Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G0/G1 phase and caused apoptosis. Piceamycin alsoinhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.

PURPOSE: Up to 10% of recurrences develop beyond 5 years after curative treatment of localized renal cell carcinoma (RCC). Clinicopathologic features were evaluated to determine which factors are associated with late recurrence. MATERIALS AND METHODS: A total of 753 patients were diagnosed with localized RCC from January 2000 to June 2008. We enrolled 225 patients who were treated surgically and had a minimal recurrence-free survival of 60 months. Patients who had recurrence beyond 5 years after nephrectomy were defined as the late recurrence group and the remaining patients as the recurrence-free group. Multivariate logistic regression analyses and the Cox proportional hazard model were used for determination of features associated with late recurrence. RESULTS: In multivariate analyses, age older than 60 (p=0.030), Fuhrman grade > or = 3 (p=0.042), and pT stage > or = pT2 (p=0.010) showed statistical association with late recurrence. The Cox proportional hazard model showed significant differences in recurrence-free survival when we classified the patients based on pT2 (p=0.007) and on patient age > or = 60 years (p=0.039). CONCLUSION: Patient age greater than 60 years, Fuhrman grade > or = 3, and tumor stage > or = pT2 are independent risk factors of recurrence more than 5 years after surgery in patients with RCC. Therefore, close lifelong follow-up is recommended for patients with these risk factors.
Carcinoma, Renal Cell* ; Humans ; Kidney ; Logistic Models ; Multivariate Analysis ; Nephrectomy ; Proportional Hazards Models ; Recurrence ; Risk Factors

PURPOSE: To predict the malignant potential of prostate cancer (PCa) according to prostate-specific antigen velocity (PSAV), PSA density (PSAD), free/total PSA ratio (%fPSA), and digital rectal examination (DRE). MATERIALS AND METHODS: From January 2009 to December 2012, 548 adult male patients were diagnosed with PCa by prostate biopsy at four hospitals in Korea. We retrospectively analyzed 155 adult male patients with an initial PSA level < or =10 ng/mL and whose PSA levels had been checked more than two times at least 6 months before they had been diagnosed with PCa, with test intervals of more than 3 months. Patients with a urinary tract infection, and patients who had previously undergone cystoscopy or surgery of the prostate were excluded. We separated patients into two groups according to Gleason sum [Gleason sum < or =7 (n=134) or Gleason sum > or =8 (n=21)] and the presence of extracapsular invasion [organ confined (n=129) or extracapsular invasion (n=26)]. Differences between the groups were compared. RESULTS: The group with a Gleason sum > or =8 or extracapsular invasion of PCa showed high PSAV and significantly lower %fPSA. There were no significant differences in PSAD and the presence of an abnormality on DRE between two groups. CONCLUSION: In PCa patients treated with other therapies besides prostatectomy, a high PSA velocity and a low %fPSA may predict high grade PCa with a Gleason sum > or =8 or the presence of extracapsular invasion.
Adult ; Aged ; Biopsy, Needle ; Digital Rectal Examination ; Humans ; Kinetics ; Male ; Middle Aged ; Neoplasm Grading ; Predictive Value of Tests ; Prognosis ; Prostate/*pathology ; Prostate-Specific Antigen/*blood ; Prostatectomy ; Prostatic Neoplasms/*pathology/surgery ; Republic of Korea ; Retrospective Studies ; Tumor Burden

PURPOSE: This study investigated the inhibitory effects of Paclitaxel by altering tubulin assembly and cisplatin exposure by binding DNA of the lens epithelial cells (LECs) during epithelial cell cultures in the capsular bag model. METHODS: In the capsular bag model, the LECs were cultured with exposure to Paclitaxel (1, 10, 100 nM) and Cisplatin (1, 10, 100 micro M) for 3 min. The effect of Paclitaxel and Cisplatin was analyzed by observing the cell number of fibroblasts per field, Western blots for type IV collagen, TUNEL assay and the Proliferating Cell Nuclear Antigen (PCNA) and Bromodeoxyuridine (BrdU) incorporated proliferating cells. RESULTS: An increase in concentration of Paclitaxel and Cisplatin resulted in a decrease in the number of fibroblasts and spindle-shaped cells. The number of proliferating cells showing PCNA positivity and BrdU incorporation in the nuclei was decreased in a dose dependent manner by treatments of Paclitaxel and Cisplatin. Expression of type IV collagen also decreased after treatment with these two agents. Results of the TUNEL assay showed no change in the apoptosis of cells with regard to an increase in concentration of Paclitaxel and Cisplatin. CONCLUSIONS: This study showed inhibitory effects of Paclitaxel and Cisplatin on the proliferation and transdifferentiation of LECs into fibroblasts using the capsular bag model.
Apoptosis ; Blotting, Western ; Bromodeoxyuridine ; Cell Count ; Cisplatin ; Collagen Type IV ; DNA ; Epithelial Cells ; Fibroblasts ; In Situ Nick-End Labeling ; Paclitaxel ; Proliferating Cell Nuclear Antigen ; Tubulin

PURPOSE: To evaluate the visual outcome and satisfaction according to postoperative refractive error in patient with cataract surgery using AMO Array(R) multifocal intraocular lens. METHODS: According to postoperative refractive errors, 120 eyes (80 patients) were inserted the AMO Array(R) multifocal intraocular lens and were divided into three groups respectively: 28 eyes were myopic group (-0.50 ~ -1.50D), 74 eyes were emetropic group (-0.50 ~ +0.50D) and 18 eyes were hyperopic group (+0.50 ~ +1.50D). In each group, distant vision, near vision and contrast sensitivity test were measured. Also the patients were questioned on their satisfaction. RESULTS: Three months after the operation, the distance uncorrected visions of the myopic, emmetropic and hyperopic group were 0.42 +/- 0.23, 0.73 +/- 0.22, 0.36 +/- 0.28 and the near uncorrected visions were 0.47 +/- 0.18, 0.65 +/- 0.03, 0.41 +/- 0.14 in each. There were no difference in satisfaction, contrast sensitivity and glare visual acuity between three groups. CONCLUSIONS: In cataract surgery using the AMO Array(R) multifocal intraocular lens, we could get the best uncorrected visual acuity in emmetopic group. There were no difference in satisfaction and vision between myopic and hyperopic group. Thus, at the time of cataract operation, the multifocal intraocular lens power should be set on emmetropia in order to improve the vision and satisfaction.
Cataract ; Contrast Sensitivity ; Emmetropia ; Glare ; Humans ; Lenses, Intraocular* ; Refractive Errors* ; Visual Acuity

PURPOSE: To evaluate the accuracy of the SRK II formula for the AMO Array(R) multifocal intraocular lens (Array lens) power calculation according to axial length. In case of refractive error more than +/- 1.0 diopter (D), we compared the accuracy of the SRK II with that of other formulas. METHODS: Participants were 178 eyes (142 patients) received the Array lens. These were divided into 3 subgroups based on axial length. Group I had 21 eyes of short axial length (less than 22.0 mm). Group II had 133 eyes of average axial length (more than 22.0mm below 24.5mm). Group III had 24 eyes of long axial length (more than 24.5mm). The difference between preoperative predicted refractive value and postoperative manifest refractive value were calculated. We compared the accuracy of the SRK II and that of SRK/T, Holladay formulas in case of refractive error more than +/- 1.0D. RESULTS: Three eyes (14.2%) in Group I, 14 eyes (10.5%) in group II and 15 eyes (62.5%) in Group III showed refractive errors more than +/- 1.0D. Fifteen eyes (62.5%) in Group III were significantly reduced to 7 eyes (29.1%) with using SRK/T, Holladay formulas. CONCLUSIONS: SRK II formula had better predictive accuracy in axial length less than 24.5mm with Array lens. But it is better to apply SRK/T or Holladay formulas when axial length is more than 24.5mm.
Lenses, Intraocular* ; Refractive Errors*

PURPOSE: We investigated the inhibitory effects of mitomycin-C (MMC) and 5-fluorouracil (5-FU) on the proliferation of the lens epithelial cells (LECs) depending on time and concentration during the epithelial cell culture using capsular bag model. METHODS: We cultured LECs using capsular bag model after exposure to various time and concentration of MMC and 5-FU. We compared the half coverage time and appearance of posterior capsule by LECs. We examined the proliferative and inhibitory effect on LECs using BrdU immune staining. We observed the morphologic change of LECs on histologic section. RESULTS: Half coverage time of posterior capsule by LEC was 18.2 +/- 3.5 days in control group, whereas 27.5 +/- 3.8 days and 26.8 +/- 4.2 days when treated with 0.2 mg/ml MMC, 50 mg/ml 5-FU for 3 minutes, repectively. The increase of concentration and the exposure time of MMC or 5-FU resulted in the delay of coverage time of posterior capsule by LECs and reduction of BrdU incorporation in the nucleus of proliferating cells. On histologic section, reduction of LECs' multilayering and few cytoplasmic organells were observed. CONCLUSIONS: Using capsular bag model, we found the inhibitory effect of MMC and 5-FU on LECs proliferation depending on the concentration and exposure time. Capsular bag model would be contribute to the study about after-cataract.
Bromodeoxyuridine ; Cytoplasm ; Epithelial Cells* ; Fluorouracil* ; Mitomycin*

Enlargement of the extraocular muscles may cause diplopia and exophthalmos. The most common cause of the exophthalmos is thyroid associated ophthalmopathy(TAO), followed by inflammatory diseases and orbital tumors. TAO has the classical features of proptosis and lid retraction. However, the diagnosis is frequently confused with other eye diseases due to various symptoms and signs. Therefore, measurement of the size of extraocular muscles in both normal and TAO patients will make diagnosis and treatment plan easier in TAO and other muscular diseases of the orbit. For the clinical application, we measured the size of muscle with and without magnification and the results were compared. Normal mean values of cross sectional length and thickness of the extraocular muscles measured by CT scan showed 8.83x 3.60 in the inferior rectus, 9.20x3.20 in the superior muscle group, 9.45x 3.48 in the medial rectus and 9.65x3.23 mm in the lateral rectus muscle with no sex differences. All four muscles showed statistically significant enlargement in TAO and the thickness showed greater increase than the length. Superior muscle group(superior rectus and levator muscle)was the most frequently involved in TAO in both sexes. There was no significant statistical difference in the methods of measurement.
Diagnosis ; Diplopia ; Exophthalmos ; Eye Diseases ; Graves Ophthalmopathy* ; Humans* ; Korea* ; Muscles* ; Muscular Diseases ; Orbit ; Sex Characteristics ; Thyroid Gland* ; Tomography, X-Ray Computed ; Troleandomycin

OBJECTIVES: The present study was aimed at exploring whether the pathogenesis of hypertension is related with an altered expression of nitric oxide synthase (NOS) isozymes, i.e., bNOS, iNOS and ecNOS. METHOD: By Western blot analysis, the expression of NOS isozymes were determined in the kidney isolated from spontaneously hypertensive rats (SHR) and their normotensive control, Wistar-Kyoto rats (WKY). The NOx (nitrite/nitrate) contents were also determined in the kidney and plasma. RESULTS: The plasma NOx was significantly increased in SHR compared with that in WKY. The basal level of NOx was higher in the medulla and cortex of the kidney in SHR compared with that in WKY rat. bNOS proteins were expressed higher in the outer medulla and cortex, and iNOS proteins were higher in the inner medulla, outer medulla and cortex in SHR. ecNOS expression did not significantly differ between the SHR and WKY. CONCLUSIONS: These results indicate that the NO generation may not be impaired, but rather increased. It is likely that the increased expression of NOS isozymes is a counter-reactive phenomenon secondary to the increased blood pressure in this model of hypertension.
Animal ; Hypertension/physiopathology ; Hypertension/enzymology* ; Isoenzymes/metabolism ; Kidney/enzymology* ; Male ; Nitrates/metabolism ; Nitrates/blood ; Nitric Oxide/biosynthesis ; Nitric-Oxide Synthase/metabolism* ; Nitrites/metabolism ; Nitrites/blood ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY

Primary duodenal tuberculosis, duodenal Crohn's disease, duodenal lymphoma, duodenal cancer is extremely rare event. Vague upper abdominal pain, weight loss(10 Kg) had been present for several months in a 52-yeer-old woman. Endoscopy revealed an irregular ulcer in the second part of the duodenum. CT of the abdomen revealed pooly defined hypodense and centrally low density masses along the hepatoduodenal ligament, with poor separation from the head of pancreas. Hypotonic duodenogram showed spiculation and smooth indentation of mucosal fold at medical aspect of sup. portion m descending duodenum. ERCP showed medially displaced distal CBD and main pancreaticduct. At first, lymphoma, cancer, Crohn's disease, duodenal tuberculosis were considered in the differential diagnosis. Endoscopic biopsy sepecimen of duodenal lesion showed atypical lymphocytes. We excluded the diagnosis of the duodenal cancer. We started anti-tubercular drugs because in our country tuberculosis is endemic. After 4 weeks anti-tuberculosis therapy, follow up endoscopy and biopsy specimens showed healing stage of duodenal ulcer and chronic granulomatous inflammation with multinucleated giant cell. Thus we concluded that when duodenal lesion which could not confirmed histopathologically it was wise to start antitubercular therapy than to perform exploraparotomic dianostic procedures.
Abdomen ; Abdominal Pain ; Biopsy ; Cholangiopancreatography, Endoscopic Retrograde ; Crohn Disease ; Diagnosis ; Diagnosis, Differential ; Duodenal Neoplasms ; Duodenal Ulcer ; Duodenum ; Endoscopy ; Female ; Follow-Up Studies ; Giant Cells ; Head ; Humans ; Inflammation ; Ligaments ; Lymphocytes ; Lymphoma* ; Pancreas ; Tuberculosis* ; Ulcer