Reduced radiosensitivity of lung cancer cells represents a pivotal obstacle in clinical oncology. The hypoxia-inducible factor (HIF)-1α plays a crucial role in radiosensitivity, but the detailed mechanisms remain elusive. A relationship has been suggested to exist between hypoxia and autophagy recently. In the current study, we studied the effect of hypoxia-induced autophagy on radioresistance in lung cancer cell lines. A549 and H1299 cells were cultured under normoxia or hypoxia, followed by irradiation at dosage ranging from 0 to 8 Gy. Clonogenic assay was performed to calculate surviving fraction. EGFP-LC3 plasmid was stably transfected into cells to monitor autophagic processes. Western blotting was used to evaluate the protein expression levels of HIF-1α, c-Jun, phosphorylated c-Jun, Beclin 1, LC3 and p62. The mRNA levels of Beclin 1 were detected by qRT-PCR. We found that under hypoxia, both A549 and H1299 cells were radio-resistant compared with normoxia. Hypoxia-induced elevated HIF-1α protein expression preferentially triggered autophagy, accompanied by LC3 induction, EGFP-LC3 puncta and p62 degradation. In the meantime, HIF-1α increased downstream c-Jun phosphorylation, which in turn upregulated Beclin 1 mRNA and protein expression. The upregulation of Beclin 1 expression, instead of HIF-1α, could be blocked by SP600125 (a specific inhibitor of c-Jun NH2-terminal kinase), followed by suppression of autophagy. Under hypoxia, combined treatment of irradiation and chloroquine (a potent autophagy inhibitor) significantly decreased the survival potential of lung cancer cells in vitro and in vivo. In conclusion, hypoxia-induced autophagy through evaluating Beclin1 expression may be considered as a target to reverse the radioresistance in cancer cells.

A 14-year girl was admitted with akinesia and difficulty walking due to gait instability after two oral doses of compound diphenoxylate (lomotil). When she was 18-month old, drowsiness and inability to walk were observed after taking lomotil, the symptoms were relieved by taking B vitamins for treatment. The laboratory tests showed the increased blood branched chain amino acid levels; gene detection indicated that the child had compound heterozygous variations of c.745G>A(p.G249S) and c.485-1G>C in the BCKDHA gene. The girl was finally diagnosed as maple syrup urine disease. The domestic and foreign literature was searched, and 11 child cases of maple syrup urine disease with onset of unsteadiness and ataxia were reported, none of whom was associated with oral administration of compound diphenoxylate.

OBJECTIVETo investigate the clinicopathologic features of reactive hyperplasia of lymph nodes in maxillofacial regions.

METHODSThirty-two patients with lymph node reactive hyperplasia (LRH) were analyzed clinicopathologically including pathomorphologic manifestation and immunohistochemical expression.

RESULTSHistopathology of 32 patients showed significant hyperplasia in folliculus lymphaticus, marginal zone lymph, paracortical area lymph, and seldom mixed hyperplasia. Immunohistochemical study showed that the hyperplastic lymphocytes were mainly composed of CD20 positive B cells positive in 23 cases(72%), CD3 positive T cell in 7 cases (22%), CD20 positive T cell and CD3 positive B cell partially as well as histiocytes in 2 cases (6%). Atypical hyperplasia was found in 10 cases.

CONCLUSIONHyperplastic lymphocytes in LRH of maxillofacial regions are mainly composed of B cells. Malignant transformation may occur in these patients with atypical hyperplasia. Regularity follow up is necessary for these patients.

Adult ; B-Lymphocytes ; Female ; Humans ; Hyperplasia ; Lymph Nodes

OBJECTIVETo investigate the relationship between extracapsular spread (ECS) of cervical metastatic lymph node and the recurrence in patients with oral squamous cell carcinoma (OSCC).

METHODSThe medical records of 74 OSCC patients with histologically confirmed cervical lymph node metastasis were reviewed. They were divided into 2 groups, ECS positive (ECS+) and ECS negative (ECS-). The treatment results were followed up. Statistical analysis, with chi-square test, and multiple logistic regression was conducted.

RESULTSThe overall recurrence rates for pN+/ECS- and pN+/ECS+ patients were 47.6% and 75.0%, respectively, and the cervical recurrence rates for pN+/ECS- and pN+/ECS+ patients were 9.5% and 46.9%, respectively (P < 0.001). Multivariate analysis showed that ECS was one of the independent prognosis factors for cervical recurrence.

CONCLUSIONSExtracapsular spread significantly increased both overall and cervical recurrence rates, and ESC may be a prognosis factor for OSCC patients.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; pathology ; Female ; Follow-Up Studies ; Humans ; Logistic Models ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; pathology ; Male ; Middle Aged ; Mouth Neoplasms ; pathology ; Neck ; pathology ; Neoplasm Recurrence, Local ; Prognosis ; Retrospective Studies

OBJECTIVEThe Chinese Children's Leukemia Group (CCLG)-acute lymphoblastic leukemia (ALL) 08 protocol for childhood ALL was established in 2008. This study aims to evaluate the drug-related toxicities of CCLG-ALL 08 protocol in the treatment of childhood ALL.

METHODSA total of 114 children with newly diagnosed ALL were treated with the CCLG-ALL 08 protocol. The protocol was divided into five phases: remission induction (VDLD), early reinforcement (CAM), consolidation therapy, delayed reinforcement (DIa & DIb) and maintenance treatment. Drug-related toxicities in each phase were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0.

RESULTSToxicities were more frequent in phase VDLD than other treatment phases, including hepatotoxicity (87.7%), dental ulcer (20.2%), hyperglycemia (20.2%), prolonged activated partial thromboplastin time (21.1%) and decreased fibrinogen (34.2%), with the incidence rates of severe adverse events at 7%, 0, 1.3%, 0.8% and 2.7% respectively. The incidence of allergic reaction to L-ASP was significantly higher in phase DIa than in phase VDLD (28.0% vs 7.9%; P<0.01), and there were no longer any allergic reactions in 15 patients who received continuing treatment with pegaspargase instead. There was no severe arrhythmia, myocardial ischemia, decreased left ventricular function, osteonecrosis, myopathy, organ failure or treatment-related mortality.

CONCLUSIONSThe drug-related toxicities of CCLG-ALL 08 protocol are common in phase VDLD, but they are mild and reversible. There is no treatment-related mortality. The CCLG-ALL 08 protocol for childhood ALL is safe.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; Asparaginase ; adverse effects ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Remission Induction

OBJECTIVETo study the cytogenetic characteristics of B cell non-Hodgkin's lymphoma (B-NHL) with bone marrow involvement, and to explore the clinical significance and prognosis.

METHODSClinical data of 126 B-NHL patients with bone marrow involvement diagnosed in our hospital were retrospectively analyzed. Chromosome banding analysis was performed after 24 h culture.

RESULTS(1) The B-NHLs included were diffuse large B-cell lymphoma (DLBCL) 38.9% (49 cases), lymphoplasmacytic lymphoma (LPL) 19% (24 cases), mantle cell lymphoma (MCL) 16.7% (21 cases), follicular lymphoma (FL) 9.5% (12 cases), marginal zone lymphoma (MZL) 8.7% (11 cases) and small lymphocytic lymphoma (SLL) 7.1%(9 cases). (2) Chromosome aberrations (CA) were detected in 52 of 126 patients (41.3%) by conventional cytogenetics (CC), including clonal CA 38 cases, and non-clonal CA 14 cases. Ploidy levels in 38 clonal CA cases were pseudodiploid (57.9%), hypodiploid (15.8%) and hyperdiploid (26.3%). The incidence of chromosomal abnormalities among DLBCL, MCL, MZL, LPL, FL and SLL was 73.4%, 38.1%, 36.4%, 8.3%, 8.3% and 11.1%, respectively. (3) Clonal CA, CA more than two kinds, and CA of chromosomes 2, 3, 9, 11, 17, 18 and 20 were associated with shorter overall survival (OS) in DLBCL. More than two kinds of CA and CA of chromosome 3, 13 were associated with shorter OS in MCL.

CONCLUSIONSThe incidence of CA was higher in aggressive lymphoma than in indolent lymphoma. Complex CA were quite common, and some specific CA might have prognostic significance.

Adolescent ; Adult ; Aged ; Bone Marrow ; pathology ; Child ; Child, Preschool ; Chromosome Aberrations ; Female ; Humans ; Lymphoma, Non-Hodgkin ; classification ; genetics ; pathology ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Young Adult

OBJECTIVETo investigate the correlation of the mRNA expression level of excision repair cross-complementing group 1 (ERCC1) gene with clinicopathological parameters and clinical outcome in patients with non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapy.

METHODSThe mRNA expression of ERCC1 in formalin-fixed paraffin-embedded primary tumor specimens was measured by real-time quantitative reverse transcriptase polymerase chain reaction. The association between ERCC1 expression levels and clinicopathological parameters in NSCLC patients was analyzed.

RESULTSThe median value of ERCC1 mRNA expression level compared with beta-actin in tumor specimens of 61 NSCLC patients was 0.48. There was no correlation between ERCC1 expression and clinicopathological parameters. Patients with low expression of ERCC1 mRNA (less than 0.35, 0.28, respectively) had a significantly longer median time to progression (TTP) (14.3 vs. 8.0 months, P = 0.028) and overall survival (OS) (28.4 vs. 12.9 months, P = 0.0064) than those with high expression. Multivariate analysis showed that a low ERCC1 mRNA expression was an independent factor for OS.

CONCLUSIONOur findings suggest that intratumoral ERCC1 mRNA expression level, although is uncorrelated with clinicopathological parameters, is an independent predictive marker for survival of the patients with NSCLC receiving platinum-based chemotherapy, and may provide critical information for personalized chemotherapy.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Neoplasms ; secondary ; Brain Neoplasms ; secondary ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; metabolism ; pathology ; secondary ; Cisplatin ; administration & dosage ; DNA-Binding Proteins ; genetics ; metabolism ; Disease-Free Survival ; Endonucleases ; genetics ; metabolism ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; drug therapy ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Paraffin Embedding ; Platinum ; administration & dosage ; Proportional Hazards Models ; RNA, Messenger ; metabolism ; Survival Rate

OBJECTIVETo explore the biomarker of manganese exposure by analyzing the relationship between manganese exposure and concentration in some biomaterials.

METHODSThe air samples were collected through the individual air sample. According to the manganese levels in the air, workers were assigned to control group, low concentration group and high concentration group, and manganese in the hair, urine, serum, blood cell and saliva from different group were measured respectively. The correlations between concentration of external manganese exposure and manganese concentrations in biomaterials, and years of employment and concentrations in biomaterials were analyzed.

RESULTSIn the high concentration group, saliva manganese was 32.17 µg/L, hair manganese was 37.39 mg/kg, urine manganese was 2.50 µg/L, plasma manganese was 29.61 µg/L, blood manganese was 14.49 µg/L, were higher than those in the control group (10.40 µg/L, 1.60 mg/kg, 0.77 µg/L, 10.30 µg/L, 4.56 µg/L respectively) (P < 0.01). The manganese concentration in the saliva was significantly correlated with airborne manganese concentration (r = 0.649, P < 0.01), with the years of employment (r = 0.404, P < 0.01), with the total exposure of manganese (r = 0.342, P < 0.01), with the manganese concentration of plasma (r = 0.303, P < 0.01) and with the manganese concentration in blood cells (r = 0.359, P < 0.01), respectively.

CONCLUSIONSThe concentration of manganese in saliva could work as a biomarker of manganese internal exposure.

Adult ; Air Pollutants, Occupational ; analysis ; Biomarkers ; analysis ; Hair ; chemistry ; Humans ; Manganese ; analysis ; blood ; urine ; Manganese Poisoning ; prevention & control ; Middle Aged ; Occupational Exposure ; prevention & control ; Saliva ; chemistry ; Young Adult

Reduced radiosensitivity of lung cancer cells represents a pivotal obstacle in clinical oncology. The hypoxia-inducible factor (HIF)-1α plays a crucial role in radiosensitivity, but the detailed mechanisms remain elusive. A relationship has been suggested to exist between hypoxia and autophagy recently. In the current study, we studied the effect of hypoxia-induced autophagy on radioresistance in lung cancer cell lines. A549 and H1299 cells were cultured under normoxia or hypoxia, followed by irradiation at dosage ranging from 0 to 8 Gy. Clonogenic assay was performed to calculate surviving fraction. EGFP-LC3 plasmid was stably transfected into cells to monitor autophagic processes. Western blotting was used to evaluate the protein expression levels of HIF-1α, c-Jun, phosphorylated c-Jun, Beclin 1, LC3 and p62. The mRNA levels of Beclin 1 were detected by qRT-PCR. We found that under hypoxia, both A549 and H1299 cells were radio-resistant compared with normoxia. Hypoxia-induced elevated HIF-1α protein expression preferentially triggered autophagy, accompanied by LC3 induction, EGFP-LC3 puncta and p62 degradation. In the meantime, HIF-1α increased downstream c-Jun phosphorylation, which in turn upregulated Beclin 1 mRNA and protein expression. The upregulation of Beclin 1 expression, instead of HIF-1α, could be blocked by SP600125 (a specific inhibitor of c-Jun NH2-terminal kinase), followed by suppression of autophagy. Under hypoxia, combined treatment of irradiation and chloroquine (a potent autophagy inhibitor) significantly decreased the survival potential of lung cancer cells in vitro and in vivo. In conclusion, hypoxia-induced autophagy through evaluating Beclin1 expression may be considered as a target to reverse the radioresistance in cancer cells.
Animals ; Apoptosis Regulatory Proteins ; genetics ; metabolism ; Autophagy ; Beclin-1 ; Cell Hypoxia ; Cell Line, Tumor ; Cell Survival ; genetics ; radiation effects ; Gene Expression Regulation, Neoplastic ; radiation effects ; Green Fluorescent Proteins ; genetics ; metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Immunoblotting ; Lung Neoplasms ; genetics ; metabolism ; pathology ; Membrane Proteins ; genetics ; metabolism ; Mice, Nude ; Microscopy, Fluorescence ; Microtubule-Associated Proteins ; genetics ; metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-jun ; metabolism ; Radiation Tolerance ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Transplantation, Heterologous ; Tumor Burden ; genetics