Bridging the gap between prostate radiology and pathology through machine learning.

BACKGROUND: Prostate cancer remains the second deadliest cancer for American men despite clinical advancements. Currently, magnetic resonance imaging (MRI) is considered the most sensitive non-invasive imaging modality that enables visualization, detection, and localization of prostate cancer, and is increasingly used to guide targeted biopsies for prostate cancer diagnosis. However, its utility remains limited due to high rates of false positives and false negatives as well as low inter-reader agreements. PURPOSE: Machine learning methods to detect and localize cancer on prostate MRI can help standardize radiologist interpretations. However, existing machine learning methods vary not only in model architecture, but also in the ground truth labeling strategies used for model training. We compare different labeling strategies and the effects they have on the performance of different machine learning models for prostate cancer detection on MRI. METHODS: Four different deep learning models (SPCNet, U-Net, branched U-Net, and DeepLabv3+) were trained to detect prostate cancer on MRI using 75 patients with radical prostatectomy, and evaluated using 40 patients with radical prostatectomy and 275 patients with targeted biopsy. Each deep learning model was trained with four different label types: pathology-confirmed radiologist labels, pathologist labels on whole-mount histopathology images, and lesion-level and pixel-level digital pathologist labels (previously validated deep learning algorithm on histopathology images to predict pixel-level Gleason patterns) on whole-mount histopathology images. The pathologist and digital pathologist labels (collectively referred to as pathology labels) were mapped onto pre-operative MRI using an automated MRI-histopathology registration platform. RESULTS: Radiologist labels missed cancers (ROC-AUC: 0.75-0.84), had lower lesion volumes (~68% of pathology lesions), and lower Dice overlaps (0.24-0.28) when compared with pathology labels. Consequently, machine learning models trained with radiologist labels also showed inferior performance compared to models trained with pathology labels. Digital pathologist labels showed high concordance with pathologist labels of cancer (lesion ROC-AUC: 0.97-1, lesion Dice: 0.75-0.93). Machine learning models trained with digital pathologist labels had the highest lesion detection rates in the radical prostatectomy cohort (aggressive lesion ROC-AUC: 0.91-0.94), and had generalizable and comparable performance to pathologist label-trained-models in the targeted biopsy cohort (aggressive lesion ROC-AUC: 0.87-0.88), irrespective of the deep learning architecture. Moreover, machine learning models trained with pixel-level digital pathologist labels were able to selectively identify aggressive and indolent cancer components in mixed lesions on MRI, which is not possible with any human-annotated label type. CONCLUSIONS: Machine learning models for prostate MRI interpretation that are trained with digital pathologist labels showed higher or comparable performance with pathologist label-trained models in both radical prostatectomy and targeted biopsy cohort. Digital pathologist labels can reduce challenges associated with human annotations, including labor, time, inter- and intra-reader variability, and can help bridge the gap between prostate radiology and pathology by enabling the training of reliable machine learning models to detect and localize prostate cancer on MRI.

Three-Dimensional Cephalometric Analysis: The Changes in Condylar Position Pre- and Post-Orthognathic Surgery With Skeletal Class III Malocclusion.

ABSTRACT: The study includes 21 adult patients with skeletal class III malocclusion who underwent orthognathic surgery and had computed tomography images records presurgery (T0) up to 6 months after the surgery (T1). The computed tomography images were analyzed three-dimensionally using the Proplan CMF 3.0 software. Different skeletal and dental parameters were used in analyzing the cephalometric analysis of the patients. The change in the condylar axis angle was evaluated on 3 planes: axial, coronal, and sagittal. The anteroposterior position of the condyle in relation to the glenoid fossa was evaluated in the sagittal plane. ∠SNB, ∠ANB, ∠Left Y-axis, ∠Right Y-axis were statistically significant (P < 0.01). Significant differences on the condylar axis angle were found between the groups on the sagittal plane (P < 0.05) whereas no significant differences were noted on the axial and the coronal plane. In the anteroposterior condylar position related to the glenoid fossa, the condyle exhibited different displacement on different condyles. The right condyle exhibited more of the posterior displacement whereas the left condyle exhibited more of anterior displacement of the condyle in relation to the glenoid fossa. Numerous studies have done regarding the changes after postsurgery using the two-dimensional cephalometric analysis. Using the 3D techniques helps us to identify the cephalometric point more accurately which thus enhances the accuracy in the cephalometric analysis. However, care should be taken not to change the axis of rotation of the condyle to prevent from the treatment relapse and to avoid temporo-mandibular disorders.

Agreement of noninvasive tear break-up time measurement between Tomey RT-7000 Auto Refractor-Keratometer and Oculus Keratograph 5M.

BACKGROUND: It is difficult to standardize assessment of dry eye in different clinical settings. Increasingly, tear stability is recognized to be important for the definition and assessment of patients with dry eye. Recently, two commercially available instruments have been made available for objectively measuring noninvasive tear break-up time (NIBUT), as an indicator of tear stability: the Tomey RT-7000 Auto Refractor-Keratometer and Oculus Keratograph (K)5M. We aim to assess the agreement of NIBUT measurements using these modalities. METHODS: This prospective cross-sectional study was carried out in a tertiary referral eye center and involved 126 consecutive dry eye patients. NIBUT assessment was performed on the right eyes of participants with both the RT-7000 and the K5M techniques, with the order of assessment randomized. The Standardized Patient Evaluation of Eye Dryness (SPEED) questionnaires were administered to assess dry eye symptoms in the 2 weeks before assessment. RESULTS: The age of the participants was 56.0±14.3 years (69.84% females). Measurements for both modalities were non-normally distributed (right-skewed). The median RT-7000 and K5M readings were 4.2 (range 0.1-10.0) and 6.4 (0.1-24.9) seconds, respectively. RT-7000 and K5M readings were poorly correlated (ρ=0.061, P=0.495). Intraclass correlation coefficient between the modalities was 0.187 (95% confidence interval -0.097 to 0.406). The Bland-Altman plot showed no systematic differences between the readings with these machines. The agreement between machines was not different in different SPEED categories. CONCLUSION: While there are theoretical and practical benefits of NIBUT for assessment of tear stability over dye-based methods, the agreement between the two modalities was poor. Hence, studies and trials assessing NIBUT should avoid using these modalities interchangeably for NIBUT assessment. More research is needed to improve consensus on how to determine NIBUT.

Transfer of radiocesium from rhizosphere soil to four cruciferous vegetables in association with a Bacillus pumilus strain and root exudation.

This study was carried out to assess the effect of Bacillus pumilus on the roots of four cruciferous vegetables with different root structures in regard to enhancement of 137Cs bioavailability in contaminated rhizosphere soil. Results revealed that B. pumilus inoculation did not enhance the plant biomass of vegetables, although it increased root volume and root surface areas of all vegetables except turnip. The pH changes due to rhizosphere acidification by B. pumilus inoculation and root exudation did not affect the bioavailability of 137Cs. However, concentrations of 137Cs in plant tissues and soil-to-plant transfer values increased as a result of the larger root volume and root surface area of vegetables due to inoculation. Moreover, leafy vegetables, which possessed larger root volume and root surface areas, had a higher 137Cs transfer value than root vegetables.

Relations of fine-root morphology on (137)Cs uptake by fourteen Brassica species.

Fourteen Brassica species consisting of seven leafy vegetables and seven root vegetables were examined for (137)Cs uptake differences in relation to their fine-root morphological characters. A pot experiment was conducted from November 2014 to February 2015 in a Phytroton using a contaminated soil of Fukushima prefecture. Leafy vegetables showed bigger root diameters, larger root surface area and larger root volume. Consequently, leafy vegetables had higher (137)Cs uptake compared to root vegetables. Among the three fine-root parameters, only root surface area was observed as a significant contributing factor to higher (137)Cs uptake in terms of transfer factor (TF, dry weight basis). Kakina exhibited higher (137)Cs TF value (0.20) followed by Chinese cabbage (0.18) and mizuna (0.17). Lower TF values were observed in turnip (0.059), rutabaga (Kitanoshou) (0.062) and radish (Ha daikon) (0.064).

Growth and (137)Cs uptake of four Brassica species influenced by inoculation with a plant growth-promoting rhizobacterium Bacillus pumilus in three contaminated farmlands in Fukushima prefecture, Japan.

The effectiveness of the plant growth-promoting rhizobacterium Bacillus pumilus regarding growth promotion and radiocesium ((137)Cs) uptake was evaluated in four Brassica species grown on different (137)Cs contaminated farmlands at Fukushima prefecture in Japan from June to August 2012. B. pumilus inoculation did not enhance growth in any of the plants, although it resulted in a significant increase of (137)Cs concentration and higher (137)Cs transfer from the soil to plants. The Brassica species exhibited different (137)Cs uptake abilities in the order Komatsuna>turnip>mustard>radish. TF values of (137)Cs ranged from 0.018 to 0.069 for all vegetables. Komatsuna possessed the largest root surface area and root volume, and showed a higher (137)Cs concentration in plant tissue and higher (137)Cs TF values (0.060) than the other vegetables. Higher (137)Cs transfer to plants was prominent in soil with a high amount of organic matter and an Al-vermiculite clay mineral type.

Evaluation of the possibility to use the plant-microbe interaction to stimulate radioactive 137Cs accumulation by plants in a contaminated farm field in Fukushima, Japan.

Field experiments in a contaminated farmland in Nihonmatsu city, Fukushima were conducted to assess the effectiveness of the plant-microbe interaction on removal of radiocesium. Before plowing, 93.3% of radiocesium was found in the top 5 cm layer (5,718 Bq kg DW(-1)). After plowing, Cs radioactivity in the 0-15 cm layer ranged from 2,037 to 3,277 Bq kg DW(-1). Based on sequential extraction, the percentage of available radiocesium (water soluble + exchangeable) was fewer than 10% of the total radioactive Cs. The transfer of (137)Cs was investigated in three agricultural crops; komatsuna (four cultivars), Indian mustard and buckwheat, inoculated with a Bacillus or an Azospirillum strains. Except for komatsuna Nikko and Indian mustard, inoculation with both strains resulted in an increase of biomass production by the tested plants. The highest (137)Cs radioactivity concentration in above-ground parts was found in Bacillus-inoculated komatsuna Nikko (121 Bq kg DW(-1)), accompanied with the highest (137)Cs TF (0.092). Furthermore, komatsuna Nikko-Bacillus and Indian mustard-Azospirillum associations gave the highest (137)Cs removal, 131.5 and 113.8 Bq m(-2), respectively. Despite the beneficial effect of inoculation, concentrations of (137)Cs and its transfer to the tested plants were not very high; consequently, removal of (137)Cs from soil would be very slow.

Transfer of radiocesium to four cruciferous vegetables as influenced by organic amendment under different field conditions in Fukushima Prefecture.

Soil-to-plant transfer of radiocesium ((137)Cs) in four cruciferous vegetables as influenced by cattle manure-based compost amendment was investigated. Komatsuna, mustard, radish and turnip were cultivated in three different (137)Cs-contaminated fields at Nihonmatsu City in Fukushima Prefecture from June to August 2012. Results revealed that organic compost amendments stimulated plant biomass production and tended to induce higher (137)Cs concentration in the cruciferous vegetables in most cases. Among the studied sites, Takanishi soil possessing low exchangeable potassium (0.10 cmolc kg(-1)) was associated with an increased concentration of (137)Cs in plants. Radiocesium transfer factor (TF) values of the vegetables ranged from 0.025 to 0.119. The increase in (137)Cs TFs was dependent on larger plant biomass production, high organic matter content, and high sand content in the studied soils. Average (137)Cs TF values for all study sites and compost treatments were higher in Komatsuna (0.072) and radish (0.059), which exhibited a higher biomass production compared to mustard and turnip. The transferability of (137)Cs to vegetables from soils was in the order Komatsuna > radish > mustard > turnip. The highest (137)Cs TF value (0.071) of all vegetables was recorded for a field where the soil had high organic matter content and a high clay proportion of 470 g kg(-1) consisting of Al-vermiculite clay mineral.

The effects of ginsenoside Rb1 on JNK in oxidative injury in cardiomyocytes.

Reactive oxygen species (ROS) can induce oxidative injury via iron interactions (i.e. Fenton chemistry and hydroxyl radical formation). Our prior work suggested that American ginseng berry extract and ginsenoside Re were highly cardioprotective against oxidant stress. To extend this study, we evaluated the protective effect of protopanaxadiol-type ginsenoside Rb1 (gRb1) on H(2)O(2)-induced oxidative injury in cardiomyocytes and explored the ROS-mediated intracellular signaling mechanism. Cultured embryonic chick cardiomyocytes (4-5 day) were used. Cell death was assessed by propidium iodide and lactate dehydrogenase release. Pretreatment with gRb1 (0.01, 0.1, or 1 µM) for 2 h and concurrent treatment with H(2)O(2) (0.5 mM) for 2 h resulted in a dose-dependent reduction of cell death, 36.6 ± 2.9% (n = 12, p < 0.05), 30.5 ± 5.1% (n = 12, p < 0.05) and 28.6 ± 3.1% (n = 12, p < 0.01) respectively, compared to H(2)O(2)-exposed cells (48.2 ± 3.3%, n = 12). This cardioprotective effect of gRb1 was associated with attenuated intracellular ROS generation as measured by 6-carboxy-2', 7'-dichlorodihydrofluorescein diacetate, preserved the mitochondrial membrane potential as determined using JC-1. In the ESR study, gRb1 exhibited the scavenging DPPH and hydroxyl radical activities. Furthermore, our data showed the increased JNK phosphorylation (p-JNK) in H(2)O(2)-exposed cells was suppressed by the pretreatment with gRb 1 (1 µM) (p < 0.01). Co-treatment of gRb1 with a specific inhibitor of JNK SP600125 (10 µM) further reduced the p-JNK and enhanced the cell survival after H(2)O(2) exposure. Collectively, our results suggest that gRb1 conferred cardioprotection that was mediated via attenuating ROS and suppressing ROS-induced JNK activation.

Effects of Triterpenoid Glycosides from Fresh Ginseng Berry on SW480 Human Colorectal Cancer Cell Line.

PURPOSE: The pharmacological activities, notably the anticancer properties, of bioactive constituents fromfresh American ginseng berry have not yet been well studied. In this study, we investigated the antiproliferative effects of fresh American ginseng berry extract (AGBE) and its representative triterpenoid glycosides using the human colorectal cancer cell line SW480. MATERIALS AND METHODS: Using high performance liquid chromatography (HPLC), the contents of 8 ginsenosides in AGBE were determined. The cell growth inhibitory effects of AGBE and three triterpenoid glycosides (ginsenosides Rb3, Re, and Rg3) were evaluated by proliferation assay and (3)H-thymidine incorporation assay. Cell cycle and apoptotic effects were analyzed by using flow cytometry after staining with propidium iodide and annexin V. RESULTS: HPLC analysis data showed that AGBE has a distinct ginsenoside profile. AGBE inhibited SW480 cell growth significantly in a time-dependent (24-96 hours) and concentration-dependent (0.1-1.0 mg/mL) manner. Ginsenosides Rb3, Re, and Rg3 also possess significant antiproliferative activities on SW480 cells. (3)H-thymidine incorporation assay indicated that AGBE and ginsenosides Rb3, Re, and Rg3 might inhibit the transferring and duplication of DNA in SW480 cells. Flow cytometric assay data suggested that AGBE arrested SW480 cells in S and G2/M phases, and significantly induced cell apoptosis. CONCLUSION: AGBE and ginsenosides Rb3, Re, and Rg3 possessed significant antiproliferative effects and induced changes of morphological appearance on SW480 cells. The mechanisms of the antiproliferation of AGBE and tested ginsenosides involved could be cell cycle arrest and induction of apoptosis.

High performance liquid chromatographic analysis and anticancer potential of Oplopanax horridus: comparison of stem and berry extracts.

Oplopanax horridus or devil's club is a herbal medicine distributed in North America. The constituents and pharmacological activities of O. horridus (OPH) are largely unknown. In this study, we assayed OPH stem and berry extracts using high performance liquid chromatography (HPLC). The anticancer potentials of extracts on different human cancer cell lines (SW-480, HCT-116, HT-29, MCF-7 and NSCLC) were determined by MTS method. The effect of stem extract on cancer cell cycle, expression of cyclin A, and apoptosis were assayed using flow cytometry. HPLC data showed that the composition of OPH stem extract is more complicated than the berry extract. The wavelength of maximum absorption of the major constituent in stem and berry is 196.0 nm and 201.9 nm, respectively. Compared to the berry extract, the stem extract showed significant potent antiproliferative effect on all the studied cell lines. The stem extract at 0.1 mg/ml arrested cancer cells in S- and G2/M-phases, and significantly induced expression of cyclin A. After treatment with 0.1 mg/ml of stem extract for 72 h, apoptotic cells were increased to 45.2%, while control was 9.6%. The cell cycle arrest and induction of apoptosis may play a critical role in cancer chemoprevention by Oplopanax horridus stem extract.

Nasolabial fold angle measurement using anterior segment optical coherence tomography in normal subjects.

PURPOSE: The human nasolabial fold angle (NFA) has been measured using MRI and photogrammetry and has been shown to decrease with age. The authors aimed to evaluate a novel method using optical coherence tomography to measure the NFA. METHODS: In this cross-sectional observational series, the authors used anterior segment optical coherence tomography (ASOCT) to image the NFA of both cheeks of 126 subjects aged 21 to 79 years. A dental vinylpolysiloxane custom-designed mould was used as a chin rest. The mean of 3 scans on each side was calculated and analysis of variance, multiple comparisons, and multiple linear regression were carried out using SPSS 11.0. RESULTS: Sixty-one subject (48.4%) were men and 65 (51.6%) were women. Mean age was 50.6 +/- 16.8 years (range, 21-79 years). The ASOCT successfully imaged the NFA in all subjects. Mean right and left NFA were 144.4 degrees +/- 17.1 degrees and 145.4 degrees +/- 17.7 degrees. The NFA were dissimilar between the 6 age categories by decade (p < 0.001). Age was the significant predictor of NFA, accounting for 55% of NFA variation. Every year accounted for a decrease of 0.78 degrees (p < 0.001) and 0.80 degrees (p < 0.001) for the right and left cheeks, respectively. Male sex resulted in an increase in NFA of 5.4 degrees (p = 0.007) and 4.0 degrees (p = 0.06) in the right and left cheeks, respectively. CONCLUSIONS: The NFA decreases with age and increases with male sex and can be measured with ASOCT accurately and easily.

Protease inhibitor-induced nausea and vomiting is attenuated by a peripherally acting, opioid-receptor antagonist in a rat model.

BACKGROUND: Protease inhibitors such as ritonavir can cause nausea and vomiting which is the most common reason for discontinuation. Rats react to nauseous and emetic stimuli by increasing their oral intake of non-nutritive substances like kaolin, known as pica behavior. In this study, we evaluated the effects of methylnaltrexone, a peripherally acting mu-opioid receptor antagonist that does not affect analgesia, on ritonavir-induced nausea and vomiting in a rat pica model. RESULTS: We observed that 24 to 48 hr after administration of oral ritonavir 20 mg/kg, kaolin consumption increased significantly in rats (P < 0.01). This increase was attenuated by pretreatment with an intraperitoneal injection of methylnaltrexone (0.3-3.0 mg/kg) in a dose dependent manner (P < 0.01) and also with naloxone (0.1-0.3 mg/kg) (P < 0.01). The areas under the curve for kaolin intake from time 0 to 120 hr were significantly reduced after administration of the opioid antagonists. Food intake was not significantly affected. Plasma naltrexone levels were measured after methylnaltrexone injection, and no detectable levels were found, indicating that methylnaltrexone was not demethylated in our experimental paradigm. CONCLUSION: These results suggest that methylnaltrexone may have potential clinical utility in reducing nausea and vomiting in HIV patients who take ritonavir.

Methylnaltrexone, a peripherally acting opioid receptor antagonist, enhances tumoricidal effects of 5-Fu on human carcinoma cells.

BACKGROUND: Methylnaltrexone, a novel peripherally acting opioid receptor antagonist, is used to treat opiate-induced constipation in cancer patients. Its effects on the activities of chemotherapeutic agents, however, have not been evaluated. In this study, the effect of methylnaltrexone on the action of 5-fluorouracil (5-FU) was tested in three human cancer cell lines. MATERIALS AND METHODS: Treatment was for 72 h and the effects on cell proliferation were measured in human SW-480 colorectal cancer cells, MCF-7 breast cancer cells and non-small cell lung cancer cells in vitro. The apoptotic effect was analyzed by using flow cytometry. The cell cycle and expression of cyclin A were assayed after staining with propidium iodide and cyclin A-fluorescein isothiocyanate. RESULTS: 5-FU decreased the cancer cell growth significantly in all three cancer cell lines in a concentration-dependent manner and methylnaltrexone enhanced the actions of 5-FU. Compared to 5-FU 10 muM alone on SW-480 cells (63.5+/-1.1%), on MCF-7 cells (58.3+/-3.1%), or on non-small cell lung cancer cells (81.3+/-1.6%), 5-FU 10 muM plus methylnaltrexone 1.0 muM reduced cancer cell growth in all three cell lines to 50.2+/-2.9% for SW-480 cells (p<0.05), 50.0+/-1.7% for MCF-7 cells (p<0.05) and 68.7+/-2.2% for lung cancer cells (p<0.01). Methylnaltrexone alone also showed anti-proliferative activity in the three cell lines. Methylnaltrexone at 1.0 muM, reduced SW-480 cell growth to 81.9+/-3.7% (p<0.01), MCF-7 cell growth to 85.9+/-2.4% (p<0.01) and lung cancer cell growth to 85.5+/-2.2% (p<0.01). Apoptosis was not induced by treatment of SW-480 cells with 1.0 or 10 muM methylnaltrexone for 48 h. However, methylnaltrexone increased the number of cells in the G(1)-phase and decreased the expression of cyclin A. CONCLUSION: At its therapeutic concentrations for opioid-induced constipation, methylnaltrexone does not attenuate and in fact may enhance the tumoricidal activity of 5-FU. Enhanced 5-FU activity may be attributed to the distinct pathways of 5-FU and methylnaltrexone, an effect that could give methylnaltrexone a complementary role in the treatment of cancer with chemotherapeutic agents.

Comparison of slitlamp optical coherence tomography and scanning peripheral anterior chamber depth analyzer to evaluate angle closure in Asian eyes.

OBJECTIVE: To evaluate the effectiveness of slitlamp optical coherence tomography (SL-OCT) and Scanning Peripheral Anterior Chamber depth analyzer (SPAC) in detecting angle closure, using gonioscopy as the reference standard. METHODS: A total of 153 subjects underwent gonioscopy, SL-OCT, and SPAC. The anterior chamber angle (ACA) was classified as closed on gonioscopy if the posterior trabecular meshwork could not be seen; with SL-OCT, closure was determined by contact between the iris and angle wall anterior to the scleral spur; and with SPAC by a numerical grade of 5 or fewer and/or a categorical grade of suspect or potential. RESULTS: A closed ACA was identified in 51 eyes with gonioscopy, 86 eyes with SL-OCT, and 61 eyes with SPAC (gonioscopy vs SL-OCT, P < .001; gonioscopy vs SPAC, P = .10; SL-OCT vs SPAC, P < .001; McNemar test). Of the 51 eyes with a closed ACA on gonioscopy, SL-OCT detected a closed ACA in 43, whereas SPAC identified 41 (P = .79). An open angle in all 4 quadrants was observed in 102 eyes with gonioscopy, but SL-OCT and SPAC identified 43 and 20 of these eyes, respectively, as having angle closure. The overall sensitivity and specificity for SL-OCT were 84% and 58% vs 80% and 80% for SPAC. CONCLUSION: Using gonioscopy as the reference, SL-OCT and SPAC showed good sensitivity for detecting eyes at risk of angle closure.

Asian ginseng enhances the anti-proliferative effect of 5-fluorouracil on human colorectal cancer: comparison between white and red ginseng.

Previous studies showed that Asian ginseng, Panax ginseng C.A. Meyer, may have anti-cancer properties. However, there is limited data exploring the use of Asian ginseng as an adjuvant to chemotherapy, and minimal mechanistic studies related to their possible synergistic activities. In this study, the content of 8 ginsenosides, Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1 and Rg3, in the extracts of white ginseng (WG) and red ginseng (RG) were determined by HPLC. Using HCT-116 human colorectal cancer cells, we compared the efficacy of WG and RG. We evaluated the synergy between ginseng and 5-fluorouracil (5-FU), and explored the mechanism of their anti-proliferative effects. As single extract, WG or RG used at concentrations of 0.1, 0.2 and 0.3 mg/mL, inhibited HCT-116 cell proliferation in a concentration-related manner. WG at 0.2 mg/mL did not show obvious synergy with 5-FU co-treatment, while RG at 0.2 and 0.3 mg/mL significantly enhanced the anti-proliferative effects of 5-FU at concentrations of 10, 50 and 100 microM (P < 0.05). Using flow cytometric assay, RG 0.3 mg/mL did not affect cancer cell apoptotic induction activity. However, the RG induced cell cycle arrest in the G1 phase, while 5-FU arrested the cell in the S phase. Different ginsenoside profiles are responsible for the observed differences in pharmacological effects. The effects of 8 ginsenosides on HCT-116 cells were assayed. Rd and Rg3 showed positive anti-proliferative effect. Our data suggested a potential for RG as an adjuvant therapy in the treatment of colorectal cancer, via a synergistic action.

High-definition optical coherence tomography imaging of the iridocorneal angle of the eye.

OBJECTIVE: To assess the ability of high-definition optical coherence tomography (HD-OCT) to image the anterior chamber angle. METHODS: Forty-five consecutive subjects with phakic eyes underwent gonioscopy and anterior chamber angle imaging with HD-OCT adapted with a 60-diopter aspheric lens mounted over the imaging aperture. The patients' fixation was directed to the side using an external fixation light, and scans were taken of the temporal and nasal quadrants. The visibility of angle structures was assessed and the diagnosis of angle closure using HD-OCT was compared with that of gonioscopy. RESULTS: The majority of subjects were Chinese (91.1%) and female (62.2%). Cross-sectional HD-OCT allowed in vivo visualization of the scleral spur in 71 of 90 quadrants (78.9%) and the termination of the Descemet membrane (Schwalbe line) in 84 of 90 quadrants (93.3%). It was possible to image the trabecular meshwork in 56 quadrants (62.2%). Angle closure was observed in 17 eyes with gonioscopy and 12 eyes with HD-OCT (P = .12, McNemar test). The 2 modalities showed good agreement for angle closure diagnosis by quadrant (kappa = 0.65). CONCLUSION: The adapted HD-OCT provided magnified views of the anterior chamber angle and allowed visualization of the Schwalbe line and trabecular meshwork in most eyes.

Variation of angle parameters in asians: an anterior segment optical coherence tomography study in a population of singapore malays.

PURPOSE: To assess variations in angle parameters using anterior segment optical coherence tomography (AS-OCT) and to investigate demographic, ocular and systemic associations of angle width. METHODS: This was a substudy of a population based, cross-sectional survey of 3280 (78.7% response rate) Malay people aged 40 to 80 years in Singapore. All participants underwent a standardized interview and ocular and systemic examination. AS-OCT was performed on 291 consecutive patients in standardized dark conditions. Angle opening distance (AOD-500) and trabecular-iris space area (TISA-500) 500 microm from the scleral spur were determined for the nasal and temporal angles. Anterior chamber depth (ACD) was also measured. RESULTS: AS-OCT measurements were analyzed in 239 (82.1%) right eyes. Mean AOD 500 was smaller in women than in men, both nasally (0.255 vs. 0.293 mm, P = 0.026) and temporally (0.245 vs. 0.286 mm, P = 0.023). Mean TISA-500 was smaller in women in the nasal quadrant only (0.104 vs. 0.117 mm, P = 0.035). Mean ACD was smaller in women than in men (2.71 vs. 2.87 mm, P = 0.001). Multiple linear regression showed that axial length and ACD were significantly associated with AOD-500 and TISA-500 both nasally (adjusted R(2) = 0.34 for AOD-500 and 0.20 for TISA-500) and temporally (adjusted R(2) = 0.35 for AOD-500 and 0.24 for TISA-500). Body mass index, HbA(1c), systolic blood pressure, intraocular pressure, cup-to-disc ratio, and central corneal thickness were not significantly associated with AOD-500, TISA-500, or ACD. CONCLUSIONS: In this Malay population, angle width measured by AS-OCT was smaller in women than in men, and in eyes with shorter axial length and shallower ACD.