Contribution of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 to Upper Tract Urothelial Cancer Risk in Taiwan.

Matrix metalloproteinase (MMP)-2 and -9, which degrade type IV collagen, are linked to cancer invasion and metastasis. Gene polymorphisms in MMP-2 and MMP-9 can influence their function, impacting cancer development and progression. This study analyzed the association between polymorphisms MMP-2 rs243865 (C-1306T), rs2285053 (C-735T), and MMP-9 rs3918242 (C-1562T) with serum concentrations of these enzymes in upper tract urothelial cancer (UTUC) patients. We conducted a case-control study with 218 UTUC patients and 580 healthy individuals in Taiwan. Genotyping was performed using PCR/RFLP on DNA from blood samples, and MMP-2 and MMP-9 serum levels and mRNA expressions in 30 UTUC patients were measured using ELISA and real-time PCR. Statistical analysis showed that MMP-2 rs2285053 and MMP-9 rs3918242 genotypes were differently distributed between UTUC patients and controls (p = 0.0199 and 0.0020). The MMP-2 rs2285053 TT genotype was associated with higher UTUC risk compared to the CC genotype (OR = 2.20, p = 0.0190). Similarly, MMP-9 rs3918242 CT and TT genotypes were linked to increased UTUC risk (OR = 1.51 and 2.92, p = 0.0272 and 0.0054). In UTUC patients, TT carriers of MMP-2 rs2285053 and MMP-9 rs3918242 showed higher mRNA and protein levels (p < 0.01). These findings suggest that MMP-2 rs2285053 and MMP-9 rs3918242 genotypes are significant markers for UTUC risk and metastasis in Taiwan.

Robotic partial nephrectomy for renal tumor: The pentafecta outcomes of a single surgeon experience.

PURPOSE: This study investigated the oncological and functional surgical outcomes for patients with renal tumor who underwent robot-assisted partial nephrectomy (PN) by a single surgeon in Taiwan from 2006 to 2019. METHODS: This retrospective study assessed patients who underwent robot-assisted PN for renal tumor. Patient data were analyzed for age, sex, body mass index, operative time and total ischemic time, surgical margin (positive/negative), and surgical complications. To evaluate functional and oncological outcomes, achievement of trifecta, and pentafecta criteria was used. Trifecta criteria were defined as a negative surgical margin, no postoperative complications, warm ischemia time <25 min. Pentafecta criteria were the trifecta criteria, >90% preservation of estimated glomerular filtration rate (eGFR) preservation, and no stage progression of chronic kidney disease at 1-year follow-up. RESULTS: Of 101 patients who received robot-assisted PN, the most common type of renal tumor was clear cell renal cell carcinoma (RCC) (38%), followed by angiomyolipoma (26%). Patient characteristics were mean age 54.59 ± 13.8 years; mean RENAL Nephrometry score 6.63 ± 2.16; mean operative time 102.34 ± 50.06 min; and warm ischemia time 20.01 ± 14.12 min. The mean eGFR was 104.43 ± 31.73 mL/min/1.73 m2 preoperatively and 89.39 ± 32.3 mL/min/1.73 m2 postoperatively. Pathologic evaluation showed malignant tumors in 57 patients, among whom achievement of trifecta criteria occurred for 39 (68.42%) and pentafecta criteria for 18 (31.57%). Operation time was the only predictor for pentafecta achievement. CONCLUSION: Robotic PN is a safe and effective approach for patients with renal tumor that can preserve most renal function and achieve oncological control. Pentafecta criteria can be used to more clearly define the surgical outcome of RAPN.

Impacts of Mir146a Genotypes on Bladder Cancer Risk in Taiwan.

The aim of this study was to investigate the association between single-nucleotide polymorphisms (SNPs) in mir146a and mir196a and bladder cancer (BLCA) risk in Taiwan. The genotypes of mir146a rs2910164 and mir196a rs11614913 were determined in 375 BLCA patients and 375 healthy controls using PCR-RFLP methodology, and their associations with BLCA risk were evaluated. The study also measured the serum expression level of mir146a using quantitative RT-PCR. The results showed that the distributions of CC, CG and GG genotypes of mir146a rs2910164 were 31.7%, 45.6% and 22.7% in the control group, and 21.9%, 44.3% and 33.8% in the case group, respectively. In logistic regression analyses, the heterozygous variant genotype CG carriers showed a marginally significant association with increased BLCA risk (OR = 1.41, 95% CI = 0.99-2.01), while the homozygous variant genotype GG carriers had a 2.17-fold increased risk of BLCA (OR = 2.17, 95%CI = 1.46-3.21). Moreover, carriers of the GG/CG genotypes had significantly higher serum levels of mir146a than those with the CC genotype (p < 0.0001), indicating a genotype-phenotype correlation. In contrast, mir196a rs11614913 was not associated with BLCA risk. Therefore, the genotypes of mir146a rs2910164 may serve as a useful biomarker for predicting the risk of BLCA.

Association of Matrix Metalloproteinase-7 Genotypes With Prostate Cancer Risk.

BACKGROUND/AIM: Prostate cancer is one of the most commonly diagnosed malignancies among males worldwide. It has been shown that MMP-7 gene is closely correlated with prostate carcinogenesis. However, the role of the MMP-7 genotypes has been seldom examined among prostate cancer patients. Therefore, the purpose of the study was to evaluate the contribution of MMP-7 promoter genotypes A-181G (rs11568818) and C-153T (rs11568819) to prostate cancer risk in Taiwan. MATERIALS AND METHODS: Two hundred and eighteen prostate cancer patients and 436 sex- and age-matched healthy controls were genotyped for MMP-7 rs11568818 and rs11568819 by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing methodologies. RESULTS: The percentages of wild-type AA, and variant AG and GG genotypes on MMP-7 rs11568818 were 85.3, 13.5, and 1.2% among the prostate cancer cases and 87.6, 10.1, and 2.3% among the healthy controls, respectively (p for trend=0.2557). Interestingly, no MMP-7 rs11568819 genotypes were identified among Taiwanese. The allelic frequency distribution also showed that the variant G allele of MMP-7 rs11568818 seemed not to be a determinant of prostate cancer risk (p=0.7977). There was no joint effect between the genotypes of MMP-7 rs11568818 and age and smoking status on prostate cancer risk. CONCLUSION: rs11568818 and rs11568819 at MMP-7 promoter region, played no role in determining personal susceptibility to prostate cancer in Taiwan.

Developing New Treatment Options for Castration-Resistant Prostate Cancer and Recurrent Disease.

Prostate cancer (PCa) is a major diagnosed cancer among men globally, and about 20% of patients develop metastatic prostate cancer (mPCa) in the initial diagnosis. PCa is a typical androgen-dependent disease; thus, hormonal therapy is commonly used as a standard care for mPCa by inhibiting androgen receptor (AR) activities, or androgen metabolism. Inevitably, almost all PCa will acquire resistance and become castration-resistant PCa (CRPC) that is associated with AR gene mutations or amplification, the presence of AR variants, loss of AR expression toward neuroendocrine phenotype, or other hormonal receptors. Treating CRPC poses a great challenge to clinicians. Research efforts in the last decade have come up with several new anti-androgen agents to prolong overall survival of CRPC patients. In addition, many potential targeting agents have been at the stage of being able to translate many preclinical discoveries into clinical practices. At this juncture, it is important to highlight the emerging strategies including small-molecule inhibitors to AR variants, DNA repair enzymes, cell survival pathway, neuroendocrine differentiation pathway, radiotherapy, CRPC-specific theranostics and immune therapy that are underway or have recently been completed.

Association of Matrix Metalloproteinase-1 Genotypes With Bladder Cancer Risk.

AIM: There is very little literature reporting the association of matrix metalloproteinase-1 (MMP1) with personal susceptibility to bladder cancer. In the current study, we carried out the first examination of the contribution of MMP1 rs1799750 to bladder cancer risk in Taiwanese. MATERIALS AND METHODS: A total of 375 bladder cancer cases and 375 healthy controls were genotyped for MMP1 rs1799750 via polymerase chain reaction-restriction fragment length polymorphism methodology and this was evaluated for association with clinicopathological factors. RESULTS: The frequencies of MMP1 rs1799750 2G/2G, 1G/2G, and 1G/1G genotypes were 35.7%, 44.8% and 19.5% in the group with bladder cancer and 32.5%, 46.4%, and 21.1% in the healthy control group (p for trend=0.6362). The odds ratios (ORs) for bladder cancer risk after adjusting for age and gender for those carrying 1G/2G and 1G/1G genotypes at MMP1 rs1799750 were 0.88 (95% CI=0.62-1.24, p=0.4357) and 0.83 (95% CI=0.61-1.26, p=0.3990), respectively, compared with the wild-type 2G/2G genotype. In allelic frequency analysis, the adjusted OR for those carrying the 1G allele at MMP1 rs1799750 was 0.87 (95% CI=0.71-1.23, p=0.3479) compared to those people carrying a 2G allele. CONCLUSION: Our findings indicated that the genotypes at MMP1 rs1799750 appear to play little role in determining personal susceptibility to bladder cancer for Taiwanese.

After remediation - Using toxicity identification evaluation of sediment contamination in the subtropical Erren river basin.

This study utilized the freshwater amphipod (Hyalella azteca) for the indication of contamination risk levels of sediment-associated contaminants in the Erren (ER1∼ER10) and Sanye Rivers (SY1∼SY5) which were contaminated by metal scrap and smelting industries for decades. Toxicity identification evaluations involving the manipulation of pore water and whole-sediment samples were conducted to identify causative pollutants. Impacts on the aquatic environment were then evaluated in order to explore how industrial development led to contaminant accumulation in sediments and resulted in biological effects. A whole-sediment TIE indicated that the major toxicant at sampling sites ER8 and SY5 was ammonia and that its toxicity was significantly reduced by the addition of zeolite. Toxicity at sampling sites ER4 and ER9 was induced by ammonia and heavy metals (Zn, Cd, Cr, As), whereas Cr was at toxic levels at ER6. ∑PAHs was another major class of contaminants at site ER2. Metals (Zn, Ni, Pb, Cd, Cr, and As) were identified as major toxic contaminants at three sites (ER3, SY1, and SY3). The application of TIEs confirmed that a causative toxicant can be identified and that its measured toxicity correlated with its concentration. In conclusion, a TIE approach was successful in demarcating most effective contaminant groups (ammonia, heavy metals, and non-polar organic compounds) in whole-sediment cores, their porewaters and potential toxicities from a highly polluted river after remediation in southern Taiwan to an invertebrate animal model H. azteca.

Cost-benefit analysis, cost-effectiveness analysis, and impact of antiepileptic drugs on the risk of fracture in patients with epilepsy: A nationwide cohort study.

PURPOSE: Although nonenzyme-inducing antiepileptic drugs (nEIAEDs) are accepted for the treatment of epilepsy, few studies have examined the costs, benefits, and cost-effectiveness of nEIAEDs in relation to the incidence of fracture among patients with epilepsy. In the present study, we performed cost-benefit and cost-effectiveness analyses comparing the influence of enzyme-inducing AEDs (EIAEDs) and nEIAEDs on the risk of fracture in this population. METHODS: A total of 4864 patients with epilepsy were classified into EIAED and nEIAED groups. Propensity score matching was applied to reduce the influence of selection bias. Clinical outcomes were measured in relation to AED fee, medical expenses associated with epilepsy and fracture, and the total number of fractures. Cost-benefit and cost-effectiveness analyses were performed for all patients. RESULTS: Patients in the unmatched EIAED cohort (n = 3686) were older and had more comorbidities. After matching, the cohorts exhibited similar features (n = 2432 each). Fracture risk was lower in the nEIAED group than in the EIAED group (HR = 0.70). The additional medical expense of nEIAEDs in fractures and epilepsy for 2 years per person was 107,731 New Taiwan dollars (NT$). The additional cost for nEIAEDs to reduce one event of fracture was $14,789,421 NT$. CONCLUSIONS: Patients with epilepsy using nEIAEDs had a lower risk of fracture than those using EIAEDs. However, the cost-benefit ratio and cost-effectiveness of such treatment were lower in the nEIAED group than in the EIAED group.

Comparison of cancer detection between 18- and 12-core prostate biopsy in Asian patients with prostate-specific antigen levels of 4-20 ng/mL.

BACKGROUND: Although prostate biopsy is an accepted option for cancer detection, there is little data regarding the clinical outcome of 18-core transrectal ultrasound (TRUS)-guided biopsy. This retrospective study compared cancer detection rates and biopsy complications between 12- and 18-core TRUS biopsy in Asian patients with prostate-specific antigen (PSA) levels between 4.0 and 20.0 ng/mL. METHODS: In total, 1120 consecutive patients with PSA levels between 4.0 and 20.0 ng/mL were divided into the 12-core (552 patients) and 18-core TRUS biopsy (568 patients) groups. The clinical outcomes of the 12- and 18-core TRUS-biopsy groups were compared. Clinical outcomes were evaluated by comparing the prostate cancer detection rates and post-biopsy complication rates. RESULTS: There were no significant group differences in the PSA levels, but the mean age was significantly older in the 12-core biopsy group than in the 18-core biopsy group (mean age, 67.0 vs. 64.0 years, respectively; p = 0.001). The abnormal digital rectal examination rate was higher in the 12-core biopsy group than in the 18-core biopsy group (39.9% vs. 24.5%, respectively; p < 0.001). The prostate cancer detection rate was significantly higher in the 18-core group than in the 12-core group [adjusted odds ratio: 2.75, 95% confidence interval = 2.04-3.01; p < 0.001], especially in patients with age ≥ 50 years, PSA < 10 and cancer clinical stage cT1. (p < 0.001). Moreover, in patients with prostate volumes >30 mL or PSA densities <0.2, the prostate cancer detection rate was significantly higher in the 18-core group than in the 12-core group. There were no differences in the complication rates (e.g., urinary retention, hematuria, urinary tract infection, and urosepsis). CONCLUSION: In Asian patients with serum PSA levels between 4.0 and 20.0 ng/mL, 18-core biopsy was associated with superior clinical outcomes to those of 12-core biopsy for detecting prostate cancer.

[Effects of different long-term fertilization on the activities of enzymes related to carbon, nitrogen, and phosphorus cycles in a red soil].

Using a microplate fluorimetric assay method, five fertilization treatments, i.e. no-fertilizer control (CK) , sole application of nitrogen (N), balanced application of nitrogen, phosphorus, and potassium fertilizer (NPK), application of pig manure (M), and combination of pig manure with balanced chemical fertilizer (MNPK) were selected to investigate the effects of different long-term fertilization regimes on the activity of five enzymes (ß-1, 4-glucosidase, ßG; cellobiohydrolase, CBH; ß-1, 4-xylosidase, ßX; ß-1, 4-N-acetylglucosaminidase, NAG; acid phosphatase, AP) in a red soil sampled from Qiyang, Hunnan Province. The results showed that compared with CK treatment, N treatment had no impact on ßG, ßX, CBH, and NAG activities but reduced AP activity, while NPK, M and MNPK treatments increased the activities of all the five enzymes. Correlation analysis indicated that all the five enzyme activities were positively correlated with the content of nitrate (r=0.465-0.733) , the content of available phosphorus (r=0.612-0.947) , soil respiration (r=0.781-0.949) and crop yield (r=0.735-0.960), while ßG, CBH and AP were positively correlated with pH (r= 0.707-0.809), only AP was significantly correlated with dissolvable organic carbon (r = -0.480). These results suggested that the activities of the measured enzymes could be used as indicators of red soil fertility under different fertilization regimes, but the five enzymes tested provided limited information on the degree of acidification induced by application of mineral nitrogen.

[Characteristics of soil pH and exchangeable acidity in red soil profile under different vegetation types].

The characteristics of soil pH and exchangeable acidity in soil profile under different vegetation types were studied in hilly red soil regions of southern Hunan Province, China. The soil samples from red soil profiles within 0-100 cm depth at fertilized plots and unfertilized plots were collected and analyzed to understand the profile distribution of soil pH and exchangeable acidity. The results showed that, pH in 0-60 cm soil from the fertilized plots decreased as the following sequence: citrus orchard > Arachis hypogaea field > tea garden. As for exchangeable acidity content, the sequence was A. hypogaea field ≤ citrus orchard < tea garden. After tea tree and A. hypogaea were planted for long time, acidification occurred in surface soil (0-40 cm), compared with the deep soil (60-100 cm), and soil pH decreased by 0.55 and 0.17 respectively, but such changes did not occur in citrus orchard. Soil pH in 0-40 cm soil from the natural recovery vegetation unfertilized plots decreased as the following sequence: Imperata cylindrica land > Castanea mollissima garden > Pinus elliottii forest ≥ Loropetalum chinensis forest. As for exchangeable acidity content, the sequence was L cylindrica land < C. mollissima garden < L. chinensis forest ≤ P. elliottii forest. Soil pH in surface soil (0-20 cm) from natural forest plots, secondary forest and Camellia oleifera forest were significantly lower than that from P. massoniana forest, decreased by 0.34 and 0.20 respectively. For exchangeable acidity content in 0-20 cm soil from natural forest plot, P. massoniana forest and secondary forest were significantly lower than C. oleifera forest. Compared with bare land, surface soil acidification in unfertilized plots except I. cylindrica land had been accelerated, and the natural secondary forest was the most serious among them, with surface soil pH decreasing by 0.52. However, the pH increased in deep soils from unfertilized plots except natural secondary forest, and I. cylindrica land was the most obvious among them, with soil pH increasing by 0.43. The effects of fertilization and vegetation type on pH and exchangeable acidity decreased with the increasing soil depth from all plots.

Binding of organic ligands with Al(III) in dissolved organic matter from soil: implications for soil organic carbon storage.

The binding characteristics of organic ligands with Al(III) in soil dissolved organic matter (DOM) is essential to understand soil organic carbon (SOC) storage. In this study, two-dimensional (2D) FTIR correlation spectroscopy was developed as a novel tool to explore the binding of organic ligands with Al(III) in DOM present in soils as part of a long-term (21-year) fertilization experiment. The results showed that while it is a popular method for characterizing the binding of organic ligands and metals, fluorescence excitation-emission matrix-parallel factor analysis can only characterize the binding characteristics of fluorescent substances (i.e., protein-, humic-, and fulvic-like substances) with Al(III). However, 2D FTIR correlation spectroscopy can characterize the binding characteristics of both fluorescent and nonfluorescent (i.e., polysaccharides, lipids, and lignin) substances with Al(III). Meanwhile, 2D FTIR correlation spectroscopy demonstrated that the sequencing/ordering of organics binding with Al(III) could be modified by the use of long-term fertilization strategies. Furthermore, 2D FTIR correlation spectroscopy revealed that the high SOC content in the chemical plus manure (NPKM) treatment in the long term fertilization experiment can be attributed to the formation of noncrystalline microparticles (i.e., allophane and imogolite). In summary, 2D FTIR correlation spectroscopy is a promising approach for the characterization of metal-organic complexes.

[Influence of double rice cropping system innovation on paddy soil profile form and soil characteristics].

Field experiments were conducted on the double rice cropping paddy field in red soil area to evaluate the influence of cropping system innovation on soil profile form and related soil characteristics. Four cropping systems of rice-rice-Chinese Milkvetch (Astragalus sinicus Linn.), forage, paddy-upland rotation, and upland were substituted for the double rice cropping system. The results indicated that compared with those under double rice cropping system, the thickness of cultivated horizon under upland cropping system increased by 4 cm, that of plow pan declined by 2 cm, > 2 mm aggregates in wet-sieved particle-size fractions increased by 6.94%, wet-sieved mean-mass diameter increased by 0.37 mm, contents of humic acid carbon and fulvic acid carbon increased by 0.15 and 0.49 g kg(-1), respectively, and quotient of aggregates water stability was 0.78 times higher. Under paddy-upland rotation, the quotient of aggregates water stability was higher (95.86), while soil nutrient contents changed a little. Under rice-rice-Chinese Milkvetch system, soil organic matter content increased by 1.3 g kg(-1), quotient of aggregates water stability declined by 8.82, but other parameters had less changes. Under forage system, the thickness of cultivated and transitional horizons increased by 2 cm and 9 cm, respectively, quotient of aggregates water stability increased by 1.39, while the contents of soil organic matter and total potassium decreased by 5.6 and 2.8 g kg(-1), respectively. Among all test cropping systems, forage system had the greatest changes in soil characteristics. It was completely feasible to substitute the local double rice cropping system for paddy-upland rotation or upland cropping, particularly in the areas where full irrigation was not available. However, attention should be paid to the decrease of soil potassium content when the cropping system innovation was practiced.