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BACKGROUND pT2+ prostate cancer (PCa), a term first used in 2004, refers to organ-confined PCa characterized by a positive surgical margin (PSM) without extracapsular extension. Patients with a PSM are vulnerable to biochemical recurrence (BCR) following radical prostatectomy (RP); however, whether adjuvant radiotherapy (aRT) is imperative to PSM after RP remains controversial. This study had the longest follow-up on pT2+ PCa after robotic-assisted RP since 2004. Moreover, we discussed our viewpoints on pT2+ PCa based on real-world experiences. AIM To conclude a 10-year surveillance on pT2+ PCa and compare our results with those of the published literature. METHODS Forty-eight patients who underwent robotic-assisted RP between 2008 and 2011 were enrolled. Two serial tests of prostate specific antigen (PSA) ≥ 0.2 ng/mL were defined as BCR. Various designed factors were analyzed using statistical tools for BCR risk. SAS 9.4 was applied and significance was defined as P < 0.05. Univariate, multivariate, linear regression, and receiver operating characteristic (ROC) curve analyses were performed for statistical analyses. RESULTS With a median follow-up period of 9 years, 25 (52%) patients had BCR (BCR group), and the remaining 23 (48%) patients did not (non-BCR group). The median time for BCR test was 4 years from the first postoperative PSA nadir. Preoperative PSA was significantly different between the BCR and non-BCR groups (P < 0.001), and ROC curve analysis of preoperative PSA suggested a cut-off value of 19.09 ng/mL (sensitivity, 0.600; specificity: 0.739). The linear regression analysis showed no correlation between time to BCR and preoperative PSA (Pearson’s correlation, 0.13; adjusted R2 = 0.026). CONCLUSION Robotic-assisted RP in pT2+ PCa of worse conditions can provide better BCR-free survival. A surgical technique limiting the PSM in favorable situations is warranted to lower the pT2+ PCa BCR rate. Preoperative PSA cut-off value of 19.09 ng/mL is a predictive factor for BCR. Based on our experiences and review of the literature, we do not recommend routine aRT for pT2+ PCa.

BACKGROUND Target therapy is licensed by United States Food and Drug Administration on certain cancers. Both sorafenib and lenvatinib are tyrosine kinase inhibitor and indicated on radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC). Lenvatinib is more effective in cancers' control than sorafenib, but causes more nephrotoxicity than sorafenib does. This case is the second published case about the serial adaptions from lenvatinib to sorafenib for improving the proteinuria and, meanwhile, achieving the therapeutic goal. CASE SUMMARY A 56-year-old man suffered from bilateral edematous lower extremities after 1-mo prescription of lenvatinib of 20 mg/d for RAI-refractory DTC. Aside from this symptom, he also developed hypertension. His laboratory showed grade-3 proteinuria (estimated 24-h urine protein: 9993 mg), hypoalbuminemia and hypercholesterolemia. Anti-vascular endothelial growth factor (VEGF) therapy-induced nephrotic syndrome was impressed. After reduced dosage of lenvatinib of 10 mg/d and related symptomatic drugs, limited improvement was observed in both adverse effects and caner control. Under this condition, we substituted sorafenib of 400 mg/d for lenvatinib of 10 mg/d. After a 5-mo prescription, not only hypertension and peripheral edema were greatly improved, but also proteinuria was improved from grade three to grade one (estimated 24-h urine protein: 962 mg). At the same time the cancer control was achieved, judged from computed tomography and laboratory evidence [thyroglobulin (Tg) before prescription of sorafenib: 354.7 ng/mL; Tg after prescription of sorafenib: 108.9 ng/mL]. CONCLUSION Adaption from lenvatinib to sorafenib is a feasible method to improve the anti-VEGF therapy-induced nephrotic syndrome and achieve the therapeutic goal at the same time.

BACKGROUND/AIM Expanded indications for patients with preoperatively suspected prostate cancer (PC) undergoing theranostic robotic-assisted laparoscopic radical prostatectomy (T-RARP) are reported. We aimed to build a nomogram of T-RARP to predict final pathologically proven PC. This study reviewed data of 153 patients that underwent T-RARP for suspected PC performed by the same surgeon. PATIENTS AND METHODS Patients' preoperative demographic and clinical characteristics included age, prostate-specific antigen (PSA) level, PSA density (PSAD), history of acute urinary retention (AUR), abnormal digital rectal examination (DRE) of the prostate, and Prostate Imaging Reporting and Data System (PI-RADS) classification at 3-T multiparametric magnetic resonance imaging (MRI). Logistic regression with backward elimination was used to select potential risk factors. RESULTS Based on Harrell's guidelines, we chose seven variables for our final model: Age, DRE corresponding with MRI, AUR, PSAD, prostate-specific antigen velocity (PSAV), PI-RADS, and biopsy pathology. A nomogram for prediction of adenocarcinoma was developed. The original C-index for the nomogram was 0.80 (95% confidence interval=0.74-0.89). The cut-off of the nomogram score for predicting PC was 50 (sensitivity=55.4%; specificity=91.9%). The receiver operating characteristic curve of the model analysis showed an area under the curve of 0.801. CONCLUSION A nomogram was produced using age, DRE-corresponding MRI, AUR, PSAD, PSAV, PI-RADS, and biopsy pathology. A preoperative nomogram prediction of prostate adenocarcinoma can help the patient and his family understand the possibility of PC and assist them in their decision-making.

Background/Aim: Incisional hernia is a complication that occurs occasionally, and surgical intervention is required to prevent more severe sequela. While there are several options for management, robotic-assisted incisional repair has not been well discussed yet. We herein report a case series of 10 patients who underwent robotic-assisted incisional hernia repair (RIHR) after robotic-assisted radical prostatectomy (RARP). The aim of the study was to examine the feasibility of incisional hernia repair with da Vinci(®) robotics. Patients and Methods: We recruited patients from a group of 2,000 consecutive patients who underwent RARP from December, 2005 to June, 2020 by a single surgeon. Patient characteristics included age, body mass index (BMI), PSA level, pathology Gleason score, and pathology TNM staging. The variants regarding the patients’ incisional hernia included incisional hernia occurrence time after RARP, defect size, operation time, console time, blood loss, and follow-up time after the herniation occurrence. Furthermore, we established a defect size of 3x2 cm(2) as the cutoff value for using mesh reinforcement or not. Results: The mean defect area was 27.7 cm(2), and the average operative time was 114.8 min, with a mean console time of 87 min. Blood loss was 32.5 ml, and the hospital stay for all patients was 3 days without complications. The mean follow-up period was 29.5 months, with no recurrence. Conclusion: RIHR is a feasible surgical method that is not inferior to the traditional open or laparoscopic repair. Furthermore, RIHR can possibly lessen the burden of both the surgeon and patient.

Although ureteroplasty with buccal mucosa graft for long-segmental ureteral stenosis has been developed long ago, evidence was still restricted to case series in published literature. This study aims to validate ureteroplasty with buccal mucosa graft (BMG) in long-segment stricture at the proximal and middle ureters under designed comparative methods. From April 2015 to January 2019, we performed robotic-assisted ureteroplasty with BMG with a two-phase design and compared ureteroplasty and BMG (phase 2 surgery) with endoscopic stenting (phase 1 surgery). Paired data of effective renal plasma flow (ERPF), glomerular filtration rate (GFR), hydronephrosis grade, and physical and psychological domains of the World Health Organization Quality of Life (WHOQOL)-BREF were compared. A total of 29 patients were enrolled, and only three (10%) patients had hydronephrosis resolution after treatment with endoscopic stenting (p = 0.250 to baseline). Compared to endoscopic ureteral stent, Hedges’ g of ureteroplasty with BMG was 0.56 (95% CI: 0.43-0.69), 0.63 (95% CI: 0.46-0.80), 0.80 (95% CI: 0.56-1.04), and 1.06 (95% CI: 0.69-1.43) in EGFR, GFR, physical domain of WHOQOL-BREF, and psychological domain of WHOQOL-BREF, respectively (All significance; p

INTRODUCTION AND OBJECTIVE:Ki67 is enhanced in interphase and mitotic phase in cell cycle, and is especially important in forming perichromosomal layer from prophase to telophase during mitosis. It...

The inflammatory process is proposed to be one of the factors to benign prostatic enlargement (BPH), and this is the first study examining the anti-inflammatory ability of phloretin in treating rats with testosterone-induced BPH. BPH would be induced by testosterone (10 mg/kg/day testosterone subcutaneously for 28 days), and the other groups of rats were treated with phloretin 50 mg/kg/day or 100 mg/kg/day orally (phr50 or phr100 group) after induction. Prostate weight and prostate weight to body weight ratio were significantly reduced in the Phr100 group. Reduced dihydrotestosterone without interfering with 5α-reductase was observed in the phr100 group. In inflammatory proteins, reduced IL-6, IL-8, IL-17, NF-κB, and COX-2 were seen in the phr100 group. In reactive oxygen species, malondialdehyde was reduced, and superoxide dismutase and glutathione peroxidase were elevated in the phr100 group. In apoptotic assessment, elevated cleaved caspase-3 was observed in rats of the phr100 group. Enhanced pro-apoptotic Bax and reduced anti-apoptotic Bc1-2 could be seen in the phr100 group. In histological stains, markedly decreased glandular hyperplasia and proliferative cell nuclear antigen were observed with reduced expression in the phr100 group. Meanwhile, positive cells of terminal deoxynucleotidyl transferase dUTP nick end labeling were increased in the phr100 group. In conclusion, the treatment of phloretin 100 mg/kg/day could ameliorate testosterone-induced BPH. Published version

This study aimed to determine the prognostic values of Ki67 and vimentin in upper tract urothelial carcinoma (UTUC) after extirpative surgery.Between 2014 and 2019, patients diagnosed with UTUC and receiving radical nephroureterectomy were included retrospectively. Nuclear MIB-1 clones and cytoplasmic VIM 3B4 clones were used to assess Ki67 and vimentin levels, respectively. A unified reading protocol was applied, and the expression level was read by a single pathologist. Receiver operating characteristic curves were utilized to determine the best threshold for Ki67 and vimentin regarding recurrence, and this level was set as the diffusive level. The outcome of recurrence-free survival (RFS) was analyzed via a Cox regression model with univariable and multivariable approaches. Survival outcomes were analyzed via Kaplan-Meier (KM) curves.A total of 247 patients were included, and the mean follow-up was 29.90 ± 6.80 months. Diffusive thresholds were 17.5% for both Ki67 and vimentin. Under multivariable Cox regression, diffusive Ki67 (hazard ratio: 4.20 [2.39-7.37], P0.001) and diffusive vimentin (hazard ratio: 5.34 [3.10-9.22], P0.001) were significant prognostic indicators of worse RFS. Diffusive Ki67 was accompanied by diffusive vimentin (chi square with Yates' correction, P = 0.015), and vice versa. In the KM curve, there was no difference between diffusive Ki67/nondiffusive vimentin and nondiffusive Ki67/diffusive vimentin (log-rank test, P = 0.073). Significant differences (log-rank test, P0.001) were seen in different combinations of diffusive Ki67/vimentin (Mean RFS: 19.76 [18.56-20.96] months), only one diffusive in Ki67 or vimentin (Mean RFS: 22.94 [21.88-24.00] months), and nondiffusive Ki67/vimentin (Mean RFS: 32.96 [32.43-33.50] months).Diffusive Ki67 and vimentin were related to each other, and they exerted equivalent and synergic effects on predicting worse RFS in UTUC.

Lymphoepithelioma-like carcinoma, named after nasopharyngeal lymphoepithelioma and rarely seen at genitourinary malignancy, accounts for 1%–2% along the upper and lower urinary tract. For its rarity, no published guideline can be adhered to. Roles of surgery and chemotherapy are solid, and rich Programmed Death-Ligand 1 characteristics may furthermore light on the possible immunotherapy. This female case had it at both upper and lower urinary tract simultaneously. No involved regional lymph nodes and no distant metastasis were investigated. No adjuvant chemotherapy was given after robotics-assisted left nephroureterectomy and bladder cuff excision with partial cystectomy, and no recurrence was observed.

Background: Cdc7-Dbf4 is a conserved serine/threonine kinase that plays an important role in initiation of DNA replication and DNA damage tolerance in eukaryotic cells. Cdc7 has been found overexpressed in human cancer cell lines and tumor tissues, and the knockdown of Cdc7 expression causes an p53-independent apoptosis, suggesting that Cdc7 is a target for cancer therapy. Only a handful Cdc7 kinase inhibitors have been reported. All Cdc7 kinase inhibitors, including PHA-767491, were identified and characterized as ATP-competitive inhibitors. Unfortunately, these ATP-competitive Cdc7 inhibitors have no good effect on clinical trial. Methods: Here, we have developed a novel drug-screening platform to interrupt the interaction between Cdc7 and Dbf4 based on Renilla reniformis luciferase (Rluc)-linked protein-fragment complementation assay (Rluc-PCA). Using drug repositioning approach, we found several promising Cdc7 inhibitors for cancer therapy from a FDA-approved drug library. Findings: Our data showed that dequalinium chloride and clofoctol we screened inhibit S phase progression, accumulation in G2/M phase, and Cdc7 kinase activity. In addition, in vivo mice animal study suggests that dequalinium chloride has a promising anti-tumor activity in oral cancer. Interestingly, we also found that dequalinium chloride and clofoctol sensitize the effect of platinum compounds and radiation due to synergistic effect. In conclusion, we identified non-ATP-competitive Cdc7 kinase inhibitors that not only blocks DNA synthesis at the beginning but also sensitizes cancer cells to DNA damage agents. Interpretation: The inhibitors will be a promising anti-cancer agent and enhance the therapeutic effect of chemotherapy and radiation for current cancer therapy. Fund: This work was supported by grants from the Ministry of Science and Technology, Ministry of Health and Welfare, and National Health Research Institutes, Taiwan. Keywords: Cdc7 inhibitor, Drug repositioning, Cancer therapy, Protein fragment complementation assay, Protein-protein interaction

Cancer has become one of the primary causes of death worldwide. Current cancer-therapy schemes are progressing relatively slowly in terms of reducing mortality, prolonging survival, time and enhancing cure rate, owing to the enormous obstacles of cancer pathophysiology. Therefore, specific diagnosis and therapy for malignant tumors are becoming more and more crucial and urgent, especially for early cancer diagnosis and cancer-targeted therapy. Derived theranostics that combine several functions into one "package" could further overcome undesirable differences in biodistribution and selectivity between distinct imaging and therapeutic agents. In this article, we discuss a chief clinical diagnosis tool - MRI - focusing on recent progress in magnetic agents or systems in multifunctional polymer nanoassemblies for combing cancer theranostics. We describe abundant polymeric MRI-contrast agents integrated with chemotherapy, gene therapy, thermotherapy, and radiotherapy, as well as other developing directions.

The Paris System (TPS) for Reporting Urinary Cytology is an international system with standardized terminology and cytomorphologic criteria that aims for better risk stratification to identify high-grade urothelial carcinoma in urinary cytology specimens. Based on TPS, the nuclear/cytoplasmic ratio (N/C ratio) of the observed urothelial cells is a crucial criterion and the cutoff values of 0.5 and 0.7 are used for the diagnosis of Atypical Urothelial Cells (AUC) and High-Grade Urothelial Carcinoma (HGUC)/Suspicious for HGUC respectively. Although the N/C ratio is a clear and measurable criterion, there are still challenges for adopting TPS into clinical practice. As urine cytology mainly relies on manual microscopic examination by cytopathologists and cytotechnologists, determining the N/C ratio through the naked eyes results in intra- and inter-observer variations and therefore generates subjective, inconsistent, and unreproducible reports. To overcome the aforementioned issues, the authors developed a deep learning-based image analysis model to assist calculating the N/C ratio and classifying urothelial cells computationally. Deidentified urine cytology slides were digitalized as whole-slide images (WSIs) for analyzing. An “active learning” method was used to improve results over time with only a small amount of upfront training data required. First, a small amount of annotated WSIs were provided to train the initial computational model. Next, the experts reviewed the results predicted by the initial model, and provide feedback for the model to learn and improve. The above steps were repeated by experts reviewing the “improved model” and providing feedbacks, thus improving the initial/intermediate models continuously until a satisfactory result was achieved. Preliminary results showed that our model was able to determine the areas of cytoplasm and nucleus in urothelial cells as well as calculate the N/C ratios using the WSI. Moreover, it enumerates the AUC and HGUC cells on the WSI and provides quantification and distribution information on the whole slide scale. This computational model provides a significant advantage as an objective tool to assist urine cytology analysis of the N/C ratio with greater accuracy and reproducibility. Citation Format: Wei-Lei Yang, Chi-Bin Li, Yen-Chuan Ou, Yi-Sheng Lin, Tang-Yi Tsao, Ming-Chen Chang, Jen-Fan Hang, Tien-Jen Liu. A deep learning model assists urine cytology reporting with computational estimates of the nuclear/cytoplasmic ratios of the urothelial cells based on the Paris System [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-069.

Purpose: The utility of indocyanine green dye (ICG) has evolved significantly to the robotic operations including Robotic Assisted Radical Prostatectomy (RARP). The technology can help the identification of sentinel lymphatic drainage in lymphadenectomy for the majority of prostate cancer (PCa) patients. We describe the potential indications of ICG for lymphadenectomy assistant in PCa patients without lymph node or distant metastasis. Materials and Methods: We prospectively analyzed PCa patients without lymph node or distant metastasis with clinical pathological stage T1c to T3a received RARP from November 2019 to May 2020. The clinical data and pathological data, including Gleason score, tumor volume, pathological stage, and surgical findings, were described. All lymph nodes were divided into ICG positive or negative. All patients were divided into low, moderate, and high risk according to the European Association of Urology PCa risk stratification. Results: Cystoscope-guided intraprostatic injection was performed successively in 34 localized PCa patients in this study. The mean age was 66.1 ± 7.8 years old. The patients' number of high, moderate, and low risk was 18, 10, 6. A total of 447 lymph nodes were identified. Two hundred and sixty-two lymph nodes were ICG positive and 181 lymph nodes were ICG negative. ICG positive rate higher in high risk patients 158/259 (61.0%) compare to intermediate/low risk patients 104/188 (55.3%). There was no statistic significant result, but lymph node could be identified in all ICG-positive tissues. There were 12 patients revealed higher Gleason grade group after RARP and two patients revealed lower Gleason grade group after RARP. There were 18 patients showed upgrade stage after RARP and 4 patients showed down stage after RARP. Conclusion: Cystoscope-guided intraprostatic ICG injection with fluorescence lymphangiography can help identify pelvic lymph nodes in RARP for PCa patients without lymph node or distant metastasis.

Background The link between elevated serum uric acid ( SUA ) levels and cardiovascular disease ( CVD )–related mortality in the elderly population remains inconclusive. Nutritional status influences both SUA and CVD outcomes. Therefore, we investigated whether SUA ‐predicted mortality and the effect‐modifying roles of malnourishment in older people. Methods and Results A longitudinal Taiwanese cohort including 127 771 adults 65 years and older participating in the Taipei City Elderly Health Examination Program from 2001 to 2010 were stratified by 1‐mg/dL increment of SUA . Low SUA (2 . Study outcomes were all‐cause and CVD ‐related mortality. Cox models were used to estimate hazard ratios ( HRs ) of mortality, after adjusting for 20 demographic and comorbid covariates. Over a median follow‐up of 5.8 years, there were 16 439 all‐cause and 3877 CVD ‐related deaths. Compared with the reference SUA strata of 4 to SUA HR , 1.16; 95% confidence interval, 1.07–1.25) and ≥8 mg/dL ( HR , 1.13; confidence interval, 1.06–1.21), with progressively elevated risks at both extremes. Similarly, increasingly higher CVD ‐related mortality was found at the SUA level HR , 1.19; confidence interval, 1.00–1.40) and ≥7 mg/dL ( HR , 1.17; confidence interval, 1.04–1.32). Remarkably, among the low SUA (CVD ‐related mortality. This modifying effect of malnourishment remained consistent across subgroups. Conclusions SUA ≥8 or CVD ‐related mortality in the elderly, particularly in those with malnourishment.

Background Gallbladder perforation is a rare but lethal condition and its diagnosis is usually difficult and delayed. Frequently, gallbladder rupture is associated with cholecystitis, but spontaneous perforation was ever described. However, spontaneous rupture of gallbladder has never been reported in patients underwent peritoneal dialysis. Case presentation We report a 62-year-old man who presented with abdominal pain for 2 days to clinic. Peritoneal dialysis-related peritonitis was diagnosed initially. It was followed by spontaneous gallbladder perforation with greenish dialysate. The patient was managed successfully by antibiotic treatment and primary closure of gallbladder perforation with external drainage. He recovered from this critical condition and stayed on dialysis. Conclusions Early diagnosis and timely surgical intervention yields a good prognosis in PD patients with gallbladder perforation. Surgical intervention and antibiotic treatment are the mainstay of treatment. Both of them should take place promptly.

Water-soluble chitosan derivative-based nanoparticles (carboxymethyl chitosan-chitooligosaccharide nanoparticles (CMC-COS NP) and sulphated chitosan-chitooligosaccharide nanoparticles (SC-COS NP)) were prepared by the formation of polyelectrolyte complexes. SC-COS NP and CMC-COS NP both induced the proliferation of mouse fibroblasts, whereas they elicited dose-dependent inhibitory effects on the proliferation of both HeLa and mouse B16 melanoma cells. Injection of SC-COS NP and CMC-COS NP modulated serum Th cytokines and stimulated the proliferation of splenic lymphocytes (CD4+ and CD8+ T cells, CD19+ B cells and NK cells) in mice, indicating the ability of these particles to regulate both humoral and cell-mediated immune responses. These properties demonstrated their promising potential for application as biomedical materials.

Background Peritoneal dialysis (PD)-related peritonitis is a serious complication that typically leads to hospitalization, catheter loss, and even mortality. Previous studies of the risk factors for peritonitis are discordant. To date, no biomarker associated with PD-related peritonitis has been investigated. However, it has been shown that serum decoy receptor 3 (DcR3) is a valuable marker in predicting the outcome of several inflammatory diseases. The aim of this study was to investigate whether serum DcR3 is a predictor of peritonitis in chronic PD patients. Methods We conducted a prospective cohort study of PD patients in the PD unit of a tertiary referral center from March 1 to November 30, 2007, and followed up until December 31, 2009. Clinical and laboratory parameters were recorded and serum DcR3 was measured to assess risk factors for developing PD-related peritonitis. Results A total of 77 patients (38 men and 39 women; mean age 58 ± 13 years) were enrolled in this study. The average time on PD was 24.5 months and 46 patients (60%) were diabetic. The mean follow-up duration was 499 ± 17 days. The rate of peritonitis incidence was 0.17 episodes per patient-year. Baseline serum DcR3 in 77 patients was 1.94 ± 1.23 ng/mL. Kaplan–Meier survival analysis showed that patients with serum DcR3 > 1.8 ng/mL had a higher risk of peritonitis than those with serum DcR3 p = 0.016). The Cox proportional hazard model further showed that high serum DcR3 (>1.8 ng/mL) was an independent risk factor for subsequent peritonitis (hazard ratio 3.61, 95% CI 1.17–11.08; p = 0.03). Conclusion Serum DcR3 was associated with increased risk of PD-related peritonitis.

The bioactivity of chitosan-carboxymethyl dextran nanoparticles (CDNP) made using chitosans with different degrees of deacetylation (DA) (CDNP98: CDNP made with 98% DA chitosan; CDNP78: CDNP made with 78% DA chitosan) were tested by analysis of their in vitro effects on HeLa tumor cell and mouse fibroblast proliferation, and their in vivo effects on the regulation of mouse serum cytokine levels. CDNPs (50 to 100 microg/ml) induced higher fibroblast proliferation than chitosans (CDNP98 > CDNP78 > chitosan), and were also more effective than chitosans in inhibition of HeLa cell proliferation in a dose-dependent manner (25 to 100 microg/ml) (CDNP78 > CDNP98 > chitosans). CDNPs also induced a higher serum IL-5 level than chitosans (CDNP98 > CDNP78 > chitosans) within 3 h, and CDNP78 had a greater impact on IL-6 regulation but regulated IL-10 over a shorter duration than CDNP98 within the first 3 h. Combined with their ability to reduce serum IL-17 at 24 h, these biocompatible, immuno-active CDNPs demonstrated the potential to be applied as biomedical materials.

Leukocyte 8-hydroxy-2′-deoxyguanosine (8-OHdG) is a surrogate marker of oxidant-induced DNA damage in patients undergoing maintenance hemodialysis (MHD). Glutathione S-transferase M1 (GST M1) is a member of the GST family of proteins, which protect cellular DNA against oxidative damage. This study tested the association of a common GST M1 gene polymorphism [GST M1(−)], known to produce a dysfunctional enzyme, with levels of 8-OHdG in peripheral blood leukocytes and all-cause mortality among MHD patients. Among 488 MHD patients and 372 gender-matched healthy subjects, the frequency of the GST M1(−) genotype was 63.1 and 60.2%, respectively. The GST M1(−) genotype was associated with significantly higher levels of leukocyte 8-OHdG compared with the GST M1(+) genotype, even after adjustment for potential confounders (P < 0.001). Moreover, GST M1(−) patients who also had a common polymorphism in the DNA repair enzyme 8-oxoguanine DNA glycosylase 1 or who underwent dialysis with a bioincompatible cellulose membrane had the highest median levels of leukocyte 8-OHdG. Multivariate Cox regression revealed that among MHD patients, GST M1(−) genotype approximately doubled the risk for all-cause mortality (hazard ratio 2.24; 95% confidence interval 1.30 to 4.51) during the mean follow-up of 34 mo. In conclusion, patients without GST M1 activity are more vulnerable to oxidative stress and are at greater risk for death compared with those who possess GST M1 activity.

Cancer stem cells (CSCs) represent a unique sub-population of tumor cells with the ability to initiate tumor growth and sustain self-renewal. Although CSC biomarkers have been described for various tumors, only a few markers have been identified for nasopharyngeal carcinoma (NPC). In this study, we show that CD24+ cells isolated from human NPC cell lines express stem cell genes (Sox2, Oct4, Nanog, Bmi-1, and Rex-1), and show activation of the Wnt/β-catenin signaling pathway. CD24+ cells possess typical CSC characteristics that include enhanced cell proliferation, increased colony and sphere formation, maintenance of cell differentiation potential in prolonged culture, and enhanced resistance to chemotherapeutic drugs. Notably, CD24+ cells produce tumors following inoculation of as few as 500 cells in immunodeficient NOD/SCID mice. CD24+ cells further show increased invasion ability in vitro, which correlates with enhanced expression of matrix metalloproteinase 2 and 9. In summary, our results suggest that CD24 represents a novel CSC biomarker in NPC.