Exosomal miR-122-3p represses the growth and metastasis of MCF-7/ADR cells by targeting GRK4-mediated activation of the Wnt/ß-catenin pathway.

Breast cancer (BC) is a common cancer whose incidence continues to grow while its medical progress has stagnated. miRNAs are vital messengers that facilitate communications among different cancer cells. This study was to reveal the correlation of miR-122-3p expression with BC metastasis and Adriamycin (ADM) resistance and its mechanism of inhibiting BC metastasis. We found that expression of miR-122-3p is negatively correlated with BC metastasis and is lower in MCF-7/ADR cells. Overexpression of miR-122-3p in MCF-7/ADR cancer cells impairs their ability to migrate, invade, and stimulate blood vessel formation. Further research found that miR-122-3p directly binds to the 3' UTR of GRK4, reducing the phosphorylation of LRP6, which activates the Wnt/ß-catenin signaling pathway, facilitating BC development and metastasis. In addition, we observed that miR-122-3p is present in MCF-7  cells, and treatment of MCF-7/ADR cells with MCF-7-derived exosomes, but not with exosomes from miR-122-3p-deficient MCF-7 cells, has identical effects to miR-122-3p overexpression. Data from xenograft experiments further suggest that excess miR-122-3p and MCF-7-derived exosomes inhibit the growth and metastasis of MCF-7/ADR cancer cells in vivo. In conclusion our data reveal that exosomal miR-122-3p may negatively regulate BC growth and metastasis, potentially serving as a diagnostic and druggable target for BC treatment.

Association between the Khorana risk score and all-cause mortality in Japanese patients with gastric and colorectal cancer: A retrospective cohort study.

BACKGROUND: The Khorana risk score (KRS) has poor predictive value for cancer-associated thrombosis in a single tumor type but is associated with early all-cause mortality from cancer. Evidence for the association between KRS and all-cause mortality in Japanese patients with gastric and colorectal cancer is limited. AIM: To investigate whether KRS was independently related to all-cause mortality in Japanese patients with gastric and colorectal cancer after adjusting for other covariates and to shed light on its temporal validity. METHODS: Data from Dryad database were used in this study. Patients in the Gastroenterology Department of Sapporo General Hospital, Sapporo, Japan, were enrolled. The starting and ending dates of the enrollment were January 1, 2008 and January 5, 2015, respectively. The cutoff date for follow-up was May 31, 2016. The independent and dependent (target) variables were the baseline measured using the KRS and final all-cause mortality, respectively. The KRS was categorized into three groups: Low-risk group (= 0 score), intermediate-risk group (1-2 score), and high-risk group (≥ 3 score). RESULTS: Men and patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 2 displayed a higher 2-year risk of death than women and those with ECOG PS 0-1 in the intermediate/high risk group for KRS. The higher the score, the higher the risk of early death; however, the relevance of this independent prediction decreased with longer survival. The overall survival of each patient was recorded via real-world follow-up and retrospective observations, and this study yielded the overall relationship between KRS and all-cause mortality. CONCLUSION: The prechemotherapy baseline of KRS was independently associated with all-cause mortality within 2 years; however, this independent predictive relationship weakened as survival time increased.

The combination of decitabine and aspirin inhibits tumor growth and metastasis in non-small cell lung cancer.

OBJECTIVE: Combination therapy has become the hallmark of lung cancer treatment, as it reduces the dosage intensity of individual drugs while increasing their efficacy. In the current study, we analyzed the combinatorial effect of decitabine and aspirin on non-small cell lung cancer (NSCLC) cell growth. METHODS: In this study, we investigated the combinatorial effect of decitabine and aspirin by MTT, colony formation, and Transwell assays. We also explored the underlying molecular mechanism via a series of in vitro and in vivo experiments. RESULTS: The combination of decitabine and aspirin regulated cell viability and migration in vitro. Moreover, the combination therapy suppressed tumor cell growth by inhibiting the ß-catenin/STAT3 signaling pathway. Our study also found that the regimen increased the phosphorylation of ß-catenin and decreased the expression of STAT3 and ß-catenin. CONCLUSION: The combined administration of decitabine and aspirin significantly reduced tumor growth compared with single-agent treatment and the control in vivo. The study results indicated that decitabine and aspirin could suppress NSCLC cell growth and metastasis via the ß-catenin/STAT3 signaling pathway.

Impact of University Mergers on Admission of Medical Students in China.

OBJECTIVE: Mergers of health science faculties in China have resulted in two different admission pathways for medical students. A uniform-code model prioritizes admission to a specific institution with secondary assignment to major. A separate-code model prioritizes admission directly to a school within an institution. This study investigates the impact of these two admission pathways on medical student selection and on the satisfaction of students with their major. METHODS: Medical students at 16 medical schools across China completed a questionnaire survey. Descriptive calculation, chi-square tests, and probit models were used for analysing the data. RESULTS: A total of 3132 completed surveys were included in the analysis. Compared with the students admitted under the uniform-code pathway, a significantly larger proportion of the students admitted under the separate-code pathway had medicine as the first preferred major (89.6% vs 79.6%, p=0.000); compared with those students enrolled into medicine not as their first preferred major, a significantly larger proportion of students enrolled into medicine as their first preferred major were willing to study medicine if choosing again (80.1% vs 62.4%, p=0.000) or to recommend the major to other students (73.3% vs 65.2%, p=0.000). Probit models showed that medical students admitted under the separate-code admission pathway were more likely to choose medicine as their first preferred major at application (ß=0.96, p=0.000); medical students admitted into medical school as their first preferred major were more likely to be willing to study medicine if choosing again (ß=0.53, p=0.000) or to recommend the medical major to other students (ß=0.18, p=0.010). CONCLUSION: Separate-code admission is more likely to result in matriculants who choose medicine as their first preferred major and are more likely to be intrinsically interested in medicine than those applicants assigned to medicine from the uniform admission process.

ß-elemene inhibits radiation and hypoxia-induced macrophages infiltration via Prx-1/NF-κB/HIF-1α signaling pathway.

Background: In cancers, tumor-associated macrophages (TAMs) play an important role in the progression, evasion of immunity and sensitivity to therapy. Unfortunately, radiation and hypoxia could induce the M2 macrophages infiltration and polarization. Materials and methods: In this study, we investigated the relevance of macrophage recruitment with radiation and hypoxia by transwell. We also evaluated the effect of ß-elemene on the infiltration of M2 macrophages and explored its underlying molecular mechanism by a series of in vitro and in vivo experiments. Results: Irradiated or hypoxia lung cancer cells recruit macrophages, and the recruitment is MCP-1 dependent. We also found that radiation and hypoxia-induced MCP-1 secretion follows upregulation of Prx-1, which leads to nuclear accumulation of NF-κB and HIF-1α expression. In addition, ß-elemene could effectively suppress this recruitment phenomenon through Prx-1/NF-κB/HIF-1α signaling. Conclusion: Our study showed that radiation and hypoxia significantly promoted the macrophages recruitment. ß-elemene could effectively suppress this recruitment phenomenon and MCP-1 expression via inhibiting Prx-1/NF-κB/HIF-1α pathways.

Merkel cell carcinoma metastatic to cervical lymph node in a patient with rheumatoid arthritis: a case report.

Merkel cell carcinoma (MCC) is a rare, aggressive skin malignancy that has a propensity for local recurrence and metastasis to the lymph nodes. In this case report, we discuss a 54-year-old female with rheumatoid arthritis (RA) who had received treatment with prednisone (15 mg/day) for symptom relief and management. The patient visited our hospital with complaints of a nodule in right preauricular area. Computed tomography (CT) scans revealed no distant metastasis. The patient underwent surgical resection and histopathological evaluation of the nodule led to the diagnosis of MCC. The patients received post-surgical treatment with 6 MeV electronic wire radiotherapy. Six months later, CT of the head, neck, abdomen and chest demonstrated a right cervical lymph node mass at the C2 level. The patient then underwent cervical lymph node biopsy and pathological diagnosis confirmed metastatic MCC. One month after the lymph node biopsy, the patients received postoperative intensity modulated radiation therapy in the biopsied area. The patient did not experience any adverse effects to the therapy. In conclusion, the MCC patients with RA can tolerate radiation therapy. As MCC is a highly malignant neoplasia, considering the immune checkpoint inhibitors can lead to immune-related adverse events, detection of MCC at earlier stages is associated with better survival. The treatment decisions of MCC patients with RA continues is still challenging.

ß-elemene inhibits tumor-promoting effect of M2 macrophages in lung cancer.

Macrophages in tumor are mostly M2-polarized and have been reported to promote tumorigenesis, which are also defined as tumor-associated macrophages (TAMs). ß-elemene has therapeutic effects against several cancers, however, it remains unknown whether ß-elemene could inhibit cancer by targeting TAMs. Herein, we examined the effect of ß-elemene on macrophages to elucidate a novel mechanism of ß-elemene in tumor therapy. We showed that the conditioned medium of M2 macrophages promoted lung cancer cells to migration, invasion and epithelial mesenchymal transition, which could be inhibited by ß-elemene. Moreover, ß-elemene regulated the polarization of macrophages from M2 to M1. ß-elemene also inhibited the proliferation, migration, invasion of lung cancer cells and enhanced its radiosensitivity. These results indicate ß-elemene suppresses lung cancer by regulating both macrophages and lung cancer cells, it is a promising drug for combination with chemotherapy or radiotherapy.

Career preferences of graduating medical students in China: a nationwide cross-sectional study.

BACKGROUND: China faces major challenges in the distribution of health professionals with serious shortages in rural areas and in the development of Primary Care Providers (PCPs). This study investigates the career preferences of medical students in China and the impact of rural backgrounds on these preferences. METHODS: Medical students in the final year of their program in 16 medical schools across China completed a 58-item survey that included questions regarding their demographic characteristics, attitudes toward practice in low resource areas, postgraduate planning, self-assessed competency, university facilities assessment, and financial situation. Descriptive calculation and Logit model were used for the analysis. RESULTS: Completed surveys from 3020 students were included in the analysis. Upon graduation, 48.5% of the medical students preferred to work in urban public hospitals and this percentage rose to 73.6% when students were asked to state their anticipated preference five years after graduation. Students' top three ranked reasons for preferred careers were "good career prospects", "living close to parents/families", and "remuneration". Those who preferred to work in rural areas upon graduation were more likely to be those who lived in rural areas when 1-15 years old (ß = 2.05, p < 0.001), had high school in rural areas (ß = 1.73, p < 0.001), or had parents' place of current residence in rural areas (ß = 2.12, p < 0.001). Similar results were found for those students who preferred to work in PCPs. CONCLUSIONS: To address the serious shortages of health professionals in rural areas and PCPs, medical schools should consider strategies to recruit more medical applicants with rural backgrounds and to orient students to rural and primary care interests.