Retrospective Analysis of Thyroid Nodules: Thyroid Cancer Risk Factors in Suzhou, China.

BACKGROUND: Thyroid nodules are common, frequently discovered in clinical practice and the incidence has increased in recent decades. They are clinically important primarily due to their malignant potential, because 2 to 5% are malignant. Correct identification of the malignancy in thyroid nodules is a diagnostic challenge, leading to potentially unnecessary surgery in patients for whom final histology is benign. Because there is no accurate preoperative detection, it is very important to predict the risk of malignancy in patients with nodular thyroid disease. METHODS: The medical records of 405 patients who underwent surgery for nodular thyroid disease were retrospectively reviewed. Then clinical parameters and preoperative serum markers were compared between benign thyroid nodular disease and thyroid cancer groups. RESULTS: Younger than 40 years (OR 2.14, 95% CI 1.02 - 4.47, p = 0.044), preoperative TSH levels equal to or higher than 1.79 mIU/L (OR 1.76, 95% CI 1.05 - 2.95, p = 0.033), TgAb positivity (OR 2.59 95% CI 1.25 - 5.37, p = 0.01) and nodules less than or equal to 1 cm (OR 5.51, 95% CI 2.61 - 11.66, p < 0.001) were associated with increased risk of thyroid cancer in patients with thyroid nodules. CONCLUSIONS: The retrospective analysis suggests that younger patients with nodular thyroid disease cannot ignore the small size nodules, especially those with higher TSH levels and TgAb positivity.

Biological effects of irradiating hepatocellular carcinoma cells by internal exposure with 125I-labeled 5-iodo-2'-deoxyuridine-chitosan drug loading nanoparticles.

In this study, the authors evaluate the biological effects of irradiation of hepatocellular carcinoma cells by internal exposure with (125)I-labeled 5-iodo-2'-deoxyuridine ((125)I-UdR)-chitosan drug loading nanoparticles ((125)I-UdR-CS-DLN). The authors observed that accumulation of nanoparticles was significantly (p<0.05) higher in hepatocellular carcinoma cells HepG2 than normal liver cells HL-7702 after treated with (125)I-UdR-CS-DLN for 30 minutes. Survival of HepG2 cells was significantly lower at (125)I-UdR-CS-DLN doses higher than 37 kBq/mL (more significant in the G1 phase and G2/M phase) than the HL-7702 cells. In addition, (125)I-UdR-CS-DLN induced a higher level of DNA double-strand breaks than (125)I-UdR, and HepG2 cells exhibited a lower level of DNA repair when compared with HL-7702 cells. In vivo animal experiments, TUNEL staining, after targeted treatment, showed that (125)I-UdR-CS-DLN induced significant cell apoptosis in rabbit hepatocellular tumors in situ than (125)I-UdR infusion at the same dose. In conclusion, hepatocellular carcinoma cells were significantly irradiated with (125)I-UdR-CS-DLN compared with (125)I-UdR, and (125)I-UdR-CS-DLN irradiation enhanced DNA damage, induced liver cancer cell apoptosis, and prevented DNA damage repair. However, evaluating the extent of damage and organ sparing in vivo should also be considered.

Growth inhibition induced by short hairpin RNA to silence survivin gene in human pancreatic cancer cells.

BACKGROUND: Survivin is known to be overexpressed in various human malignancies, including pancreatic cancer, and mediates cancer cell proliferation and tumor growth, so the regulation of this molecule could be a new strategy for treating pancreatic cancer. In this study, short hairpin RNAs (shRNAs) specific to survivin were introduced into human pancreatic cancer Patu8988 cells to investigate the inhibitory effects on survivin expression and cell proliferation in vitro and in vivo. METHODS: Three kinds of shRNA specific to the survivin gene were designed and cloned into eukaryotic expression plasmid pGenesil-1 vector. Subsequently the recombinant plasmids were transfected into human pancreatic cancer Patu8988 cells with lipfectamineTM 2000 reagent. The mRNA and protein expressions of survivin in the transiently transfected Patu8988 cells were determined by RT-PCR, flow cytometry, and Western blotting analysis. The proliferation inhibition rates of stably transfected Patu8988 cells were determined by MTT assay. The antitumor activities of the three kinds of survivin-shRNA plasmids were evaluated in BALB/c nude mice inoculated with Patu8988 cells and bearing human pancreatic cancer. RESULTS: The three survivin-shRNA plasmids named pGenesil-1-survivin-1, pGenesil-1-survivin-2 and pGenesil-1-survivin-1+2 (with double interfering RNA sites) were successfully constructed, and were confirmed by restriction enzyme cutting and sequencing. At 48 hours after transfection, the expression of survivin mRNA and protein was inhibited in Patu8988 cells transfected with pGenesil-1-survivin-1, pGenesil-1-survivin-2, and pGenesil-1-survivin-1+2 when compared with that of either pGenesil-1-NC (with scrambled small interfering RNA) transfected cells or control cells (P<0.05). The MTT results showed that the proliferation rates of Patu8988 cells stably transfected with survivin-shRNA plasmids were reduced when compared with that of either pGenesil-1-NC transfected cells or control cells (P<0.01). Furthermore, when Patu8988 cells stably transfected with survivin-shRNA were injected into BALB/c nude mice, tumor growth was dramatically lower and the tumor was smaller than that of either pGenesil-1-NC transfected cells or control cells (P<0.01). The inhibitory effect of pGenesil-1-survivin-1 was the best among the three kinds of survivin-shRNA plasmids, but no combination of inhibitory effects was found in pGenesil-1-survivin-1+2. CONCLUSIONS: shRNAs specific to survivin have gene silencing effects and inhibit pancreatic cancer cell proliferation. shRNA activity against survivin could be of potential value in gene therapy for pancreatic cancer. However, shRNAs with double combining sites did not significantly enhance the interference compared with single site shRNAs, therefore further studies on this are needed.