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1.
Transl Androl Urol ; 13(3): 433-441, 2024 Mar 31.
Article in English | MEDLINE | ID: mdl-38590967

ABSTRACT

Background: ARASENS has demonstrated the efficacy and safety for darolutamide (DARO) with androgen deprivation therapy (ADT) plus docetaxel in metastasis hormone-sensitive prostate cancer (mHSPC). There is a lack of reports for DARO with ADT in mHSPC though the regimen is used in clinical from time to time. Moreover, recent studies have supported the importance of early and rapid prostate-specific antigen (PSA) reduction, which correlates with reduced disease progression and improved survival in patients with mHSPC. This study aims to evaluate PSA reduction as a primary endpoint for DARO with ADT in the treatment of mHSPC and to evaluate the real-world short-term PSA control of DARO with ADT from two leading medical centers in China. Methods: We retrospectively reviewed the clinical records of patients with mHSPC receiving ADT and DARO (600 mg, b.i.d.). The collection of data spanned from March 1, 2022, to July 31, 2023. The main observation indicators were PSA level and drug-related adverse events (AE) after medication. PSA levels were closely monitored prior to treatment initiation and at 2-week intervals, as well as at 1, 3, and 6 months after the initiation of treatment. We also conducted an analysis to determine the proportion of patients achieving a PSA reduction of 50% or more (PSA50) and 90% or more (PSA90) as well as the percentage of patients with a notable decrease in PSA level to 0.2 ng/mL and PSA nadir of ≤0.02 ng/mL. Results: Fifty-one patients were included in the study, with a median age of 73 years. At diagnosis of HSPC, the majority of patients had a Gleason score ≥8 (n=40, 78.40%) and a median baseline PSA level of 88 ng/mL. Approximately 45.1% (n=23) of patients had a Charlson Comorbidity Index over 1 and were receiving one or more nontumor-related treatments. The median follow-up time was 9.3 months (range, 1.16-15.8 months). The median reductions in PSA levels compared to baseline were 84.37%, 91.48%, 94.67% and 99.81% at 2 weeks, 1 month, 3 months and 6 months after administration of DARO with ADT, respectively. The median time to PSA50, PSA90, significant PSA reduction (PSA <0.2 ng/mL), and PSA nadir (PSA <0.02 ng/mL) was 0.97, 1.27, 1.98, and 2.08 months, respectively. AE mainly included fatigue (two patients) and arm pain (one patient), all of which were grade I or II AE. No grade III or AE were observed. Conclusions: For treating prostate cancer, DARO with ADT has good early efficacy, demonstrating prompt and substantial control of PSA levels, with a favorable safety profile.

2.
Front Oncol ; 13: 1243118, 2023.
Article in English | MEDLINE | ID: mdl-38090493

ABSTRACT

Purpose: The purpose of this research is to evaluate the association between HER-2 expression and clinicopathological features in patients with non-muscle-invasive bladder cancer (NMIBC). Methods: Between 2019 and 2022, 204 patients treated with Transurethral resection of the bladder tumor (TURBT) were included in this study. Data of pathologic T (pT) stage, grades of the tumor, age, sex, tumor size and number of the tumors were collected and compared according to the expression level of the human epidermal growth factor 2 (HER-2). ROC curve analysis was performed to assess the discriminative ability of HER-2 expression for tumors grades and pT stage. Multivariable logistic regression analysis were used to evaluate the association between HER-2 expression and tumor grades and pT stage. Results: Patients were divided into low grade (110, 53.9%) and high grade groups (94, 46.1%) according to the tumor grade. Pathologic stage consisted of pTa in 166 (81.4%) and pT1 in 38 (18.6%). HER-2 expression was semi quantitatively scored to 0 in 44 (21.6%), 1 in 58 (28.4%), 2 in 91 (44.6%), and 3 in 11 (5.4%) cases. HER-2 expression was significantly associated with tumor stages and histological grades, but not with sex, tumor size or number of tumors. The AUC for combination of HER-2 expression with tumor stages and histological grades was 0.652 (p < 0.003) and 0.727 (p < 0.001), respectively. Conclusion: This study demonstrated that HER-2 expression is associated with tumor stages and histological grades in NMIBC. It has diagnostic value for cystoscopic biopsy.

3.
Sci Total Environ ; 888: 163611, 2023 Aug 25.
Article in English | MEDLINE | ID: mdl-37172835

ABSTRACT

New particle formation (NPF) represents a significant source of aerosol particles in the atmosphere; however, the NPF mechanisms remain uncertain, hindering the understanding and assessment of its environmental effects. Hence, we investigated the nucleation mechanisms in multicomponent systems including two inorganic sulfonic acids (ISAs), two organic sulfonic acids (OSAs), and dimethylamine (DMA) by combining quantum chemical (QC) calculations and molecular dynamics (MD) simulations, and evaluated the comprehensive effect of ISAs and OSAs on DMA-driven NPF. The QC results showed that the (Acid)2(DMA)0-1 clusters were strongly stable, and the (ISA)2(DMA)1 clusters exhibited higher stability than the (OSA)2(DMA)1 clusters because ISAs (sulfuric and sulfamic acids) provided more H-bonds and stronger proton transfer than OSAs (methanesulfonic and ethanesulfonic acids). ISAs readily engaged in dimer formation, whereas the stability of trimer clusters was mainly regulated by the synergistic effects of ISAs and OSAs. OSAs participated in cluster growth earlier than ISAs. Our results revealed that ISAs promote cluster formation, whereas OSAs facilitate the growth of clusters. The synergistic effect of ISAs and OSAs should be further investigated in areas with high [OSAs]: [ISAs].

4.
Int J Hyperthermia ; 40(1): 2157499, 2023.
Article in English | MEDLINE | ID: mdl-36576108

ABSTRACT

PURPOSE: Clinically, the management of cystic renal masses is tricky. The study aims to evaluate the safety and efficacy of laparoscopic microwave ablation-assisted partial nephrectomy (LMAPN) for cystic renal tumors. METHODS AND MATERIALS: Between November 2017 and January 2022, LMAPN was performed on 43 patients (29 men and 14 women; age range: 22-80 years; median age 54 years) with Bosniak category III (n = 15) or IV (n = 28) cystic renal tumors (size range: 1.2-5.0 cm; mean size 2.8 cm). The median follow-up period was 26 months (range: 7-56 months). Baseline and perioperative data, pathological features, renal function, postoperative complications and oncologic outcomes were collected and evaluated. RESULTS: Forty-three cystic renal tumors were successfully managed by LMAPN. The mean operating time was 79 min (range: 40-130 min). The mean time of renal pedicle clamping was 19 min (range: 12-25 min). Mean intraoperative blood loss was 28.4 mL (range: 10-80 mL). The mean postoperative hospitalization duration was 4 days (range: 2-6 days). Negative surgical margins were diagnosed in all cases. During the follow-up, no patient appeared with distant metastasis, wound or peritoneal cavity implantation. No major but minor complications of Clavien-Dindo grade I were encountered after the operation. The 1-, 3- and 4-year overall survival rate was 100%, 96.6% and 88.5%, respectively. CONCLUSION: This is the first study focusing on LMAPN for cystic renal tumors, demonstrating its favorable feasibility, safety and disease control. Long-term follow-up is necessary to draw conclusions on the preference and advantages of the new therapeutic approach.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Laparoscopy , Male , Humans , Female , Middle Aged , Young Adult , Adult , Aged , Aged, 80 and over , Microwaves/therapeutic use , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Kidney/physiology , Nephrectomy/methods , Laparoscopy/methods , Retrospective Studies , Treatment Outcome , Carcinoma, Renal Cell/surgery
5.
J Environ Sci (China) ; 126: 103-112, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36503740

ABSTRACT

Organosulfate (OSA) nanoparticles, as secondary organic aerosol (SOA) compositions, are ubiquitous in urban and rural environments. Hence, we systemically investigated the mechanisms and kinetics of aqueous-phase reactions of 1-butanol/1-decanol (BOL/DOL) and their roles in the formation of OSA nanoparticles by using quantum chemical and kinetic calculations. The mechanism results show that the aqueous-phase reactions of BOL/DOL start from initial protonation at alcoholic OH-groups to form carbenium ions (CBs), which engage in the subsequent esterification or oligomerization reactions to form OSAs/organosulfites (OSIs) or dimers. The kinetic results reveal that dehydration to form CBs for BOL and DOL reaction systems is the rate-limiting step. Subsequently, about 18% of CBs occur via oligomerization to dimers, which are difficult to further oligomerize because all reactive sites are occupied. The rate constant of BOL reaction system is one order of magnitude larger than that of DOL reaction system, implying that relative short-chain alcohols are more prone to contribute OSAs/OSIs than long-chain alcohols. Our results reveal that typical long-chain alcohols contribute SOA formation via esterification rather than oligomerization because OSA/OSI produced by esterification engages in nanoparticle growth through enhancing hygroscopicity.


Subject(s)
Alcohols , Fatty Alcohols , Aerosols , Butanols , Polymers , 1-Butanol
6.
Front Oncol ; 12: 893877, 2022.
Article in English | MEDLINE | ID: mdl-36185298

ABSTRACT

Purpose: To determine whether complete blood count (CBC) based inflammatory parameters can be used as markers predicting testicular germ cell tumors (TGCT). Material and methods: Between 2013 to 2018 the data of 58 patients with testicular TGCT undergoing radical orchiectomy and 54 malignancy-free healthy men were retrospectively analyzed as tumor group and control group. Patient baseline characteristics including age, pathological stage and pre-surgery CBC based inflammatory parameters including neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), systemic immune-inflammation index (SII), lymphocyte ratio (LR), neutrophil ratio (NR), mean platelet volume (MPV) and red cell distribution width (RDW) were analyzed and compared between tumor group and control group. Receiver operating characteristic (ROC) curve were used analyzing data with significantly difference to assess the discriminative ability of the markers for TGCT, area under the curve (AUC), cut-off value, sensitivity and specificity were calculated. The binary logistic regression model was used to evaluate the association between significant inflammatory markers and risk of TGCT. Results: Mean age of the tumor and control group was 41.1 ± 15.36 and 44.89 ± 9.2 years, respectively. Mean NLR, SII and RDW were significantly higher in tumor group compared with control group with P=0.005, P=0.001 and P=0.016, respectively; there were no significantly differences of age, PLR, LMR, LR, NR, MPV and RDW between groups. The ROC curve for NLR, SII and RDW was plotted in the diagnosis of TGCT and tumor progression, the cut-off value for NLR, SII and RDW were found as 3.38 (AUC: 0.704, sensitivity=51.4%, specificity=88.6%, P=0.003), 881.24 (AUC: 0.725, sensitivity=45.7%, specificity=91.4%, P=0.001) and 0.14 (AUC: 0.63, sensitivity=28.6%, specificity=97%, P=0.063), respectively. Patients were divided into two groups according to the threshold values, respectively. By using the multivariable logistic regression models, NLR ≥ 3.38 (OR, 5.86; 95% CI, 1.67-20.65, P=0.006) and SII ≥ 881.24 (OR, 4.89; 95% CI, 1.48-15.32, P=0.009) were independent risk factors predicting TGCT. Significantly statistical difference of pathological stage was also found between groups with respect to NLR cut-off values (P=0.034) and SII cut-off values (P=0.049). Combined the data together, NLR and SII both exhibited good differential diagnosis potential which could be used as markers predicting the TGCT. Conclusion: As the CBC based inflammation parameters, both NLR and SII could be used as effective tumor markers predicting the TGCT, and higher NLR and SII are associated with higher pathological stage. In addition, SII is a more powerful tool among these two inflammatory markers.

7.
J Environ Sci (China) ; 114: 211-220, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35459487

ABSTRACT

Methyl-hydroxy-cyclohexadienyl radicals (OTAs) are the key products of the photooxidation of toluene, with implications for the fate of toluene. Hence, we investigated the photooxidation mechanisms and kinetics of three main OTAs (o-OTA, m-OTA, and p-OTA) with NO2 using quantum chemical calculations as well as the fate of OTAs under the different concentration ratios of NO2 and O2. The mechanism results show that the pathway of H-abstraction by NO2 to anti-HONO (anti-H-abstraction) is more favorable than the syn-H-abstraction pathway, because the strong interaction between OTAs and NO2 is formed in the transition states of the anti-H-abstraction pathways. The branching ratios of the anti-H-abstraction pathways are more than 99% in the temperature range of 216-298 K. The total rate constant of the OTA-NO2 reaction is 9.9 × 10-12 cm3/(molecule∙sec) at 298 K, which is contributed about 90% by o-OTA + NO2, and the main products are o-cresol and anti-HONO. The half-lives of the OTA-NO2 reaction in some polluted areas of China are 35 times longer than those of the OTA-O2 reaction. In the atmosphere, the NO2- and O2- initiated reactions of OTAs have the same ability to form cresols as [NO2] is up to 142.1 ppmV, which is impossible to achieve. It implies that under the experimental condition, the [NO2]/[O2] should be controlled to be less than 7.8 × 10-5 to simulate real atmospheric oxidation of toluene. Our results reveal that for the photooxidation of toluene, the yield of cresol is not affected by the concentration of NO2 under the atmospheric environment.


Subject(s)
Nitrogen Dioxide , Toluene , Cresols , Hydroxyl Radical , Kinetics
8.
Front Oncol ; 12: 1079622, 2022.
Article in English | MEDLINE | ID: mdl-36713540

ABSTRACT

Purpose: To investigate the role of inflammatory factors including systemic immune-inflammation index (SII) and neutrophil to lymphocyte ratio (NLR) in predicting Gleason Score (GS) and Gleason Score upgrading (GSU) in localized prostate cancer (PCa) after radical prostatectomy (RP). Methods: The data of 297 patients who underwent prostate biopsy and RP in our center from January 2014 to March 2020 were retrospectively analyzed. Preoperative clinical characteristics including age, values of tPSA, total prostate volume (TPV), f/t PSA ratio, body mass index (BMI), biopsy GS and inflammatory factors including SII, NLR, lymphocyte to monocyte (LMR), neutrophil ratio (NR), platelet to lymphocyte ratio (PLR), lymphocyte ratio (LR), mean platelet volume (MPV) and red cell distribution (RDW) as well as pathological T (pT) stage were collected and compared according to the grades of RP GS (GS ≤ 6 and GS≥7), respectively. ROC curve analysis was used to confirm the discriminative ability of inflammatory factors including SII, NLR and their combination with tPSA for predicting GS and GSU. By using univariate and multivariate logistic regression analysis, the association between significant inflammatory markers and grades of GS were evaluated. Results: Patients enrolled were divided into low (GS ≤ 6) and high (GS≥7) groups by the grades of GS. The median values of clinical factors were 66.08 ± 6.04 years for age, 36.62 ± 23.15 mL for TPV, 26.16 ± 33.59 ng/mL for tPSA and 0.15 ± 0.25 for f/t PSA ratio, 22.34 ± 3.14 kg/m2 for BMI, 15 (5.1%) were pT1, 116 (39.1%) were pT2 and 166 (55.9%) were pT3. According to the student's t test, patients in high GS group had a greater proportion of patients with pT3 (P<0.001), and higher NLR (P=0.04), SII (P=0.037) and tPSA (P=0.015) compared with low GS group, the distribution of age, TPV, f/t PSA ratio, BMI, LMR, NR, PLR, LR, MPV and RDW did not show any significantly statistical differences. The AUC for SII, NLR and tPSA was 0.732 (P=0.007), 0.649 (P=0.045) and 0.711 (P=0.015), with threshold values of 51l.08, 2.3 and 10.31ng/mL, respectively. According to the multivariable logistic regression models, NLR ≥ 2.3 (OR, 2.463; 95% CI, 0.679-10.469, P=0.042), SII ≥ 511.08 (OR, 3.519; 95% CI 0.891-12.488; P=0.003) and tPSA ≥ 10.31 ng/mL (OR, 4.146; 95% CI, 1.12-15.35; P=0.033) were all independent risk factors associated with higher GS. The AUC for combination of SII, NLR with tPSA was 0.758 (P=0.003) and 0.756 (P=0.003), respectively. GSU was observed in a total of 48 patients with GS ≤ 6 (55.17%). Then patients were divided into 2 groups (high and low) according to the threshold value of SII, NLR, tPSA, SII+tPSA and NLR+tPSA, respectively, when the GSU rates were compared with regard to these factors, GSU rate in high level group was significantly higher than that in low level group, P=0.001, 0.044, 0.017, <0.001 and <0.001, respectively. Conclusion: High SII, NLR and tPSA were associated with higher GS and higher GSU rate. SII was likely to be a more favorable biomarker for it had the largest AUC area compared with tPSA and NLR; the combination of SII or NLR with tPSA had greater values for predicting GS and GSU compared with NLR, SII or tPSA alone, since the AUC area of combination was much higher. SII, NLR were all useful inflammatory biomarkers for predicting GS and detecting GSU among localized PCa patients with biopsy GS ≤ 6.

9.
J Environ Sci (China) ; 105: 56-63, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34130839

ABSTRACT

Mineral particles are ubiquitous in the atmosphere and exhibit an important effect on the photooxidation of volatile organic compounds (VOCs). However, the role of mineral particles in the photochemical oxidation mechanism of VOCs remains unclear. Hence, the photooxidation reactions of acrolein (ARL) with OH radical (OH) in the presence and absence of SiO2 were investigated by theoretical approach. The gas-phase reaction without SiO2 has two distinct pathways (H-abstraction and OH-addition pathways), and carbonyl-H-abstraction is the dominant pathway. In the presence of SiO2, the reaction mechanism is changed, i.e., the dominant pathway from carbonyl-H-abstraction to OH-addition to carbonyl C-atom. The energy barrier of OH-addition to carbonyl C-atom deceases 21.33 kcal/mol when SiO2 is added. Carbonyl H-atom of ARL is occupied by SiO2 via hydrogen bond, and carbonyl C-atom is activated by SiO2. Hence, the main product changes from H-abstraction product to OH-adduct in the presence of SiO2. The OH-adduct exhibits a thermodynamic feasibility to yield HO2 radical and carboxylic acid via the subsequent reactions with O2, with implications for O3 formation and surface acidity of mineral particles.


Subject(s)
Hydroxyl Radical , Silicon Dioxide , Atmosphere , Kinetics , Minerals
10.
Front Oncol ; 11: 812319, 2021.
Article in English | MEDLINE | ID: mdl-35047413

ABSTRACT

PURPOSE: To evaluate the diagnostic values of systemic immune-inflammation index (SII) and neutrophil-lymphocyte ratio (NLR) in patients with localized prostate cancer (PCa). METHODS: Between January 2014 and December 2019, 117 patients with benign prostate hyperplasia (BPH) and 278 patients with localized PCa who underwent radical prostatectomy (RP) were included in this study. The inflammatory markers including SII, NLR, platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), lymphocyte ratio (LR), neutrophil ratio (NR), mean platelet volume (MPV), and red cell distribution (RDW) of these two groups were examined and analyzed. ROC curve analysis was performed to assess the discriminative ability of inflammatory markers and their combination with tPSA for PCa. The binary logistic regression model was used to evaluate the association between significant inflammatory markers and risk of PCa. RESULTS: The pathological results from RP specimen comprised 72 (25.90%) patients with pT1, 168 (60.43%) patients with pT2, and 38 (13.67%) patients with pT3. According to Student's t test, patients with PCa had higher NLR (p = 0.034), SII (p = 0.008), and NR (p = 0.004), and lower LR (p = 0.025), MPV (p = 0.003), and TPV (p = 0.022) compared with patients with BPH; the distribution of age, PLR, LMR, RDW, f/t PSA ratio, and BMI did not show any significant differences. The AUC for NLR, SII, NR, and tPSA was 0.697 (p = 0.015), 0.719 (p < 0.001), 0.647 (p = 0.009), and 0.708 (p < 0.001), with threshold values of 1.6, 471.86, 65.15%, and 12.89 ng/ml, respectively. Patients were divided into two groups according to the threshold values, respectively. By using the multivariable logistic regression models, NLR ≥ 1.6 (OR, 2.731; 95% CI, 0.937-7.961, p = 0.042), SII ≥ 471.86 (OR, 1.274; 95% CI 0.473-3.433; p = 0.033), and PSA ≥ 12.89 ng/ml (OR, 1.443; 95% CI, 0.628-3.944; p = 0.014) were independent risk factors associated with PCa. The AUC for combination of NLR, SII, and NR with tPSA was 0.705 (p < 0.001), 0.725 (p < 0.001), and 0.704 (p < 0.001), respectively. CONCLUSION: This study demonstrated that SII, NLR, and NR were all independent risk factors of PCa. These factors alone could provide better screen methods for PCa before biopsy. In addition, SII is a more powerful tool among these three inflammatory markers associated with PCa. Besides, combination of SII and NLR with tPSA had not much advantage compared with themselves alone.

11.
Cancer Cell Int ; 20: 461, 2020.
Article in English | MEDLINE | ID: mdl-32982583

ABSTRACT

BACKGROUND: Large-scale initiatives like The Cancer Genome Atlas (TCGA) performed genomics studies on predominantly Caucasian kidney cancer. In this study, we aimed to investigate genomics of Chinese clear cell renal cell carcinoma (ccRCC). METHODS: We performed whole-transcriptomic sequencing on 55 tumor tissues and 11 matched normal tissues from Chinese ccRCC patients. We systematically analyzed the data from our cohort and comprehensively compared with the TCGA ccRCC cohort. RESULTS: It found that PBRM1 mutates with a frequency of 11% in our cohort, much lower than that in TCGA Caucasians (33%). Besides, 31 gene fusions including 5 recurrent ones, that associated with apoptosis, tumor suppression and metastasis were identified. We classified our cohort into three classes by gene expression. Class 1 shows significantly elevated gene expression in the VEGF pathway, while Class 3 has comparably suppressed expression of this pathway. Class 2 is characterized by increased expression of extracellular matrix organization genes and is associated with high-grade tumors. Applying the classification to TCGA ccRCC patients revealed better distinction of tumor prognosis than reported classifications. Class 2 shows worst survival and Class 3 is a rare subtype ccRCC in the TCGA cohort. Furthermore, computational analysis on the immune microenvironment of ccRCC identified immune-active and tolerant tumors with significant increased macrophages and depleted CD4 positive T-cells, thus some patients may benefit from immunotherapies. CONCLUSION: In summary, results presented in this study shed light into distinct genomic expression profiles in Chinese population, modified the stratification patterns by new molecular classification, and gave practical guidelines on clinical treatment of ccRCC patients.

12.
Environ Res ; 186: 109568, 2020 07.
Article in English | MEDLINE | ID: mdl-32344213

ABSTRACT

Xylenes are important aromatic hydrocarbons having broad industrial emissions and profound implication to air quality and human health. Generally, homogeneous atmospheric oxidation of xylenes is initiated by hydroxyl radical (OH) resulting in minor H-abstraction and major OH-addition pathways. However, the effect of mineral particles on the homogeneous atmospheric oxidation mechanism of xylenes is still not well understood. In the present study, the heterogeneous atmospheric oxidation of xylenes on mineral particles (TiO2) is examined in detail. Both the experimental data and theoretical calculations are combined to achieve the feast. The experimental results detected a major H-abstraction (≥87.18%) and minor OH-addition (≤12.82%) pathways for the OH-initiated heterogeneous oxidation of three xylenes on TiO2 under ultraviolet (UV) irradiation. Theoretical calculations demonstrated favorable H-abstraction on methyl group of xylenes by surface OH with large exothermic energies, because of the reason that their methyl group rather than the phenyl ring is more occupied by TiO2 via hydrogen bonding. Furthermore, the particle monitor and acute risk assessment results indicated that the H-abstraction products significantly enhance the formation of particulate matter and health risk to human beings. Taken together, these results indicate that the atmospheric oxidation mechanism of xylenes is altered in the presence of mineral particles, highlighting the necessity to re-evaluate its implication in the environment and human health.


Subject(s)
Particulate Matter , Xylenes , Humans , Hydroxyl Radical , Kinetics , Minerals , Oxidation-Reduction
13.
Int J Oncol ; 54(1): 390-398, 2019 01.
Article in English | MEDLINE | ID: mdl-30431089

ABSTRACT

Vascular endothelial growth inhibitor (VEGI) has been identified as an anti­angiogenic cytokine. However, the effects of VEGI174 protein, and its functional domain peptides V7 and V8, on renal cell carcinoma (RCC) remain unknown. In the present study, the protein and peptides were biosynthesised as experimental agents. The A498 and 786­O RCC cell lines, and an established mouse xenograft model, were separately treated with VEGI174, V7 or V8. Cellular functions, including proliferation, migration and invasion, were subsequently detected. Cell migration and invasion were monitored using the xCELLigence system. Furthermore, tumour growth and mouse behaviours, including mobility, appetite and body weight, were assessed. The results demonstrated that VEGI174, V7 and V8 inhibited the proliferation, migration and invasion of A498 and 786­O cell lines when administered at concentrations of 1 and 100 pM, 10 nM and 1 µM. The inhibitory effects exhibited dose­ and time­dependent antitumour activity. Furthermore, VEGI174, V7 and V8 inhibited tumour growth in A498 and 786­O xenograft mice. In the A498 xenografts, the tumour growth inhibition (TGI) rates in the VEGI174­, V7­ and V8­treated groups were 71, 20 and 31%, respectively. In the 786­O xenografts, the TGI rates in the VEGI174­, V7­ and V8­treated groups were 34, 26 and 31%, respectively. There was no significant loss in body weight and no cases of mortality were observed for all treated mice. In conclusion, VEGI174, V7 and V8 exhibited potential antitumour effects and were well tolerated in vivo. V7 and V8, as functional domain peptides of the VEGI174 protein, may be studied for the future treatment of RCC.


Subject(s)
Alternative Splicing , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Peptides/administration & dosage , Tumor Necrosis Factor Ligand Superfamily Member 15/chemistry , Animals , Carcinoma, Renal Cell/genetics , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival , Dose-Response Relationship, Drug , Gene Expression Regulation, Neoplastic , Humans , Kidney Neoplasms/genetics , Mice , Peptides/pharmacology , Protein Domains , Tumor Necrosis Factor Ligand Superfamily Member 15/genetics , Xenograft Model Antitumor Assays
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