China ; Clinical Trials as Topic ; methods ; Humans ; Organizational Policy ; Publishing ; standards ; Registries

Objective To report the clinical outcome and prognostic factors for locally recurrent nasopharyngeal carcinoma(NPC)treated with intensity modulated radiotherapy(IMRT).Methods From January 2001 to August 2004,the data of 132 such NPC patients were analyzed retrospectively;104 male and 28 female with a median of 44.5 years(range 21-73 years).Ninety-eight patients(74.2%)were confirmed by biopsy as having NPC:9 with WHO TypeⅡand 89 WHO TypeⅢ.The other 34 patients were only diagnosed by MRI scan because of the extension/invasion was in the base of skull and/or cavernous sinus.Median interval time were 24 months(range 6-184 months).According to the 1992 Chinese Fuzhou Staging System:stageⅠ3.8 %,Ⅱ10.6 %,Ⅲ22.0% andⅣa 63.6%;T1 5.3%,T2 10.6%,T3 22.7% and T4 55.3%.Twenty-two patients had recurrence in the neck lymph nodes.IMRT was given with the sequential tomotherapy system(NOMOS Peacock systems)of 6 MV X-rays.Prescription dose was 60-70 Gy in GTV,with the fractional dose of 1.94-2.8 Gy.Sixty patients were also supplemented with two to six courses of cisplatin-based chemotherapy.Results The median volume of GTV was 39.5 cm~3(range 0.8-158.9 cm~3).The D95,V95,mean dose and fractionation dose of GTV was 66.9 Gy,98.3%,69.8 Gy and 2.32 Gy,respectively.The median follow-up time was 12 months(range,2-47 months).The 1-,2-and 3-year local progression-free rate was 96.4%,88.4% and 85.3%,respectively.The overall 1-,2-and 3-year survival rate was 6.5.9%,49.6% and 41.6%,respectively.Eleven patients developed distant metastases.Forty-seven patients were observed to devdop mucosa necrosis and/or massive hemorrhage in the nasopharynx.On univariate and multivariate analysis,fractional dose and vohane of GTV were significant prognostic factors for overall survival(P=0.016,0.009).Conclusions The local control and survival rate can be improved for patients with locally recurrent nasopharygeal carcinoma after treatment of intensity modulated radiotherapy.The fractional dose and volume of GTV are independent prognostic factors for the overall survival. The main death reasons are mucosa necrosis and/or massive hemorrhage in the nasopharynx.

OBJECTIVETo assess the association of male infertility with CAG repeat polymorphism of the androgen receptor (AR) gene by meta-analysis.

METHODSWe identified the case-control studies on the relationship of male infertility with CAG repeats of the AR gene by searching Medline/PubMed and CBM databases, and conducted meta-analysis on the data obtained with the RevMan 4.2 software.

RESULTSThirty-two eligible articles were selected in this study, including 3,153 idiopathic infertile men and 2,314 controls. The combined data statistics showed that all the infertile men had a significantly higher mean of CAG repeats than the controls (SMD = 0.27, 95% CI: 0.17-0.37, P < 0.01). The specific SMD between the infertile patients and controls was 0.29, 95% CI: 0.08-0.50 for the azoospermic men, 0.27, 95% CI: 0.13-0.41 for the moderate oligozoospermic men, and 0.18, 95% CI: 0.02-0.33 for the severe oligozoospermic cases. The results of sensitivity analyses were consistent with those mentioned above.

CONCLUSIONThe increased length of CAG repeats in the AR gene may be correlated with the risk of the impairment of spermatogenesis.

Humans ; Infertility, Male ; etiology ; genetics ; Male ; Polymorphism, Genetic ; Receptors, Androgen ; genetics ; Trinucleotide Repeats

Objective To analyse the preliminary clinical results of intensity modulated radiation therapy (IMRT) for 122 untreated nasopharyngeal carcinoma (NPC)pafients.Methods 122 NPC pa- tients received IMRT alone from Feb.2001 to Jun.2004,with 31 females and 91 males,and a median age of 45 years(range 25-66).According to the Fuzhou Stage Classification,there were StageⅠ11 patients, StageⅡ34,StageⅢ62,and StageⅣa 15.IMRT was carried out using an inverse planning system (COR- VUS 5.0,Peacock plan) developed by the NOMOS Corp.The treatment was given with the Multi-leaf Inten- sity Modulating Collimator (MIMIC) using a slice-by-slice arc rotation approach.The prescription dose was 68 Gy/30f to the nasopharynx gross tumor volume (GTV_(nx)),60-66 Gy/30f to positive neck lymph nodes (GTV_(nd)),60 Gy/30f to the first clinical target volume (CTV_1) and 54 Gy/30f to the second clinical target volume (CTV_2).Kaplan-Meier method was used to calculate the overall survival rate (OS),distant metas- tasis-free survival rates (DMFS),and local-regional control rates from the last date of therapy.Log-rank test was used to detect the difference between groups.Results The median follow-up time was 20 months ( range 6 to46 months).The 1-,2-,and 3-year OS was 95.2%,91.4%,85.1%,DMFS was 91.9%, 88.6%,85.6%,and the local-regional control rates was 96.5%,93.2%,93.2%,respectively.Statistics of the local control rate was insignificant either for advanced T(T3+T4) stage or early T(T1+T2) stage diseases(P=0.148).The 2-year regional control rate was insignificant either for patients with N(+) or N (-),but the 2-year DMFS was significant both for patients with N(+) and N(-)lesions(P=0.004).For 17 patients who failed,there were two with residual disease and one with recurrence at the primary site (17.6%),three patients in the neck (17.6%),twelve patients (70.6%) in distant metastases.Conclu- sions Intensity modulated radiation therapy does provide excellent local-regional control for untreated NPC, especially in patients with advanced T stage or N(+) lesion.Distant metastasis is the main cause of failure. N (+) is significantly correlated with distant metastasis.

OBJECTIVETo study the prevalence and clinical characteristics of the A to G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene in familial diabetes in Shanghai, Jiangsu and Zhejiang Province of China.

METHODSThe mt3243 A to G mutation in 770 randomly selected, unrelated probands of diabetic pedigrees were screened by PCR-RFLP technique and PCR-direct sequencing. Genetic and clinical analyses were further performed in the probands and their family members.

RESULTSThirteen diabetic patients (13/770, 1.69%) with mt3243 A to G mutation were detected. Eleven diabetic patients and 8 normal glucose tolerance (NGT) first-degree relatives of these 13 probands were also found bearing the mutation. Seventeen patients were associated with sensory hearing loss. In the 24 patients harboring the mutation, the majority had lower body mass index (BMI), 18 showed typical maternal inheritance, 15 had sensory hearing loss, 13 had insulin resistance and 14 required insulin therapy due to secondary failure to oral hypoglycemic agents.

CONCLUSIONThe mutation of mt3243 A to G in the mitochondrial tRNA(Leu(UUR)) gene is an important cause of diabetes in Shanghai, Jiangsu and Zhejiang Province of China. Mitochondrial gene mutation diabetes (MDM) is clinically characterized by early onset, emaciation, maternal inheritance, sensorineural hearing loss, and lower islet beta cell function, and some have insulin resistance.

Asian Continental Ancestry Group ; genetics ; China ; epidemiology ; DNA, Mitochondrial ; genetics ; Deafness ; genetics ; Diabetes Mellitus ; genetics ; Genetic Testing ; Hearing Loss, Sensorineural ; genetics ; Humans ; Insulin Resistance ; genetics ; Molecular Sequence Data ; Mutation ; Prevalence ; RNA, Transfer, Amino Acyl ; genetics

Objective：The aim of this study was to evaluate radiation induced temporomandibular joint damage in the patients with nasopharyngeal carcinoma, and its correlative factors were analyzed. Methods： From November 7, 1966 to July 2, 1999, 352 patients with nasopharyngeal carcinoma received radical conventional radiotherapy were eligible for this analysis. The total dose of the temporomandibular joint were 51.90－ 78.89 gray and the overall treatment time were 35－ 141 days. The endpoint was the distance between two dens incisivus medialis (DDIM). The relationship between total doses and temporomandibular joint lesion was illustrated with curve estimation. Multivariate analysis with Logistic Regress was performed to evaluate the significance of prognostic variables on temporomandibular joint lesion. Results： The patient of DDIM60.00－ 70.00 gray, and >70.00－ 78.89 gray were 46.4％ , 53.5％ , and 62.3％ , respectively (P=0.050); and in the patients who insisted in opening mouths practice or not were 51.6％ and 61.7％ respectively (P=0.028); and in patients at age of 18－ 42 and 43－ 71 were 54.1％ and 62.7％ respectively(P=0.040). They were all significant prognostic factors for radiation induced temporomandibular joint lesion. Conclusion： Radiation induced temporomandibular joint lesion in radiation treated NPC patients was serious. The total dose of temporomandibular joint, opening mouths practice and age are three significant prognostic factors.

Antibodies, Viral ; blood ; China ; epidemiology ; Female ; Humans ; Immunoglobulin G ; blood ; Male ; SARS Virus ; immunology ; isolation & purification ; Seroepidemiologic Studies ; Severe Acute Respiratory Syndrome ; epidemiology ; virology

OBJECTIVETo investigate the genetic and clinical features of mutations and sequence variations of the transcription factor 1 gene (TCF1, HNF-1A) in Chinese with familial early-onset and/or multiplex diabetes mellitus.

METHODSAll ten exons of the TCF1 gene were screened, including exon and intron junctions, by direct sequencing method in 341 unrelated Chinese subjects, including 80 healthy controls and 261 probands of early-onset and/or multiplex diabetes pedigrees.

RESULTSFive mutations were found in all. Four of the 5 different TCF1 mutations were newly identified novel mutations(T82M, Q130H, G253G, P353fsdelACGGGCCTGGAGC), mean body mass index of mutation carriers was 21.9 kg/m (2), and insulin secretion was impaired in the mutation carriers. In this study, the maturity-onset diabetes of the young type III (MODY3) only accounted for 3% of Chinese early-onset diabetes. Moreover, eleven substitutions were identified in 261 probands. Of them, three variants IVS1-8 (G-->A), IVS1 -128 (T-->G ) and IVS2+21 (G-->A) were not observed in 80 healthy controls and one of them IVS1-8 (G-->A) was not reported previously and the two promoter variants co-segregated with diabetes.

CONCLUSIONTCF1 gene is not a common cause of early-onset and/or multiplex diabetes among Chinese patients.

Adult ; Asian Continental Ancestry Group ; genetics ; China ; Diabetes Mellitus ; ethnology ; genetics ; pathology ; Female ; Gene Frequency ; Genotype ; Hepatocyte Nuclear Factor 1-alpha ; genetics ; Humans ; Male ; Mutation ; Polymerase Chain Reaction

OBJECTIVETo study the effect of overexpression of Smad7 gene on cell proliferation in human bronchial epithelial cell lines.

METHODSHuman bronchial epithelial cell lines, BEP2D and BERP35T2 cells, were cotransfected with the mammalian expression vectors PCISmad7.neo and pMyc-SEAP, the latter was ac-myc cis-acting enhancer element fused with alkaline phosphatase (SEAP) reporter gene. Expression of c-myc, p15 and p21 mRNA was detected by RT-PCR before and after stable transfection of Smad7 into BEP2D and BERP35T2 cells in order to study the regulation of TGF-beta-mediated growth inhibition.

RESULTSAfter BEP2D and BERP35T2 cells transfected with Smad7, the transcriptional activity of c-myc was significantly increased. Smad7 overexpressing cells showed upregulation of c-myc expression and downregulation of p15 and p21 expression, which contributed to the loss of TGF-beta responses in these cells.

CONCLUSIONOverexpression of Smad7 may facilitate cell proliferation by antagonizing TGF-beta-mediated antiproliferative gene responses.

Bronchi ; cytology ; Cell Proliferation ; Cell Transformation, Neoplastic ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p15 ; biosynthesis ; genetics ; Cyclin-Dependent Kinase Inhibitor p21 ; biosynthesis ; genetics ; Epithelial Cells ; cytology ; Humans ; Proto-Oncogene Proteins c-myc ; biosynthesis ; genetics ; Signal Transduction ; Smad7 Protein ; biosynthesis ; genetics ; Transfection ; Transforming Growth Factor beta ; biosynthesis ; genetics

OBJECTIVETo analyze the factors affecting pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients.

METHODSA retrospective cohort study was carried out to analyze the clinical data of 141 breast cancer patients treated with neoadjuvant chemotherapy. The factors affecting pCR and the changes of tumor receptor status before and after treatment were analyzed.

RESULTSAmong all the 141 patients, 21 patients (14.9%) achieved pCR. The rate of pCR achieved by regimens of anthracycline combined with taxane was higher (16.8%, 19/113) than that by anthracycline-containing regimens (7.1%, 1/14). The dose intensity of anthracycline had a significant correlation with pCR rate (P < 0.05). The pCR rate in the relative dose intensity of taxane ≥ 0.85 arm was higher than that of < 0.85 arm (P = 0.02). Eighty patients (56.7%) had completed more than 4 cycles of chemotherapy and the median time to achieve pCR was 6 (3 to 10) cycles. The pCR rate had a significant difference between patients < 6 and ≥ 6 cycles (7.1% vs. 22.5%,P = 0.01). Multivariate analysis showed that tumor size measured by palpation ≤ 5 cm and ≥ 6 chemotherapy cycles were significantly related with pCR rate (P < 0.05). In all the 21 pCR patients, the pre-treatment ER(-), PR(-), HER-2(-) statuses were in 14, 14 and 17 patients, respectively. The status of ER, PR, HER-2 of most patients (74.2%, 69.7% and 87.7%, respectively) was not changed after treatment. Among the patients with changes in receptor status, ER changed from negative to positive was in the majority (37.1%, 13/35 vs. 12.9%, 4/31, P < 0.05), and the percentage of changes in PR and HER-2 status had no significant differences.

CONCLUSIONSThe regimens of anthracycline combined with taxane can achieve a higher pCR rate. The lymph node and receptor status before therapy have no significant correlation with pCR. Patients who have primary tumor size ≤ 5 cm, ≥ 6 chemotherapy cycles and enough dose intensity are easier to achieve pCR. The receptor status before and after therapy should be determined, and according to any positive results, physicians can chose HER-2 targeted therapy and/or endocrine therapy after surgery to benefit the patients.

Adult ; Aged ; Aged, 80 and over ; Anthracyclines ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Bridged-Ring Compounds ; administration & dosage ; Chemotherapy, Adjuvant ; Dose-Response Relationship, Drug ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoadjuvant Therapy ; methods ; Proportional Hazards Models ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Remission Induction ; Retrospective Studies ; Taxoids ; administration & dosage ; Tumor Burden