Analysis of the clinical factors affecting excellent response of Iodine-131 treatment for pulmonary metastases from differentiated thyroid cancer.

Background: Iodiene-131 (131I) treatment is the primary therapeutic approach for imaging 131I-avid pulmonary metastases. The response to radioiodine (RAI) treatment is an important prognostic factor in patients with pulmonary metastases from differentiated thyroid cancer (DTC). Patients who achieve an excellent response (ER) to 131I treatment show significantly reduced disease-related mortality. This study aimed to retrospectively analyse the clinical data and therapeutic effects of 131I treatment in patients with DTC and pulmonary metastases and to screen out the clinical factors affecting ER. Materials and methods: The study included a total of 75 patients with exclusively Iodine-131 avid (131I-avid) pulmonary metastases who underwent 131I treatment. Relevant clinical data for these patients were collected. Following treatment, the status of DTC metastatic lesions was categorized as follows: excellent response (ER), biochemical incomplete response (BIR), structural incomplete response (SIR), or indeterminate response (IDR). Gender, age at diagnosis, pathological type, stages (TNM), stimulated thyroglobulin (sTg) value before initial 131I treatment, metastatic nodule size, and type of post-treatment whole body scan (Rx-WBS) were recorded. Mono-factor analysis and binary logistic regression analyses were used to identify the factors that might affect the ER in DTC pulmonary metastases. The receiver operating characteristic (ROC) curve of the sTg value was used to predict the ER of 131I treatment. Results: All 75 patients with exclusively 131I-avid pulmonary metastases received 131I treatment and underwent follow-up. Out of the 75 patients, 26 achieved ER, resulting in an excellent response rate of 34.7 % (26/75). Among them, 25 (25/26, 96.2 %) achieved an ER after undergoing two rounds of 131I treatment. Binary logistic regression analysis showed that the factors influencing DTC pulmonary metastases excellent response were lower sTg levels [odds ratio (OR) = 0.998, P < 0.001], micronodular metastases (OR = 0.349, P = 0.001) and focal distribution on Rx-WBS imaging (OR = 0.113, P = 0.001). The area under the ROC curve for sTg value predicting ER was 0.876, and the cut-off value was 26.84 ng/mL, with a sensitivity and specificity of 87.9 % and 80.3 %, respectively. Conclusions: 131I treatment is effective for 131I-avid pulmonary metastases of DTC. Some patients who underwent 131I treatment achieved ER. Most patients with ER were obtained after two rounds of 131I treatments. Patients with sTg values before initial 131I treatment lower than 26.84 ng/mL, micronodular metastases, and focal distribution on Rx-WBS imaging were more likely to achieve ER.

Silencing circ_0000644 inhibits papillary thyroid cancer cell malignancy by combining with miR-671-5p to release the inhibition on ANXA2.

BACKGROUND: Papillary thyroid cancer (PTC) is life-threatening due to its malignant progression. Considerable evidence demonstrates that circular RNA (circRNA) regulates PTC development. This study aims to explore the mechanism of circ_0000644 modulating PTC malignant progression. METHODS: The RNA levels of circ_0000644, microRNA-671-5p (miR-671-5p) and annexin A2 (ANXA2) were detected by quantitative real-time polymerase chain reaction. Western blot was performed to check protein expression. Cell proliferation and cell apoptosis were investigated by 5-ethynyl-29-deoxyuridine and flow cytometry. Angiogenic capacity, migration and invasion were analyzed by tube formation assay and transwell assay. The interaction between miR-671-5p and circ_0000644 or ANXA2 was identified by dual-luciferase reporter assay. Xenograft mouse model assay was performed to analyze the effect of circ_0000644 on tumor formation in vivo. RESULTS: Circ_0000644 and ANXA2 expression was significantly upregulated, while miR-671-5p was downregulated in PTC tissues and cells when compared with control groups. Circ_0000644 knockdown inhibited PTC cell proliferation, tube formation, migration, and invasion, but induced apoptosis in vitro. Moreover, circ_0000644 knockdown led to delayed tumorigenesis in vivo. In addition, circ_0000644 acted as a miR-671-5p sponge and mediated PTC cell tumor properties through miR-671-5p. ANXA2 was identified as a target gene of miR-671-5p, and its overexpression relieved miR-671-5p-induced effects in PTC cells. Furthermore, circ_0000644 depletion inhibited ANXA2 production by combining with miR-671-5p. CONCLUSION: Circ_0000644 depletion repressed PTC cell tumor properties through the miR-671-5p/ANXA2 axis.

Tumor-initiating cells contribute to radiation resistance in primary human renal clear cell carcinomas by activating the DNA damage checkpoint response.

The use of radiotherapy in patients with clear cell renal carcinoma (ccRCC) is predominantly limited to palliation of metastases or control of local growth, because ccRCC cells readily develop radioresistance. The mechanisms underlying ccRCC resistance remain elusive. The present study demonstrated that ccRCC cells that survive fractionated radiation treatment display tumor-initiating cell (TIC) characteristics, such as high self-renewal and tumorigenic capacities, and overexpress stemness genes. ccRCC cells that survived fractionated radiation exhibited increased activation of the DNA damage checkpoint response and G2/M phase arrest compared with sham-irradiated cells. The results of the present study suggest that ionizing radiation destroys the bulk of tumor cells within ccRCC, but spares TICs; this subpopulation confers ccRCC radioresistance and may cause tumor recurrence or relapse following radiotherapy. Furthermore, these findings indicate that the DNA damage checkpoint response may serve as a potential therapeutic target for overcoming resistance of TICs in patients with ccRCC.

Preliminary study of brain glucose metabolism changes in patients with lung cancer of different histological types.

BACKGROUND: Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors. This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types. METHODS: One hundred and twenty patients with primary untreated lung cancer, who visited People's Hospital of Zhengzhou University from February 2012 to July 2013, were divided into three groups based on histological types confirmed by biopsy or surgical pathology, which included adenocarcinoma (52 cases), squamous cell carcinoma (43 cases), and small-cell carcinoma (25 cases). The whole body 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) of these cases was retrospectively studied. The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM) software, with 50 age-matched and gender-matched healthy controls for comparison. RESULTS: The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction. The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal, bilateral superior and middle temporal and inferior and middle temporal gyrus. Besides, the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group. The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255) was larger than those in the adenocarcinoma group (total voxel value 1217) and squamous cell carcinoma group (total voxel value 1292). CONCLUSIONS: The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.

Endoplasmic reticulum stress protects human thyroid carcinoma cell lines against ionizing radiation-induced apoptosis.

Radiotherapy is one of the most effective forms of cancer treatment, used in the treatment of a number of malignant tumors. However, the resistance of tumor cells to ionizing radiation remains a major therapeutic problem and the critical mechanisms determining radiation resistance are poorly defined. In the present study, a cellular endoplasmic reticulum (ER) stress microenvironment was established through the pretreatment of cultured thyroid cancer cells with tunicamycin (TM) and thapsigargin (TG), in order to mimic the ER stress response in a tumor microenvironment. This microenviroment was confirmed through the X­box binding protein 1 splice process, glucose­regulated protein 78 kD and ER degradation­enhancing α­mannosidase­like mRNA expression. A clonogenic assay was used to measure cancer cell resistance to 60Co­Î³ following TM pretreatment; in addition, human C/EBP homologous protein (CHOP) mRNA expression was determined and apoptosis assays were performed. The results showed that TM or TG pretreatment inhibited CHOP expression and reduced the apoptotic rate of cells. Furthermore, the results demonstrated that the induced ER stress response rendered cancer cells more resistant to ionizing radiation­induced apoptosis. Therefore, the ER stress pathway may be a potential therapeutic target in order to improve the clinical efficiency of radiotherapy.

Thyroid tumor-initiating cells: increasing evidence and opportunities for anticancer therapy (review).

Accumulating evidence supports the notion that thyroid cancer is initiated by tumor-initiating cells (TICs) (commonly known as cancer stem cells), which are thought to play a crucial role in malignant progression, therapeutic resistance and recurrence. Thyroid TICs have been isolated and identified using specific biomarkers (such as CD133), the side population, sphere formation and aldehyde dehydrogenase activity assays. Although their characteristics remain largely unknown, TICs provide an attractive cellular mechanism to explain therapeutic refractoriness. Efforts are currently being directed toward the identification of therapeutic strategies that could target these cells. The present review discusses the cellular origins of TICs and the main approaches used to isolate and identify thyroid TICs, with a focus on the remaining challenges and opportunities for anticancer therapy.

[Comparative study on the efficacy of intracoronary infusion with various types of autologous bone marrow stem cells for patients with dilated cardiomyopathy].

OBJECTIVE: To compare the effects of intracoronary infusion of mononuclear stem cells (MNCs) or mesenchymal stem cells (MSCs) in patients with dilated cardiomyopathy (DCM). METHODS: DCM patients with left ventricular ejection fraction(LVEF) < 40% were randomized to intracoronary infusion of MNCs [(5.1 ± 2.0) × 10(8), n = 16] or MSCs [(4.9 ± 1.7) × 10(8), n = 17] or equal volume normal saline (n = 20) through the guiding catheter. Changes of left ventricular end-diastolic diameter (LVEDd), LVEF and myocardium perfusion defects were assessed before and at (30 ± 3) days and (90 ± 7) days after the procedure. Malignant cardiovascular events were also recorded. RESULTS: (1) One month after the procedure, LVEF in transplantation groups significantly increased compared to before procedure (all P < 0.05), and significant increase of LVEF was observed only in MSCs transplantation group compared to control group (P < 0.05). However, absolute changes of LVEDd and perfusion defects of myocardium were similar among and within groups (P > 0.05). (2) Comparing with before procedure and control group, LVEF in transplantation groups increased significantly in three months after the procedure (P < 0.05), but there were no significant differences between transplantation groups (P > 0.05). LVEDd and myocardium perfusion defects in transplantation groups improved significantly compared with that of before procedure (P < 0.05), while significant decrease of myocardium perfusion defects was only observed in patients treated with MSCs compared with control group at three months after procedure (P < 0.05). (3) There were no significant differences in major cardiovascular events between transplantation group and control during follow-up (P > 0.05). CONCLUSIONS: Intracoronary bone marrow stem cells transplantation is safe and effective for DCM patients while the efficacy of MSCs and MNCs transplantation is comparable.