Traditional chemotherapeutic drugs have shown limited clinical curative effects in antitumor therapy. The application of multidrug combination and adjuvant-drug carriers is a feasible strategy to overcome the limitations while minimizing the dosage of single drug and acquiring the synergistic effects in tumor therapy. However, the systemic toxicity, drug resistance, and tumor recurrence are still unavoidable. Here we develop core-shell nanoparticles (NPs) to encapsulate paclitaxel (PTX) and gemcitabine (GEM) for breast cancer therapy. We find that the NPs could encapsulate PTX and GEM, with an encapsulation efficiency of 96.3 and 95.13%, respectively. Moreover, the drug loading of these NPs is 2.71% (PTX) and 2.64% (GEM). Notably, the co-delivery of GEM and PTX performs enhanced anticancer effect compared with the PTX alone or GEM alone therapy at the same concentration, which indicates a synergistic effect. Moreover, encapsulation of PTX and GEM by methoxy poly(ethylene glycol)-poly(lactide-coglycolide) also shows enhanced anticancer effects (81.5% tumor inhibition) and reduced systemic toxicity in vivo compared with free drugs (65% tumor inhibition). Together with those results, co-delivery of PTX and GEM by methoxy poly(ethylene glycol)-poly(lactide-coglycolide) might have important potencies in clinical applications for breast cancer therapy.
Background This study aimed to investigate the clinical and pathological characteristics, and the recurrence and prognostic factors of borderline ovarian tumors (BOTs). Methods The data of 286 patients admitted to hospital and followed up for more than ten months were analyzed retrospectively to study the clinicopathological characteristics and related factors of recurrence. Results The median age of the patients was 42.06 ± 14.97 years, and the duration of the follow-up ranged from 10–109 months. During the follow-up period, 40 patients had a recurrence. Of these patients, 36 were ≤ 40 years, and patients with premenopausal recurrence accounted for 20.5% (36/176). In patients undergoing conservative treatment or radical operations, the recurrence rates were 21.3% and 1.8%, respectively, and they were 13.4% (36/268) in patients at Federation International of Gynecology and Obstetrics (FIGO) stage I, and 22.2% (4/18) in patients at an advanced stage. Postoperative pathology revealed that 40 patients had micropapillary tumors, among whom ten patients (25%) had a recurrence, and 19 patients had complications with interstitial infiltration. Of these 19 patients, six had a recurrence (31.5%). Another 22 patients had complications with calcified sand bodies; among these, eight patients (36.4%) had a recurrence. All the differences were statistically significant (P < 0.05). There were four cancer-related deaths during the follow-up period. Late FIGO stage, conservative operation, and a high level of carbohydrate antigen 125 (CA125) were independent risk factors for the recurrence of BOTs. Conclusion BOTs usually occur in women under 40 years, have an occult onset, and half of the patients have no obvious clinical manifestations. Serum CA125 level can be used as a tumor marker to detect BOTs and the risk of its recurrence. Operation mode and FIGO stage are important independent factors for the recurrence of BOTs.
PDZ‐LIM domain‐containing Protein 2 (PDLIM2) has been reported to be downregulated in ovarian cancer. However, its exact function and mechanism in regulating ovarian cancer progression have not been elucidated. This work researched the exert effect and mechanism of PDLIM2 on ovarian cancer progression. Briefly, PDLIM2 expression in clinical tissues of ovarian cancer patients and cells was investigated by qRT‐PCR and Western blot. The function of PDLIM2 on the proliferation, colony formation, migration and invasion of ovarian cancer cells was explored via cell counting kit‐8, colony formation and Transwell assays. To verify whether PDLIM2 regulates ovarian cancer progression via regulating the transforming growth factor‐β (TGF‐β)/Smad pathway, exogenous TGF‐β (10 ng/mL) treatment was performed on the PDLIM2‐overexpressed ovarian cancer cells. PDLIM2 effect on the in vivo growth of ovarian cancer cells was researched by establishing a xenograft tumor model. Immunohistochemistry and Western blot were performed to protein expression in cells and tissues. As a result, PDLIM2 was low‐expressed in ovarian cancer tissues/cells. PDLIM2 upregulation attenuated the proliferation, colony formation, migration, invasion and epithelial‐mesenchymal transition (EMT) of ovarian cancer cells, and inactivated the TGF‐β/Smad pathway. The opposite results were found in the PDLIM2‐silenced ovarian cancer cells. Exogenous TGF‐β treatment abrogated the inhibition of PDLIM2 on the malignant behavior of ovarian cancer cells. PDLIM2 upregulation attenuated the in vivo growth and EMT of ovarian cancer cells. Thus, PDLIM2 attenuates the proliferation, migration, invasion and EMT of ovarian cancer cells via inactivating the TGF‐β/Smad pathway. PDLIM2 may be a usefully target for ovarian cancer treatment.
A portable on-site gas flow standard device based on the standard meter method is designed to ensure metering accuracy in the natural gas trade. The standard device is optimized using CFD simulation technology. The acquisition of high and low frequency pulse signals, video photoelectric signals, and manual trigger signals is realized. Non-fixed-point measurement is realized by corrected linear interpolation of fixed-point and least-squares construction of the instrument coefficient correlation. The flow rate range of the device is (0.65~650) m3/h and the expanded uncertainty is 0.33 % (k=2). The device is compact, portable, and can be carried on a vehicle for on-site application. The device is compared with the bell-type gas flow standard device and the sonic nozzle gas flow standard device of Hebei Metrology Supervision and Inspection Institute. The experimental results show that the En value of the device is 0.67, and the measurement repeatability is better than 0.12 %.
Cancer remains to be a leading cause of death worldwide, accounting for almost 10 million deaths in 2018. Radiation therapy (RT) is a common nonsurgical treatment in the management of patients with cancer that reduces disease recurrence and improves overall survival. However, preclinical RT modeling for accelerated bench-to-bedside translation of combination therapies is largely missing. While genetically engineered mouse models (GEMM) faithfully recapitulate human disease, conventional linear particle accelerator systems, commonly utilized in clinical settings, are not suited for state-of-the-art, imageguided targeted RT (IGRT) of these murine autochthonous tumors. Thus, we employed the CyberKnife (Accuray) platform for IGRT of GEMM-derived non-small cell lunger cancer (NSCLC) lesions. The CyberKnife (CK) is a stereotactic radiosurgery system (SRS) delivering high-dose RT precisely to the target area with minimal damage to the surrounding tissues based on intra-fraction image-guidance.Material and methods: GEMM-derived NSCLC flank tumors driven by oncogenic Kras (Kras LSL-G12D/+ ) and deletion of Tp53 (Trp53 fl/fl ) were irradiated using the CK RT platform.We applied IGRT of 2, 4, 6, and 8 Gy using field sizes of 5 to 12.5 mm to average gross tumor volumes (GTV) of 0.9 cm 3 (minimal 0.03 cm 3 ) using Xsight Spine Tracking (Accuray) spine-based tumor localization. Results:We found that a 0 mm planning target volume (PTV) margin is sufficient for IGRT of murine tumors using the CK. Furthermore, we analyzed the impact of CK-mediated IGRT on tumor infiltrating leukocytes by flow cytometry. We observed that higher RT doses (6-8 Gy) decreased absolute cell numbers of lymphocytes and myeloid cells by approximately half compared to low doses (2-4 Gy) or mock treated tumors within one hour, but even with low dose RT (2 Gy) tumor infiltrating leukocytes (TIL) were found to be reduced after 8 to 24 hours and recovered partly after 3 days. Conclusion:In summary, we here demonstrate that the CK RT system allows for targeted IGRT of murine tumors with high precision and thus constitutes a novel promising platform for translational mouse RT studies, particularly performed in a longitudinal multimodal manner.
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