Gene mutation landscape of a rare patient with acute megakaryoblastic leukemia after treatment of intracranial germ cell tumor.

Introduction: It was first reported that germ cell tumor patients suffer from hematologic malignancies 37 years ago. Since then, the number of relevant reports has increased each year, with most cases being mediastinal germ cell tumor. Theories have been proposed to explain this phenomenon, including a shared origin of progenitor cells, the effects of treatment, and independent development. However, up to now, no widely accepted explanation exists. The case with acute megakaryoblastic leukemia and intracranial germ cell tumor has never been reported before and the association is far less known. Methods: We used whole exome sequencing and gene mutation analysis to study the relationship between intracranial germ cell tumor and acute megakaryoblastic leukemia of our patient. Results: We report a patient who developed acute megakaryoblastic leukemia after treatment for an intracranial germ cell tumor. Through whole exome sequencing and gene mutation analysis, we identified that both tumors shared the same mutation genes and mutation sites, suggesting they originated from the same progenitor cells and differentiated in the later stage. Discussion: Our findings provide the first evidence supporting the theory that acute megakaryoblastic leukemia and intracranial germ cell tumor has the same progenitor cells.

COVID-19 or treatment associated immunosuppression may trigger hepatitis B virus reactivation: A case report.

BACKGROUND: Since the initial recognition of coronavirus disease 2019 (COVID-19) in Wuhan, this infectious disease has spread to most areas of the world. The pathogenesis of COVID-19 is yet unclear. Hepatitis B virus (HBV) reactivation occurring in COVID-19 patients has not yet been reported. CASE SUMMARY: A 45-year-old hepatitis B man with long-term use of adefovir dipivoxil and entecavir for antiviral therapy had HBV reactivation after being treated with methylprednisolone for COVID-19 for 6 d. CONCLUSION: COVID-19 or treatment associated immunosuppression may trigger HBV reactivation.

The aberrant expression or disruption of desmocollin2 in human diseases.

The desmosome is a member of intercellular junctions that named 'anchoring junction', which contributes to the integrity and homeostasis of tissue structure and function of multicellular living organisms. As an important component of the desmosome and the most widely distributed isoform of desmocollins (DSCs), desmocollin2 (DSC2) has been demonstrated to be essential for the unity of epithelial cells, and served as a vital regulator in signaling processes such as epithelial morphogenesis, differentiation, wound healing, cell apoptosis, migration, and proliferation. Recent studies suggested that the aberrant expression or disruption of DSC2 might lead to some disorders, including heart disorders, certain cancers, and some other human diseases. The distinctions in expression and regulation mechanisms of DSC2 in different human diseases provided a potential target for diagnosis and individualized treatment. Further research is required to certify the signaling capacity of DSC2 and to shed light on the down-stream consequences of the signaling for us to understand the new area of DSC2 biology and the development of certain diseases. This review summarizes the molecular structure and dynamics of desmosome and DSC2, the relationship between the disruption or aberrant expression of DSC2 and human diseases and related molecular mechanisms, as well as the possible prospects.

Reversal of Chemoresistance in Human Lung Cancer Cell Line A549/Taxol by Synthetic Second Mitochondria-Derived Activator of Caspase Peptide.

BACKGROUND: Chemoresistance is a leading cause of treatment failure in advanced lung cancer, including that with the extensively prescribed taxol. Recently, a series of structurally unique second mitochondria-derived activators of caspase (Smac) that act as antagonists of inhibitor of apoptosis proteins (IAPs) have been discovered, exhibiting the ability of inducing enhanced apoptosis of various cancer cell types when combined with chemotherapy. In the present study, we synthesized the second mitochondria-derived activator of caspase peptide (Smac-N7 for short) and explored its capacity in combination with taxol in vitro. METHODS: The sensitivity assay and reversal ability of Smac-N7 were tested by MTT. Flow cytometry was used to analyze apoptosis of cells with Annexin V/PI double staining technique. Cell cloning ability was performed to reflect its biological behavior in each group. RESULTS: Concentrations with inhibitory rates < 10% were selected as the reversal value of Smac-N7 peptide using MTT. The reversal folds were 2.52, 3.26, 3.67, and 5.4 in taxol + Smac-N7 (0.0390625, 0.078125, 0.15625, 0.3125 µg/mL, respectively), and concentrations of Smac-N7 and reversal folds appeared in an obvious positive correlation (r(s) = 1, p = 0.000). Apoptosis analyzed at 48 hours by flow cytometry showed the apoptotic rates in taxol and 0.0390625, 0.078125, 0.15625, and 0.3125 µg/mL Smac-N7 + taxol groups were 15.4 ± 1.09%, 20.8% ± 2.18%, 28.4% ± 4.17%, 37.64% ± 6.41%, and 46.6% ± 7.76%, respectively. Concentrations of Smac-N7 appeared to have negative correlations with PE and SF (r(s) = -1, p < 0.05), which showed that the cells' cloning ability in 0.3125 µg/mL Smac-N7 + taxol group was worse than that of other groups. CONCLUSIONS: When combined with taxol, 0.3125 µg/mL Smac-N7 peptide may significantly increase taxol-induced apoptosis in chemoresistant A549/taxol lung cells at 48 hours, and is potentially useful as a reversal agent in lung cancer therapy.

Effect of Second mitochondria-derived activator of caspase in combination with Docetaxel on lung cancer cell A549.

This study was to investigate inhibiting effect of structurally unique Second mitochondria-derived activator of caspase (Smac) in combination with Docetaxel on lung cancer cell line A549. Results showed that the expression of Smac in transfected A549 cells was higher than the control cells both at mRNA level and protein level (P<0.05). Smac over-expression induced a little apoptosis, however, when treated with Docetaxel together, the cells showed a higher apoptosis rate. The apoptosis rate was significantly increased in Smac + Docetaxel group when compared with that in Smac group and Docetaxel group (P<0.05). Cells cloning ability in Smac + Docetaxel group was worse than that of other groups (P<0.05), cell mass formed in relatively small quantities and sparse location. Thus, over-expression of Smac increases the sensitivity of lung cancer A549 cells to Docetaxel treatment, and transfection of Smac to tumor cells might provide a potential therapy modality.

A systematic review of risk factors for brain metastases and value of prophylactic cranial irradiation in non-small cell lung cancer.

BACKGROUND: The incidence of brain metastases (BM) varies in patients with non-small cell lung cancer (NSCLC), calls into question the value of prophylactic cranial irradiation (PCI). It is possible that clinicopathologic characteristics are associated with the development of BM, but these have yet to be identified in detail. Thus, we conducted the present meta-analysis on risk factors for BM and the value of PCI in patients with NSCLC. METHODS: Eligible data were extracted and the risk factors for BM and the value of PCI in patients with NSCLC were analyzed by calculating the pooled odds ratio (OR). Heterogeneity was detected using Q and I-squared statistics, and publication bias was tested by funnel plots and Egger's test. RESULTS: Six randomized controlled trials with a focus on the value of PCI and 13 eligible studies with a focus on risk factors for BM were included. PCI significantly reduced the incidence of BM in patients with NSCLC (p=0.000, pooled OR=0.34, 95% confidence interval = 0.37-0.59). Compared with non-squamous cell carcinoma, squamous cell carcinoma was associated with a low incidence of BM in patients with NSCLC (p=0.000, pooled OR=0.47, 95% confidence interval =0.34- 0.65). The funnel plot and Egger's test suggested that there was no publication bias in the current meta-analysis. CONCLUSIONS: This meta-analysis provides statistical evidence that compared with non-squamous cell carcinoma, squamous cell carcinoma can be used as a predictor for BM in patients with NSCLC, and PCI might reduce the incidence of BM in patients with NSCLC, but does not provide a survival benefit.

MUTYH association with esophageal adenocarcinoma in a Han Chinese population.

Adenocarcinoma of esophagus (AE) is a complex disease, affected by a variety of genetic and environmental factors. Much evidence has shown that the MutY glycosylase homologue (MUTYH) plays a key role in the pathogenesis of many cancers. However, there have been no reports on influence on AE in the Han Chinese population. The objective of this study was to investigate this issue. A gene-based association study was conducted using three single nucleotide polymorphisms(SNPs) reported in previous studies. The three SNPs (rs3219463, rs3219472, rs3219489) were genotyped in 207 unrelated AE patients and 249 healthy controls in a case-control study using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The results revealed that the genotype distribution of rs3219472 differed between the case and control groups (OR=1.66,95%CI=1.11-2.48, P=0.012 ), indicating that an association may exist between MUTYH and AE. These findings support a signifcant role for MUTYH in AE pathogenesis in the Han Chinese population.

The correlation between tumor-infiltrating Foxp3+ regulatory T cells and cyclooxygenase-2 expression and their association with recurrence in resected head and neck cancers.

The aim of this study was to investigate the correlation between tumor-infiltrating CD4+ CD25(high) Foxp3+ naturally occurring regulatory T cells (Foxp3+ nTregs) and cyclooxygenase-2 (COX-2) expression and their association with local recurrence in resected head and neck cancers. Intratumoral COX-2 and Foxp3+ nTregs expressions were retrospectively assessed using immunohistochemistry. Associations between the clinicopathological characteristics and either intratumoral COX-2 expression or number of Foxp3+ nTregs were tested using the Chi-square test. The correlation between the number of Foxp3+ nTregs and COX-2 expression was tested using Spearman's rank correlation test. Associations between recurrence-free survival (RFS) and either intratumoral COX-2 expression or number of Foxp3+ nTregs were calculated using the Kaplan-Meier method, and factors that may influence the RFS were analyzed by Cox regression. The five-year RFS for all patients was 35.09%. Patient clinicopathological characteristics had no relationship with intratumoral COX-2 expression or the number of Foxp3+ nTregs. However, a positive correlation between intratumoral COX-2 expression and the number of Foxp3+ nTregs was observed (P < 0.001). The RFS of patients with elevated COX-2 expression was significantly worse than that of patients without intratumoral COX-2 expression (P = 0.0228). The RFS of patients with tumors containing >6 Foxp3+ cells was significantly worse than that of patients with tumors containing ≤6 Foxp3+ cells (P = 0.0020). However, by Cox regression analysis, the RFS of all patients was not influenced by intratumoral COX-2 expression (P = 0.100) or the number of Foxp3+ nTregs (P = 0.071). Tumor-infiltrating CD4+ CD25(high) Foxp3+ nTregs were positively correlated with intratumoral COX-2 expression and were associated with a worse RFS in univariate analysis.

[Statistical study on correlation between cerebral arteriovenous malformation and hemodynamic aneurysms].

OBJECTIVE: to explore the characteristic factors of arteriovenous malformation (AVM) which have statistically significant correlation with hemodynamic aneurysms. METHODS: from August 1999 to July 2009, the clinical and imaging indices of 363 consecutive patients with AVM were retrospectively reviewed and entirely statistically analyzed. There were 229 male patients and 137 female patients, the mean age at the time of presentation was 28 ± 13 years. By using SPSS 16.0 medical statistic software, the correlation were analyzed between hemodynamic aneurysms and 13 characteristic factors associated with AVM through the methods of unit-factor and multi-factor analysis. Finally, the risk of the correlative factors filtered were evaluated. RESULTS: the crosstabs analysis of unit-factor strongly suggested that the following factors, including age, location (supertentorium, subtentorium), size, number of main feeding arteries, number of drainage veins, ectasis of drainage veins, contralateral supply, and supply by both anterior and posterior circulation, were correlated with hemodynamic aneurysms. And the results of regression analysis of multi-factors indicated the following factors, including age, number of main feeding arteries, and contralateral supply, were positively correlated with hemodynamic aneurysms and the number of drainage veins were negatively correlated with hemodynamic aneurysms. CONCLUSION: the factors including age, number of main feeding arteries, number of drainage veins and contralateral supply, are highly correlated with hemodynamic aneurysms.

Clinical observation on chemical damage of nephron and the preventive and therapeutic effects of Baoshen Mixture on it.

OBJECTIVE: To observe the change of nephron damaged by chemotherapy and to evaluate the effect of Baoshen Mixture (, BSM) in protecting and treating damaged nephrons. METHODS: Four hundred tumor patients with normal renal function and ready to receive chemotherapy were randomly assigned to two groups. Both groups received one cycle of chemotherapy program of 28-30 days with conventional hydratization, alkalization and chloridization. To the 200 cases in the treated group BSM was given orally thrice a day, 150 mL every time for 15 successive days and the other 200 cases in the control group were treated by chemotherapy alone. The clinical efficacy was compared after treatment, and the changed condition of damaged nephrons were monitored dynamically and compared at different time points (the 3rd, 7th, 14th and 21st day after chemotherapy) by measuring the micro-globulin beta(2) (beta(2)-MG), albumin (Alb) and immunoglobulin G (IgG) levels in urine with radioimmunoassay (RIA). RESULTS: (1) The effective rates in the treated group at the 4 time points of observation were all higher than those in the control group respectively (P<0.05 or P<0.01); (2) Less occurrence of abnormal beta(2)-M, Alb and IgG levels on the 14th and 21st day in the treated group took place compared to that in the control group (P<0.01); (3) Urinary levels of beta(2)-MG, Alb and IgG reached the peak on the 7th day in both groups, and then, they came down gradually and returned to the normal level on the 21st day. However, comparison between the two groups showed that all the three parameters in the treated group on day 3, 14 and 21 were lower than the respective one at the corresponding time points in the control group (P<0.05 or P<0.01). CONCLUSION: The chemotherapy damage on nephron is regular in time, and reversible when treated suitably. TCM shows a marked effect in protecting and treating the damage on nephron caused by chemotherapy.