Combined effects of all-trans-retinoic acid and trichostatin A on the induction of differentiation of thyroid carcinoma cells / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>The effectiveness rate of all-trans-retinoic acid (RA) is only about 30% in the clinical application of inducing thyroid carcinoma differentiation. In addition, there are severe toxic side effects, which limit its clinical application. Phase I-III clinical studies have been conducted on the combined application of two or more kinds of inductors in tumors. Nevertheless, the combination of RA with histone deacetylase inhibitors is rarely reported. This article studied the effects of differentiation for papillary thyroid carcinoma and follicular thyroid carcinoma cell lines induced by RA combined with trichostatin A (TSA), enhancing the effect of induction, while reducing the toxic side effects of a single drug, to provide a theoretical basis for preclinical trials.</p><p><b>METHODS</b>After incubation with RA combined with TSA, K1 and FTC-133 were grouped into Group 1 (RA 10(-4) mol/L plus TSA 1.65 x 10(-7) mol/L), Group 2 (RA 1 x 10(-4) mol/L plus TSA 3.31 x 10(-7) mol/L), Group 3 (RA 10(-5) mol/L plus TSA 1.65 x 10(-7) mol/L), Group 4 (RA 1 x10(-5) mol/L plus TSA 3.31 x 10(-7) mol/L) by four varied concentrations and three time points (12 h, 24 h, and 48 h). The cell proliferation, conformation, toxic effect, and induced differentiation on K1 and FTC-133 cell lines were studied microscopically with hematoxylin-eosin (HE) to observe cell quantity and morphology, methyl-thiazolyl-tetrazolium (MTT) to calculate cell survival rates, and electrochemiluminescence analysis measuring in vitro thyroglobulin (Tg) levels.</p><p><b>RESULTS</b>The research showed that K1 and FTC-133 cells had cell spacing increases, with an outer edge of smooth, nuclear chromatin condensation after RA combined TSA. Survival rate were assessed by an analysis of variance (ANOVA) by concentration and time point, F values of K1 and FTC-133 were 23.52 and 170.14, and 57.09 and 224.35, respectively. There were significant differences for both cells (P < 0.01). The SNK analysis indicated that survival rates were in the order of Group 2 < Group 1 < Group 4 < Group 3. Tg was also assessed by ANOVA, F values of K1 were 69.63 and 101.07, and F values of FTC-133 were 79.77 and 81.72 (P < 0.01). Group 1 was compared with Group 3 of K1 and FTC-133 by the least significant difference (LSD) method, and there was no statistical difference between the two group (P = 0.06, 0.2, respectively; P > 0.05), yet a significant difference was seen between the other Groups.</p><p><b>CONCLUSIONS</b>Lower concentrations of RA combined with lower concentrations of TSA have both inhibited cell proliferation, decreased toxicity of the drugs, and increased the effect of K1 and FTC-133 cell differentiation. The mechanism of action may be that TSA has pretranscription DNA regulation and that RA has posttranscriptional signal regulation to enhance the effects of inhibited proliferation and differentiation of cells by transcription systems.</p>

Dosimetry-guided 131I therapy for differentiated thyroid carcinoma with diffuse pulmonary metastases / 中华核医学杂志

Objective To determine the activities of 131I for treating differentiated thyroid carcinoma with diffuse pulmonary metastases ( DTC-DPM ) from the perspective of internal radiation dosimetry.Methods According to Medical Internal Radiation Dosimetry (MIRD) schema, the activity constraint,from which the whole bdy retention at 48 h should not exceed 2.96 GBq (2.96 GBq rule), was converted to dose-rate constraint(DRC) to lungs at 48 h ( DRCLU ·48 h ) in 131I therapy for DTC-DPM. Based on the assumption of DRCLU·48 h at 48 h in lung, the fractions of whole body activities ( F48 ), the effective half times of 131I in lungs ( TLL ) and the remainder of body ( TRB ) were 0.6-0.9, 20- 120 h, and 10- 20 h, respectively. The maximum safe activities of 131I for different human phantoms from the Organ Level Internal Dose Assessment (OLINDA) software were calculated. Results According to MIRD schema and 2.96 GBq rule, DRCLU ·48 h should not exceed 46.4 mGy/h in 131I therapy for DTC-DPM. Depending on varying F48 h,TLL and TRB, the maximum safe activities of 131I were 6.77-81.36, 5.29-56.20, 5.08-55.19 and 3.87-40. 52 GBq for the male adult, female adult, 15-year-old, and 10-year-old patients with DTC-DPM, respec tively. Conclusion Dosimetry-guided 131I therapy for DTC-DPM considers adequately the differences of 131I kinetics in individual patients and can adjust administered activities of 131I on the precondition of avoiding radiological pneumonitis and pulmonary fibrosis.

Relationship between the management of Graves' disease and the course of Graves' ophthaimopathy:a systematic review / 中华核医学杂志

Objective To perform literature search and review on the controversial relationship between therapies of hyperthyroidism due to Graves'disease(GD)and the course of Graves'ophthalmopathy(CA)).Methods We searched the database of MEDLINE(1966-2006.3),EMBASE(1984-2005),Cochrane Library(2006 No.1),CBMdisc(1978.1-2006.4)and CNKI(1994-2006).The methodological quality of the studies selected for review was assessed according to the quality assessment criteria suggested by the Cochrane systematic review guideline.Meta-analysis was performed by RevMan 4.2 software.Results Eight studies were included in the systematic review.Meta-analysis showed that there was statistically significant difference between 131I and other forms of therapy[surgery or antithyroid drugs(ATD)](test value:2.31,5.97,3.70,5.55;all P＜0.05)in aggravation of exophthalmos and symptom improvement in patients without receiving thyroxine during the early stage to prevent hypothyroidism.However,there was no statisti cally significant differenee in the above relationship between surgery and ATD therapy in those patients already receiving thyroxine supplement(test value:0.27,0.99;all P＞0.05).There were not yet any studies on the impact between early prevention of hypothyroidism after 131I therapy and GO.Conclusions Based on meta-analysis on literature data,if early measures are not performed to prevent hypothyroidism after 131I therapy,it may induce or aggravate GO more frequently than ATD or surgical treatment.Symptomatic relief of GO after 131I therapy is also less effective than the other 2 forms of therapy.Therefore.131I therapy should be delivered carefully in those patients with GO.

Evaluation of thyroglobulin mRNA in peripheral blood of patients with differentiated thyroid carcinoma after remnant ablation / 中华核医学杂志

Objective The aim of this study was to evaluate the diagnostic value of thyroglobulin(Tg)mRNA in peripheral blood samples of patients with differentiated thyroid carcinoma(DTC)after remnant ablation.Methods Tg mRNA Was detected by reverse transcription-polymerase chain reaction(RT-PCR)in peripheral blood of 162 patients.SPSS 13.0 was used for date analysis.Results The Tg mRNA assay had higher sensitivity than the conventional serum Tg measurement[86.61%(97/112)vs 53.57%(60/112),X2=29.153,P＜0.001]which Was the"gold standard"for the identification of recurrence or metastases.In the anti-Tg antibodies(TgAb)positive DTC patients,the sensitivity of Tg mRNA was higher than that of serum Tg[86.54%(45/52)vs 0]in identifying recurrent or metastatic thyroid disease(X2=79.322,P＜0.001).There was a significantly positive correlation between Tg mRNA expression and the clinical stages(Kendall correlation coefficient=0.515,P＜0.001).There was no difference of Tg mRNA expression in peripheral blood among ages,sex,pathological types and location of metastases,respectively(Kendall correlation coefficient=0.020,0.069,0.050 and 0.028;all P＞0.05).Conclusions Circulating Tg mRNA is a more sensitive marker than serum Tg in identifying recurrent or metastatic DTC,particulady in patients during levo-thyroxine(l-T4)therapy and with TgAb-positive.The DTC patients who have positive expression of Tg mRNA indicates poor prognosis.

Construction of the recombinant adenovirus carrying sodium/iodide symporter gene / 生物医学工程学杂志

Human Sodium/Iodide symporter gene cDNA was amplified from thyroid tissue of the patient suffering from Graves disease by RT-PCR, and T/A cloned into pGEM-TEasy-NIS for sequencing, subcloned into shuttle plasmid pAdTrack-CMV which contained a green fluorescent protein (GFP) gene, and then forwarded to homologous recombinant in the bacteria BJ5183 that already contained AdEasy-1 plasmid. Positive recombinant adenovirus vector was selected, packaged and amplified in the 293 cells to obtain recombinant adenovirus. The results showed that the recombinant AdNIS was correctly constructed and confirmed by restriction enzyme analysis and PCR. The viral titer was 2. 5 - 3 x 10(9) efu/ml. So, the recombinant adenovirus vector carrying hNIS was successfully constructed, thus providing a basis for researches on 131I therapy in nonthyroid carcinoma.

Long-term effects and complications of intravascular brachytherapy / 生物医学工程学杂志

Since the introduction of percutaneous transluminal coronary angioplasty, restenosis has remained the most challenging problem facing interventional cardiologist. Intravascular radiation is a feasible and promising adjunctive therapy in restenosis treatment by suppressing both neointimal proliferation and constrictive remodeling, while there are growing concerns about its long-term effects and complications in clinical perspectives as well as dosing and paradoxical stimulation. Current comments on them may well favor the choice of comprehensive treatment protocol for clinicians.

Basic study of dopamine transporter imaging with 131I-beta-CIT / 生物医学工程学杂志

beta-CIT was labeled with 131I by the peracetic acid method. Cat model of Parkinsonism was set up with MPTP. Each of normal and PD model cats was given an injection of 74 MBq/0.5 ml 131I-beta-CIT into the femur vein. Then the blood samples were obtained at 4 h and 20 h, the radioactivity was counted with calibrator. The biodistribution data of 131I-beta-CIT in cat body was calculated (ID%/g). The cats were subjected to imaging at 0.5 h, 1 h, 2 h, 4 h, 20 h after the administration of radiopharmaceutical. The radioactivity in striatum and cerebellum was measured and striatal specific binding ratios were calculated. The Results showed that the radio chemical purity of 131I-beta-CIT was 97.62% +/- 0.31%. The 131I-beta-CIT remained stable for at least 4 h after incubation with water and serum respectively. Following intravenous administration in cats, 131I-beta-CIT showed high accumulation in striatum. The study of imaging in cats showed that striatal specific uptake of 131I-beta-CIT at 20 h after injection was 4.83 +/- 0.82 in normal cats and 2.92 +/- 0.66 in PD cats. There was a significant reduction of striatal tracer uptake in PD cats, compared to the controls. The results of biodistribution study was in agreement with the results of imaging study. These results suggest that beta-CIT is an ideal agent for dopamine transporter imaging and can be used for the diagnosis of Parkinson's disease.

Comparative analysis of outcome of radioiodine and antithyroid medication in treating Graves'disease in children and adolescents:a systematic evaluation / 中华内分泌代谢杂志

Objective To evaluate the difference in efficacy and safety between ~(131)Ⅰand antithyroid drugs (ATD)in the treatment of Graves'disease in children and adolescents.Methods MEDLINE(1966-2005), Cochrane Central Register of Controlled Trials(Cochrane Library Issue 2,2006),EMBASE(1984-2004), CBMDISK(1978-2005)and CNKI(1994-2006)were searched by computer.Isotopes(1989-2004),Radiologia Pratica(1986-2005),Chinese Journal of Endocrinology and Metabolism(1985-2004),and Endocrinology and Metabolism Clinics of North America(1988-2001)were manually searched.Trials comparatively analyzed ~(131)Ⅰand antithyroid drugs on the treatment of Graves'disease in children and adolescents were included.The quality of the study methodologies such as randomization,blinding and allocation concealment was evaluated and meta-analysis was performed by Revman 4.2 software.Results Five non-randomized controlled trials involving 538 patients were included.Among these trials one was prospective and the rest were all retrospective.~(131)Ⅰwas more effective in increasing the complete remission and decreasing the rate of recurrence as compared with ATD,but the rate of hypothyroidism was significantly increased after ~(131)Ⅰtreatment.Conclusion Based on the five studies,the evidence suggests that ~(131)Ⅰtherapy is effective and safe for children and adolescents,and the total curative effects in Graves'disease are superior to ATD.However great shortage of randomized controlled trial(RCT),and problems concerning randomization,blind method,follow-up and statistic analysis still exist in clinical controlled trials, hence more RCT with high quality should be conducted.

Diagnostic value of serum thyroglobulin autoantibody on recurrence and/or metastasis following surgery in patients with differentiated thyroid carcinoma / 中华内分泌代谢杂志

Objective To evaluate the clinical significance of serum thyroglobulin autoantibody(TGAb) in thyroglobulin(TG)-negative and TGAb-positive patients with differentiated thyroid carcinoma(DTC)after thyroid ablation and ascertain the optimal operating point(OOP)of TGAb.Methods A total of 169 patients with histologically confirmed DTC and thyroid remnant ablation showed TG-negative and TGAb-positive results which were assessed by electrochemiluminescence immunoassay(ECLIA).The cases were divided into group A(59 cases)and group B(110 cases)with or without evidence of recurrence or metastasis,respectively.The receiver operating characteristic(ROC)curve and positive likelihood ratio of different threshold values were analysed according to their serum TGAb level.Results Serum TGAb level(1368?1343)IU/ml in group A was significantly higher than that(154?539)IU/ml in group B(P1000 IU/ml was 1.12 times that of 204 IU/ml≤TGAb≤1000 IU/ml,4.03 times that of 100 IU/ml≤TGAb