circMTO1/miR-30c-5p/SOCS3 axis alleviates oral submucous fibrosis through inhibiting fibroblast-myofibroblast transition.

BACKGROUND: circRNAs have been shown to participate in diverse diseases; however, their role in oral submucous fibrosis (OSF), a potentially malignant disorder, remains obscure. Our preliminary experiments detected the expression of circRNA mitochondrial translation optimization 1 homologue (circMTO1) in OSF tissues (n = 20) and normal mucosa tissues (n = 20) collected from Hunan Xiangya Stomatological Hospital, and a significant decrease of circMTO1 expression was showed in OSF tissues. Therefore, we further explored circMTO1 expression in OSF. METHODS: Target molecule expression was detected using RT-qPCR and western blotting. The migration and invasion of buccal mucosal fibroblasts (BMFs) were assessed using wound healing and Transwell assays. The interaction between miR-30c-5p, circMTO1, and SOCS3 was evaluated using dual luciferase, RNA immunoprecipitation (RIP), and RNA pull-down assays. The colocalisation of circMTO1 and miR-30c-5p was observed using fluorescence in situ hybridisation (FISH). RESULTS: circMTO1 and SOCS3 expression decreased, whereas miR-30c-5p expression increased in patients with OSF and arecoline-stimulated BMFs. Overexpression of circMTO1 effectively restrained the fibroblast-myofibroblast transition (FMT), as evidenced by the increase in expression of Coll I, α-SMA, Vimentin, and the weakened migration and invasion functions in BMFs. Mechanistic studies have shown that circMTO1 suppresses FMT by enhancing SOCS3 expression by sponging miR-30c-5p and subsequently inactivating the FAK/PI3K/AKT pathway. FMT induced by SOCS3 silencing was reversed by the FAK inhibitor TAE226 or the PI3K inhibitor LY294002. CONCLUSION: circMTO1/miR-30c-5p/SOCS3 axis regulates FMT in arecoline-treated BMFs via the FAK/PI3K/AKT pathway. Expanding the sample size and in vivo validation could further elucidate their potential as therapeutic targets for OSF.

Accumulation of p53 is prognostic for aromatase inhibitor resistance in early-stage postmenopausal patients with ER-positive breast cancer.

OBJECTIVE: Studies have indicated that p53 protein accumulation exerts an adverse effect on the survival of breast cancer patients; however, the prognostic value of p53 protein accumulation for aromatase inhibitor (AI) resistance in ER-positive breast cancer is uncertain. METHODS: The expression level of p53 protein was detected by immunohistochemistry in primary early-stage ER-positive breast tumor specimens from 293 postmenopausal breast cancer patients who received first-line AI treatment (letrozole, anastrozole, or exemestane) until relapse, and analysis was performed to determine whether expression of p53 protein affected the response to endocrine therapy. RESULTS: Of the 293 invasive ductal carcinomas, 65.4% were positive for p53 protein expression. All patients received AI therapy as first-line treatment until relapse. The 5-year disease-free survival rates in p53-positive and p53-negative patients were 78% and 89%, respectively. Patients with primary breast tumors that had p53 protein accumulation showed significantly more resistance to AI treatment (hazard ratio=1.729, 95% confidence interval=1.038-2.880, P=0.035). CONCLUSION: This study demonstrated that p53 protein accumulation was helpful in choosing patients who may benefit from AI treatment and is a prognostic marker in ER-positive early-stage breast cancer.

Quantitative analysis of tumor shrinkage due to chemotherapy and its implication for radiation treatment planning in limited-stage small-cell lung cancer.

BACKGROUND: The optimal timing of chemoradiotherapy in limited-stage small-cell lung cancer (LS-SCLC) hasn't been established, although evidence from studies supported that patients can benefit from early radiation therapy. The purpose of this study was to quantify tumor shrinkage in response to induction chemotherapy (IC), evaluate the impact of tumor shrinkage on radiation dosimetric parameters and determine its implication for the timing of radiation therapy for patients with LS-SCLC. METHODS: Twenty patients with LS-SCLC who were treated with IC followed by concomitant radiation therapy were investigated retrospectively. Ten patients received 1 cycle of IC, and 10 patients received 2 cycles of IC. Pre-IC CT imaging was coregistered with a simulation CT, and virtual radiation plans were created for pre- and post-IC thoracic disease in each case. The changes in the gross target volume (GTV), planning target volume (PTV) and dosimetric factors associated with the lungs, esophagus and heart were analyzed. RESULTS: The mean GTV and PTV for all of the patients decreased by 60.9% and 40.2%, respectively, which resulted in a significant reduction in the radiation exposure to the lungs, esophagus and heart. Changes in the PTV and radiation exposure of normal tissue were not significantly affected by the number of chemotherapy cycles delivered, although patients who received 2 cycles of IC had a greater decrease in GTV than those who received only 1 cycle of IC (69.6% vs. 52.1%, p = 0.273). CONCLUSIONS: Our data showed that targeting the tumor post-IC may reduce the radiation dose to normal tissue in patients with LS-SCLC. However, the benefit to the normal tissue was not increased by an additional cycle of IC. These findings suggest that the first cycle of chemotherapy is very important for tumor shrinkage and that initiating thoracic radiation therapy at the second cycle of chemotherapy may be a reasonable strategy for timing of radiation therapy in LS-SCLC treatment.

Factors associated with the misdiagnosis of sentinel lymph nodes using touch imprint cytology for early stage breast cancer.

Accurate intraoperative diagnosis of sentinel node metastasis enables the surgeon to make an immediate decision to proceed to axillary lymph node dissection (ALND), thereby avoiding the economic and psychological costs of a second operation. The present study aimed to evaluate the clinical value of touch imprint cytology (TIC) and investigate the potential factors associated with misdiagnosis. A total of 366 patients with Tis-T2 breast carcinoma were included after undergoing successful sentinel lymph node biopsy (SLNB). TIC was routinely performed intraoperatively, and the results were compared with definitive histological assessments of serial sections (SS) with hematoxylin and eosin (H&E) staining. A total of 992 SLNs from 366 patients were used in the study. Based on the final histological diagnosis, the sensitivity, specificity and overall accuracy of TIC was 76.6, 98.8 and 92.3%, respectively, on a per patient basis, and 79.9, 98.9 and 96.1%, respectively, on a per node basis. TIC was significantly more sensitive for macrometastasis than micrometastasis (80.0 vs. 28.6%, P<0.01). Of 9 total 'false positives', 3 were due to micrometastasis which were not identified by serial section with H&E staining, 4 were actual false-positives which were due to interpretation error, and 2 were due to sampling error. The majority of the false-negatives (28 of 30 SLNs) were due to micrometastasis in the SLNs (sampling error). In conclusion, TIC is feasible for clinical use and is able to detect macrometastasis in the SLNs of early stage invasive breast cancer patients with an acceptable accuracy while its ability to detect micrometastasis is limited.

[Experimental study of combined target treatments using PYM-BAC5 and 131I-BAC5 to nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Combined therapy has been advocated for modern tumor treatment; the combined target therapy is a valuable research direction. Based on the previous research of nasopharyngeal carcinoma (NPC) radioimmunotherapy, this experiment was designed to develop two immunoconjugates of the monoclonal antibody BAC(5):PYM-BAC(5) and (131)I-BAC(5), and to assess the inhibition effects of their combined treatment on the NPC CNE-2 cells cultured in vitro. METHODS: Dextran T40 was used as media to link PYM and BAC(5). The conjugate PYM-BAC(5) was identified by testing its immunoactivity and the inhibition to mycobacterium. BAC(5) was labeled with (131)I by Chloramin-T method. Five experimental groups were set up:(1)PYM-BAC(5) group, (2)free PYM group, (3)(131)I-BAC(5) group, (4)(131)I-mIgG group, (5)the combined target treatment group ( (131)I-BAC(5)+PYM-BAC(5)). The antitumor effects of the five groups were assessed with MTT method. RESULTS: The 50% inhibition doses(IC(50)) of PYM-BAC(5) group and PYM group were 46.57 microg/ml and 316.7 microg/ml, respectively. The IC(50) of (131)I-BAC(5) group and (131)I-mIgG group to CNE2 were 4.42 x 10(5) Bq/ml and >11.1 x 10(5) Bq/ml,respectively. In the combined target treatment group(PYM-BAC(5)+(131)I-BAC(5)),the IC(50) of PYM-BAC(5) was 7.01 microg/ml and of (131)I-BAC(5) was 0.54 x 10(5) Bq/ml, which much less than other separate treatment groups. CONCLUSION: The inhibition effects of the target treatment ((131)I-BAC(5) and PYM-BAC(5)) on the NPC CNE-2 cells are stronger than non-target treatment (free PYM and (131)I-BAC(5)). The combined target treatment of the two immune ((131)I-BAC(5)+PYM-BAC(5)) conjugates gets stronger inhibition effects than their separate treatment.