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1.
Front Public Health ; 9: 678738, 2021.
Article in English | MEDLINE | ID: mdl-34268290

ABSTRACT

Background: Infections are the second leading cause of death among patients undergoing hemodialysis. However, preventive measures against infectious diseases are limited and have not been made mandatory for patients. Objective: To investigate the incidence of infectious diseases before and during the coronavirus disease (COVID-19) pandemic. Design: A historical comparative study of a prospective cohort. Setting(s): February 1, 2015 to January 31, 2020 was defined as the period before the mitigative confrontation of the COVID-19 pandemic in China. The period from February 1 to June 29, 2020 was defined as the period of mitigative confrontation of the COVID-19 pandemic in China. Participants: A cohort of patients undergoing hemodialysis whose infectious disease episodes were documented prospectively in the hemodialysis unit of the Third Affiliated Hospital of Guangzhou Medical University since February 1, 2015. Methods: Mandatory mask-wearing and reinforced hand-hygiene education were implemented to prevent COVID-19 from January 23, 2020 in China. The incidence of infectious episodes, including catheter-related infection, digestive tract infection, upper respiratory tract infection (UTRI), pneumonia, and infection at other sites, were documented and compared in the periods before and during the pandemic. Results: The historical control group consisted of 157 patients, with 79 patients in the COVID-19 prevention group. The mask-wearing rate of patients increased from 1.5 to 100%. Hand sanitizer consumption increased significantly during the COVID-19 pandemic. The compliance rates of hand hygiene increased from 66, 75.5, to 55% in physicians, nurses, and other employees before the pandemic to 90.5, 92.5, and 76.5%, respectively. The incidences of UTRI and pneumonia decreased during the pandemic (p < 0.001). Notably, catheter-related and digestive tract infections also decreased during the pandemic (p = 0.003 and 0.034, respectively). A matched-pair study was conducted to further analyze the 79 individual changes in the incidences of infectious disease before and during the pandemic. As a result, the incidences of UTRI, pneumonia, catheter-related infections, digestive tract infections, and infections at other sites all decreased during the pandemic. Conclusions: The present study indicated an association between mandatory mask-wearing and reinforced hand hygiene education and decreased respiratory, catheter-related, and digestive tract infection episodes in the hemodialysis unit.


Subject(s)
COVID-19 , Communicable Diseases , Hand Hygiene , China/epidemiology , Hemodialysis Units, Hospital , Humans , Pandemics , Prospective Studies , Renal Dialysis/adverse effects , SARS-CoV-2
2.
Oncologist ; 26(8): e1434-e1444, 2021 08.
Article in English | MEDLINE | ID: mdl-33675070

ABSTRACT

PURPOSE: The purpose of this study was to investigate the predictive capability of neutrophil-to-apolipoprotein A1 ratio (NAR) for predicting overall survival (OS) among patients with hepatocellular carcinoma (HCC) receiving transarterial chemoembolization (TACE). PATIENTS AND METHODS: We investigated the clinical features of 554 patients with HCC receiving TACE and assessed NAR's predictive value for OS with 222 patients (the discovery cohort) and 332 patients (the validation cohort). The association of NAR with circulation lectin-type oxidized low-density lipoprotein receptor-1-positive (LOX-1+ ) polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) was illustrated. RESULTS: Multivariate Cox regression revealed that lymphocyte count; Tumor, Node, Metastasis (TNM) stage; and NAR were independent prognostic factors in the discovery cohort. The validation cohort confirmed the independent prognostic value of TNM stage and NAR. Patients with low NAR (<2.7) displayed significantly increased OS in the discovery cohort (59.8 months vs. 21 months), the validation group (38.0 months vs. 23.6 months), and the total cohort (44.1 months vs. 22.0 months). A Cox proportional hazards model was used to combine Cancer of the Liver Italian Program (CLIP) score with discretized NAR. C-index illustrated that NAR-integrated CLIP score was the best model compared with NAR and CLIP score. Furthermore, NAR-CLIP presented superior predictive capacity for 10-, 20-, 30-, 40-, 50-, and 60-month survival compared with CLIP score by survival receiver-operator characteristic analysis in the discovery cohort, validation cohort, and total cohort. NAR was significantly associated with LOX-1+ PMN-MDSCs by linear regression. CONCLUSION: This study identified NAR as an independent predictor for OS among patients with HCC receiving TACE. NAR reflected circulation LOX-1+ PMN-MDSC level. IMPLICATIONS FOR PRACTICE: The present study identified neutrophil-to-apolipoprotein A1 ratio (NAR) as an independent predictor for overall survival among patients with hepatocellular carcinoma receiving transarterial chemoembolization. NAR reflected circulation level of lectin-type oxidized low-density lipoprotein receptor-1-positive polymorphonuclear myeloid-derived suppressor cells.


Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Apolipoprotein A-I , Carcinoma, Hepatocellular/therapy , Humans , Liver Neoplasms/therapy , Neutrophils , Retrospective Studies , Treatment Outcome
3.
Commun Biol ; 4(1): 252, 2021 02 26.
Article in English | MEDLINE | ID: mdl-33637832

ABSTRACT

In this era of immune checkpoint inhibitors, inflammatory adverse events of anti-cancer therapies continue to pose a major challenge. Glucocorticoids, as the mainstay, were limited by serious side effects. Glucocorticoids induce myeloid-derived suppressor cells (MDSCs), and lactoferrin-induced polymorphonuclear MDSCs (PMN-MDSCs) were shown to relieve inflammatory conditions. Combined treatment with dexamethasone (DXM) and lactoferrin increased the generation of PMN-MDSCs in vitro (DXM/lactoferrin PMN-MDSCs) compared to DXM or lactoferrin treatment alone. DXM/lactoferrin PMN-MDSCs were distinct from tumor PMN-MDSCs in vivo with regard to gene expression profiles. DXM upregulated the myeloid cell response to lactoferrin by inducing the lactoferrin receptor Lrp1. DXM/lactoferrin PMN-MDSCs presented anti-bacterial capability, increased PGE2 production, increased survival capability, and decreased tumor tissue homing. Transfer of DXM/lactoferrin PMN-MDSCs relieved cisplatin-induced acute kidney failure, bleomycin-induced interstitial pneumonia, and allergic pneumonitis effectively without promoting tumor development. Our study shows that DXM/lactoferrin PMN-MDSCs are a promising cell therapy for inflammatory adverse events of anti-cancer therapies.


Subject(s)
Acute Kidney Injury/therapy , Adoptive Transfer , Anti-Inflammatory Agents/pharmacology , Dexamethasone/pharmacology , Lactoferrin/pharmacology , Lung Diseases, Interstitial/therapy , Myeloid-Derived Suppressor Cells/drug effects , Myeloid-Derived Suppressor Cells/transplantation , Pneumonia/therapy , Acute Kidney Injury/chemically induced , Acute Kidney Injury/immunology , Acute Kidney Injury/metabolism , Animals , Bleomycin , Cell Line, Tumor , Cisplatin , Disease Models, Animal , Drug Therapy, Combination , Female , Humans , Lung Diseases, Interstitial/chemically induced , Lung Diseases, Interstitial/immunology , Lung Diseases, Interstitial/metabolism , Male , Mice, Inbred BALB C , Mice, Inbred C57BL , Myeloid-Derived Suppressor Cells/immunology , Myeloid-Derived Suppressor Cells/metabolism , Ovalbumin , Phenotype , Pneumonia/chemically induced , Pneumonia/immunology , Pneumonia/metabolism
4.
Aging (Albany NY) ; 13(1): 437-449, 2020 12 03.
Article in English | MEDLINE | ID: mdl-33290259

ABSTRACT

Chronic hepatitis B (CHB) has been reported to be associated with impaired prognosis for patients with nasopharyngeal carcinoma (NPC). However, the latent mechanism is unclear. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) induce immune suppression in CHB and promote the development of hepatocellular carcinoma. Lectin-type oxidized LDL receptor-1 (LOX-1) was recently identified as a specific marker for PMN-MSDC. We found NPC survivors with CHB had high levels of LOX-1+ PMN-MDSCs. LOX-1+ PMN-MDSCs significantly reduced T cell proliferation and activation. Endoplasmic reticulum stress was induced in LOX-1+ PMN-MDSCs. In addition, LOX-1+ PMN-MDSCs increased their expression of NOX2, a key reactive oxygen species (ROS)-related genes, and levels of ROS illustrated by the DCFDA test. The ROS inhibitor N-acetylcysteine abrogated the suppression of LOX-1+ PMN-MDSCs on T cell activation. The EBV DNA-positivity rate was higher in NPC survivors with CHB than in NPC patients without CHB. Those presenting with positive EBV DNA displayed higher LOX-1+ PMN-MDSC levels. LOX-1+ PMN-MDSCs suppressed the CD8+ T cell response against EBV. This study revealed LOX-1+ PMN-MDSC accumulation and activation in NPC survivors with CHB. LOX-1+ PMN-MDSCs might suppress the host immune response to EBV through ER stress/ROS pathway. These results explained the association of CHB with unfavorable NPC prognosis.


Subject(s)
Hepatitis B, Chronic/immunology , Herpesvirus 4, Human/immunology , Immune Tolerance/immunology , Myeloid-Derived Suppressor Cells/immunology , Nasopharyngeal Carcinoma/immunology , Nasopharyngeal Neoplasms/immunology , Neoplasm Recurrence, Local/immunology , Acetylcysteine/pharmacology , Adult , Aged , CD8-Positive T-Lymphocytes/immunology , Cell Proliferation , Endoplasmic Reticulum Stress/drug effects , Endoplasmic Reticulum Stress/immunology , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/immunology , Epstein-Barr Virus Nuclear Antigens/immunology , Female , Free Radical Scavengers/pharmacology , Hepatitis B, Chronic/complications , Humans , Lymphocyte Activation/drug effects , Lymphocyte Activation/immunology , Male , Middle Aged , Myeloid-Derived Suppressor Cells/metabolism , NADPH Oxidase 2/genetics , NADPH Oxidase 2/metabolism , Nasopharyngeal Carcinoma/complications , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Neoplasms/complications , Nasopharyngeal Neoplasms/therapy , Prognosis , Reactive Oxygen Species/immunology , Scavenger Receptors, Class E/metabolism , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Viral Matrix Proteins/immunology
5.
J Immunol ; 205(1): 36-44, 2020 07 01.
Article in English | MEDLINE | ID: mdl-32444391

ABSTRACT

Group 2 innate lymphoid cells (ILC2s) play an important role in the control of tissue inflammation and homeostasis. However, the role of ILC2s in patients with end-stage renal disease (ESRD) has never been illustrated. In this study, we investigated ILC2s in ESRD patients and their clinical significance. Results showed that the frequencies and absolute numbers of ILC2s, not group 1 innate lymphoid cells or innate lymphoid cell precursors, were significantly elevated in the peripheral blood of ESRD patients when compared with those from healthy donor controls. Moreover, ILC2s from ESRD patients displayed enhanced type 2 cytokine production and cell proliferation. Plasma from ESRD patients significantly increased ILC2 levels and enhanced their effector function after in vitro treatment. The expression of phosphorylation of STAT5 in ILC2s, as well as the amounts of IL-2 in plasma, were increased in ESRD patients when compared with those from healthy donors. Clinically, ESRD patients with higher ILC2 frequencies displayed lower incidence of infectious complications during a mean of 21 month follow-up study. The proportions of ILC2s were negatively correlated with the prognostic biomarkers of chronic kidney disease, including serum parathyroid hormone, creatinine, and phosphorus, whereas they were positively correlated with serum calcium. These observations indicate that ILC2s may play a protective role in ESRD.


Subject(s)
Immunity, Innate , Kidney Failure, Chronic/immunology , Lymphocyte Subsets/immunology , Adult , Animals , Biomarkers/blood , Case-Control Studies , Cell Proliferation , Cells, Cultured , Cytokines/metabolism , Disease Progression , Female , Follow-Up Studies , Healthy Volunteers , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/therapy , Lymphocyte Count , Lymphocyte Subsets/metabolism , Male , Middle Aged , Primary Cell Culture , Prognosis , Renal Dialysis/statistics & numerical data
6.
Front Immunol ; 11: 577253, 2020.
Article in English | MEDLINE | ID: mdl-33584644

ABSTRACT

Background: The specific mechanism of cardiovascular and cerebrovascular vasculopathy in the context of end-stage renal disease has not been elucidated. In the present study, we investigated the clinical impact of myeloid-derived suppressor cells (MDSCs) on hemodialysis patients and their mechanism of action. Methods: MDSCs were tested among 104 patients undergoing hemodialysis and their association with overall survival (OS) and cardiovascular and cerebrovascular events was determined. Results: Hemodialysis patients presented a significantly higher level of monocytic MDSCs (M-MDSCs) compared to healthy controls. M-MDSC were tested 3 months after first testing among 103 hemodialysis patients, with one patient not retested due to early death. The repeated results of M-MDSC levels were consistent with the initial results. Patients with persistent high level of M-MDSCs presented decreased OS, as well as increased stroke and acute heart failure events. As illustrated by multivariate Cox regression, M-MDSC was an independent predictor for OS and stroke events of hemodialysis patients. T cell proliferations were significantly abrogated by hemodialysis-related M-MDSCs in a dose-dependent manner. Besides, M-MDSCs presented higher levels of CXCR4 and VLA-4 compared to monocytes, which indicated their enhanced capability to be recruited to atherosclerotic lesions. The expression of arginase I and activity of arginase was also significantly raised in hemodialysis-related M-MDSCs. Human coronary arterial endothelial cells (HCAECs) presented increased capability to migration by coculture with M-MDSCs, compared with monocyte group. Arginase inhibitor and L-arginine abrogated the immune suppressive function and induction of HCAECs migration of hemodialysis related M-MDSC. Plasma IFN-γ, TNF-α and IL-6 were elevated in hemodialysis patients compared with healthy control. M-MDSC level was positively related to IL-6 level among hemodialysis patients. The plasma of hemodialysis patients induced M-MDSCs significantly compared with plasma from health donors. Besides, IL-6 neutralizing antibody significantly abrogated the induction. Neutralizing antibody of IFN-γ and TNF-α partially decreased the generation of arginase of the induced M-MDSC. Conclusions: M-MDSCs were elevated in ESRD patients under hemodialysis, and they exhibited a strong association with the risk of cardiovascular and cerebrovascular diseases. Hemodialysis related M-MDSC presented enhanced recruitment to atherosclerotic lesions, promoted the migration of endothelial cells through exhaustion of local L-arginine.


Subject(s)
Cardiovascular Diseases/epidemiology , Cerebrovascular Disorders/epidemiology , Endothelial Cells/physiology , Kidney Failure, Chronic/therapy , Myeloid-Derived Suppressor Cells/immunology , Antibodies, Blocking , Arginase/metabolism , Cell Proliferation , Cells, Cultured , Humans , Interferon-gamma/metabolism , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/mortality , Lymphocyte Activation , Renal Dialysis , Survival Analysis , Tumor Necrosis Factor-alpha/metabolism
8.
Ther Clin Risk Manag ; 14: 1975-1986, 2018.
Article in English | MEDLINE | ID: mdl-30349276

ABSTRACT

PURPOSE: The effect of glucocorticoid(s) on connective tissue disease (CTD)-related interstitial lung disease (ILD) is controversial. This multicenter study aimed to identify glucocorticoid-sensitive patients using a radiomics approach. METHODS: A total of 416 CTD-ILD patients who began glucocorticoid treatment at the discretion of the attending physician, with or without cyclophosphamide, were included in this study. High doses were defined as pulsed intravenous methylprednisolone, an initial dose of 1 mg/kg/day of prednisolone or 0.8 mg/kg/day of methylprednisolone. Low doses were defined as those less than high doses. Radiomics features were manually extracted from primary lung lesions delineated on computed tomography images, and selected by variance, univariate feature selection, and least absolute shrinkage and selection operator regression model. The prediction models were developed using data from 309 patients from two centers and externally validated in 107 patients from four other hospitals. RESULTS: Treatment response in the training and validation groups was 38.5% and 36.4%, respectively. Eleven radiomics features were selected from 1,029 features with predictive value. Random forest models built for radiomics features to predict treatment response yielded a sensitivity of 0.897. The calibration curve of a nomogram demonstrated good agreement between prediction and observation. Decision curve analysis indicated that glucocorticoid was beneficial if the predicted response rate was 50%-60% for an individual. High doses of glucocorticoids and cyclophosphamide yielded superior efficacy. CONCLUSION: Radiomics-based predictive models reliably identified glucocorticoid-sensitive CTD-ILD patients. Short-term, high-dose glucocorticoid with cyclophosphamide yielded promising results as a potential therapy.

10.
Immunology ; 154(1): 144-155, 2018 05.
Article in English | MEDLINE | ID: mdl-29211299

ABSTRACT

A recent study indicated that Lectin-type oxidized LDL receptor-1 (LOX-1) was a distinct surface marker for human polymorphisms myeloid-derived suppressor cells (PMN-MDSC). The present study was aimed to investigate the existence LOX-1 PMN-MDSC in hepatocellular carcinoma (HCC) patients. One hundred and twenty-seven HCC patients, 10 patients with mild active chronic hepatitis B, 10 liver cirrhosis due to hepatitis B, 10 liver dysplastic node with hepatitis B and 50 health control were included. LOX-1+  CD15+ PMN-MDSC were significantly elevated in HCC patients compared with healthy control and patients with benign diseases. LOX-1+  CD15+ PMN-MDSC in circulation were positively associated with those in HCC tissues. LOX-1+  CD15+ PMN-MDSCs significantly reduced proliferation and IFN-γ production of T cells with a dosage dependent manner with LOX-1-  CD15+ PMNs reached negative results. The suppression on T cell proliferation and IFN-γ production was reversed by ROS inhibitor and Arginase inhibitor. ROS level and activity of arginase of LOX-1 + CD15+ PMN were higher in LOX-1+  CD15+ PMN-MDSCs than LOX-1-  CD15+ PMNs, as well as the expression of the NADPH oxidase NOX2 and arginase I. RNA sequence revealed that LOX-1+ CD15+ PMN-MDSCs displayed significantly higher expression of spliced X-box -binding protein 1 (sXBP1), an endoplasmic reticulum (ER) stress marker. ER stress inducer induced LOX-1 expression and suppressive function for CD15+ PMN from health donor. For HCC patients, LOX-1+  CD15+ PMN-MDSCs were positively related to overall survival. Above all, LOX-1+  CD15+ PMN-MDSC were elevated in HCC patients and suppressed T cell proliferation through ROS/Arg I pathway induced by ER stress. They presented positive association with the prognosis of HCC patients.


Subject(s)
Carcinoma, Hepatocellular/metabolism , Endoplasmic Reticulum Stress , Fucosyltransferases/metabolism , Lewis X Antigen/metabolism , Liver Neoplasms/metabolism , Myeloid-Derived Suppressor Cells/metabolism , Scavenger Receptors, Class E/metabolism , Arginase/metabolism , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/pathology , Case-Control Studies , Cell Proliferation , Cells, Cultured , Coculture Techniques , Humans , Interferons/metabolism , Liver Neoplasms/immunology , Liver Neoplasms/pathology , Lymphocyte Activation , Myeloid-Derived Suppressor Cells/immunology , Myeloid-Derived Suppressor Cells/pathology , Reactive Oxygen Species/metabolism , Signal Transduction , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
11.
Medicine (Baltimore) ; 96(26): e7373, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28658162

ABSTRACT

BACKGROUND & AIMS: Nutritional interventions for malnutrition in cancer patients can be helpful. However, concise intervention recommendations remain controversial. Thus, the aim of this study was to report on a nutrition intervention conducted by a multidisciplinary team of specialist nurses and to explore the effect of nutritional intervention on cancer patients. METHODS: This prospective clinical trial study enrolled 110 colorectal cancer patients undergoing chemotherapy. The patients were evaluated upon admission using the 2002 Nutritional Risk Screening system (NRS-2002). The patients were randomly divided into intervention and control groups including 55 patients each. Patients in the control group were administered a normal diet, while those in the intervention group received individual recipes developed by a team of professional nurses, clinical doctors, dietitian, family caregivers, and the patients themselves. Patient weight and serum albumin and prealbumin levels were compared between the 2 groups at different time points. RESULTS: There was a significant difference in patient weight and serum albumin and prealbumin levels before and after nutrition intervention in the intervention group (P < .05). In the control group, weight did not change during ordinary diet guidance. Serum albumin level was slightly improved after 12 cycles of chemotherapy, similar to the prealbumin results. There were statistically significant differences in serum albumin and prealbumin levels between the intervention and control groups after nutrition intervention (P < .05). However, there was no statistically significant difference in weight between the groups after nutrition intervention (P > .05). CONCLUSION: A multidisciplinary team approach for nutrition intervention conducted by specialist nurses improved prealbumin levels in colorectal cancer patients undergoing chemotherapy, with no weight change.


Subject(s)
Colorectal Neoplasms/diet therapy , Colorectal Neoplasms/drug therapy , Nurse Specialists , Patient Care Team , Biomarkers, Tumor/blood , Body Weight , Caregivers , Colorectal Neoplasms/blood , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Nutritional Status , Nutritionists , Patient Education as Topic , Serum Albumin/analysis , Treatment Outcome
12.
Oncotarget ; 8(28): 45391-45398, 2017 Jul 11.
Article in English | MEDLINE | ID: mdl-28512268

ABSTRACT

BACKGROUND: Advance directives are a sensitive issue among traditional Chinese people, who usually refrain from mentioning this topic until it is imperative. Medical decisions for cancer patients are made by their families, and these decisions might violate patients' personal will. OBJECTIVES: This study aimed to examine the acceptance of advance directives among Chinese cancer patients and their families and patient participation in this procedure and, finally, to analyze the moral risk involved. RESULTS: While 246 patients and their family members refused official discussion of an advance directive, the remaining 166 patients and their families accepted the concept of an advance directive and signed a document agreeing to give up invasive treatment when the anti-cancer treatment was terminated. Of these, only 24 patients participated in the decision making. For 101 patients, anti-cancer therapy was ended prematurely with as many as 37 patients not told about their potential loss of health interests. MATERIALS AND METHODS: Participants were 412 adult cancer patients from 9 leading hospitals across China. An advance directive was introduced to the main decision makers for each patient; if they wished to sign it, the advance directive would be systematically discussed. A questionnaire was given to the oncologists in charge of each patient to evaluate the interaction between families and patients, patients' awareness of their disease, and participation in an advance directive. CONCLUSIONS: Advance directives were not widely accepted among Chinese cancer patients unless anti-cancer therapy was terminated. Most cancer patients were excluded from the discussion of an advance directive.


Subject(s)
Advance Directives , Decision Making , Neoplasms/epidemiology , Neoplasms/psychology , Patient Preference , Adult , Aged , Awareness , Family , Female , Humans , Male , Middle Aged , Patient Acceptance of Health Care , Patient Participation
13.
Oncotarget ; 8(15): 24380-24388, 2017 Apr 11.
Article in English | MEDLINE | ID: mdl-28412745

ABSTRACT

Myeloid Derived Suppressor Cell (MDSC) has been raised to be a novel target for multiple cancers. However, target agents on MDSC have not display promising efficacy. One of the critical reasons shall be less optimal patient selection. In the present study, we aimed to identify clinical parameters relevant to MDSC level in hepatocellular carcinoma (HCC) patients for future MDSC targeted therapy. In the present study, a series of 55 HCC patients (testing group) and 20 healthy donors were analyzed investigating frequencies of MDSC in peripheral blood mononuclear cells (PBMC). As a result, we found that MDSC level was increased in HCC patients compared to healthy donors (10.33% vs 1.54%, p < 0.0001). The monocytes (r2 = 0.2875, p < 0.0001), neutrophils (r2 = 0.3630, p < 0.0001) and platelet counts (r2 = 0.0828, p = 0.0331) in circulation was positively associated with MDSC level. Then, the prognostic value of the above predictors was determined in a retrospective database of 255 HCC patients (validation group). The baseline characteristics of testing and validation group were similar. Multivariate analysis by Cox regression revealed that neutrophil count was an independent predictor for overall survival (OS) (p = 0.000, HR 1.065, 95% CI 1.028-1.103), with the rest parameters failed to reach a significant result. In summary, the present study firstly identified blood neutrophil counts was a predictor of MDSC level in PBMC for HCC patients. And, patients with higher neutrophil count level might be the optimal patient subgroup for MDSC targeted therapy.


Subject(s)
Carcinoma, Hepatocellular/blood , Liver Neoplasms/blood , Neutrophils/pathology , Adult , Aged , Carcinoma, Hepatocellular/pathology , Female , Humans , Liver Neoplasms/pathology , Male , Middle Aged , Prognosis
14.
Kidney Int ; 91(5): 1236-1242, 2017 05.
Article in English | MEDLINE | ID: mdl-28215666

ABSTRACT

Myeloid-derived suppressor cells (MDSCs) are recently identified immune suppressive cells in multiple chronic inflammations. Here, we investigated MDSCs in patients with end-stage renal disease (ESRD) and their clinical significance in these patients and healthy individuals (49 each). Polymorphonuclear and mononuclear MDSCs were investigated by flow cytometry. Patients with ESRD before hemodialysis presented a significantly higher level of polymorphonuclear MDSCs. Depletion of polymorphonuclear-MDSCs resolved T cell IFN-γ responses. By co-culture, T cell proliferation and the production of IFN-γ were abrogated by the addition of polymorphonuclear MDSCs in a dose-dependent manner. Both of these effects were reversed by a reactive oxygen species inhibitor. The levels of reactive oxygen species were higher in polymorphonuclear MDSCs derived from patients with ESRD than from normal individuals. The mRNA level of NOX2, the key protein complex responsible for reactive oxygen species production, was higher in ESRD-related polymorphonuclear MDSCs. The phospho-STAT3 level, a key activator of MDSCs, was higher in ESRD-related polymorphonuclear MDSCs. Finally, the polymorphonuclear MDSC level before and after hemodialysis was positively related to infectious diseases. Patients with ESRD were dichotomized into 2 groups by the amount of polymorphonuclear MDSCs. Patients with high levels of polymorphonuclear MDSCs presented with a higher incidence of infectious events. Thus, polymorphonuclear MDSCs were elevated in ESRD patients with strong immune-suppressive capability through a phospho-STAT3/reactive oxygen species pathway. Hence, polymorphonuclear MDSCs might increase the risk of infectious complications.


Subject(s)
Immune Tolerance/immunology , Infections/immunology , Kidney Failure, Chronic/immunology , Myeloid-Derived Suppressor Cells/immunology , T-Lymphocytes/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Cell Proliferation , Coculture Techniques , Female , Flow Cytometry , Follow-Up Studies , Humans , Incidence , Infections/epidemiology , Interferon-gamma/immunology , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Male , Membrane Glycoproteins/metabolism , Middle Aged , Myeloid-Derived Suppressor Cells/metabolism , NADPH Oxidase 2 , NADPH Oxidases/metabolism , Prospective Studies , RNA, Messenger/metabolism , Reactive Oxygen Species/metabolism , Renal Dialysis , STAT3 Transcription Factor/metabolism , T-Lymphocytes/physiology , Young Adult
17.
Tumour Biol ; 37(3): 2951-9, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26411670

ABSTRACT

The prognosis of hepatocellular carcinoma (HCC) patients receiving transcatheter arterial chemoembolization (TACE) is far from being identified. The present study aimed to assess the role of blood cell counts, routine liver function tests, and alanine aminotransferase to hemoglobin ratio (AHR) in predicting the progression-free survival (PFS) of these patients. A total of 243 HCC patients receiving TACE were analyzed retrospectively. Cancer of the Liver Italian Program (CLIP) score system was indentified to be the best score system for this patient subgroup according to the Akaike information criterion (AIC) index and linear trend χ (2). Then, prognostic value of parameters was determined by integration into the CLIP score system. As a result, AHR was confirmed to be an independent predictor for the PFS of HCC patients receiving TACE (p = 0.001) with the other parameters failing to reach statistical significance. Moreover, AHR improved the performance of CLIP by adjusting into it, thus improving its discriminatory ability. AHR defined ≤0.4583 as low level and >0.4583 as high level. And, patients were also dichotomized into two groups accordingly. HCC patients receiving TACE with low AHR presented higher 1 year DCR (41.9 vs 18.1 %) compared with patients with high AHR levels. Furthermore, AHR level was associated with prognostic factors such as lower ALP, total bilirubin, and portal vein thrombosis. In summary, the present study firstly indentified AHR as an independent prognostic factor in HCC patients receiving TACE. The subgroup of HCC patients with lower AHR presented preferable disease control and were the idealistic candidates for TACE.


Subject(s)
Alanine Transaminase/blood , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic , Hemoglobins/analysis , Liver Neoplasms/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/mortality , Child , Disease Progression , Female , Humans , Liver Neoplasms/blood , Liver Neoplasms/mortality , Male , Middle Aged
18.
Asian Pac J Cancer Prev ; 16(15): 6311-6, 2015.
Article in English | MEDLINE | ID: mdl-26434835

ABSTRACT

BACKGROUND: In mainland China, awareness of disease of elderly cancer patients largely relies on the patients' families. We developed a staged procedure to improve their awareness of disease. MATERIALS AND METHODS: Participants were 224 elderly cancer patients from 9 leading hospitals across Southern China. A questionnaire was given to the oncologists in charge of each patient to evaluate the interaction between family and patients, patient awareness of their disease and participation in medical decision-making. After first cycles of treatment, increased information of disease was given to patients with cooperation of the family. Then patient awareness of their disease and participation in medical decision-making was documented. RESULTS: Among the 224 cancer elderly patients, 26 (11.6%) made decisions by themselves and 125 (55.8%) delegated their rights of decision- making to their family. Subordinate family members tended to play a passive role in decision-making significantly. Patients participating more in medical decision-making tended to know more about their disease. However, in contrast to the awareness of disease, patient awareness of violation of medical recommendations was reversely associated with their participation in medical decision-making. Improvement in awareness of diagnosis, stages and prognosis was achieved in about 20% elderly cancer patients. About 5% participated more actively in medical decision-making. CONCLUSIONS: Chinese elderly cancer patient awareness of disease and participation in medical decision-making is limited and relies on their family status. The staged procedure we developed to improve patient awareness of disease proved effective.


Subject(s)
Decision Making , Family Relations , Health Knowledge, Attitudes, Practice , Neoplasms/pathology , Neoplasms/therapy , Patient Education as Topic/methods , Aged , Aged, 80 and over , China , Female , Humans , Male , Middle Aged , Neoplasm Staging , Neoplasms/diagnosis , Patient Participation , Prognosis
19.
Tumour Biol ; 36(4): 2263-9, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25409616

ABSTRACT

The platelet count, as an inflammation marker, is involved in the progress of tumor invasion. However, the prognostic value of platelet counts and the platelet-to-lymphocyte ratio (PLR) has not been investigated in patients with advanced hepatocellular carcinoma (HCC). This study aimed to determine the prognostic value of platelet counts and PLR in HCC patients. A total of 243 ethnic Chinese advanced HCC patients from two major hospitals, not receiving systemic sorafenib, were analyzed retrospectively. The prognostic value of differential blood cell counts and PLR for overall survival (OS) was determined by integrating the Cancer of the Liver Italian Program (CLIP) score system and model for end-stage liver disease by using a stepwise model of multivariate Cox regression. The Kaplan-Meier method and receiver operating characteristic (ROC) curves were utilized accordingly. PLR was confirmed to be an independent predictor for OS (p < 0.01), while the remaining parameters had no predictive value. Then, advanced HCC patients were dichotomized into two groups based on the PLR value (≤111.23 or >111.23), according to ROC analysis. Patients with a high PLR had a lower 3-month survival rate (37.6 vs. 57.6%) compared with patients with a low PLR. PLR was associated with aggressive malignant behavior, characterized by distant metastasis and portal vein thrombosis. Additionally, PLR was not associated with the CLIP score and Child-Pugh grade. PLR was identified as an independent prognostic factor for advanced HCC patients not receiving systemic sorafenib; the predictive ability of PLR partially relies on its association with the aggressive nature of HCC.


Subject(s)
Blood Platelets/pathology , Carcinoma, Hepatocellular/blood , Liver Neoplasms/blood , Lymphocytes/pathology , Adult , Aged , Aged, 80 and over , Blood Cell Count , Carcinoma, Hepatocellular/pathology , Female , Humans , Kaplan-Meier Estimate , Liver Neoplasms/pathology , Male , Middle Aged , Platelet Count , Prognosis
20.
Asian Pac J Cancer Prev ; 16(18): 8665-70, 2015.
Article in English | MEDLINE | ID: mdl-26745134

ABSTRACT

BACKGROUND AND AIMS: Hepatitis B virus (HBV) reactivation was reported to be induced by transcatheter arterial chemoembolization (TACE) in HBV-related hepatocellular carcinonma (HCC) patients with a high incidence. The effective strategy to reduce hepatitis flares due to HBV reactivation in this specific group of patients was limited to lamivudine. This retrospective study was aimed to investigate the efficacy of prophylactic entecavir in HCC patients receiving TACE. METHODS: A consecutive series of 191 HBV-related HCC patients receiving TACE were analyzed including 44 patients received prophylactic entecavir. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 copies/ml higher than nadir the level, and hepatitis flares due to HBV reactivation were the main endpoints. RESULTS: Patients with or without prophylactic were similar in host factors and the majorities of characteristics regarding to tumor factors, HBV status, liver function and LMR. Notably, cycles of TACE were parallel between the groups. Ten (22.7%) patients receiving prophylactic entecavir reached virologic response. The patients receiving prophylactic entecavir presented significantly reduced virologic events (6.8% vs 54.4%, p=0.000) and hepatitis flares due to HBV reactivation (0.0% vs 11.6%, p=0.039) compared with patients without prophylaxis. Kaplan-Meier analysis illustrated that the patients in the entecavir group presented significantly improved virologic events free survival (p=0.000) and hepatitis flare free survival (p=0.017). Female and Eastern Cooperative Oncology Group (ECOG) performance status 2 was the only significant predictors for virological events in patients without prophylactic antiviral. Rescue antiviral therapy did not reduce the incidence of hepatitis flares due to HBV reactivation. CONCLUSION: Prophylactic entecavir presented promising efficacy in HBV-related cancer patients receiving TACE. Lower performance status and female gender might be the predictors for HBV reactivation in these patients.


Subject(s)
Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/methods , Guanine/analogs & derivatives , Hepatic Artery , Hepatitis B virus/drug effects , Hepatitis B/therapy , Liver Neoplasms/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/administration & dosage , Carcinoma, Hepatocellular/virology , Case-Control Studies , Child , Female , Follow-Up Studies , Guanine/administration & dosage , Hepatitis B/virology , Humans , Liver Neoplasms/virology , Male , Middle Aged , Neoplasm Staging , Prognosis , Retrospective Studies , Virus Activation/drug effects , Young Adult
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