Caffeine (1,3,7-trimethylxanthine), a central nervous system stimulant, is contained in various foods, beverages and over-the-counter medications. Sulfadimethoxine (SDM) is one of the anti-thyroid agents and induces proliferation of thyroid capsule in two stage thyroid carcinogenesis model using N-bis(2-hydroxypropyl)nitrosamine (DHPN). In this study, we examined the effect of caffeine on fibrous proliferation of thyroid capsule in DHPN and SDM-treated rats. Five-week-old male F344 rats were given a single subcutaneous injection of DHPN (2,800 mg/kg, body weight). Starting one week thereafter, SDM (1,000 ppm in drinking water) with or without caffeine (1,500 ppm in diet) was administered for 12 weeks. All animals were autopsied and histopathological examination of the thyroid glands was performed. Thyroid follicular proliferative changes were induced in all rats treated with DHPN+SDM. In addition, the proliferation of perithyroidal fibrous tissue and pleomorphic thyroid follicular cells within the capsule were observed in DHPN+SDM treated group. Caffeine would not be related to these lesions in this experimental condition. although pentoxifylline, a methyl xanthine derivative, has an anti fibrotic effects.
Wang, Jia-Ni;Xu, Li-Hua;Zeng, Wei-Gen;Hu, Pan;Rabkin, Samuel D.;Liu, Ren-Rin
Asian Pacific Journal of Cancer Prevention
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v.16
no.3
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pp.1241-1245
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2015
Background: Thyroid carcinoma is the most common malignancy of the endocrine organs. Although the majority of thyroid cancer patients experience positive outcomes, anaplastic thyroid carcinoma is considered one of the most aggressive malignancies. Current therapeutic regimens do not confer a significant survival benefit, and new therapies are urgently needed. Oncolytic herpes simplex virus (oHSV) may represent a promising therapy for cancer. In the present study, we investigated the therapeutic effects of a third-generation HSV vector, $G47{\Delta}$, on various human thyroid carcinoma cell lines in vitro. Two subcutaneous (s.c.) models of anaplastic thyroid carcinoma were also established to evaluate the in vivo anti-tumor efficacy of $G47{\Delta}$. Materials and Methods: The human thyroid carcinoma cell line ARO, FRO, WRO, and KAT-5, were infected with $G47{\Delta}$ at different multiplicities of infection (MOIs) in vitro. The survival rates of infected cells were calculated each day. Two s.c. tumor models were established using ARO and FRO cells in Balb/c nude mice, which were intratumorally (i.t.) treated with either $G47{\Delta}$ or mock. Tumor volumes and mouse survival times were documented. Results: $G47{\Delta}$ was highly cytotoxic to different types of thyroid carcinomas. For ARO, FRO, and KAT-5, greater than 30% and 80% of cells were killed at MOI=0.01 and MOI=0.1, respectively on day 5. WRO cells displayed modest sensitivity to $G47{\Delta}$, with only 21% and 38% of cells killed. In the s.c. tumor model, both of the anaplastic thyroid carcinoma cell lines (ARO and FRO) were highly sensitive to $G47{\Delta}$; $G47{\Delta}$ significantly inhibited tumor growth and prolonged the survival of mice bearing s.c. ARO and FRO tumors. Conclusions: The oHSV $G47{\Delta}$ can effectively kill different types of human thyroid carcinomas in vitro. $G47{\Delta}$ significantly inhibited growth of anaplastic thyroid carcinoma in vivo and prolonged animal survival. Therefore, $G47{\Delta}$ may hold great promise for thyroid cancer patients.
Background: Differentiated thyroid cancer (DTC) is a cancer group that shares molecular and cellular origin but shows different clinical courses and prognoses. Several prognostic factors have been reported for predicting recurrence for individual patients. This literature review aimed to evaluate prognostic scores for predicting recurrence of DTC. Materials and Methods: A search of the MEDLINE database for articles published until December 2015 was carried out using the terms "thyroid neoplasms AND (recurrent OR persistent) AND (score OR model OR nomogram)". Studies were eligible for review if they indicated the development of prognostic scoring models, derived from a group of independent prognostic factors, in predicting disease recurrence in DTC patients. Results: Of the 308 articles obtained, five were eligible for evaluation. Two scoring models were developed for DTC including both papillary and follicular carcinoma, one for papillary carcinoma, and the other two for papillary microcarcinoma. The number of patients included in the score development cohort ranged from 59 to 1,669. The number of evaluated potential prognostic factors ranged from 4 to 25. Tumor-related factors were the most common factors included in the final scores, with cervical lymph node metastases being the most common. Only two studies showed internal validation of the derived score. Conclusions: There is a paucity of prognostic scores for predicting disease recurrence in patients with DTC, in particular for follicular thyroid carcinoma. Several limitations of the created scores were found. Performance of the scores has not been adequately studied. Comprehensive validation in multiple cohorts is recommended before widespread use.
This study developed internal dose coefficients for radioiodine, tailored to the Korean population, by incorporating the Korean biokinetic model along with the Korean S values. The observed differences in dose coefficients for Koreans compared to the International Commission on Radiological Protection (ICRP) reference values noticeably varied depending on physical half-lives of iodine isotopes. For longer-lived isotopes such as I-125 and I-129, significant differences in thyroid dose coefficients were observed, with ratios (Korean/ICRP) from 0.30 to 0.55, indicating that actual doses for Koreans can be considerably lower than those evaluated based on the ICRP data. However, for short-lived iodine isotopes, such as I-131, the thyroid dose coefficients were comparable to the ICRP reference values (ratio = 0.95-0.98). These comparable dose coefficients resulted from the lower thyroidal iodine uptake in the Korean model being almost entirely offset by the higher thyroid self-absorption S values in the Korean phantoms. Additionally, this study delves into the substantial differences in absorbed dose coefficients for non-thyroidal regions and effective dose coefficients, which arose not only from physiological/anatomical variability but also technical differences in phantom design. The use of Korean-specific dose coefficients is advisable particularly in scenarios predicting elevated doses, yielding a more precise and clinically relevant dose assessment.
Background: Differentiated thyroid cancer is the most common endocrine malignancy with a generally good prognosis. Knowing long-term outcomes of each patient helps management planning. The study was conducted to develop and validate a clinical prognostic score for predicting disease remission in patients with differentiated thyroid cancer based on patient, tumor and treatment factors. Materials and Methods: A retrospective cohort study of 1,217 differentiated thyroid cancer patients from two tertiary-care hospitals in the Northeast of Thailand was performed. Associations between potential clinical prognostic factors and remission were tested by Cox proportional-hazards analysis in 852 patients (development cohort). The prediction score was created by summation of score points weighted from regression coefficients of independent prognostic factors. Risks of disease remission were estimated and the derived score was then validated in the remaining 365 patients (validation cohort). Results: During the median follow-up time of 58 months, 648 (76.1%) patients in the development cohort had disease remission. Five independent prognostic factors were identified with corresponding score points: duration from thyroid surgery to $^{131}I$ treatment (0.721), distant metastasis at initial diagnosis (0.801), postoperative serum thyroglobulin level (0.535), anti-thyroglobulin antibodies positivity (0.546), and adequacy of serum TSH suppression (0.293). The total risk score for each patient was calculated and three categories of remission probability were proposed: ${\leq}1.628$ points (low risk, 83% remission), 1.629-1.816 points (intermediate risk, 87% remission), and ${\geq}1.817$ points (high risk, 93% remission). The concordance (C-index) was 0.761 (95% CI 0.754-0.767). Conclusions: The clinical prognostic scoring model developed to quantify the probability of disease remission can serve as a useful tool in personalized decision making regarding treatment in differentiated thyroid cancer patients.
Lee, Ji Hye;Koo, Jin Suk;Roh, Seong Soo;Park, Ji Ha;Seo, Bu Il
The Korea Journal of Herbology
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v.34
no.3
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pp.45-53
/
2019
Objectives : In present study, we investigated a therapeutic effect of Astragali Radix on hypothyroidism rat model induced by 6-Propyl-2-thiouracil (PTU). Methods : Six-week-old male Sprague-Dawley rats were divided into five groups : Group one included the normal mice. Group two was administrated PTU. Group three and four were administrated the aqueous extract of Astragali Radix 150 and 300 mg/kg before start of PTU treatment. Group five (Positive control) was administrated with levothyroxine 0.5 mg/kg. During this moment the body weight, liver $H_2O_2$ and catalase (CAT) amount, serum thyroid hormone, serum asparte aminotransferase (AST) and alanine aminotransferase (ALT), gland weights were measured with histopathological changes of thyroid glands. These results were compared with levothyroxine 0.5 mg/kg treated rats. Results : The PTU treatment lead to marked decreases of body weight, level of thyroid hormone in serum and liver CAT activation. Also, PTU treatment increased thyroid gland weight, thyroid gland hormone TSH, liver $H_2O_2$ amount and level of AST in serum. On the other hands, the administration of Astragali Radix extract increased body weight gains and ameliorated histopathological changes of thyroid such as hyperplasia of follicular cells with of follicular colloid contents and sizes. In addition, the administration of Astragali Radix extract increased level of $T_4$ in serum, CAT activation in liver. Moreover, the administration of Astragali Radix extract decreased levels of TSH and AST in serum and $H_2O_2$ amount in liver Conclusions : This study suggests that Astragali Radix extract has therapeutic effects on hypothyroidism via promoting thyroid hormone production.
Kim, Dae-Joong;Han, Beom-Seok;Ahn, Byeong-Woo;Kim, Chang-Ok;Choi, Kwang-Sik;Lee, Joon-Sup
Proceedings of the Korean Society of Applied Pharmacology
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1994.04a
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pp.339-339
/
1994
It has been reported that Indole-3-carbinol (I3C), a naturally occurring compound In cruclferous vegetables, exerts anticarcinogenic activity In several organs In rodents. The modifying effects of I3C were therefore assessed uging a rat multi-organ carcinogenesis model. A total of 100 male Sprague-Dawley rats were divided Into 3 groups. Animals of groups 1 and 2 were sequentially treated with diethylnitrosamine (DEN; 100 mg/kg b.w., i.p.), N-methylnitrosourea (NNU; 20 mg/kg b.w., 4 times for 2 weeks, i.p), and dihydroxy-di-N-propylnitrosauine (DHPN; 0.1% In d.w. for 2 weeks) for 4 weeks (DMD treatment). Animals of groups 1 and 3 were given the diet of 0.25% I3C for 20 weeks after DMD initiation and then were given basal diet for 28 weeks. All animals were sacrificed at week 24 and 52, respectively. I3C has been clearly demonstrated promoting effects on the development of glutathione S-transferase placental form (GST-P) positive hepatic foci at 24 weeks of the experiment. And I3C also exerted promoting potential In the hepatocellular adenoma (4/14; 29%) and the adenoma (7/14; 50%) of the thyroid gland at 52 weeks of the experiment. Therefore, I3C may promote hepatocarcinogenesis and thyroid tumorigenesis in the rat multi-organ carcinogenesis model.
Background: Pax8 and peroxisome proliferator-activated receptor gamma 1 gene (Pax8-$PPAR{\gamma}1$) are important factors in tumors. Several studies have suggested that follicular thyroid cancer may arise from Pax8- $PPAR{\gamma}1$ rearrangement. In order to have a better understanding of the association between Pax8-$PPAR{\gamma}1$ rearrangement and follicular thyroid cancer, we conducted the presenmt meta-analysis. Materials and Methods: The information was extracted from PubMed, EMBASE and Web of Science. Statistic analysis was performed with Stata12.0 software. Odds ratios (ORs) were calculated using a fixed-effects model. We also performed heterogeneity and publication bias analyses. Results: Nine studies including 198 follicular thyroid cancer patients and 268 controls were considered eligible. The frequency of Pax8-$PPAR{\gamma}1$ rearrangement was significantly higher in the follicular thyroid cancer group than in the control group, with a pooled OR of 6.63 (95%CI=3.50-12.7). In addition, through subgroup analysis, the OR between Pax8-$PPAR{\gamma}1$ rearrangement and follicular thyroid cancer was 6.04 (95%CI = 3.18-11.5) when using benign tumor tissues as controls. The OR for the method subgroup was 9.99 (95% CI =4.86-20.5) in the RT-PCR. Conclusions: The final results demonstrated that Pax8-$PPAR{\gamma}1$ rearrangement has significant association with follicular thyroid cancer.
Thyroid hormone(T3) stimulates hepatic lipogenesis by increasing expression of genes, indluding acetyl-CoA carboxylase and fatty acid synthase. S14 protein, which is thougth to be involved in lipid metabolism , appears to respond in parallel . Effect of T3 on lipogenesis in white and brown adipose tissue are less clear, and may be complicated by indirect effects of the hormone. We developed an adipocytes system where the indirect effects of thyroid hormone are abolished and direct effects of T3 on lipogenesis could be tested. Fat accumulation was mesured by Oil-Red O staining. Insulin clearly enhanced fat accumulation by 2-fold . Isobutylemethylxanthie(IBMX) apeared to inhibit insulin -stimulated fat accumulation. Dexamethasone increased insulin-stimulatedfat accumulation about 1.3-fold. confluent adipocytes were cultured in serum-free medium or medium containing 10% fetal calf serum or 10% fetal calf serum stripped of thyroid hormone and lipogenesis, assessed by the incorporation of 3H2O , was measured. Medium without serum or supplemented with T3-depleted serum did not amplify the stimulatory effect of T3 on lipogenesis compared to medium containing 10% fetal calf seru. Dexamethasone alone led to a decrease inlopogenesis of about 50 % in white adipocytes and 25% in brown adipocytes. However, dexamethasone amplified the lipogenic respnse to T3 by about 30% in whit eadipocytes and 60% in brown adipocytes. T3(1$\mu$M) stimulated lipogenesis and acetyl-CoA carboxylase and fatty acid syntase mRNA levels up to 2 -fold in both types of adipocytes. It seems that these adipocytes systems are as useful model to study the effects of hormones on lipogenic gene expression as well as lipogenesis.
Radioiodide uptake in thyroid follicular epithelial cells, mediated by a plasma membrane transporter, sodium iodide symporter (NIS), provides a first step mechanism for thyroid cancer detection by radioiodide injection and effective radioiodide treatment for patients with invasive, recurrent, and/or metastatic thyroid cancers after total thyroidectomy. NIS gene transfer to tumor cells may significantly and specifically enhance internal radioactive accumulation of tumors following radioiodide administration, and result in better tumor control. NIS gene transfers have been successfully performed in a variety of tumor animal models by either plasmid-mediated transfection or virus (adenovirus or retrovirus)-mediated gene delivery. These animal models include nude mice xenografted with human melanoma, glioma, breast cancer or prostate cancer, rats with subcutaneous thyroid tumor implantation, as well as the rat intracranial glioma model. In these animal models, non-invasive imaging of in vivo tumors by gamma camera scintigraphy after radioiodide or technetium injection has been performed successfully, suggesting that the NIS can serve as an imaging reporter gene for gene therapy trials. In addition, the tumor killing effects of I-131, ReO4-188 and At-211 after NIS gene transfer have been demonstrated in in vitro clonogenic assays and in vivo radioiodide therapy studies, suggesting that NIS gene can also serve as a therapeutic agent when combined with radioiodide injection. Better NIS-mediated imaging and tumor treatment by radioiodide requires a more efficient and specific system of gene delivery with better retention of radioiodide in tumor. Results thus far are, however, promising, and suggest that NIS gene transfer followed by radioiodide treatment will allow non-invasive in vivo imaging to assess the outcome of gene therapy and provide a therapeutic strategy for a variety of human diseases.
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