Drug release control and anti-inflammatory effect of biodegradable polymer surface modified by gas phase chemical functional reaction.

The plasma technique has been widely used to modify the surfaces of materials. The purpose of this study was to evaluate the probability of controlling the prednisolone delivery velocity on a polylactic acid (PLA) surface modified by plasma surface treatment. Surface modification of PLA was performed at a low-pressure radio frequency under conditions of 100 W power, 50 mTorr chamber pressure, 100-200 sccm of flow rate, and Ar, O2, and CH4gases. The plasma surface-modified PLA was characterized using scanning emission microscope, x-ray photoelectron spectroscopy (XPS), and contact angle measurements.In vitroevaluations were performed to determine cellular response, drug release behavior, and anti-inflammatory effects. The PLA surface morphology was changed to a porous structure (with a depth of approximately 100 µm) and the surface roughness was also significantly increased. The XPS results demonstrated higher oxygenized carbon contents than those in the non-treated PLA group. The prednisolone holding capacity increased and the release was relatively prolonged in the surface-modified PLA group compared to that in the non-treated PLA group. In addition, cell migration and proliferation significantly increased after PLA treatment alone. The activity of cytokines such as cyclooxygenase-2 (COX-2), tumor necrosis factor-a (TNF-α), interleukin (IL-1ß), and IL-6 were considerably reduced in the plasma-treated and prednisolone holding group. Taken together, surface-modified PLA by plasma can provide an alternative approach to conventional physicochemical approaches for sustained anti-inflammatory drug release.

High-response room-temperature NO2 gas sensor fabricated with thermally reduced graphene oxide-coated commercial cotton fabric.

Electronic textile-based gas sensors with a high response for NO2 gas were fabricated using reduced graphene oxide (rGO)-coated commercial cotton fabric (rGOC). Graphene oxide (GO) was coated on cotton fabric by simply dipping the cotton into a GO solution. To investigate the relationship between the degree of reduction and the sensing response, the GO-coated fabrics were thermally reduced at various temperatures (190, 200, 300, and 400 °C). The change in the amount of oxygen functional groups on the rGOCs was observed by x-ray photoelectron spectroscopy, Raman spectroscopy, and x-ray diffraction patterns. The maximum sensing response of 45.90 % at 10 ppm of NO2 gas at room temperature was exhibited by the rGOC treated at 190 °C, which was the lowest heat-treatment temperature. The high response comes from the greater amount of oxygen functional groups compared to other rGOC samples, and the tubular structure of the cotton.

A prospective, multicenter study on the clinical effectiveness of abiraterone in metastatic castration-resistant prostate cancer in Korea: Pre- vs. post-chemotherapy.

PURPOSE: The proper treatment sequence for administering abiraterone acetate plus prednisolone (AAP) and chemotherapeutic agents has not yet been elucidated for metastatic castration-resistant prostate cancer (mCRPC). Hence, this study evaluated the effectiveness and safety of AAP in pre- and post-chemotherapy settings using real-world data. MATERIALS AND METHODS: This prospective, multicenter, open-label, observational study included 506 patients with mCRPC. Patients were classified according to the timing of chemotherapy into pre- and post-chemotherapy groups. The effectiveness and safety of AAP were compared between the groups; the prostate-specific antigen (PSA) response, PSA progression-free survival, and radiologic progression-free survival were assessed; and adverse drug reactions were recorded. RESULTS: Among the included patients, 319 and 187 belonged to the pre- and post-chemotherapy groups, respectively. Risk classification was similar between the two groups. The PSA response was 61.8% in the pre-chemotherapy group and 39.0% in the post-chemotherapy group (p<0.001). The median time to PSA progression (5.00 vs. 2.93 mo, p=0.001) and radiologic progression-free survival (11.84 vs. 9.17 mo, p=0.002) were significantly longer in the pre-chemotherapy group. Chemotherapy status was associated with PSA (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.09-1.77) and radiologic progression (HR 1.66, 95% CI 1.18-2.33) during AAP treatment. Adverse drug reactions were reported at similar frequencies in both groups. CONCLUSIONS: In this postmarketing surveillance, AAP benefited patients with mCRPC, especially in settings before chemotherapy was administered, resulting in a high PSA response and longer PSA and radiologic progression-free survival with tolerable adverse drug reactions.

Corrigendum: Correction of the Figure. Trends of stratified prostate cancer risk in a single Korean province from 2003 to 2021: A multicenter study conducted using regional training hospital data.

This corrects the article on p. 140 in vol. 64, PMID: 36882172.

Early Detection of Secondary Bladder Urothelial Carcinoma and Disseminated Bone Metastases with Normal Prostate-Specific Antigen Level after Pelvic Salvage Radiotherapy in Prostate Cancer.

This report describes the case of a 65-year-old man who presented with gross hematuria and a history of pelvic salvage radiotherapy for prostate cancer. Cystoscopy and transurethral resection of the bladder revealed urothelial carcinoma. Subsequently, disseminated bone metastases were detected with normal prostate-specific antigen (PSA) levels, and palliative radiotherapy and systemic chemotherapy were administered. Because gross hematuria can appear in both acute/chronic cystitis and bladder cancer in patients who have undergone pelvic radiotherapy for prostate cancer, close follow-up along with a detailed evaluation is needed. In addition, because prostate cancer disease progression with normal PSA levels may be associated with specific pathological findings, a detailed evaluation of symptoms and a careful review of pathologic reports are important.

SAMHD1-induced endosomal FAK signaling promotes human renal clear cell carcinoma metastasis by activating Rac1-mediated lamellipodia protrusion.

Human sterile α motif and HD domain-containing protein 1 (SAMHD1) has deoxyribonucleoside triphosphohydrolase (dNTPase) activity that allows it to defend against human immunodeficiency virus type I (HIV-1) infections and regulate the cell cycle. Although SAMHD1 mutations have been identified in various cancer types, their role in cancer is unclear. Here, we aimed to investigate the oncogenic role of SAMHD1 in human clear cell renal cell carcinoma (ccRCC), particularly as a core molecule promoting cancer cell migration. We found that SAMHD1 participated in endocytosis and lamellipodia formation. Mechanistically, SAMHD1 contributed to the formation of the endosomal complex by binding to cortactin. Thereafter, SAMHD1-stimulated endosomal focal adhesion kinase (FAK) signaling activated Rac1, which promoted lamellipodia formation on the plasma membrane and enhanced the motility of ccRCC cells. Finally, we observed a strong correlation between SAMHD1 expression and the activation of FAK and cortactin in tumor tissues obtained from patients with ccRCC. In brief, these findings reveal that SAMHD1 is an oncogene that plays a pivotal role in ccRCC cell migration through the endosomal FAK-Rac1 signaling pathway.

Trends of stratified prostate cancer risk in a single Korean province from 2003 to 2021: A multicenter study conducted using regional training hospital data.

PURPOSE: To identify changes in prostate cancer (PCa) risk-stratification during the last two decades in Korea, where the social perception of PCa was limited due to a relatively low incidence but has recently been triggered by the rapidly increasing incidence of benign prostate hyperplasia. MATERIALS AND METHODS: Retrospective data of patients who had received a diagnosis of PCa in a single Korean province (Daegu-Gyeongsangbuk) at all seven training hospitals in the years 2003, 2007, 2011, 2015, 2019, and 2021 were subjected to analysis. Changes in PCa risk-stratification were investigated with respect to serum prostate-specific antigen (PSA), Gleason score (GS), and clinical stage. RESULTS: Of the 3,393 study subjects that received a diagnosis of PCa, 64.1% had high-risk disease, 23.0% intermediate, and 12.9% low-risk disease. The proportion diagnosed with high-risk disease was 54.8% in 2003, 30.6% in 2019, but then increased to 35.1% in 2021. The proportion of patients with high PSA (>20 ng/mL) steadily decreased from 59.4% in 2003 to 29.6% in 2021, whereas the proportion with a high GS (>8) increased from 32.8% in 2011 to 34.0% in 2021, and the proportion with advanced stage disease (over cT2c) increased from 26.5% in 2011 to 37.1% in 2021. CONCLUSIONS: In this retrospective study, conducted in a single Korean province, high-risk PCa accounted for the largest proportion of newly registered Korean PCa patients during the last two decades and increased in the early 2020s. This outcome supports the adoption of nationwide PSA screening, regardless of current Western guidelines.

Current treatment patterns within 1 year after prostate cancer diagnosis in Korean patients over 75 years old: a retrospective multicenter study.

Background: We aimed to evaluate the current status of first-line treatment options for prostate cancer in patients aged ≥75 years in Korea. Materials and methods: The study included 873 patients diagnosed with biopsy-proven prostate cancer at 5 institutions in Korea from January 2009 to December 2018. Inclusion criteria were aged ≥75 years at diagnosis, prostate biopsy with ≥12 cores, and follow-up period ≥1 year. Clinical data were retrospectively collected from electronic medical records. Results: Primary treatment for prostate cancer in patients aged ≥75 years included androgen deprivation therapy (ADT) (n = 614), radical prostatectomy (RP) (n = 114), and radiation therapy (n = 62). Among patients with RP, nine patients received ADT before RP. The RP group was younger with better Eastern Cooperative Oncology Group Performance Status (ECOG PS), lower initial prostate-specific antigen (PSA), Gleason score (GS), max percent positive cores, less positive cores, and less advanced clinical Tumor Node Metastasis (TNM) stage compared with the ADT group. Multivariate analysis showed that age, ECOG PS, and PSA were independent prognostic factors for RP. When the ADT group was classified by therapeutic regimens, the most common therapeutic regimen was maximal androgen blockade (MAB) (n = 571), and leuprolide + bicalutamide (n = 330) was the most common MAB regimen. Multivariate analysis for secondary treatment showed that age, ECOG PS, GS, and clinical N1 or M1 stage were independent predictive factors. Enzalutamide was the most preferred treatment for tertiary treatment. Conclusion: In patients with prostate cancer aged ≥75 years, the most common treatment option was MAB, and the leuprolide + bicalutamide was the most common MAB regimen. Age, ECOG PS, and PSA are the useful indicators of surgical treatment, which increased during the study period. Younger patients with high GS and advanced clinical stage were more likely to undergo secondary treatment.

Nanophotosensitizers Composed of Phenyl Boronic Acid Pinacol Ester-Conjugated Chitosan Oligosaccharide via Thioketal Linker for Reactive Oxygen Species-Sensitive Delivery of Chlorin e6 against Oral Cancer Cells.

Chlorin E6 (Ce6)-incorporated nanophotosensitizers were fabricated for application in photodynamic therapy (PDT) of oral cancer cells. For this purpose, chitosan oligosaccharide (COS) was conjugated with hydrophobic and reactive oxygen species (ROS)-sensitive moieties, such as phenyl boronic acid pinacol ester (PBAP) via a thioketal linker (COSthPBAP). ThdCOOH was conjugated with PBAP to produce ThdCOOH-PBAP conjugates and then attached to amine groups of COS to produce a COSthPBAP copolymer. Ce6-incorporated nanophotosensitizers using the COSthPBAP copolymer were fabricated through the nanoprecipitation and dialysis methods. The Ce6-incorporated COSthPBAP nanophotosensitizers had a small diameter of less than 200 nm with a mono-modal distribution pattern. However, it became a multimodal and/or irregular distribution pattern when H2O2 was added. In a morphological observation using TEM, the nanophotosensitizers were disintegrated by the addition of H2O2, indicating that the COSthPBAP nanophotosensitizers had ROS sensitivity. In addition, the Ce6 release rate from the COSthPBAP nanophotosensitizers accelerated in the presence of H2O2. The SO generation was also higher in the nanophotosensitizers than in the free Ce6. Furthermore, the COSthPBAP nanophotosensitizers showed a higher intracellular Ce6 uptake ratio and ROS generation in all types of oral cancer cells. They efficiently inhibited the viability of oral cancer cells under light irradiation, but they did not significantly affect the viability of either normal cells or cancer cells in the absence of light irradiation. The COSthPBAP nanophotosensitizers showed a tumor-specific delivery capacity and fluorescence imaging of KB tumors in an in vivo animal tumor imaging study. We suggest that COSthPBAP nanophotosensitizers are promising candidates for the imaging and treatment of oral cancers.

Validation of MRI-Based Models to Predict MGMT Promoter Methylation in Gliomas: BraTS 2021 Radiogenomics Challenge.

O6-methylguanine-DNA methyl transferase (MGMT) methylation prediction models were developed using only small datasets without proper external validation and achieved good diagnostic performance, which seems to indicate a promising future for radiogenomics. However, the diagnostic performance was not reproducible for numerous research teams when using a larger dataset in the RSNA-MICCAI Brain Tumor Radiogenomic Classification 2021 challenge. To our knowledge, there has been no study regarding the external validation of MGMT prediction models using large-scale multicenter datasets. We tested recent CNN architectures via extensive experiments to investigate whether MGMT methylation in gliomas can be predicted using MR images. Specifically, prediction models were developed and validated with different training datasets: (1) the merged (SNUH + BraTS) (n = 985); (2) SNUH (n = 400); and (3) BraTS datasets (n = 585). A total of 420 training and validation experiments were performed on combinations of datasets, convolutional neural network (CNN) architectures, MRI sequences, and random seed numbers. The first-place solution of the RSNA-MICCAI radiogenomic challenge was also validated using the external test set (SNUH). For model evaluation, the area under the receiver operating characteristic curve (AUROC), accuracy, precision, and recall were obtained. With unexpected negative results, 80.2% (337/420) and 60.0% (252/420) of the 420 developed models showed no significant difference with a chance level of 50% in terms of test accuracy and test AUROC, respectively. The test AUROC and accuracy of the first-place solution of the BraTS 2021 challenge were 56.2% and 54.8%, respectively, as validated on the SNUH dataset. In conclusion, MGMT methylation status of gliomas may not be predictable with preoperative MR images even using deep learning.

Should Contemporary Western Guidelines Based on Studies Conducted in the 2000s Be Adopted for the Prostate-Specific Antigen Screening Policy for Asian Men in the 2020s?

Though prostate cancer (PCa) is the second most common cancer world widely, there exist substantial differences exist between Asia and the west. Genetic susceptibility and lifestyle may contribute to disproportionately lower incidences and mortalities of PCa in Asian countries, but the differences in diagnostic practices are also likely to contribute, and a large part of them may be explained by the lesser chance of prostate-specific antigen (PSA) testing. In the US, about half of men aged over 50 years had been exposed to the screening test in the early 2000s. The shifts in the risk stratification from the high-risk dominant disease in the late 1980s to the low-risk dominant disease in the early 2000s led to criticism regarding the unconditional nature of PSA-based screening. Based on the conflicting outcomes from the randomized clinical trials which investigated the benefit of PSA testing, US Preventive Study Task Force recommended ceasing mass screening in 2012. Accordingly, guidelines begin to emphasize shared decision-making on the PSA testing narrowing their scopes to men aged 55 to 69 years since 2013. Though most Asian countries have not begun to recognize PCa as a major agenda item until the 2010s, a clear trend of expanding incidence of it implies that the time to come to reconsider PSA testing as a higher priority in the public health sphere in the 2020s. Concerns regarding over-diagnosis and over-treatment of insignificant diseases are imperative. However, the distinctive epidemiologic characteristics of PCa in Asia areas, such as low exposure to the repetitive PSA testing, the recent increase in its incidence driven by the elderly and super-elderly, and racial differences should be considered when it comes to the establishment of screening policy utilizing PSA test.

Reactive Oxygen Species and Folate Receptor-Targeted Nanophotosensitizers Composed of Folic Acid-Conjugated and Poly(ethylene glycol)-Chlorin e6 Tetramer Having Diselenide Linkages for Targeted Photodynamic Treatment of Cancer Cells.

Folic acid-conjugated nanophotosensitizers composed of folic acid (FA), poly(ethylene glycol) (PEG) and chlorin e6 (Ce6) tetramer were synthesized using diselenide linkages for reactive oxygen species (ROS)- and folate receptor-specific delivery of photosensitizers. Ce6 was conjugated with 3-[3-(2-carboxyethoxy)-2,2-bis(2-carboxyethoxymethyl)propoxy]propanoic acid (tetra acid, or TA) to make Ce6 tetramer via selenocystamine linkages (TA-sese-Ce6 conjugates). In the carboxylic acid end group of the TA-sese-Ce6 conjugates, FA-PEG was attached again using selenocystamine linkages to make FA-PEG/TA-sese-Ce6 conjugates (abbreviated as FAPEGtaCe6 conjugates). Nanophotosensitizers were fabricated by a dialysis procedure. In the morphological observations, they showed spherical shapes with small diameters of less than 200 nm. Stability of the aqueous FAPEGtaCe6 nanophotosensitizer solution was maintained (i.e., their particle sizes were not significantly changed until 7 days later). When H2O2 was added to the nanophotosensitizer solution, the particle size distribution was changed from a monomodal pattern to a multimodal pattern. In addition, the fluorescence intensity and Ce6 release rate from the nanophotosensitizers were also increased by the addition of H2O2. These results indicated that the nanophotosensitizers had ROS-sensitive properties. In an in vitro cell culture study, an FAPEGtaCe6 nanophotosensitizer treatment against cancer cells increased the Ce6 uptake ratio, ROS generation and light-irradiated cytotoxicity (phototoxicity) compared with Ce6 alone against various cancer cells. When the folic acid was pretreated to block the folate receptors of the Y79 cells and KB cells (folate receptor-overexpressing cells), the intracellular Ce6 uptake, ROS generation and thereby phototoxicity were decreased, while the MCF-7 cells did not significantly respond to blocking of the folate receptors. These results indicated that they could be delivered by a folate receptor-mediated pathway. Furthermore, an in vivo pulmonary metastasis model using Y79 cells showed folate receptor-specific delivery of FAPEGtaCe6 nanophotosensitizers. When folic acid was pre-administered, the fluorescence intensity of the lungs was significantly decreased, indicating that the FAPEGtaCe6 nanophotosensitizers had folate receptor specificity in vitro and in vivo. We suggest that FAPEGtaCe6 nanophotosensitizers are promising candidates for a targeted photodynamic therapy (PDT) approach against cancer cells.

The national-wide incidence of prostate-specific antigen testing trend for a decade in Korea by age group.

PURPOSE: To document nationwide serum prostate-specific antigen (PSA) testing trends over the past decade and to investigate the impact of testing on prostate cancer (PCa) detection. MATERIALS AND METHODS: Using annual National Health Insurance Service of Korea data for the period 2006 to 2016, PSA testing rates were investigated for men aged ≥40 years by decade, and associations between test rates and registered PCa cases were analyzed. RESULTS: During the study period, the incidence of PCa increased about threefold (4,415 in 2006 to 15,046 in 2016). PCa incidences increased with age (p<0.001) and about 60% of cases were over 70 years old. Despite a fourfold increase in PSA testing (246,911 in 2006 to 937,548 in 2016), the average exposure rate among all men was only 7.27% in 2016, and the mean number of repeat tests for those that did not develop PCa during the study period was 2.9. PSA test rates increased with age and in 2016 were 1.65% for those in their 40s, 4.90% for those in their 50s, 12.0% for those in their 60s, 19.2% for those in their 70s, and 21.6% for those aged ≥80. Regardless of the age groups, a significant association was found between PSA test numbers and the detection of PCas. CONCLUSIONS: In contrast to the soaring incidence of PCa especially in those aged over 70 years who have a more frequent chance for PSA testing triggered by concomitant voiding symptoms, low exposure in general and among relatively younger men favors a countrywide screening policy.

A new link between apoptosis induced by the metformin derivative HL156A and autophagy in oral squamous cell carcinoma.

The metformin derivative HL156A exerts antitumoral effects in various cancers. Despite evidence in the literature, the underlying molecular mechanisms have not been clearly elucidated. Here, we examined the antiproliferative role and mechanism of HL156A in oral squamous cell carcinoma (OSCC). Using MTT and colony formation assays, we found that HL156A exerts an antiproliferative effect in oral cancer cells in a concentration-dependent manner. Flow cytometry was used to analyze the cell cycle distribution and apoptosis. Exposure to HL156A induced cell cycle arrest at the G2/M transition and increased apoptosis rates, associated with the increased caspase-3/PARP activity. On the other hand, HL156A induced autophagy, as demonstrated by autophagic vacuole staining and quantification of autolysosome-associated LC3BI/II proteins. Interestingly, inhibition of autophagy with chloroquine (CQ) increased the extent of apoptosis and promoted the antiproliferative effect of HL156A in OSCC cell lines, suggesting that autophagy mitigates HL156A-induced apoptosis. The relevance of these observations was confirmed in an in vivo system, as cotreatment with HL156A and CQ inhibited tumor growth in a xenograft mouse model of oral cancer. These results showed that HL156A has an antiproliferative effect associated with cell cycle arrest and apoptosis and induces autophagy to protect cells against apoptosis.

Effect of Oxygen Functional Groups in Reduced Graphene Oxide-Coated Silk Electronic Textiles for Enhancement of NO2 Gas-Sensing Performance.

An electronic textile-based NO2 gas sensor was fabricated using commercial silk and graphene oxide (GO). It showed a fast response time and excellent sensing performance, which was simply accomplished by modifying the heat-treatment process. The heat treatment was conducted at 400 °C and different heating rates of 1, 3, and 5 °C/min. Compared with our previous research, the response time significantly decreased, from 32.5 to 3.26 min, and we found that the highest response was obtained with the sensor treated at a heating rate of 1 °C/min. To find the reason for this enhanced sensing performance, the morphology, structure, and chemical composition of the reduced GO (rGO) were investigated, depending on the thermal treatment process, using scanning electron microscopy, X-ray diffraction, Raman spectroscopy, and X-ray photoelectron spectroscopy. We also measured the temperature-dependent resistance of rGO, which was well described by the fluctuation-induced tunneling (FIT) model. These results revealed that the rGO thermally treated with 1 °C/min of heating rate had the largest amount of oxygen groups. This means that the oxygen functional groups play an important role in NO2 gas-sensing performance.

Ciprofloxacin-Releasing ROS-Sensitive Nanoparticles Composed of Poly(Ethylene Glycol)/Poly(D,L-lactide-co-glycolide) for Antibacterial Treatment.

Since urinary tract infections (UTIs) are closely associated with oxidative stress, we developed ROS-sensitive nanoparticles for ciprofloxacin (CIP) delivery for inhibition of UTI. Poly(D,L-lactide-co-glycolide) (PLGA)- selenocystamine (PLGA-selenocystamine) conjugates were attached to methoxypoly(ethylene glycol) (PEG) tetraacid (TA) (TA-PEG) conjugates to produce a copolymer (abbreviated as LGseseTAPEG). Selenocystamine linkages were introduced between PLGA and TA to endow reactive oxygen species (ROS) sensitivity to nanoparticles. CIP-incorporated nanoparticles of LGseseTAPEG copolymer were fabricated by W/O/W/W emulsion method. CIP-incorporated nanoparticles responded to H2O2 and then their morphologies were disintegrated by incubation with H2O2. Furthermore, particle size distribution of nanoparticles was changed from mono-modal distribution pattern to multi-modal distribution pattern by addition of H2O2. CIP release from nanoparticles of LGseseTAPEG copolymer was faster in the presence of H2O2 than in the absence of it. In antibacterial study using Escherichia coli (E. coli), free CIP and free CIP plus empty nanoparticles showed dose-dependent inhibitory effect against growth of bacteria while CIP-incorporated nanoparticles have less antibacterial activity compared to free CIP. These results were due to that CIP-incorporated nanoparticles have sustained release properties. When free CIP or CIP-incorporated nanoparticles were introduced into dialysis membrane to mimic in vivo situation, CIP-incorporated nanoparticles showed superior antibacterial activity compared to free CIP. At cell viability assay, nanoparticles of LGseseTAPEG copolymer have no acute cytotoxicity against L929 mouse fibroblast cells and CCD986sk human skin fibroblast cells. We suggest LGseseTAPEG nanoparticles are a promising candidate for CIP delivery.

The significance of the visible tumor on preoperative magnetic resonance imaging in localized prostate cancer.

OBJECTIVES: We investigated the relationship between tumor characteristics and visible tumors on magnetic resonance imaging (MRI) and examined the prognosis of tumor detection on MRI compared with no tumor detection in localized prostate cancer. MATERIALS AND METHODS: We reviewed 214 patients with pT2N0M0 prostate cancer who underwent radical prostatectomy between January 2009 and December 2016. All the patients underwent MRI preoperatively. The patients were divided into 2 groups postoperatively: no visible tumor on the MRI group (n = 96, 44.9%) and visible tumor on the MRI group (n = 118, 55.1%). The visible tumor was defined as Prostate Imaging Reporting and Data System, version 2 Grade ≥ 3 on MRI. Age, prostate-specific antigen, prostate volume, positive surgical margin (PSM), lymphovascular invasion, and biochemical recurrence (BCR) were compared between the 2 groups. We also assessed the relationship between visible tumors on MRI and oncologic characteristics. RESULTS: The visible tumor on the MRI group showed a higher Gleason score ≥4 + 3 [45.8% versus (vs.) 17.7%], high frequency of postoperative PSMs (28.8% vs. 16.7%), and higher BCR rate (17.8% vs. 7.3%) than the no visible tumor on the MRI group. The Kaplan-Meier analysis for BCR-free survival also showed a significant difference (P = 0.006). In multivariate Cox regression analysis, the detection of tumors on MRI was associated with a higher BCR risk [hazard ratio: 3.35; 95% confidence interval (CI): 1.36-8.27; P = 0.009]. We found a positive association between visible tumors on MRI and primary Gleason pattern of ≥4 (odds ratio: 4.31; 95% CI: 2.21-8.40; P < 0.001). CONCLUSIONS: In localized prostate cancer, BCR was significantly more frequent when the tumor was detected on MRI, and a visible tumor on MRI was associated with the Gleason score. Therefore, attention should be paid to the possibility of high-grade prostate cancer when a tumor is detected on MRI before radical prostatectomy, and active follow-up may be needed postoperatively.

Combinatorial Effect of Cold Atmosphere Plasma (CAP) and the Anticancer Drug Cisplatin on Oral Squamous Cell Cancer Therapy.

Cold atmospheric plasma (CAP) has been extensively investigated in the local treatment of cancer due to its potential of reactive oxygen species (ROS) generation in biological systems. In this study, we examined the synergistic effect of combination of CAP and cisplatin-mediated chemotherapy of oral squamous cell carcinoma (OSCC) in vitro. SCC-15 OSCC cells and human gingival fibroblasts (HGF-1) cells were treated with cisplatin, and then, the cells were irradiated with CAP. Following this, viability and apoptosis behavior of the cells were investigated. The viability of SCC-15 cells was inhibited by cisplatin with a dose-dependent manner and CAP treatment time. HGF-1 cells also showed decreased viability by treatment with cisplatin and CAP. Combination of 1 µM cisplatin plus 3 min of CAP treatment or 3 µM cisplatin plus 1 min of CAP treatment showed a synergistic anticancer effect with appropriate cytotoxicity against normal cells. ROS generation and dead cell staining were also increased by the increase in CAP treatment time. Furthermore, tumor-suppressor proteins and apoptosis-related enzymes also increased according to the treatment time of CAP. We showed the synergistic effect of cisplatin and CAP treatment against SCC-15 cells with low cytotoxicity against normal cells.

Efficacy and safety of dose escalation in male patients with overactive bladder showing poor efficacy after low-dose antimuscarinic treatment: A retrospective multicenter study.

PURPOSE: To analyze the efficacy and safety of standard-dose antimuscarinic treatment on male patients with overactive bladder (OAB) symptoms showing poor efficacy after low-dose antimuscarinics. MATERIALS AND METHODS: We retrospectively reviewed the data of 566 male patients aged ≥40 with OAB symptoms between January 2017 and June 2018. They were treated with low-dose antimuscarinics for at least 4 weeks and showed poor efficacy; therefore, they were switched to standard dose antimuscarinic treatment (5 mg of solifenacin) for ≥12 weeks. The international prostate symptom score (IPSS) and overactive bladder symptom score (OABSS) at baseline (V0), 4 weeks (V1), and 12 weeks (V2) were analyzed. Post void residual urine volume (PVR) was also recorded. RESULTS: The median age, body mass index, and prostate-specific antigen levels were 69.0 years, 24.2 kg/m², and 1.24 ng/dL, respectively. The mean value of the total IPSS and OABSS significantly decreased between V0 and V2 (from 16.73 to 13.69 and 7.33 to 5.34, respectively, all p<0.001). All component scores from each questionnaire demonstrated a significant decrease except for numbers three and six on the IPSS questionnaire. PVR was increased from V0 to V2 (36.40 to 68.90 mL, p=0.015). Four and nine patients experienced constipation and thirst, respectively, and all adverse effects were graded as ≤2. CONCLUSIONS: Standard dose antimuscarinic treatment using solifenacin (5 mg) may be a safe and effective treatment for patients with OAB symptoms refractory to low-dose antimuscarinic treatment.