High Risk Thyroid Nodule Discrimination and Management by Modified TI-RADS.

OBJECTIVE: Thyroid cancer is the most common primary malignant disorder of the thyroid. We aimed to illustrate the modified TI-RADS report system for differentiating malignant thyroid nodules from benign ones, and especially its role in the management of high risk nodules. METHODS: In this retrospective study, 5,162 healthy individuals who underwent thyroid ultrasound according to modified TI-RADS from January 2014 to December 2014 were enrolled and followed up during the whole 5 years, and the medical data were investigated and reviewed. RESULTS: The total detection rate of thyroid nodules was 39.40%. The total detection rate of thyroid cancer was 0.66%. Most thyroid cancers were single-shot, located at unilateral, at early clinical stages, without lymph node metastases, and with low recurrence risk. All patients had thyroid papillary carcinoma, except one thyroid medullary carcinoma. Based on modified TI-RADS classification, at the end of 5 years follow-up, more changes of thyroid nodules grade status were observed in grades 4a and above. The higher the grade status, the more malignant advances were occurred. The modified TI-RADS report system played an instructional role in adding medical treatment choice and decision for clinicians. CONCLUSION: The modified TI-RADS report system plays an important role in thyroid benign and malignant nodule identification and management.

High Expression of Nuclear Transcription Factor-κB is Associated with Cisplatin Resistance and Prognosis for Ovarian Cancer.

BACKGROUND: Abnormal activation of the nuclear transcription factor-κB (NF-κB) signaling pathway plays a crucial role in the chemoresistance of tumor cells. This study aimed to explore the significance of NF-κB in the chemoresistance of ovarian cancer. MATERIALS: We performed immunohistochemical staining for evaluating the expression of NF-κB in cancer tissues. The MTT assay was performed for analyzing cell proliferation, Western blotting was performed to quantify NF-κB p65, and flow cytometry was used to determine the apoptosis rate. RESULTS: Nuclear NF-κB p65 over-expression was closely associated with ovarian cancer with advanced FIGO stage, residual disease ≥1 cm, low histologic grade, platinum resistance and refractory, chemotherapy resistance (P< 0.05). FIGO stage I-II and residual disease <1 cm were associated with complete response (CR) to chemotherapy, while FIGO stage I-II, residual disease <1cm and absence of lymph node (LN) metastasis were associated with platinum sensitivity. In multivariate logistic regression, residual disease ≥1 cm was a risk factor for response to chemotherapy, while the over-expression of nuclear NF-κB p65 was a risk factor for sensitivity to chemotherapy. In the ROC curves, nuclear NF-κB p65 expression had the discriminative ability for sensitivity to chemotherapy (AUC = 0.637, P = 0.021). Furthermore, nuclear NF-κB p65 expression was an independent prognostic factor. Western blotting showed that NF-κB p65 level in cisplatin-resistant cells (C13* and A2780cp) was significantly higher than that in cisplatin-sensitive cells (OV2008 and A2780s) (P < 0.05), and this increased expression could be suppressed by NF-κB inhibitor-PDTC treatment. The proliferation inhibitory rates of cisplatin in C13* and A2780cp cells increased after PDTC treatment in a concentration-dependent manner. PDTC treatment could also enhance cisplatin-induced apoptosis. CONCLUSION: NF-κB was associated with the clinicopathological features, chemoresistance, and prognosis of ovarian cancer. The NF-κB inhibitor PDTC can enhance cisplatin sensitivity of platinum-resistant C13* and A2780cp ovarian cancer cells.

Effects of poly (ADP-ribosyl) polymerase (PARP) inhibitor on cisplatin resistance & proliferation of the ovarian cancer C13* cells.

BACKGROUND & OBJECTIVES: Drug resistance is the primary cause of failure in the treatment of cancers. It has been suggested that the enhancement of DNA repair capability may be responsible for the drug resistance of the tumour cells, and poly(ADP-ribosyl)ation plays an important role in DNA repair. This study investigated the effect of PARP inhibitor 3-aminobenzamide (3-AB) on the cisplatin resistance and proliferation of the cisplatin-resistant ovarian cancer C13 FNx01 cells in vitro. METHODS: C13 FNx01 cells were treated with various concentrations of 3-AB in vitro. MTT assay was used to determine the effect of 3-AB on the cisplatin sensitivity and proliferation of cells. The expression levels of PARP-1 mRNA and protein in the C13 FNx01 cells were examined using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, and changes caused by 3-AB treatment were investigated. Immunofluorescence microscopy was used to detect the localization and expression of the PARP-1 proteins before and after treatment with 5 mmol/l 3-AB. RESULTS: The inhibitory ratio and the cisplatin sensitivity of C13 FNx01 cells significantly increased with the increase of the concentration of 3-AB (P<0.05). The RT-PCR analysis revealed that the expression of PARP-1 mRNA was decreased when platinum (Pt) and 3-AB were combined. The expression levels of PARP-1 protein were decreased by 23.15 ± 2.53, 59.11 ± 2.23 and 73.24 ± 3.88 per cent, respectively, in C13 FNx01 cells with the increase of the concentration of 3-AB (P<0.05). The immunofluorescence microscopy results indicated that the expression level of PARP-1 protein was significantly decreased after treatment with 3-AB (P,<0.05). INTERPRETATION & CONCLUSIONS: 3-AB inhibited the proliferation activity of C13 FNx01 cells, and increased the cellular sensitivity to cisplatin. Our findings show that the PARP inhibitor 3-AB can downregulate the expression of PARP-1 at transcriptional and translational levels in C13 FNx01 cells.

Highly selective fluorescent OFF-ON thiol probes based on dyads of BODIPY and potent intramolecular electron sink 2,4-dinitrobenzenesulfonyl subunits.

Two highly selective OFF-ON green emitting fluorescent thiol probes (1 and 2) with intense absorption in the visible spectrum (molar extinction coefficient ε is up to 73 800 M(-1) cm(-1) at 509 nm) based on dyads of BODIPY (as electron donor of the photo-induced electron transfer, i.e.PET) and 2,4-dinitrobenzenesulfonyl (DNBS) (as electron acceptor of the PET process) were devised. The single crystal structures of the two probes were determined. The distance between the electron donor (BODIPY fluorophore) and the electron acceptor (DNBS) of probe 2 is larger than that of probe 1, as a result the contrast ratio (or the PET efficiency) of probe 2 is smaller than that of probe 1. However, fluorescence OFF-ON switching effects were observed for both probe 1 and probe 2 in the presence of cysteine (the emission enhancement is 300-fold for probe 1 and 54-fold for probe 2). The fluorescence OFF-ON sensing mechanism is rationalized by DFT/TDDFT calculations. We demonstrated with DFT calculations that DNBS is ca. 0.76 eV more potent to accept electrons than the maleimide moiety. The probes were used for fluorescent imaging of cellular thiols.