Objective Accumulating evidence has indicated that neurodevelopmental defects may underlie the pathophysiology of bipolar disorder (BD). Insulin-like growth factors (IGFs) are a family of neurotrophic factors that are essential for the survival and development of neurons. The present study aims to investigate whether IGF-2 signaling is implicated in the pathophysiological processes of BD. Method 50 healthy controls and 78 patients with BD, including 23 patients who diagnosed acute depressive episode and 55 patients who diagnosed acute manic episode, were recruited in this study. The 17-item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale (YMRS) were used to assess the severity of the depressive and manic symptoms, respectively. The serum IGF-2 level was determined by an enzyme-linked immunosorbent assay (ELISA). The Kolmogorov-Smirnov and Mann-Whitney U tests were used for between-group comparisons and spearman analysis was used to analyze correlations. Results Patients with BD had lower serum IGF-2 levels (66.08 ± 21.22 ng/ml) when compared to healthy controls (88.72 ± 31.55 ng/ml). BD patients were divided into manic episode and depressive episode subgroups. We found that serum IGF-2 levels were reduced in both the mania and depression subgroups (mania: 67.19 ± 21.52 ng/ml, depression: 63.43 ± 20.67 ng/ml; P < 0.001), while no significant difference was observed between two groups ( P > 0.05). Spearman correlation analyses revealed that the levels of serum IGF-2 were negatively correlated with the YMRS scores in BD patients (r = -0.522, P < 0.001). Furthermore, IGF-2 was found to be an independent contributor to the severity of symptoms in patients with manic episodes ( B = -0.610, t = -5.299, P < 0.001). Conclusion Lower serum IGF-2 levels were found in BD patients and correlated with the severity of the manic symptoms in these patients during manic episodes. These results suggest that reduced IGF-2 levels might be involved in the pathophysiology of BD, and serum IGF-2 could be a peripheral biomarker for the evaluation of the severity of manic symptoms in BD patients.
Hepatocellular carcinoma is a serious health problem worldwide, especially in Asian countries, such as China. However, there are difficulties in diagnosing and treating hepatocellular carcinoma. The alteration of fucosylated proteins was closely associated with carcinogenesis. This study is designed to evaluate the early diagnostic value of associated detection of fucosylated alpha-fetoprotein (fuc-AFP), fucosylated des-γ-carboxy prothrombin (fuc-DCP), and fucosylated glypican 3 (fuc-GPC3) in hepatocellular carcinoma.All serum specimens collected from patients were diagnosed by complete clinicopathological examination and then subjected to the associated detection of fuc-AFP, fuc-DCP, and fuc-GPC3 by protein microarray. Canonical discriminant analysis was adopted to discriminate between the hepatocellular carcinoma group and the benign liver disease group.A total of 51 patients with hepatocellular carcinoma and 47 patients in the benign liver disease group were included in this study. Fuc-AFP, fuc-DCP, and fuc-GPC3 were significantly higher in the hepatocellular carcinoma group than in the benign liver disease group. The sensitivity, specificity, and accuracy of canonical discriminant analysis classification were 80.4%, 97.9%, and 88.8%, respectively.Fuc-AFP, fuc-DCP, and fuc-GPC3 are effective and useful tumor biomarkers. Associated measurement of these biomarkers with canonical discriminant analysis classification is a promising method for the early diagnosis of hepatocellular carcinoma.
Abstract Purpose: As an antipsychotic agent that targets multiple neurotransmitter receptors, olanzapine has been added to antiemetic therapies. However, olanzapine is rarely used in the real-world antiemetic strategies for breast cancer patients who suffered chemotherapy-induced nausea and vomiting. Therefore, in this study, we comprehensively reviewed the antiemetic researches related to olanzapine and pooled analyzed the results from clinical studies to confirm the efficacy of olanzapine in preventing nausea and vomiting in breast cancer. Methods: PubMed, Web of Science, EMBASE, and Cochrane Central databases were searched from inception through April 19, 2021. Both prospective and retrospective studies were eligible. The primary outcomes were complete response (defined as no vomiting and no use of rescue medications) and no nausea rate. Results: Five studies were identified in the systematic review, four of which with 466 breast cancer patients were included in the pooled analysis. In the acute period (0-24 hours), the olanzapine group had significantly higher rates of complete response (71.3% vs 48.1%, odds ratio [OR]: 2.66, 95% confidence interval [CI] 1.39-5.11, p = 0.003) and no nausea (70.0% vs 43.0%, OR: 3.55, 95% CI 1.76-7.18, p = 0.04) than the placebo group. While in the delayed period, the olanzapine group was also superior to the placebo group in terms of the complete response (82.5% vs 63.3%, OR: 3.81, 95% CI 1.58-9.15, p = 0.003) and no nausea (66.3% vs 51.9%, OR: 2.08, 95% CI 1.03-4.21, p = 0.04) rates. During the overall period in prospective studies, the proportions of complete response (50.0% vs 34.2%, OR: 1.93, p = 0.04) and no nausea (51.3% vs 25.3%, OR: 3.40, p = 0.0006) in the olanzapine group were higher than those in the placebo group. Conclusion: Highly emetogenic chemotherapy breast patients could benefit from olanzapine-contained antiemetic therapy. Furthermore, since the cost is low, olanzapine is worth further clinical application and promotion.
Objectives Des-gamma-carboxyprothrombin (DCP) is an important serum biomarker for the clinical screening of hepatocellular carcinoma (HCC). This study aimed to evaluate the value of DCP for the early diagnosis of alpha-fetoprotein (AFP)-negative hepatitis B virus (HBV)-related HCC. Methods We retrospectively enrolled patients with AFP-negative HBV-related HCC and benign liver disease. Serum DCP levels in all participants were measured by chemiluminescent enzyme immunoassay. The value of DCP for the early diagnosis of AFP-negative HBV-related HCC was evaluated by receiver operating characteristic curve (ROC) and area under the curve (AUC) analyses. Results A total of 210 patients, including 87 cases with AFP-negative HBV-related HCC and 123 control cases with chronic HBV infection (CHB) or liver cirrhosis (LC), were included. Serum DCP levels were significantly increased in patients with AFP-negative HBV-related HCC compared with those with CHB or LC. The AUC for DCP for distinguishing between the two groups was 0.731 (95% confidence interval (CI), 0.657 to 0.805) and that for early diagnosis was 0.685 (95%CI, 0.596 to 0.774). Conclusions DCP may be a favorable biomarker to improve the early diagnosis rate of AFP-negative HBV-related HCC.
NY-ESO-1 belongs to the cancer testis antigens (CTA) family, and is identified in a variety of tumors. Certain studies have demonstrated that NY-ESO-1 predicts tumor recurrence and treatment response. No reports are currently available regarding the correlation between NY-ESO-1 and the recurrence of hepatocellular carcinoma (HCC) following surgery. The purpose of the present study was to evaluate the association between NY-ESO-1 and relapse of HCC and to explore the possible mechanisms for this correlation. A total of 120 HCC patients were analyzed for the expression of NY-ESO-1 by immunohistochemistry (IHC). A stable NY-ESO-1 over-expressed HepG2 cell line (ESO-HepG2) was established to determine the biological effects of NY-ESO-1 on cell proliferation, cell cycle and migration by using the xCELLigence DP system, flow cytometry and xCELLigence SP system. NY-ESO-1 was positive in 28 of 120 (23.3%) HCC tumor tissues. NY-ESO-1 was not detectable in adjacent normal liver tissues. A close correlation was found between NY-ESO-1 expression and the recurrence of HCC following surgery (P=0.007). Kaplan-Meier analysis showed a shorter recurrence-free survival (RFS) for patients positive for NY-ESO-1 (log-rank test, P=0.003). The Cox regression model demonstrated that NY-ESO-1 expression was a significant independent predictor for the recurrence of HCC following curative surgery (P=0.022). Compared with HepG2 cells, ESO-HepG2 cells have increased migration but not proliferation ability. In conclusion, NY-ESO-1 expression is associated with worse HCC outcome following surgery, and the mechanism for this finding may be that NY-ESO-1 increases tumor cell migration.
The majority of patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage that excludes them from potentially curative surgical treatment. Lenvatinib is associated with a high objective response rate (ORR) (40.6%) in advanced HCC, indicating the potential for tumor downstaging and conversion to surgical intervention. We report the case of a patient with recurrent, advanced HCC who achieved a partial response and downstaging following third-line treatment with lenvatinib but missed the opportunity for conversion hepatectomy.A male Chinese patient aged 42 years presented with an obstructive liver lesion, revealed by CT imaging to be a single tumor in segments V and VIII of the liver, without macrovascular invasion. The patient had chronic hepatitis B infection, Barcelona Clinic Liver Cancer (BCLC) Stage A, normal liver function (Child-Pugh Score 5 and Grade A) and AFP level 4.45 ng/mL. The patient underwent a successful hepatectomy but experienced recurrence 14 months later. The recurrent tumor was detected at an early stage and the patient underwent successful radiofrequency ablation and transarterial chemoembolization. After a further 11 months, the patient experienced a second relapse characterized by multiple disseminated metastases in the left and right lobes of the liver and possible macrovascular invasion, equal to BCLC Stage B/C. The patient received lenvatinib and achieved a partial response with complete disappearance of a number of lesions, recovering to BCLC Stage A and becoming eligible for liver transplantation. However, the patient refused surgery and after 4 months experienced progressive disease.Our case suggests that radical treatment, such as conversion hepatectomy or liver transplantation, should be undertaken quickly following downstaging and within the expected PFS time associated with lenvatinib. However, further studies are required to provide additional evidence for this treatment strategy.
Corrigendum: Lower serum insulin-like growth factor 2 level in patients with bipolar disorder is associated with the severity of manic symptoms during manic episodes
To investigate the expression of interleukin-6 (IL-6) and β-catenin in oral squamous cell carcinoma (OSCC) and its clinicopathological significance.The serum IL-6 concentration in 110 OSCC patients and 109 healthy controls were determined by chemiluminescence analysis. IL-6 and β-catenin expression levels in 68 tumor specimens of OSCC patients undergoing surgical treatment and 6 normal mucosal tissues were determined by immunohistochemistry method. The correlation between IL-6 and β-catenin and clinicopathological parameters and their prognostic value were analyzed. SPSS 22.0 software package was used for data analysis.Chemiluminescence method showed that the serum IL-6 content of OSCC patients was significantly increased (P＜0.001). Immunohistochemical results demonstrated that high expression of IL-6 in OSCC tissues was remarkably associated with cervical lymph node metastasis(P=0.017), pathological differentiation(P=0.014), recurrence and distant metastasis (P=0.048). OSCC patients with high IL-6 expression showed a poor prognosis by Kaplan-Meier survival analysis. Multivariate Cox regression analysis showed that high expression of IL-6 was an independent risk factor affecting the prognosis of patients with OSCC(P＜0.05). β-catenin hyperexpression was associated with pathological differentiation(P=0.006) and overall poor survival in OSCC patients. Spearman correlation analysis showed a positive correlation between IL-6 and β-catenin expression in OSCC (P＜0.001).Serum IL-6 is expected to be a biomarker for detection of OSCC, and IL-6 and β-catenin expression in tumour tissues can be used as markers to evaluate the poor prognosis of OSCC.
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