Multifunctional proteglycan, versican, is recently recognized as a gene related to tumor metastasis. Versican may maintain or inhibit cell growth, affect cell adherence and regulate the mutual interaction between cells or cell and matrix. Higher expression of versican always correlates with worse prognosis.

Objective To explore the value of combined detection with MMP-9 and uPA in the progno-sis of pancreatic carcinoma. Methods By immunohistochemistry PV methods,the expression of MMP-9 and uPA was respectively studied in 63 surgical specimens of primary pancreatic carcinoma and the survival time of patients with pancreatic carcinoma was analysed. Results The expressions of MMP-9 and uPA were positively related(r=0. 573,P=0. 000). The expression of MMP-9 and uPA significantly correlated with differentiation (r= -0. 271,P=0. 032;r= -0. 333,P=0. 008),TNM stages(r= -0. 449,P=0. 000;r= -0. 430,P=0. 000)and lymph node metastasis(r=0. 329,P=0. 009;r=0. 400,P=0. 001),separately. The expression of MMP-9 had also a significant correlation with tumer size(r= -0. 297,P=0. 018)and distant metastasis(r=0. 320,P=0. 011). Univariate analysis identified that tumor size(χ2 =8. 766,P=0. 012),differentiation(χ2 =29. 050,P=0. 000),clinical stage(χ2 =24. 940,P=0. 000),distant metastasis(χ2 =12. 846,P=0. 000), lymph node metastasis(χ2 =15. 457,P=0. 000),MMP-9(χ2 =32. 700,P=0. 000)and uPA(χ2 =41. 495,P=0. 000)were significantly associated with prognosis. Kaplan-Meier survival analysis showed that 1-year survival rate of patients with MMP-9 ( -),uPA ( -)were significantly longer than that of the patients with MMP-9( ﹢),uPA( ﹢),respectively(χ2 =32. 700,P=0. 000;χ2 =41. 495,P=0. 000);1-year survival rate of patients with MMP-9( -)/uPA( -)was significantly longer than the others( Log-rank test,χ2 = 54. 892, P=0. 000). COX regression revealed that differentiation(RR=2. 315,P=0. 004),clinical stage(RR=1. 694, P=0. 002),MMP-9(RR=0. 165,P=0. 000)and uPA(RR=0. 244,P=0. 007)was independent prognostic factors in pancreatic carcinoma. Conclusion They may have a synergistic function in the the process of growth and invasion in pancreatic cancer between MMP-9 and uPA,and the posssible mechanism is that uPA activate degradation of MMP-9,which is not favorable to prognosis. Combined analysis of MMP-9 and uPA may lead to a more reliable prognostic estimation,as the beneficial supplement of the differentiation,and clinical stage to judge the prognosis of pancreatic cancer.

Objective To study the expressions of S100A4 and urokinase plasminogen activator(uPA) in pancreatic cancer cells and their correlation with patients prognosis.Methods The expressions of S100A4 and uPA were examined in 63 surgical specimens of primary pancreatic carcinoma by suing immunohistochemistry PV methods,and correlation of their expressions and prognosis of pancreatic cancer was analyzed.Results ( 1 ) Positive immunostaining for S100A4 and uPA was observed in 74.6％ (47 cases) and 65.1％ (44 cases) of 63 pancreatic cancer samples respectively.(2) The positive expressions of S100A4 and uPA were significantly correlated in pancreatic cancer( P =0.000,r =0.567 ).( 3 ) The expression of S100A4 significantly correlated with TNM stages( P =0.002 ),lymph node metastasis ( P =0.002 ) and distant metastasis ( P =0.007 ).The expression of uPA had a significant correlation with TNM stages ( P =0.002),lymph node metastasis ( P =0.001 )and differentiation(P =0.003).(4) Kaplan-Meier survival analysis showed that the median survival (21 months) of patients with S100A4 ( - ) was significantly longer than the median survival ( 9 months) of the patients with S100A4( + )(P=0.000) ;the median survival(9 months) of patients with uPA( + ) was significantly shorter than the median survival ( 18 months) of the patients with uPA ( - ) ( P =0.000) ; the median survival(23 months)of 13 patients with S100A4( - )/uPA( - )was significantly longer than the median survival of other cases ( Log-rank test,x2 =54.444,P =0.000).( 5 ) Cox regression model ( x2 =53.974,P =0.000 )analysis suggested:the differentiation(P =0.004),lymph node metastasis(P =0.017) 、S100A4( + ) expression ( P =0.000) and uPA ( + ) expression ( P =0.001 ) were independent prognostic factors for pancreatic cancer.Conclusion S100A4 and uPA are highly expressed in pancreatic cancer cells,and S100A4 expression has positive correlation with uPA expression,which indicates that the overexpression of S100A4 and uPA maybe poor prognosis factors for pancreatic cancer patients.S100A4 maybe promote extracellular matrix and basement membrane degradation by up-regulation of uPA protein expression,and ultimately promote tumor invasion and metastasis,which is not favorable to prognosis.They may be potential indicators of metastasis and predictors for prognosis of pancreatic cancer.

Animals ; Apoptosis ; Endotoxins/toxicity* ; Heart/drug effects* ; MAP Kinase Signaling System ; Myocardium/pathology* ; Rats ; Rats, Wistar ; Receptors, Calcium-Sensing/metabolism*

OBJECTIVETo report on clinical, genetic and molecular characterization of two Chinese families with Leber's hereditary optic neuropathy.

METHODSOphthalmological examinations have revealed variable severity and age at onset of visual loss among the probands and other matrilineal relatives of both families. The entire mitochondrial genome of the two probands was amplified with PCR in 24 overlapping fragments using sets of oligonucleotide primers.

RESULTSThe ophthalmological examinations showed that penetrance was 12.5% and 30.0% respectively in the two families. Sequence analysis of the complete mitochondrial genomes in these pedigrees has identified unreported homoplasmic T8821G mutation in the ATPase 6 gene and distinct sets of polymorphisms belonging to haplogroups M10a. The T8821G mutation has occurred at the extremely conserved nucleotide (conventional position 99) of the ATPase6. Thus, this mutation may alter structural formation of ATPase6, thereby leading to failure in the synthesis of ATP involved in visual impairment.

CONCLUSIONAbove observations have suggested that the ATPase6 T8821G mutation may be involved in the pathogenesis of optic neuropathy in these families.

Adolescent ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; DNA, Mitochondrial ; genetics ; Female ; Humans ; Male ; Mitochondrial Proton-Translocating ATPases ; genetics ; Molecular Sequence Data ; Optic Atrophy, Hereditary, Leber ; enzymology ; genetics ; Pedigree ; Point Mutation ; Young Adult

Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancer, with a 5-year survival rate of less than 15%-19%, and more than 80% of the patients with lung cancer have progressed to advanced stage (Stage IIIb-IV) when they are clearly diagnosed. The comprehensive treatment mainly based on chemotherapy as the primary form is now considered as the major therapy method for advanced NSCLC without actionable driver gene mutations. Pemetrexed plus platinum doublet as well as single-agent pemetrexed are respectively the first-line major regimens recommended by guidelines and the second-line optional regimens. Yet the third-line treatment or beyond in advanced NSCLC is not evidence-based but conducted based on patients' previous medications, which is one of the most commonly used clinical methods. As pemetrexed is a multi-target chemotherapy drug with high efficiency but low toxicity, pemetrexed re-challenge strategy in advanced NSCLC is also a reasonable choice. We report one effective individual case that adopted pemetrexed re-challenge strategy in advanced NSCLC for three times, and at the same time conduct the relevant literature review.
Carcinoma, Non-Small-Cell Lung ; diagnostic imaging ; drug therapy ; Female ; Humans ; Lung Neoplasms ; diagnostic imaging ; drug therapy ; Middle Aged ; Pemetrexed ; administration & dosage ; Positron Emission Tomography Computed Tomography