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To estimate the oncologic outcomes of radical prostatectomy (RP) and high-dose intensity-modulated radiotherapy (IMRT) with short-term androgen-deprivation therapy (ADT) in relatively young men with unfavorable intermediate-risk prostate cancer, as defined by the National Comprehensive Cancer Network (NCCN-UIR-PC).
We enrolled relatively young men (≤65 years) from the Taiwan Cancer Registry who had been diagnosed as having NCCN-UIR-PC and who had received RP or high-dose IMRT (at least ≥72 Gy) with short-term ADT (4-6 months). After propensity score matching of the confounders, Cox proportional regression was used to model the time from the index date (i.e., date of diagnosis) to all-cause death, biochemical failure (BF), locoregional recurrence (LRR), and distant metastasis (DM).
The corresponding adjusted hazard ratios (95% confidence intervals) of the risk of all-cause death, BF, LRR, and DM were 2.76 (1.36-5.60,
= 0.0050), 2.74 (1.72-4.84,
< 0.0001), 1.28 (1.09-1.90,
= 0.0324), and 2.11 (1.40-4.88,
= 0.0052), respectively.
RP is superior to high-dose IMRT with short-term ADT in terms of oncologic outcomes for relatively young men with UIR-PC.
RP is superior to high-dose IMRT with short-term ADT in terms of oncologic outcomes for relatively young men with UIR-PC.Red pear is a popular fruit that is appreciated for its attractive and distinctive appearance and mild flavor. In this study, we investigated the mechanism underlying the red coloration of pear skin using the 'Xinqihong' cultivar-which was selected as a spontaneous bud sport mutant of the 'Xinli 7'(Pyrus betulifolia Rehd.) variety and has a stronger red color that is retained in the mature fruit-as an experimental model. We compared the phenotype and gene expression patterns of the two varieties and found no significant differences at the early stage of fruit development. TDO inhibitor However, although the red color of 'Xinli 7' fruits began to fade 107 days after full bloom, that of 'Xinqihong' fruits persisted until the time of harvest. Transcriptome sequencing identified 639 genes that were differentially expressed between the two varieties, including genes related to light, calcium, and hormone signaling (e.g., PbPIF3, PbGA2ox, and the calmodulin related genes). Moreover, anthocyanin biosynthesis genes were downregulated as the red color of 'Xinli 7' fruits faded. These results provide insight into the molecular basis of color differences in red pears that can be useful for improving its fruit quality and commercial value.Hypoxic cancer cells meet their growing energy requirements by upregulating glycolysis, resulting in increased glucose consumption and lactate production. Herein, we used a unique approach to change in anaerobic glycolysis of cancer cells by lactate calcium salt (CaLac). Human colorectal cancer (CRC) cells were used for the study. Intracellular calcium and lactate influx was confirmed following 2.5 mM CaLac treatment. The enzymatic activation of lactate dehydrogenase B (LDHB) and pyruvate dehydrogenase (PDH) through substrate reaction of CaLac was investigated. Changes in the intermediates of the tricarboxylic acid (TCA) cycle were confirmed. The cell viability assay, tube formation, and wound-healing assay were performed as well as the confirmation of the expression of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF). In vivo antitumor effects were evaluated using heterotopic and metastatic xenograft animal models with 20 mg/kg CaLac administration. Intracellular calcium and lactate levels were increased following CaLac treatment in CRC cells under hypoxia. Then, enzymatic activation of LDHB and PDH were increased. Upon PDH knockdown, α-ketoglutarate levels were similar between CaLac-treated and untreated cells, indicating that TCA cycle restoration was dependent on CaLac-mediated LDHB and PDH reactivation. CaLac-mediated remodeling of cancer-specific anaerobic glycolysis induced destabilization of HIF-1α and a decrease in VEGF expression, leading to the inhibition of the migration of CRC cells. The significant inhibition of CRC growth and liver metastasis by CaLac administration was confirmed. Our study highlights the potential utility of CaLac supplementation in CRC patients who display reduced therapeutic responses to conventional modes owing to the hypoxic tumor microenvironment.The effect of calcium nitrate (CN) dosages from 0 to 3% (of cement mass) on the properties of fresh cement paste rheology and hardening processes and on the strength of hardened concrete with two types of limestone-blended composite cements (CEM II A-LL 42.5 R and 42.5 N) at different initial (two-day) curing temperatures (-10 °C to +20 °C) is presented. The rheology results showed that a CN dosage up to 1.5% works as a plasticizing admixture, while higher amounts demonstrate the effect of increasing viscosity. At higher CN content, the viscosity growth in normal early strength (N type) cement pastes is much slower than in high early strength (R type) cement pastes. For both cement-type pastes, shortening the initial and final setting times is more effective when using 3% at +5 °C and 0 °C. At these temperatures, the use of 3% CN reduces the initial setting time for high early strength paste by 7.4 and 5.4 times and for normal early strength cement paste by 3.5 and 3.4 times when compared to a CN-free cement paste. The most efficient use of CN is achieved at -5 °C for compressive strength enlargement; a 1% CN dosage ensures the compressive strength of samples at a -5 °C initial curing temperature, with high early strength cement exceeding 3.5 MPa but being less than the required 3.5 MPa in samples with normal early strength cement.Apicomplexan parasites are obligatory intracellular protozoa. In the case of Toxoplasma gondii, Neospora caninum or Besnoitia besnoiti, to ensure proper tachyzoite production, they need nutrients and cell building blocks. However, apicomplexans are auxotrophic for cholesterol, which is required for membrane biosynthesis. P-glycoprotein (P-gp) is a transmembrane transporter involved in xenobiotic efflux. However, the physiological role of P-gp in cholesterol metabolism is unclear. Here, we analyzed its impact on parasite proliferation in T. gondii-, N. caninum- and B. besnoiti-infected primary endothelial cells by applying different generations of P-gp inhibitors. Host cell treatment with verapamil and valspodar significantly diminished tachyzoite production in all three parasite species, whereas tariquidar treatment affected proliferation only in B. besnoiti. 3D-holotomographic analyses illustrated impaired meront development driven by valspodar treatment being accompanied by swollen parasitophorous vacuoles in the case of T.
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