P53­microRNA interactions regulate the response of colorectal tumor cells to oxaliplatin under normoxic and hypoxic conditions.

Oxaliplatin (OXA)­containing regimens are used as first­line chemotherapy in colorectal cancer (CRC). However, OXA resistance remains a major challenge in CRC treatment. CRC cells that adapt to hypoxia can potentially develop OXA resistance, and the underlying molecular mechanisms still need to be further investigated. In the current study, the OXA drug sensitivity of two CRC cell lines, HCT116 (TP53WT) and HT29 (TP53MT), was compared under both normoxic and hypoxic conditions. It was found that under normoxic condition, HCT116 cells showed significantly higher OXA sensitivity than HT29 cells. However, both cell lines showed remarkable OXA resistance under hypoxic conditions. It was also revealed that P53 levels were increased after OXA and hypoxia treatment in HCT116 cells but not in HT29 cells. Notably, knocking down P53WT decreased normoxic but increased hypoxic OXA sensitivity in HCT116 cells, which did not exist in HT29 cells. Molecular analysis indicated that P53WT activated microRNA (miR)­26a and miR­34a in OXA treatment and activated miR­23a in hypoxia treatment. Cell proliferation experiments indicated that a high level of miR­23a decreased OXA sensitivity and that a high level of miR­26a or miR­34a increased OXA sensitivity in HCT116 cells. Additionally, it was demonstrated that miR­26a, miR­34a and miR­23a affect cell apoptosis through regulation of MCL­1, EZH2, BCL­2, SMAD 4 and STAT3. Taken together, the present findings revealed the dual function of P53 in regulating cellular chemo­sensitivity and highlighted the role of P53­miR interactions in the response of CRC cells to OXA chemotherapy under normoxic and hypoxic conditions.

Application of tumor-targeting peptide-decorated polypeptide nanoparticles with doxorubicin to treat osteosarcoma.

Osteosarcoma is the most common primary malignant bone tumor in childhood and adolescence. Currently, surgery combined with chemotherapy is the main treatment for osteosarcoma. However, the long-term survival of patients with metastatic osteosarcoma is unsatisfactory. Therefore, new treatment methods to improve the prognosis of patients with osteosarcoma are required. The present study aimed to develop nanocarriers with both tumor targeting and reduction responsiveness abilities, and to improve the therapeutic effect and reduce toxicity by loading traditional small molecule antitumor drugs. The tumor targeting peptide-decorated, doxorubicin (DOX)-loaded mPEG-P(Phe-co-Cys) nanoparticles were developed successfully through the ring-opening polymerization of amino acids. The peptide VATANST (STP) can specifically bind with vimentin, which is highly expressed on the osteosarcoma cell surface, resulting in tumor targeting effects. The nanoparticle is core-shell structured to protect the loaded DOX during blood flow. The disulfide bonds within the nanoparticles are sensitive to the osteosarcoma microenvironment, which has high glutathione (GSH) levels. Under the enhanced permeability and retention and active tumor targeting effects, the STP-decorated DOX-loaded nanoparticles accumulated in tumor tissues. High GSH levels can rupture disulfide bonds, resulting in the controlled release of DOX, which will cause necrosis of tumor cells. The characteristics of the synthesized nanoparticles, DOX release profiles in vitro and in vivo, cytotoxicity analysis, animal study, and safety evaluation were performed. The nanoparticles could increase the tumor inhibition efficiency against osteosarcoma and reduce the side effects of DOX to major organs. The STP-decorated mPEG-P(Phe-co-Cys) nanoparticles might be a suitable drug delivery system for DOX to treat osteosarcoma.

Recurrent borderline phyllodes tumor in nipple: a rare case report and review of the literature.

Phyllodes tumor (PT) of the breast is a rare tumor. They are usually located in the four quadrants of the mammary gland and may also appear below the nipple. Although there have been a number of cases reported, here we report a very rare case of this tumor in an unusual location. The patient has been diagnosed with right breast borderline PT, who accepted breast-conserving surgery. Twelve months after surgery we found right nipple enlargement, without nipple discharge, ipsilateral and contralateral breast without palpable mass. Interestingly, ultrasound showed a lesion in the right nipple: a hypoechoic mass with a diameter of 2.0 cm was seen in the nipple, with no significant calcification. The patient underwent nipple-sparing mastectomy without postoperative adjuvant radiotherapy. Histopathological and immunohistochemical analysis demonstrated a borderline PT. There were no signs of recurrence after two years of follow-up. We consider that wide surgical resection and negative margin are still the main methods for the treatment of recurrent borderline PTs.

Does Choice of Reconstruction Type Affect Survival in Patients With Metastatic Breast Cancer?

BACKGROUND: To compare the breast cancer-specific survival (BCSS) and overall survival (OS) between patients who underwent implant or tissue reconstruction after mastectomy with distant metastatic breast cancer (MBC). MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results database, we enrolled 371 female MBC cases diagnosed during the years 2004-2014. Patients were subdivided into implant (176) and tissue groups (195) for survival comparison between the two groups. The end points were BCSS and OS. Comparisons of the distribution of clinicopathologic characteristics were evaluated by chi-square test and Fisher exact test. Survival outcomes were compared by Kaplan-Meier model and multivariate Cox regression model for known clinicopathologic variables in both the entire population and in the reconstruction cohorts. RESULTS: In the entire cohort, patients with implant exhibited distinctly better BCSS (log rank, P = 0.002) and OS (log rank, P = 0.001) than patients with tissue reconstruction. Multivariate Cox regression model revealed that patients, who received prosthetic implants, were married, and progesterone receptor-positive group showed better survival rates in BCSS and OS. In addition, after stratification of the implant group and tissue groups according to clinicopathologic variables, the survival rate of patients in the implant group was higher than that in the tissue reconstruction group under the influence of factors, such as married, estrogen receptor-negative, nonradiotherapy, and chemotherapy. CONCLUSIONS: Our study provides further survival evidence supporting the practice of mastectomy with prosthetic implant reconstruction in patients with MBC under certain conditions.

20(S)-Ginsenoside Rg3-loaded electrospun membranes to prevent postoperative peritoneal adhesion.

Postoperative peritoneal adhesions are one of the most common surgical complications. In this study, we developed a 20(S)-ginsenoside Rg3-loaded methoxy poly (ethylene glycol)-block-poly(L-lactide-co-glycolide) (mPEG-b-PLGA) electrospun membrane (PEM/Rg3) that could not only serve as a physical barrier, but also as a drug delivery system that releases 20(S)-ginsenoside Rg3 constantly to prevent postoperative peritoneal adhesions. The characteristics of PEM/Rg3, including scanning electron microscopy, water contact angle, and mechanical analyses, were assessed. Degradation and drug release assays of PEM/Rg3 were performed. The anti-adhesion efficacy of PEM/Rg3 was evaluated in an abdomen-cecum mouse model. The adhesion scores, adhesion areas, hematoxylin and eosin (H&E) staining, immunofluorescence, and western blotting were assessed. The 20(S)-ginsenoside Rg3 loaded mPEG-b-PLGA electrospun fibers were successfully fabricated. The fibers were smooth, with no obvious drug crystals. PEM/Rg3 membranes were biodegradable and could be degraded gradually to release 20(S)-Ginsenoside Rg3 constantly from the membranes. The animal study showed that PEM/Rg3 exhibited an excellent adhesion prevention ability when compared with the control group, the PEM group, and polylactic acid (PLA) commercial membrane (Surgiwrap™) group. Immunofluorescence and western blotting studies showed that PEM/Rg3 inhibited the expressions of interleukin 1 (IL-1), interleukin 6 (IL-6), and reactive oxygen species modulator-1 (ROMO1). The 20(S)-ginsenoside Rg3-loaded mPEG-b-PLGA electrospun membranes exhibited satisfactory anti-adhesion efficacy by inhibiting inflammatory responses and oxidative stress. This composite represents a promising strategy to prevent postoperative peritoneal adhesions.