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Limited data exist regarding the utility and validity of the 21-gene recurrence score (RS) in patients with de novo metastatic breast cancer (dnMBC). This study aimed to investigate the practice patterns as well as associated survival outcomes based on 21-gene RS in dnMBC. The Surveillance, Epidemiology, and End Results Oncotype database was queried for women with hormone receptor-positive and Her2-negative dnMBC. A total of 153 patients were identified, including 62.7% and 37.3% of patients who had RS < 26 and ≥ 26, respectively. Patients with RS ≥ 26 were more likely to receive chemotherapy compared to those with RS < 26 (61.4% vs. 28.1%, p < 0.001). Patients with RS ≥ 26 had an inferior breast cancer-specific survival (BCSS) (2-year BCSS: 84.3% vs. 89.5, p = 0.067) and overall survival (OS) compared to those with RS < 26 (2-year OS: 76.9% vs. 87.4%, p = 0.018). The multivariate Cox proportional hazard models showed that those with RS ≥ 26 had a significantly inferior BCSS (hazard ratio [HR] 2.251, 95% confidence interval [CI] 1.056–4.799, p = 0.036) and OS (HR 2.151, 95%CI 1.123–4.120, p = 0.021) compared to those with RS < 26. The 21-gene RS assay is an important prognostic factor in patients with dnMBC. [ABSTRACT FROM AUTHOR]

Many undergoing in vitro fertilization-embryo transfer (IVF-ET) procedures treatments have been tried for older infertile patients, but still can not reverse the aging effect on oocyte, and infertility treatment is expensive, even for people in developed countries. The study aimed to compare outcomes following the application of luteal phase ovulation induction (LPOI) and ultra-short gonadotropin-releasing hormone agonist (GnRH-a) protocols in patients aged more than 40 years undergoing IVF-ET and to examine the effectiveness and feasibility of LPOI. A total of 266 IVF-ET cycles in 155 patients aged 40 years and over were retrospectively analyzed. Of these patients, 105 underwent the ultra-short GnRH-a protocol (GnRH-a group) and 50 underwent LPOI (LPOI group). Various clinical outcomes were compared between these two groups using either t-tests or the chi-square test. The study showed patients in the LPOI group required a higher dosage of human menopausal gonadotropin and a lower dosage of recombinant follicle stimulating hormone than those in the GnRH-a group. Furthermore, though the total dosage of gonadotropin was higher in the LPOI, its cost was lower. Finally, fertilization rates were higher and high-quality embryo rates were lower in the LPOI group, and the live birth rate of LPOI group is higher than (GnRH-a group). These between-group differences were all significant (P < 0.05). Compared with the ultra-short GnRH-a protocol, LPOI may enable higher 2-pronuclear embryo fertilization rates and lower gonadotropin costs to be achieved, indicating that LPOI might be an ideal choice for older patients undergoing IVF-ET. [ABSTRACT FROM AUTHOR]

Myotubularin related protein 7 (MTMR7), a key member of the MTMR family, depicts phosphatase activity and is involved in myogenesis and tumor growth. We have previously identified MTMR7 in the proteomic profile of mouse spermatogonial stem cell (SSC) maturation and differentiation, implying that MTMR7 is associated with neonatal testicular development. In this study, to further explore the distribution and function of MTMR7 in mouse testis, we studied the effect of Mtmr7 knockdown on neonatal testicular development by testicular and SSC culture methods. Our results revealed that MTMR7 is exclusively located in early germ cells. Deficiency of MTMR7 by morpholino in neonatal testis caused excessive SSC proliferation, which was attributable to the aberrant PI3K/AKT signaling activation. Altogether, our study demonstrates that MTMR7 maintains SSC homeostasis by inhibiting PI3K/AKT signaling activation. [ABSTRACT FROM AUTHOR]

Background: The development of nanoparticle drug delivery systems with targeted ligands has the potential to increase treatment efficiency in ovarian cancer. Methods: We developed a 21-amino acid peptide, YTRDLVYGDPARPGIQGTGTF (L-FP21) conjugated to polyethylenimine (PEI) and methoxy polyethylene glycol (mPEG) to prepare a nanoparticle drug vehicle to target follicle-stimulating hormone receptor (FSHR) in ovarian cancer. At the same time, we optimized the ligand of the nanoparticle vehicle using D-peptides, which consist of D-amino acids (D-FP21). Nanoparticle vehicles carrying the therapeutic gene plasmid growth-regulated oncogene alpha (pGRO-α) short hairpin RNA (shRNA) (FP21-PEG-PEI/pGRO-α) were prepared for further investigation. Results: Compared with L-FP21, D-FP21 exhibited improved biological stability and higher uptake rate for FSHR-expressing ovarian cancer cells. The cytotoxicity of the L, D-FP21-PEG-PEI/pGRO-α complexes were significantly lower than that of the PEI/pGRO-α complex. The nanoparticle drug with the targeted ligand showed higher transfection efficiencies and improved anti-proliferation effects for ovarian cancer cells than that without the targeted ligand (mPEG-PEI/pGRO-α). Furthermore, an in vivo evaluation of an antitumor assay indicated that D-FP21-PEG-PEI/pGRO-α inhibited the growth of tumor spheroids considerably more than L-FP21-PEG-PEI/pGRO-α; their tumor inhibition rates were 58.5% and 33.3%, respectively. Conclusions: D-FP21-PEG-PEI/plasmid DNA is a safe and efficient gene delivery vehicle for ovarian cancer targeted therapy. [ABSTRACT FROM AUTHOR]

The distinct hormone molecules and receptors, such as follicle-stimulating hormone receptor (FSHR) in ovarian cancer, provide opportunities for more precisely targeted therapy. We previously developed FSHR-mediated nanoparticles and found that FSH peptides on the surface of nanoparticles improved the delivery of short interfering RNA (siRNA) into ovarian cancer cells. However, the high toxicity of the nanoparticles and the transient silencing of the siRNA in vivo limited further study. Here, we developed FSH peptide-conjugated nanoparticles with an increased amount of polyethylene glycol (PEG) grafting and encapsulated short hairpin RNA (shRNA) to silence the target gene, growth-regulated oncogene α (gro-α). The nanoparticle complexes exhibited good stability over three weeks. Expression of the target gene, gro-α, was significantly down-regulated by gro-α shRNA-loaded nanoparticles conjugated with FSH peptides (FSH33-G-NP) in FSHR-positive HEY cells. Cell proliferation, migration, and invasion were also inhibited by FSH33-G-NP. Tumor growth was delayed significantly in the mice treated with FSH33-G-NP. No significant loss of body weight or severe toxic effects were observed in any groups. In conclusion, gro-α shRNA-loaded nanoparticles conjugated with FSH peptides overcame the drawbacks of the in vivo application of RNAi therapeutics and polymer-based nanocarriers and showed safe antitumor efficacy. Our study might contribute to the application of FSHR-based targeted therapy and imaging in cancer. [ABSTRACT FROM AUTHOR]

In vitro interaction of osthol (Ost) and fluconazole (FLC) was investigated against 11 fluconazole-resistant clinical isolates of Candida albicans. Synergistic activities were determined using the checkerboard microdilution assay. The results of agar diffusion test confirmed the synergistic interaction. We used an enteric material Eudragit S100 for preparation of Ost nanoparticle (Ost-NP) to improve the oral bioavailability, biological activity of Ost. The physicochemical characteristics of Ost-S100-NP revealed Ost-S100-NP with mean particle size of 55.4±0.4 nm, encapsulation efficiency of 98.95±0.06%, drug loading efficiency of 23.89±0.25%, yield of 98.5±0.1% and a polydispersity index (PDI) of 0.165. As the Ost concentration-time curve showed, Ost-S100-NP can increase the plasma concentration and relative bioavailability of Ost compared with Ost-suspension by oral administration. In vivo, Ost-S100-NP enhanced the therapeutic efficacy of Ost against FLC-resistant C. albicans in immunosuppressed candidiasis mice model. The available information strongly suggests that Ost-S100-NP may be used as a promising compound against drug-resistant fungi. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a common malignant neoplasm of the head and neck which is harmful to human's health. Radiotherapy is commonly used in the treatment of NPC and it induces immediate cell cycle arrest and cell apoptosis. However, the mechanism remains unknown. Evidences suggested the activation of Ataxia telangiectasia mutated (ATM) pathway and Smad pathway are 2 of the important crucial mediators in the function of radiotherapy. In this study, we performedin vitroassays with human nasopharyngeal carcinoma CNE-2 cells andin vivoassays with nude mice to investigate the role of the ATM and Smad pathways in the treatment of nasopharyngeal carcinoma with radiotherapy. The results suggested that radiation induced activation of ATM pathway by inducing expression of p-ATM, p-CHK1, p-CHK2, p15 and inhibiting expression of p-Smad3. In addition, Caspase3 expression was increased while CDC25A was decreased, leading to cell cycle arrest and cell apoptosis. On the other hand, activation of Smad3 can inhibited the ATM pathway and attenuated the efficacy of radiation. In summary, we suggest that both ATM and Smad pathways contribute to the cell cycle arrest and cell apoptosis during nasopharyngeal carcinoma cells treated with radiation. [ABSTRACT FROM PUBLISHER]

In this study, the complete mitogenome sequence of Ostrinia furnacalis was described. The assembled mitogenome is 15,241 bp in length with an extreme bias of high AT content (80.9%) (GenBank accession no. MN747041). The mitochondrial genome contains 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (12S rRNA and 16S rRNA) genes, and a control region (D-loop region). The mitochondrial gene order was identical to that observed in most lepidopteran genomes, nine PCGs were located on the H-strand, others were located on the L-strand. 12 PCGs were initiated by typical ATN codons, except for COI with CGA instead. 21 tRNAs had the typical cloverleaf structure, while the DHU arm of the trnS1 gene did not form a stable stem-loop structure. The 'ATAGT(A)'-like motif and a 19 bp poly-T stretch at the down-stream of the rrnS gene were observed in the A + T-rich region. The phylogenetic analysis showed that the relationship of O. furnacalis is very close to the three species in the subfamily Pyraustinae: O. nubilalis, O. penitalis and Loxostege sticticalis, and all the subfamilies of Spilomelinae, Pyraustinae, Crambinae and Nymphulinae within Crambidae formed monophyletic groups with the highest bootstrap value support. [ABSTRACT FROM AUTHOR]