OBJECTIVETo study the effect of hyperthermia on expressions of multidrug resistance (MDR) genes in tongue squamous cell carcinoma cell line Tca8113 and its MDR cell line Tca8113/CBDEA and intracellular ADM concentration.

METHODSCell lines were hyperthermia-treated (42 degrees C for 0.5 h), 4 h and 24 h later real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) detected expressions of MDR relative genes (MDR1, MRPI, GST-pi) and HTS 7000 Plus Bio Assay Reader measured intracellular ADM concentration.

RESULTSExpressions of MDR1, MRPI, GST-'pi genes in Tca8113/CBDEA significantly descended at 4 h and 24 h post-hyperthermia (P < 0.01). Expressions of MDR1, MRP1 genes in Tca8113 significantly descended at 4 h and 24 h post-hyperthermia (P < 0.05), but there was not statistical difference between 4 h and 24 h post-hyperthermia. GST-pi expression had not statistical descent at 4 h, but there was significantly descend at 24 h post-hyperthermia (P < 0.01). Drug tolerance decreased and hyperthermia increased intracellular drug concentration in Tca8113/CBDEA and Tca8113 (P < 0.01).

CONCLUSIONHyperthermia enhance chemotherapy effect and reverse MDR genes expression in tongue squamous cell carcinoma cell line. It is suggested that hyperthermia could be used as a method to overcome MDR, which is worth more investigation.

Carcinoma, Squamous Cell ; Cell Line ; Cell Line, Tumor ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; Tongue Neoplasms

This study investigated the relationship among the severity of hearing impairment,vestibular function and balance function in patients with idiopathic sudden sensorineural hearing loss (ISSNHL).A total of 35 ISSNHL patients (including 21 patients with vertigo) were enrolled.All of the patients underwent audiometry,sensory organization test (SOT),caloric test,cervical vestibular-evoked myogenic potential (cVEMP) test and ocular vestibular-evoked myogenic potential (oVEMP) test.Significant relationship was found between vertigo and hearing loss grade (P=0.009),and between SOT VEST grade and hearing loss grade (P=0.001).The abnormal rate of oVEMP test was the highest,followed by the abnormal rates of caloric and cVEMP tests,not only in patients with vertigo but also in those without vertigo.The vestibular end organs were more susceptible to damage in patients with vertigo (compared with patients without vertigo).Significant relationship was found between presence of vertigo and SOT VEST grade (P=0.010).We demonstrated that vestibular end organs may be impaired not only in patients with vertigo but also in patients without vertigo.The cochlear and vestibular impairment could be more serious in patients with vertigo than in those without vertigo.Vertigo does not necessarily bear a causal relationship with the impairment of the vestibular end organs.SOT VEST grade could be used to reflect the presence of vertigo state in the ISSNHL patients.Apart from audiometry,the function of peripheral vestibular end organs and balance function should be evaluated to comprehensively understand ISSNHL.Better assessment of the condition will help us in clinical diagnosis,treatment and prognosis evaluation of ISSNHL.

BACKGROUNDOverexpression of G-protein coupled receptor 34 (GPR34) affects the progression and prognosis of human gastric adenocarcinoma, however, the role of GPR34 in gastric cancer development and progression has not been well-determined. The current study aimed to investigate the effect of GPR34 knockdown on the proliferation, migration, and apoptosis of HGC-27 gastric cancer cells and the underlying mechanisms.

METHODSThe expression of GPR34 in gastric cancer cell line HGC-27 was detected by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. HGC-27 cells were employed to construct the stable GPR34 knockdown cell model in this study. Real-time RT-PCR and Western blotting were applied to validate the effect of short hairpin RNA (ShRNA) on the expression of GPR34 in HGC-27 gastric cells. The proliferation, migration of these cells were examined by Cell Counting Kit-8 and transwell. We also measured expression profile of PI3K/PDK1/AKT and ERK using Western blotting.

RESULTSThe ShRNA directed against GPR34 effectively inhibited both endogenous mRNA and protein expression levels of GPR34, and significantly down-regulated the expression of PIK3CB (P < 0.01), PIK3CD (P < 0.01), PDK1 (P < 0.01), phosphorylation of PDK1 (P < 0.01), Akt (P < 0.01), and ERK (P < 0.01). Furthermore, GPR34 knockdown resulted in an obvious reduction in HGC-27 cancer cell proliferation and migration activity (P < 0.01).

CONCLUSIONSGPR34 knockdown impairs the proliferation and migration of HGC-27 gastric cancer cells in vitro and provides a potential implication for therapy of gastric cancer.

Apoptosis ; genetics ; physiology ; Blotting, Western ; Cell Line, Tumor ; Cell Proliferation ; genetics ; physiology ; Humans ; RNA, Small Interfering ; genetics ; Real-Time Polymerase Chain Reaction ; Receptors, Lysophospholipid ; genetics ; metabolism ; Stomach Neoplasms ; genetics ; metabolism

OBJECTIVETo evaluate the effectiveness of cerebral revascularization in the treatment of intractable aneurysms and to discuss the indications, surgical techniques, and the outcome of the revascularization.

METHODSDuring the recent 4-year period, 9 radical artery grafts were performed in patients with intractable or giant internal carotid artery (ICA) aneurysms. The indications for cerebral revascularization included parent vessel occlusion during the treatment of the intractable aneurysms with poor collateral circulation or the young patients. Modified techniques were taken to use the main trunk of superficial temporal artery (STA) as donor, while M3 branches near the bifurcation of the M2 segment of the middle cerebral artery (MCA) were chosen as the recipient arteries. STA-Radial artery (RA)-MCA bypass was followed by parent vessel occlusion via chronic cervical ICA ligation or balloon occlusion.

RESULTSPostoperative angiography demonstrated the patency of the grafts in eight cases. The procedure of the parent vessels occlusion was uneventful in these patients. Follow-up showed the patients were in excellent conditions after successful treatment of aneurysms. Significantly delayed filling of the graft was revealed in one patient, who could not tolerate balloon occlusion test and occlusion of parent artery failed.

CONCLUSIONSExtracranial-to-intracranial bypass followed by parent vessel occlusion is a safe and effective method to treat intractable ICA aneurysms. Radical artery as graft can offer high-flow revascularization with less complications. Combined surgical and endovascular treatment might be the future direction for the treatment of the difficult aneurysms.

Adolescent ; Adult ; Carotid Artery, Internal ; surgery ; Cerebral Arteries ; surgery ; Cerebral Revascularization ; methods ; Female ; Follow-Up Studies ; Humans ; Intracranial Aneurysm ; diagnosis ; surgery ; Ligation ; Male ; Middle Aged

OBJECTIVETo explore the correlation of chemotherapy efficacy in tongue squamous cell carcinoma(SCC) with expression level of P-glycoprotein(Pgp), multidrug resistance-associated protein (MRP), lung resistance-related protein (LRP), glutathiones-tranferase (GST-pi), DNA topo-isomerase II alpha (Topo II alpha).

METHODSThe expression patterns of Pgp, MRP, LRP, GST-pi and Topo II alpha in 40 patients (pre and post-chemotherapy, respectively) with tongue SCC were examined by immunohistochemically labelled streptavidin bioein method (LsAB).

RESULTSThe expression ratios of Pgp, MRP, LRP, GST-pi and Topo II alpha in pre-chemotherapy cases were 47.5%, 50%, 35%, 45%, 82.5%, respectively. No relations between expression of Pgp, MRP, LRP, GST-pi, Topo II alpha and clinic indexes were established (P > 0.05). Expression ratios of Pgp, MRP in post-chemotherapy cases were higher than that in pre-chemotherapy cases (P < 0.05). Expression of Pgp and MRP showed relevance with drug resistance (P < 0.05). The co-expression was common, the ratios of co-expression of Pgp, MRP, GST-pi and MRP, GST-pi in chemotherapy non-responders were 40% and 50%, respectively, but 0 in responders.

CONCLUSIONThe intrinsic multidrug resistance of tongue SCC is relevant to the effects of Pgp, MRP, GST-pi.

ATP-Binding Cassette, Sub-Family B, Member 1 ; biosynthesis ; genetics ; Adult ; Antigens, Neoplasm ; Carcinoma, Squamous Cell ; metabolism ; DNA Topoisomerases, Type II ; biosynthesis ; genetics ; DNA-Binding Proteins ; Female ; Glutathione S-Transferase pi ; Glutathione Transferase ; biosynthesis ; genetics ; Humans ; Isoenzymes ; biosynthesis ; genetics ; Male ; Middle Aged ; Multidrug Resistance-Associated Proteins ; biosynthesis ; genetics ; Neoplasm Proteins ; biosynthesis ; genetics ; Random Allocation ; Tongue Neoplasms ; metabolism ; Vault Ribonucleoprotein Particles ; biosynthesis ; genetics

OBJECTIVETo identify a naturally presented HLA-A2-restricted epitope of MAGE-A3 antigen, FLWGPRALV (MAGE-A3(271 - 279)), on the surface of a human hepatocellular carcinoma (HCC) cell line HLE.

METHODSSynthetic peptide FLWGPRALV, served as positive control target, was analyzed by HPLC and HPLC-ESI-TOF-MSMS, in order to determine its HPLC elution time, mass-spectrometric characteristics and the lowest detection limitation by the two approaches. 3 x 10(9) HLE cells were collected, peptides naturally presented by major histocompatibility complex (MHC) molecules on the cell surface were isolated by mild acid elution, and concentrated by lyophilization, then the mixtures of peptides were fractioned by HPLC. The ingredient ranged from 2 min before the elution time determined by the synthetic peptide to 2 min after that was collected, concentrated by lyophilization, and analyzed by HPLC-ESI-TOF-MSMS, to identify the existence of the MAGE-A3(271 - 279) peptide.

RESULTSThe HPLC-ESI-TOF-MSMS detection provided an evidence for the existence of a doubly charged ion of (m/z)(2) 529.9, which was further analyzed by collision induced dissociation. The doubly charged ion was ultimately identified as the MAGE-A3(271 - 279) peptide, its amino sequence was FLWGPRALV and its molecular weight was 1058.4 Da.

CONCLUSIONSMAGE-A3(271 - 279) epitope could be naturally presented by HLA-A2 molecules to the surface of HCC cell line and MAGE-A3(271 - 279) peptide may have potential immunotherapeutic value in HCC patients.

Amino Acid Sequence ; Antigen Presentation ; Antigens, Neoplasm ; analysis ; isolation & purification ; Carcinoma, Hepatocellular ; immunology ; pathology ; Cell Line, Tumor ; Chromatography, High Pressure Liquid ; Epitopes, T-Lymphocyte ; analysis ; isolation & purification ; HLA-A2 Antigen ; immunology ; Humans ; Liver Neoplasms ; immunology ; pathology ; Mass Spectrometry ; Neoplasm Proteins ; analysis ; isolation & purification

Objective To investigate the effects of vitamin D on synthesis and secretion of lubricin in chondrocytes at the cellular level. Methods Rat articular chondrocytes were stimulated by TNF-α. Normal and inflammatory chondrocytes were treated by different doses of vitamin D respectively. ELISA and Western Blot were used to detect the secretion of lubricin in the supernatant and the synthesis level in the cells. Results TNF-α significantly reduced the activity of both normal chondrocytes and chondrocytes in inflammatory state. TNF-α also significantly reduced the expression of lubricin in the cells and supernatant. 1α,25(OH)2D3 increased the activity of both normal chondrocytes and chondrocytes in inflammatory state. 1α,25(OH)2D3 significantly elevated the secretion and expression of supernatant and intracellular lubricin only in chondrocytes stimulated by TNF-α in a dose-dependent manner, but not in normal chondrocytes. Conclusions Vitamin D can promote the secretion and expression of lubricin in inflammatory state chondrocytes, which may act as one of the mechanisms of vitamin D protecting the cartilage surface in osteoarthritis.

OBJECTIVETo evaluate and compare the clinical efficacy and safety of the highly selective alpha receptor antagonist tamsulosin and its combination with the M receptor antagonist tolterodine in the treatment of refractory lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH).

METHODSWe included in this study 184 BPH patients with refractory LUTS with the disease course of 4 weeks to 2 years, whose LUTS were not alleviated after a week's treatment with tamsulosin. The patients were randomly divided into Groups A and B, the former (n=89) treated with tamsulosin at 0.2 mg qd and the latter (n=95) given tolterodine at 2 mg bid in addition to tamsulosin medication, both for 4 weeks. Scores on IPSS, QOL and Qmax were obtained before and after the treatment, and the improvement of LUTS evaluated after the medication.

RESULTSThe tamsulosin group showed no significant differences before and after the treatment in the scores on IPSS (13.23 +/- 4.39 vs. 12.21 +/- 4.07), QOL (4.23 +/- 1.27 vs 3.53 +/- 0.95) and Qmax ([12.3 +/- 8.39] ml/s vs. [14.1 +/- 8.62] mls) (P > 0.05), while the combination group exhibited significantly higher scores on IPSS and QOL and lower score on Qmax after the medication than before it (IPSS: 14.45 +/- 5.31 vs. 6.56 +/- 2.03, P < 0.05; QOL: 4.45 +/- 0.79 vs. 2.34 +/- 0.73, P < 0.05; Qmax: [11.4 +/- 9.21] ml/s vs. [15.5 +/- 8.35] ml/s, P < 0.01). No severe complications were found in any of the cases.

CONCLUSIONCombination of tamsulosin and tolterodine can significantly alleviate refractory LUTS and improve QOL without causing serious adverse events in BPH patients.

Adrenergic alpha-1 Receptor Antagonists ; therapeutic use ; Aged ; Aged, 80 and over ; Benzhydryl Compounds ; therapeutic use ; Cresols ; therapeutic use ; Humans ; Male ; Middle Aged ; Muscarinic Antagonists ; therapeutic use ; Phenylpropanolamine ; therapeutic use ; Prostatic Hyperplasia ; drug therapy ; Sulfonamides ; therapeutic use ; Tolterodine Tartrate ; Treatment Outcome

Objective:To evaluate the effects of subclinical hypothyroidism during pregnancy treated with LT 4 on the growth and neuropsychology of offspring aged 0-36 months. Methods:A maternal-infant cohort was established in healthy singleton pregnant women aged 20-45 years without history of thyroid disease. Women developing subclinical hypothyroidism during pregnancy were treated with LT4. The weight, length, and head circumference of the offspring were recorded between 0 to 36 months after birth. Meanwhile, infant nutrition and family support were investigated. The Neuropsychological Development Questionnaire of 0-6 year old children was used to evaluate the neurodevelopment of offspring.Results:A total of 186 mother-infant pairs were included. All subjects were divided into the euthyroidism(ETH) group( n=136) and subclinical hypothyroidism(SHT) group( n=50) according to maternal thyroid function during pregnancy. The Z-scores(adjusted by months of age and gender) of weight, length, weight/length at birth, weight/length at 1 month, head circumference at 6 months, length at 8 months, weight/length at 24 months of SHT group were lower than those of the ETH group( P<0.05). Furthermore, the language competence of the SHT offspring at 12 months of age was also lower than that of the ETH group( P<0.05). Maternal subclinical hypothyroidism treated with LT 4 did not significantly affect preterm delivery, low birth weight, and developmental quotient <85, but reduced the risk of macrosomia(AOR 0.206, 95% CI 0.046-0.929, P=0.040). Conclusion:Although women with subclinical hypothyroidism received LT 4 treatment during pregnancy, the offspring still may suffer adverse effects on their growth and neural development.

Objective To investigate the clinical features of IgG4-related autoimmune pancreatitis (IgG4-related AIP).Methods A prospective cohort study on IgG4 related disease (IgG4-RD) was carried out in Peking Union Medical College Hospital during December 2010 to June 2012,a total of 50 patients were recruited,including 14 IgG4-related AIP patients.The clinical manifestations,laboratory tests results,radiographic findings,histopatholo-gical lesions and response to treatment were analyzed.Results Fourteen AIP patients accounted for 28％ of IgG4-RD,of whom 9 cases were male,5 females,with the mean age of (55±10) (range 41-71) years.Painless obstructive jaundice was the major manifestation of AIP.All patients had extra-pancreatic organ involvement,including salivary glands enlargement (10 cases),lymph nodes swollen (7 cases),and bile duct tree (6 cases),lung (6 cases),kidney (2 cases),lacriminal gland (2 cases),retroperitoneal tissue (1 case),mesentery (1 case),and prostate (1 case) involvement.Serum levels of IgG4 subclass in all patients were significantly increased,with mean concentration of (11 ±10) (range 1.4-35.2) g/L.Radiographic findings showed diffuse (13 cases) or focal (1 case) pancreatic enlargement with irregular narrowing of the pancreatic duct (4 cases).Histopathological examinations were performed in 12 patients,which revealed massive infiltration with lymphocytes and IgG4 positive plasma cells with remarkable tissue fibrosis.Response to glucocorticosteroid or combined steroid and immunosuppressants were good.Conclusion IgG4-related AIP is a subtype of chronic pancreatitis,which is characterized by specific clinical spectrum,serological markers,radiographic and histopathological features.Glucocorticosteroid is the first choice,which can significantly improve the clinical and imaging abnormalities.