The prognostic significance of growth pattern, tumor budding, poorly differentiated clusters, desmoplastic reaction pattern and tumor-stroma ratio in colorectal cancer and an evaluation of their relationship with KRAS, NRAS, BRAF mutations

Article

作者: Cakir, I Ebru ; Cakir, I. Ebru ; Unal Kocabey, Duygu ; Kocabey, Duygu Unal

Growth pattern (GP), tumor budding (TB), poorly differentiated clusters (PDC), desmoplastic reaction pattern (DRP) and tumor-stroma ratio (TSR) are prognostic histomorphological parameters in colorectal cancer (CRC). Correlations between these parameters, their individual prognostic values, and their relationship with KRAS/NRAS/BRAF mutations have not been comprehensively examined. We aimed to investigate these associations, which have not been previously explored in this combination. 126 CRC cases were included. GP, TB, PDC, DRP and TSR were evaluated by two experienced pathologists. KRAS/NRAS/BRAF mutation profile were determined using qPCR. Demographic, clinicopathological and survival data were recorded. Interrelations were investigated by statistical analysis. Infiltrative GP was more frequent in high-score TB, PDC-G3, and stroma-high tumors (p < 0.05). High-score TB was more common in PDC-G3 and stroma-high tumors (p < 0.05). Immature DRP was more frequent in stroma-high tumors (p = 0.014). Among histomorphological parameters, a significant relationship was found only between infiltrative GP and the presence of KRAS mutation (p = 0.023). Moreover, GP was significantly associated with pT, lymphatic invasion, perineural invasion (p < 0.05). Effects on survival were assessed using Kaplan-Meier method and Cox proportional hazards model. TB and PDC were identified as independent predictors of overall survival. Higher TB score (p = 0.008) and higher PDC grade (p = 0.013) lead to worse survival. Interestingly, GP, DRP, TSR or KRAS/NRAS/BRAF mutations were not associated with overall survival. Our results highlight the prognostic significance of TB and PDC. We suggest incorporating TB and PDC into routine CRC reports. The association of KRAS mutation with infiltrative GP supports its role in the acquisition of invasive behavior.

2024-12-01·Journal of Hazardous Materials

Simultaneous removal of nutrients and pharmaceuticals and personal care products using two-stage woodchip bioreactor-biochar treatment systems

Article

作者: Tang, Shuai ; Si, Buchun ; Timalsina, Haribansha ; Kandume, Jason ; Circenis, Sophie ; Bhattarai, Rabin ; Cooke, Richard ; Zhou, Hongxu ; Zheng, Wei

The co-occurrence of nutrients and pharmaceuticals and personal care products (PPCPs) in sewage effluent can degrade water quality of the receiving watersheds. This study investigated the simultaneous removal of excess nutrients and PPCP contaminants by developing a novel woodchip bioreactor and biochar (B²) treatment system. The result revealed that woodchip bioreactors could effectively remove nitrate via a denitrification process and adsorb some PPCPs. Biochar as a secondary treatment system significantly reduced the concentrations of PPCPs and dissolved reactive phosphorus (DRP) (p < 0.05), compared to the woodchip bioreactor. The removal efficiencies of all targeted contaminants by the B² system were evaluated using various hydraulic retention times (HRTs) and biochar types (pelletized versus granular biochar). Longer HRTs and smaller biochar particles (granular biochar) could enhance the removal efficiencies of targeted contaminants. Average contaminant removals were 77.25 % for nitrate-N, 99.03 % for DRP, 69.51 % for ibuprofen, 73.65 % for naproxen, 91.09 % for sitagliptin, and 96.96 % for estrone, with woodchip bioreactor HRTs of 12 ± 1.4 h and granular biochar HRTs of 2.1 ± 0.1 h. Notably, the second-stage biochar systems effectively mitigated by-products leaching from woodchip bioreactors. The presence of PPCPs in the woodchip bioreactors enriched certain species, such as Methylophilus (69.6 %), while inhibiting other microorganisms and reducing microbial community diversity. Furthermore, a scaled-up B² system was analyzed and assessed, indicating that the proposed engineering treatment system could provide decades of service in real-world applications. Overall, this study suggests that the B² system has promising applications for addressing emerging and conventional contaminants.

2024-11-01·International Journal of Biological Macromolecules

Acid-triggered rattan ball-like β-glucan carrier embedding doxorubicin to synergistically alleviate precancerous lesions of gastric cancer via p53 and PI3K pathways

Article

作者: Cao, Xiangyu ; Zhang, Shuchen ; Chen, Junliang ; Yang, Shuanglong ; Su, Wentao ; Wang, Yuxiao ; Li, Tiejing ; Zhu, Rugang ; Shi, Xueying ; Feng, Xin

The early intervention of precancerous lesions of gastric cancer (PLGC) is crucial for improving the survival of patients with gastric cancer. Traditional pharmaceuticals for the treatment of PLGC are limited by side effects, thus developing innovative drug carrier that are more efficient but without the undesirable side effects is required. Here, we proposed an acid-triggered mushroom-derived β-glucan carrier embedding doxorubicin (DOX) to circumvent drug cytotoxicity and synergistically alleviate PLGC based on the controlled conformational transformation. The triple helix β-glucan extracted from Dictyophora rubrovolvata (DRP) loaded doxorubicin driven by pH and DMSO regulation, forming two rattan ball-like nanoparticles (DRP-DOX(pH) and DRP-DOX(DMSO)) via its collapse and recombination of triple-helix conformation. The findings revealed that DRP-DOXs achieved acid-triggerable and sustained drug delivery with an average particle size of 500 nm and 550 nm. In vitro evaluation of GES-1 cells showed DRP-DOXs reduced reactive oxygen species (ROS) production and altered mitochondrial membrane potential. Compared to DRP-DOX(DMSO) and DRP, DRP-DOX(pH) could more effectively downregulate cellular oxidative stress and inflammation to eventually alleviate PLGC, by regulating the p53 and PI3K pathways to mitigate gastric mucosa damage. Consequently, the nature-derived β-glucan delivery nanovesicle holds great promising applications in reducing drug toxicity and suppressing the development of PLGC.

100 项与 Age DRP(AVVA) 相关的药物交易

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