Associations Between Serum Reproductive Hormone Concentrations and Hormonal Receptor Status Among Postmenopausal Chinese Women With Breast Cancer: An Observational Study.

Background and Objectives: Reproductive hormones and receptors play crucial roles in breast cancer development and progression. The association between preoperative serum reproductive hormone levels and receptor status in postmenopausal women with breast cancer remains unclear. Therefore, this study investigated the relationship between serum reproductive hormone concentrations and patient characteristics and hormone receptor status among postmenopausal Chinese women with breast cancer. Materials and Methods: The medical records of 352 postmenopausal breast cancer patients who underwent an operation between October 2007 and October 2010 at the Department of Breast Tumor Surgery of Zhejiang Cancer Hospital were retrospectively evaluated. Serum levels of reproductive hormones were measured before surgery by liquid-chromatography tandem mass spectrometry. Hormone receptor levels were measured by an immunohistochemical assay using a mouse monoclonal antibody. The associations between serum hormone concentrations and hormone receptors were investigated by analysis of covariance. Results: In this patient cohort, the serum level of luteinizing hormone (LH) declined with PMP duration. The median LH concentration was significantly higher in patients within 5 years of PMP than that in patients with PMP duration exceeding 5 years (23 vs. 18.32 mIU/ml, P <.0001). Significantly more patients with strong estrogen receptor (ER) or progesterone receptor (PR) expression had postmenopausal durations of less than 5 years compared to those with postmenopausal durations greater than 5 years (103 vs. 61 cases, P = .019; 93 vs. 46 cases, P = .0005). While most patients either lacked (97.1%) or co-expressed (84.3%) ER and PR, some patients expressed either ER or PR alone. ER and PR expression were negatively associated with receptor-tyrosine kinase erbB-2 (HER2) expression in postmenopausal patients with breast cancer. Meanwhile, increased ER and PR expression were associated with decreased serum levels of LH or follicle-stimulating hormone (FSH). Conclusion: Decreased serum LH and FSH levels were associated with increased ER and PR expressions and decreased HER2 expression in postmenopausal patients with breast cancer.

Effects of Gonadotropin-Releasing Hormone Analogs on Ovarian Function Against Chemotherapy-Induced Gonadotoxic Effects in Premenopausal Women With Breast Cancer in China: A Randomized Clinical Trial.

IMPORTANCE: Studies of the use of gonadotropin-releasing hormone analogs (GnRHa) to protect ovarian function have shown mixed results. OBJECTIVE: To determine whether administering GnRHa during chemotherapy in premenopausal women with breast cancer can reduce ovarian impairment. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial, conducted at the Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital and Zhejiang Cancer Hospital in China, was an open-label trial involving premenopausal women aged 18 to 49 years with operable stage I to III breast cancer for which treatment with adjuvant or neoadjuvant cyclophosphamide-containing chemotherapy was planned in 2 parallel groups: treatment with chemotherapy with or without GnRHa. Enrollment occurred from September 2015 to August 2017, and follow-up ended December 2020. The data were analyzed in March 2021. A total of 405 patients were enrolled in the study, among whom 27 patients (6.7%) quit participation voluntarily, 33 (8.1%) did not meet the inclusion criteria and were excluded, and 15 (3.7%) were lost to follow-up. Ultimately 330 patients were included in the primary analysis, including 29 patients with baseline anti-Müllerian hormone levels less than 0.5ng/ mL. INTERVENTIONS: Eligible patients were randomly assigned (1:1) to receive chemotherapy with (n = 165) or without (n = 165) GnRHa. In patients randomized to receive GnRHa, 3.6 mg of goserelin or 3.75 mg of leuprorelin was injected subcutaneously once every 28 days from 1 to 2 weeks before the first cycle of chemotherapy to 4 weeks after the last cycle of chemotherapy. MAIN OUTCOMES AND MEASURES: The primary end point was the rate of premature ovarian insufficiency (POI) at 12 months after chemotherapy. Premature ovarian insufficiency was defined as anti-Müllerian hormone levels of less than 0.5 ng/mL in this study. The secondary end point was overall survival (OS) and tumor-free survival (TFS). RESULTS: A total of 330 eligible patients could be evaluated with complete data, among whom 301 patients (91.2%; GnRHA group: mean [SD] age, 40.6 [6.7] years; control group: mean [SD] age, 40.2 [5.9] years) were eligible for primary end point analysis. At 12 months after the completion of chemotherapy, the POI rate was 10.3% (15 of 146) in the GnRHa group and 44.5% (69 of 155) in the control group (odds ratio, 0.23; 95% CI, 0.14-0.39; P < .001). Anti-Müllerian hormone resumption in the GnRHa group was significantly better than that in the control group (15 of 25 vs 6 of 44; odds ratio, 4.40; 95% CI, 1.96-9.89; P < .001). After a median follow-up of 49 months (range, 25-60 months), the differences in 4-year OS and TFS between the 2 groups were not significant. A post hoc analysis showed that in patients younger than 35 years, the TFS was higher in the GnRHa group than in the control group (93% vs 62%; P = .004; hazard ratio, 0.15; 95% CI, 0.03-0.82; P = .03). CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that administering GnRHa in treatment with chemotherapy for premenopausal patients with breast cancer reduces the risk of POI, which promotes the recovery of ovarian function. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02518191.

Combined radiotherapy and chemotherapy versus radiotherapy alone in elderly patients with nasopharyngeal carcinoma: A SEER population-based study.

ABSTRACT: Currently, the impact of chemotherapy (CT) on survival outcomes in elderly patients with nasopharyngeal carcinoma (NPC) receiving radiation therapy (RT) remains controversial. This retrospective study aims to investigate survival outcomes in a cohort of elderly NPC patients receiving RT alone or together with CT.Clinical data on 529 NPC patients aged 65 years and older extracted from the Surveillance, Epidemiology, and End Results registry (2004-2015) was collected and retrospectively reviewed. In this cohort, 74 patients were treated with RT alone and 455 individuals received RT and CT. We used propensity score matching with a 1:3 ratio to identify correlations between patients based on 6 different variables. Kaplan-Meier analysis was used to evaluate overall (OS) and cancer-specific survival (CSS). The differences in OS and CSS between the 2 treatment groups were compared using the Log-rank test and Cox proportional hazards models.The estimated 5-year OS and CSS rates for all patients were 49.5% and 59.3%, respectively. The combination of RT and CT provided longer OS than RT alone (53.7% vs 36.9%, P = .002), while no significant difference was observed in CSS (61.8% vs 51.7%, P = .074) between the 2 groups. Moreover, multivariate analysis demonstrated that the combination of CT and RT correlated favorably with OS and CSS. Subgroup analyses showed that the combination of RT and CT correlated better with both OS and CSS in patients with stage T3 or N2 or stage III.Among NPC patients aged 65 years and older, treatment with RT and CT provided longer OS than RT alone. Furthermore, the combination of RT and CT showed a better correlation with OS and CSS in NPC patients with stage T3 or N2 or stage III.

Different Risk Target Volumes for Nasopharyngeal Carcinoma Treated with Simultaneous Integrated Boost Intensity-Modulated Radiotherapy.

Background and Objectives: Although intensity-modulated radiotherapy (IMRT) provides promising survival advantages and fewer late complications in patients with nasopharyngeal cancer (NPC), appropriated target volumes and prescribed doses are still being explored. This study aimed to propose different risk target volumes and corresponding prescribed doses in our center and to evaluate the physical basis and efficacy of this protocol based on the long-term survival of NPC patients. Methods and Materials: We retrospectively assessed patients with histology-proven non-metastatic NPC treated with definitive IMRT using our protocol of different risk target volumes and corresponding prescribed doses based on the orderly stepwise pattern of tumor spread. We described the delineation for different risk target volumes and the design of IMRT planning for an NPC case. Additionally, we compared the dosimetric distributions between the China protocol and our protocol through two NPC cases. The patterns of failure and locoregional control were the primary endpoints. All survival outcomes were calculated using the Kaplan-Meier method. Results: From January 2013 to December 2014, a total of 335 patients were treated; the median follow-up for patients who survived was 70 months. All patients completed IMRT using our protocol. Twenty-five patients developed locoregional recurrence, and all recurrences occurred within the high-dose target volumes. The rates of locoregional recurrence-free survival, distant metastasis-free survival, progression-free survival, and overall survival at 5 years were 92.2%, 92.1%, 85.9%, and 86.3%, respectively. The biological effective doses of the prescribed doses in our protocol were similar to those of the China and 0615 protocols. Moreover, our protocol offered a reduction in D1 and D2 in the primary gross tumor volume (GTV), while V30 and V40 in normal tissues were lower. Conclusion: Our protocol of different risk target volume delineations and corresponding prescribed doses based on the stepwise pattern of tumor spread resulted in favorable locoregional control with no relapse outside the GTV.

Therapeutic patterns and outcomes in older patients (aged ≥65 years) with stage II-IVB Nasopharyngeal Carcinoma: an investigational study from SEER database.

Purpose: Currently, the optimal treatment regimens for older nasopharyngeal carcinoma (NPC) patients remained unclear. The aim of this retrospective study is to investigate therapeutic patterns and survival outcomes for a cohort of older NPC patients receiving radiation therapy (RT) with or without chemotherapy (CT). Methods: The clinical data of 529 patients with aged ≥65 years and NPC, who were identified within the Surveillance, Epidemiology, and End Results (SEER) registry (years 2004-2015), were collected and retrospectively reviewed. Among these patients, 74 patients treated with RT alone and 455 cases were administrated for RT plus CT. Kaplan-Meier analysis was used to evaluate overall survival (OS) and cancer-specific survival (CSS). The differences in OS and CSS were compared using Log-rank test. Results: The estimated OS and CSS rates at 5 years were 48.9% and 59.6%, respectively. Univariate analysis indicated that age, histology, T stage, and clinical stage were independent prognosticators of OS and CSS, while treatment option was only associated with OS. Multivariate analysis demonstrated that age, T stage, histology, and therapeutic strategy were correlated with OS, while age, T stage and histology were independent prognostic factors of CSS. Subgroup analyses showed that the combination of RT and CT yielded better OS and CSS in patients with stage T3 or N2 or III. Conclusion: Among these NPC patients with aged ≥65 years reported in the SEER database, treatment with RT plus CT provided longer OS than those treated with radiation therapy alone. Moreover, the combination of RT and CT obtained favorable OS and CSS in NPC patient stage T3 or N2 or III.

Methodology of dose calculation for external beam radiation combined with high dose rate brachytherapy in the era of 3-dimensional treatment planning system.

Intracavitary application of brachytherapy (BT) sources followed by external beam radiation is essential for the local treatment of carcinoma of the cervix, postate, and nasopharynx. Dose distribution of external beam radiation plus BT can be challenging for the planning system because of their dose calculation by 2 different treatment planning system (TPS). The aims of this study were to introduce a novel iterative method of dose calculation preformed in the Pinnacle plan and evaluate a combined dose distribution for external beam radiation and BT.Because it is often the goal of the planner to produce plan with uniform dose throughout the target volume and normal tissue, we present an Iridium-192 calculation program using American Association of Physicists in Medicine Task Group 43 formula and export it to other commercialized TPS though the combined dose distribution of external beam radiation and BT can be shown. To illustrate such an improved procedure, we present the treatment plans of 2 patients treated with external beam radiation plus BT.Dose distribution of the single BT source were calculated with the Plato post loading TPS and the program model, and the results of 2 methods were similar. A nasopharyngeal case and a cervical case were shown in Pinnacle with this program. The total dose distribution of BT combined with EBRT was showed in compute tomography images. And the corresponding dose volume histogram figures could be displayed correctly in Pinnacle TPS.We demonstrated a novel iterative method of dose calculation preformed in the Pinnacle plan to produce a combined dose distribution for external beam radiation and BT. We used it to evaluate the dose of target volume and normal tissues in the treatment of external beam radiation plus BT.

Influence of concurrent chemotherapy on locoregionally advanced nasopharyngeal carcinoma treated with neoadjuvant chemotherapy plus intensity-modulated radiotherapy: A retrospective matched analysis.

Neoadjuvant chemotherapy (NAC) combined with intensity-modulated radiotherapy (IMRT) plus concurrent chemotherapy (CC) will be the new standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC) patients. However, many patients fail to receive CC for multiple reasons. We aimed to investigate long-term survival outcomes and toxicities in these patients with NPC treated with additional NAC plus concurrent chemoradiotherapy (CCRT) or IMRT alone. In total, 1,378 previously untreated, newly diagnosed locoregionally advanced NPC patients receiving NAC plus IMRT with or without CC were retrospectively reviewed. We used a propensity score-matched (PSM) method with 1:1 matching to identify paired patients according to various covariates. Survival outcomes and toxicities were compared between the two groups. In total, 288 pairs were identified. With a median follow-up of 86 (range: 8-110) months, the estimated 5-year locoregional relapse-free survival, distant metastasis-free survival, progression-free survival (PFS), and overall survival rates in patients treated with NAC plus CCRT vs. NAC plus IMRT alone were 96.1% vs. 94.7% (P = 0.201), 93.7% vs. 89.8% (P = 0.129), 91.3% vs. 85.1% (P = 0.024), and 93.0% vs. 90.6% (P = 0.362), respectively. Multivariate analysis showed that CC omission was a prognostic factor for worse PFS. In a subgroup analysis, PFS did not differ significantly between two groups of female patients or aged <60 years or stage T1-2 or stage N0-1 disease. However, fewer acute complications were observed in the NAC plus IMRT alone group. NAC with IMRT alone confers similar survival rates and less acute toxicities. Specifically, NAC plus IMRT alone may be enough for female patients <60 years with stage T1-2 or stage N0-1. However, a prospective randomised trial is needed to validate these results.

An experimental study on the prosthesis produced by inactivated autologous subcutaneous adipose tissue and skin dermal tissue in a mini-pig model.

BACKGROUND: Autologous adipose tissue grafting is a valuable strategy for breast reconstruction in breast cancer patients. However, adipose tissue is absorbed and liquefies easily, and the cosmetic effects do not last. The purpose of this study is to evaluate the cosmetic effects and histopathologic changes of the prostheses produced by inactivated autologous subcutaneous adipose tissue and dermal outer capsule in the mini-pig model. METHODS: This prospective study was conducted in 6 Bama adult female mini-pigs weighing 15.5-20 kg. Autologous subcutaneous adipose tissue and dermis were harvested and made into the different prostheses. Then, the prostheses were implanted into abdominal subcutaneous tissue of the mini-pigs. At the 14th and 30th day after implantation, the skin appearances were observed, and the prostheses were harvested. The histopathologic changes of adipocytes and dermis in the different prostheses were evaluated. RESULTS: In vitro experiments showed that there were no significant changes in the size and histomorphology of autologous adipose tissue and/or dermis in the different prostheses. However, the results of the in vivo experiment found that the prosthesis produced by the inactivated adipose tissue with a dermal outer capsule produced the best cosmetic effect and the least fibrous connective tissue proliferation around the prosthesis. Moreover, the fewest proliferative fibrous connective tissues and infiltrated inflammatory cells were found in the adipocytes wrapped by dermis. The adipocyte morphology was normal. CONCLUSIONS: Results in this animal model indicated that the prosthesis produced by inactivated autologous subcutaneous adipose tissue with a dermal outer capsule may be a promising prosthesis for breast reconstruction. Validation of this new prosthesis requires more experiments to assess the long-term cosmetic effects and histopathologic changes.

Additional induction chemotherapy to concurrent chemotherapy and intensity-modulated radiotherapy with or without nimotuzumab in first-line treatment for locoregionally advanced nasopharyngeal carcinoma: a propensity score matched analysis.

Background: The aim of this study is to assess the survival benefits of additional induction chemotherapy before concurrent chemotherapy, intensity-modulated radiotherapy and nimotuzumab in patients with locoregionally advanced nasopharyngeal carcinoma. Methods: Clinical data from 1104 nonmetastatic nasopharyngeal carcinoma patients diagnosed between May 2008 and April 2014 were retrospectively reviewed. All patients received addition of induction chemotherapy to concurrent chemoradiotherapy with or without nimotuzumab. A propensity score matched method was used to identify paired patients according to various covariates. Results: In total, 120 pairs were selected by propensity score matched method. At a median follow-up time of 56 months (10-99 months), the 5-year locoregional relapse-free survival, distant metastases-free survival, progression-free survival and overall survival rates in patients treated with nimotuzumab vs. without nimotuzumab were 91.6% vs. 91.1% (P= 0.957), 95.8% vs. 83.9% (P= 0.007), 87.4% vs. 81.3% (P= 0.225), 94.5% vs. 85.6% (P= 0.058), respectively. Multivariate analysis revealed that nimotuzumab was an independent prognosticator of OS and DMFS. Conclusions: Nimotuzumab is an effective treatment option for locoregionally advanced nasopharyngeal carcinoma, and the addition of induction chemotherapy to concurrent chemoradiotherapy and nimotuzumab could obtain the best survival benefits.

Efficacy and Safety of Nimotuzumab Plus Radiotherapy With or Without Cisplatin-Based Chemotherapy in an Elderly Patient Subgroup (Aged 60 and Older) With Nasopharyngeal Carcinoma.

OBJECTIVE: This study was conducted to assess the efficacy and safety of nimotuzumab combined with radiotherapy (RT) in elderly patients with nasopharyngeal carcinoma. MATERIALS AND METHODS: The clinical data of 75 nasopharyngeal carcinoma patients, who were initially treated with nimotuzumab combined with RT, were collected and retrospectively reviewed from December 2008 to April 2014. They were aged 60 to 81 years (median 64 years). The distribution of disease was stage II in 10 (13.3%), stage III in 33 (44.0%), and stage IV in 32 (42.7%). Among these patients, 59 cases received cisplatin-based chemotherapy. Survival outcomes and treatment toxicity were analyzed using IBM SPSS 19.0 software. RESULTS: With a median follow-up of 45 months (range, 13-78 months), the estimated 3-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), progression failure-free survival (PFS), and overall survival (OS) rates were 95.6%, 95.5%, 98.6%, 89.7%, and 89.2%, respectively. In the subgroup, 3-year OS rate in the patients with concurrent chemotherapy was 90.5% and 77.4% in patients without concurrent chemotherapy (Log-Rank = 1.795, P = .180). Univariate analysis showed that T stage and clinical stage were correlated with OS. Multivariate analysis indicated that age, T stage and tumor response at the end of treatment were independent prognosticators. Nine patients experienced grade 3 to 4 acute mucositis and 26 patients experienced grade 3-4 leukocytopenia, with no cases of skin rash and infusion reaction. Twelve patients developed mild liver function damage. No serious gastrointestinal or renal toxicities were observed. CONCLUSION: The efficacy of combined nimotuzumab with RT in elderly NPC patients was encouraging and the toxicities were accepted. In addition, nimotuzumab provides a better option for elderly patients who cannot be tolerate chemotherapy.

Treatment Outcomes of 257 Patients with Locoregionally Advanced Nasopharyngeal Carcinoma Treated with Nimotuzumab Plus Intensity-Modulated Radiotherapy with or without Chemotherapy: A Single-Institution Experience.

OBJECTIVES: To report the long-term outcome and toxicity of locoregionally advanced nasopharyngeal carcinoma (LA NPC) treated with nimotuzumab (h-R3) plus intensity-modulated radiotherapy (IMRT) with or without chemotherapy. METHODS: From May 2008 to March 2014, 3022 newly histology-proven, nonmetastatic NPC patients were retrospectively reviewed; among them, 257 patients treated with h-R3 were enrolled in this study. The patients' age range was between 10 and 76 years. The distribution of patients by disease stage was 150 (58.4%) in stage III, 88 (34.2%) in stage IV A, and 19 (7.4%) in stage IV B. All the patients received the treatment of h-R3 plus IMRT, and from them, 239 cases were also treated with cisplatin-based chemotherapy. Acute and late radiation-related toxicities were graded according to the Acute and Late Radiation Morbidity Scoring Criteria of Radiation Therapy Oncology Group. The accumulated survival was calculated according to the Kaplan-Meier method. Log-rank test was used to compare the survival difference. Multivariate analysis was performed using Cox's proportional-hazard model. RESULTS: All 257 patients had completed combined treatment; 231 patients received h-R3 plus IMRT with induction chemotherapy (IC), while 26 patients received only h-R3 plus IMRT. With a median follow-up of 48 months (range, 13-75 months), the estimated 5-year local recurrence-free survival, regional recurrence-free survival, distant metastases-free survival, progression-free survival, and overall survival (OS) rates were 94.3%, 94.8%, 91.9%, 83.4%, and 86.2%, respectively. Univariate analysis showed that age, T stage, clinical stage, and IC were related with OS. Multivariate analysis indicated that T stage and IC were independent prognostic factors for OS. The incidence of grade 3 to 4 acute mucositis and leukocytopenia was 10.9% and 19.8%, respectively, with no cases of skin rash and infusion reaction. Xerostomia was the most common late complication, and the degree of dry mouth in most survivors was mild to moderate at the last follow-up time. CONCLUSION: h-R3 plus IMRT with or without chemotherapy showed promising outcomes in terms of locoregional control and survival without increasing the incidence of radiation-related toxicities for patients.

Efficacy and safety of nimotuzumab with neoadjuvant chemotherapy followed by concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma.

We assessed the efficacy and safety of nimotuzumab plus neoadjuvant chemotherapy followed by concurrent chemoradiotherapy for Chinese patients with locoregionally advanced nasopharyngeal carcinoma. Clinical data from 210 nonmetastatic nasopharyngeal carcinoma patients diagnosed between May 2008 and April 2014 were retrospectively reviewed. All patients were initially treated with nimotuzumab plus neoadjuvant chemotherapy followed by concurrent chemoradiotherapy. Ninety-five patients received cisplatin-based adjuvant chemotherapy. The median follow-up duration was 48 months. Locoregional relapse and distant metastases occurred in 16 patients (16/210, 7.6%) and 18 patients (18/210, 8.6%), respectively. The 5-year local recurrence-free survival, regional recurrence-free survival, distant metastases-free survival, progression-free survival, and overall survival rates were 95.6%, 94.4%, 91.7%, 84.0%, and 88.7%, respectively. Univariate analysis revealed that concurrent chemotherapy regimens and clinical stage correlated with overall survival, and that adjuvant chemotherapy, N stage, clinical stage, and tumor response at the end of treatment were correlated with progression-free survival. In the multivariate analysis, concurrent chemotherapy regimens, clinical stage, and tumor response were important prognosticators. Grade 3/4 leukocytopenia was experienced by 24 patients (11.4%), and 6 patients (2.9%) developed mild liver damage during the period of neoadjuvant chemotherapy. Grade 3/4 acute mucositis was experienced by 13 patients (6.2%), and 12 patients (5.7%) experienced grade 3/4 leukocytopenia during the concurrent chemotherapy. The efficacy of nimotuzumab plus neoadjuvant chemotherapy followed by concurrent chemotherapy in locoregionally advanced nasopharyngeal carcinoma patients was encouraging and the toxicities were tolerable.

Downregulation of miR­429 and inhibition of cell migration and invasion in nasopharyngeal carcinoma.

Viral, dietary and genetic factors have been implicated in nasopharyngeal carcinoma (NPC), however, the molecular mechanism underlying its pathogenesis remains to be fully elucidated. MicroRNAs (miRNAs) have been reported to be important in NPC tumorigenesis, with a previous miRNA microarray study showing the downregulation of miRNA (miR)­429 in NPC cells. However, the possible mechanisms of action of miR­429 have not been examined. In the present study, the expression profiles of miR­429 were detected using reverse transcription­quantitative polymerase chain reaction analysis in CNE­1 and CNE­2 cells, which are two generally used NPC cells with different degrees of differentiation. Subsequently, cell proliferation, invasion and migration were analyzed in miR­429­overexpressing CNE­2 cells, and the modulatory function of miR­429 was also investigated using two target genes, zinc finger E­Box­binding homeobox 1 (ZEB1) and CRK­like (CRKL), by transfection with miR­429 mimic or anti­miR­429. Significant changes in the expression of miR­429 were detected, particularly in low­differentiated CNE­2 cells, with higher levels of epidemicity and malignancy. Additional results revealed that miR­429 inhibited the invasion and migration of the CNE­2 cells, whereas no significant effect on cell growth was observed. In addition, the mRNA and protein expression levels of the two target genes, ZEB1 and CRKL, were negatively regulated by miR­429, demonstrated through gain­of­function and loss­of­function investigations, indicating that these two functional downstream targets may be involved in the inhibitory effects of miR­429 on NPC migration and invasion. miR­429 may act as a negative regulatory factor of NPC tumorigenesis, involving the functions of its downstream targets, ZEB1 and CRKL. The results suggested miR­429 as a potential candidate for miRNA­based prognosis or therapy against NPC.

miR-195 is a key regulator of Raf1 in thyroid cancer.

Proto-oncogene Raf1 serves as a part of the mitogen-activated protein kinases/extracellular signal-regulated kinase signal transduction pathway and regulates cell migration, apoptosis, and differentiation. Although a large number of studies have shown that Raf1 is overexpressed in various kinds of cancer, little is known about the association between Raf1 and miRNAs in thyroid carcinoma. This study proves that Raf1 is overexpressed in thyroid cancer, which has been confirmed by many other studies. Besides, we identify that Raf1 is a direct target of miR-15a/b, miR-16, and miR-195 by dual luciferase reporter assay. We also find that the expression of miR-195 is downregulated in 50 pairs of thyroid tumor tissues compared to the adjacent nontumor tissues, while there is no difference in the expression of miR-15a/b and miR-16 between the groups. Furthermore, exogenous overexpression of miR-195 significantly inhibits the protein expression of Raf1 and blocks the thyroid cancer cell proliferation. Our findings delineate a novel mechanism for the regulation of Raf1 in thyroid cancer, which may help to provide a new direction for the treatment of thyroid cancer.