuanced understanding of the HCC immunological milieu, proposing CCR4 + CD73 + stromal cells as critical to HCC pathogenesis and patient stratification.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Chemokine CCL17; Female; Male; Prognosis; Receptors, CCR4; Middle Aged; Biomarkers, Tumor; 5'-Nucleotidase; Retrospective Studies; Tumor Microenvironment; GPI-Linked Proteins; Aged; Adult
PubMed: 38914802
DOI: 10.1007/s00432-024-05832-0 -
Scientific Reports Jun 2024Caffeic acid phenethyl ester (CAPE) and its derivatives exhibit considerable effects against hepatocellular carcinoma (HCC), with unquestioned safety. Here we...
Caffeic acid phenethyl ester (CAPE) and its derivatives exhibit considerable effects against hepatocellular carcinoma (HCC), with unquestioned safety. Here we investigated CAPE derivative 1' (CAPE 1') monotherapy to HCC, compared with sorafenib. HCC Bel-7402 cells were treated with CAPE 1', the IC50 was detected using CCK-8 analysis, and acute toxicity testing (5 g/kg) was performed to evaluate safety. In vivo, tumor growth after CAPE 1' treatment was evaluated using an subcutaneous tumor xenograft model. Five groups were examined, with group 1 given vehicle solution, groups 2, 3, and 4 given CAPE 1' (20, 50, and 100 mg/kg/day, respectively), and group 5 given sorafenib (30 mg/kg/day). Tumor volume growth and tumor volume-to-weight ratio were calculated and statistically analyzed. An estimated IC50 was 5.6 µM. Acute toxicity tests revealed no animal death or visible adverse effects with dosage up to 5 g/kg. Compared to negative controls, CAPE 1' treatment led to significantly slower increases of tumor volume and tumor volume-to-weight. CAPE 1' and sorafenib exerted similar inhibitory effects on HCC tumors. CAPE 1' was non-inferior to sorafenib for HCC treatment, both in vitro and in vivo. It has great potential as a promising drug for HCC, based on effectiveness and safety profile.
Topics: Sorafenib; Caffeic Acids; Phenylethyl Alcohol; Carcinoma, Hepatocellular; Animals; Humans; Liver Neoplasms; Cell Line, Tumor; Mice; Xenograft Model Antitumor Assays; Antineoplastic Agents; Cell Proliferation; Mice, Nude; Mice, Inbred BALB C; Male
PubMed: 38914695
DOI: 10.1038/s41598-024-65496-1 -
Scientific Reports Jun 2024This study aimed to establish a machine learning (ML) model for predicting hepatic metastasis in esophageal cancer. We retrospectively analyzed patients with esophageal...
This study aimed to establish a machine learning (ML) model for predicting hepatic metastasis in esophageal cancer. We retrospectively analyzed patients with esophageal cancer recorded in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2020. We identified 11 indicators associated with the risk of liver metastasis through univariate and multivariate logistic regression. Subsequently, these indicators were incorporated into six ML classifiers to build corresponding predictive models. The performance of these models was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. A total of 17,800 patients diagnosed with esophageal cancer were included in this study. Age, primary site, histology, tumor grade, T stage, N stage, surgical intervention, radiotherapy, chemotherapy, bone metastasis, and lung metastasis were independent risk factors for hepatic metastasis in esophageal cancer patients. Among the six models developed, the ML model constructed using the GBM algorithm exhibited the highest performance during internal validation of the dataset, with AUC, accuracy, sensitivity, and specificity of 0.885, 0.868, 0.667, and 0.888, respectively. Based on the GBM algorithm, we developed an accessible web-based prediction tool (accessible at https://project2-dngisws9d7xkygjcvnue8u.streamlit.app/ ) for predicting the risk of hepatic metastasis in esophageal cancer.
Topics: Humans; Machine Learning; Esophageal Neoplasms; Liver Neoplasms; Male; Female; Middle Aged; Aged; Retrospective Studies; Risk Factors; ROC Curve; SEER Program
PubMed: 38914571
DOI: 10.1038/s41598-024-63213-6 -
Journal of Radiology Case Reports 2024Rectal cancer Is a Common malignant pathology; its usual spread in volves the liver and lungs. The occurrence of renal metastases is exceptional. CT scanning aims to...
Rectal cancer Is a Common malignant pathology; its usual spread in volves the liver and lungs. The occurrence of renal metastases is exceptional. CT scanning aims to evaluate extension and may incidentally reveal a renal mass, which can be better characterized through MRI and ultrasound. We describe a case of a solitary renal metastasis from rectal cancer and underscore the significant role of imaging in positively diagnosing this uncommon pathology.
Topics: Humans; Rectal Neoplasms; Kidney Neoplasms; Tomography, X-Ray Computed; Male; Magnetic Resonance Imaging; Middle Aged; Adenocarcinoma; Diagnosis, Differential
PubMed: 38910585
DOI: 10.3941/jrcr.v18i1.5233 -
Journal of Zhejiang University.... Jun 2024Interferon regulatory factor 1 (IRF-1) is a member of the IRF family. It is the first transcription factor to be identified that could bind to the interferon-stimulated... (Review)
Review
Interferon regulatory factor 1 (IRF-1) is a member of the IRF family. It is the first transcription factor to be identified that could bind to the interferon-stimulated response element (ISRE) on the target gene and displays crucial roles in the interferon-induced signals and pathways. IRF-1, as an important medium, has all of the advantages of full cell cycle regulation, cell death signaling transduction, and reinforcing immune surveillance, which are well documented. Current studies indicate that IRF-1 is of vital importance to the occurrence and evolution of multifarious liver diseases, including but not limited to inhibiting the replication of the hepatitis virus (A/B/C/E), alleviating the progression of liver fibrosis, and aggravating hepatic ischemia-reperfusion injury (HIRI). The tumor suppression of IRF-1 is related to the clinical characteristics of liver cancer patients, which makes it a potential indicator for predicting the prognosis and recurrence of liver cancer; additionally, the latest studies have revealed other effects of IRF-1 such as protection against alcoholic/non-alcoholic fatty liver disease (AFLD/NAFLD), cholangiocarcinoma suppression, and uncommon traits in other liver diseases that had previously received little attention. Intriguingly, several compounds and drugs have featured a protective function in specific liver disease models in which there is significant involvement of the IRF-1 signal. In this paper, we hope to propose a prospective research basis upon which to help decipher translational medicine applications of IRF-1 in liver disease treatment.
Topics: Interferon Regulatory Factor-1; Humans; Liver Diseases; Animals; Liver Neoplasms; Signal Transduction; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Reperfusion Injury; Cholangiocarcinoma
PubMed: 38910492
DOI: 10.1631/jzus.B2300159 -
Combinatorial Chemistry & High... Jun 2024Gastric cancer (GC) is a frequent malignant neoplasm found in China. Despite numerous therapeutic methodologies to ameliorate the well-being of GC patients, their...
BACKGROUND
Gastric cancer (GC) is a frequent malignant neoplasm found in China. Despite numerous therapeutic methodologies to ameliorate the well-being of GC patients, their efficiency remains inadequate.
OBJECTIVE
Rosmanol (RML) is a phenolic diterpene compound with antioxidant and anticancer activities. In the current research, the apoptotic efficacy of RML on methylnitronitrosoguanidine (MNNG)-induced GC model was determined.
MATERIALS AND METHODS
The rats were allocated into four sets, viz., normal control, MNNG (200 mg/kg bw) + NaCl, MNNG + RML (20 mg/kg), and RML (20 mg/kg) orally treated for 20 weeks.
RESULTS
The results exposed that GC rats revealed higher (P<0.05) levels of TBARS and reduced antioxidant status in the stomach and liver tissues counter to other groups. In contrast, the TBARS level was substantially alleviated (P<0.05) and restored the antioxidant status in RMLadministered rats. Histopathologic assessment of gastric tissue unveiled that an MNNG-induced group presented squamous cell carcinoma with keratin pearls. The administration of RML reduced GC incidence, and only mild dysplasia was observed. Further, RML alleviated Bcl-2, P13K, AKT, and HMGB1, as evidenced by RT-PCR and Western blot analysis.
CONCLUSION
Furthermore, RML triggered caspase-mediated mitochondrial apoptosis through the inactivation of the PI3K/AKT/HMGB1 pathway, eventually leading to GC cell death. This highlights that RML may be a potential natural antioxidant employed as a chemoprotective agent in GC rats.
PubMed: 38910269
DOI: 10.2174/0113862073297703240613073134