Chemical Targeting of GAPDH Moonlighting Function in Cancer Cells Reveals Its Role in Tubulin Regulation

SummaryGlycolytic enzymes are attractive anticancer targets. They also carry out numerous, nonglycolytic “moonlighting” functions in cells. In this study, we investigated the anticancer activity of the triazine small molecule, GAPDS, that targets the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). GAPDS showed greater toxicity against cancer cells compared to a known GAPDH enzyme inhibitor. GAPDS also selectively inhibited cell migration and invasion. Our analysis showed that GAPDS treatment reduced GAPDH levels in the cytoplasm, which would modulate the secondary, moonlighting functions of this enzyme. We then used GAPDS as a probe to demonstrate that a moonlighting function of GAPDH is tubulin regulation, which may explain its anti-invasive properties. We also observed that GAPDS has potent anticancer activity in vivo. Our study indicates that strategies to target the secondary functions of anticancer candidates may yield potent therapeutics and useful chemical probes

Bare-metal stents versus drug-eluting stents in large (≥3.5mm) single coronary artery: Angiographic and clinical outcomes at 6 months

SummaryBackgroundAlthough drug-eluting stents (DES) have been shown to dramatically reduce restenosis and improve the rate of event-free survival in large randomized trials, the benefit of DES appears to be limited to restenosis. In large arteries, it is not clear which type of stent is more superior in angiographic and clinical outcomes between DES and bare-metal stents (BMS). We compared the angiographic and clinical outcomes of DES versus BMS in large arteries (≥3.5mm).MethodTwo hundred and forty patients from March 2002 to March 2007 received stents; 196 patients were treated with DES (44.9% sirolimus-eluting stents; 43.9% paclitaxel-eluting stents; 11.2% zotarolimus-eluting stents) and 44 with cobalt–chromium BMS for single de novo lesions in a large vessel. All subjects received aspirin, clopidogrel, and/or cilostazol as the standard antiplatelet regimen. The angiographic and clinical outcomes were evaluated at 6 months.ResultsFor the baseline characteristics, there were no significant differences between the DES and BMS groups. In addition, for the initially implanted stent there was no difference in the length, stent diameter, and lesion site between the two groups. After 6 months, the follow-up angiogram showed that in-stent diameter restenosis and late loss was more common with BMS than DES (39±21% vs. 19±17%, p=0.007; 1.44±0.83mm vs. 0.62±0.58mm, p=0.009, respectively). However, the target-lesion revascularization/target-vessel revascularization, and total major adverse cardiac events showed no significant differences between the groups (5.3% vs. 3.6%, p=0.62; 5.3% vs. 4.6%, p=0.86, respectively).ConclusionThe DES and cobalt–chromium BMS placed in large coronary arteries showed equally favorable 6-month clinical outcomes, although the 6-month angiographic results appeared more favorable in the DES group than in the BMS group

Trichilemmal Carcinoma of the Upper Eyelid: A Case Report

We report a very rare case of trichilemmal carcinoma (TLC) involving the upper eyelid. To the best of our knowledge, this is the first report of trichilemmal carcinoma of the upper eyelid in Korea. A 51-year-old man presented to our hospital complaining of a bloody discharge from his left upper eyelid. He had a soft and lobulated mass on the palpebral conjunctiva. An incisional biopsy revealed trabecular growth of tumor cells with clear cytoplasm, prominent nucleoli, frequent mitoses, and foci of trichilemmal keratinization. Immunohistochemically, the lesion was positive for p53 and negative for CD 34. A diagnosis of TLC was made, and total excision of the mass and reconstruction of the eyelid were performed. Trichilemmal carcinoma is a rare malignant tumor, though it appears to be an indolent neoplasm with no metastatic potential. The treatment of choice for trichilemmal carcinoma of the eyelid is complete excision with tumor-free margins due to the locally invasive nature of the lesion

Clinical and Endoscopic Recurrence after Surgical Resection in Patients with Crohn's Disease

Background/AimsThe natural history of Crohn's disease (CD) is characterized by a remitting and relapsing course and a considerable number of patients ultimately require bowel resection. Moreover, postoperative recurrence is very common. Relatively few studies have investigated the postoperative recurrence of CD in Korea. The aim of the current study was to assess postoperative recurrence rates - both clinical and endoscopic - in CD as well as factors influencing postoperative recurrence.MethodsElectronic medical records of patients who underwent surgery due to CD were reviewed and analyzed. Patients with incomplete surgical resection, a follow-up period of less than a year, and a history of strictureplasty or perianal surgery were excluded.ResultsOf 112 CD patients, 39 patients had history of bowel resection, and 34 patients met the inclusion criteria. Among them, 26 were male (76%) and the mean age of onset was 32.8 years. The mean follow-up period after operation was 65.4 months. Cumulative clinical recurrence rates were 8.8%, 12.5%, and 33.5% at 12, 24, and 48 months, respectively. Use of immunomodulators for prophylaxis was the only predictor of clinical recurrence in univariate analysis (P=0.042). Of 21 patients who had undergone follow-up colonoscopy after surgery, cumulative endoscopic recurrence rates were 33.3%, 42.9%, and 66.1% at 6, 12, and 24 months, respectively. No significant predicting factor for endoscopic recurrence was detected.ConclusionsPostoperative recurrence rates in Korean patients with CD are high, and endoscopic recurrence rates are comparable to those reported from Western studies. Appropriate medical prophylaxis seems to be important for preventing postoperative recurrence in CD

A Rare Case of Radial Arteriovenous Fistula After Coronary Angiography

The percutaneous transfemoral approach has been routinely used for cardiac catheterization and coronary angioplasty. Local vascular complications following angioplasty are seen in 5% to 10% of patients, especially in those who need prolonged anticoagulation. Transradial access for coronary procedures dramatically reduces access site complications. We report a rare case of radial arteriovenous fistula, which developed after coronary angiography perfomed using the transradial approach

A Rare Case of Radial Arteriovenous Fistula After Coronary Angiography

The percutaneous transfemoral approach has been routinely used for cardiac catheterization and coronary angioplasty. Local vascular complications following angioplasty are seen in 5% to 10% of patients, especially in those who need prolonged anticoagulation. Transradial access for coronary procedures dramatically reduces access site complications. We report a rare case of radial arteriovenous fistula, which developed after coronary angiography perfomed using the transradial approach

Autoimmune Hypoglycemia in a Patient with Characterization of Insulin Receptor Autoantibodies

BackgroundType B insulin resistance syndrome is a manifestation of autoantibodies to the insulin receptor that results in severe hyperglycemia and acanthosis nigricans. However, the mechanisms by which these autoantibodies induce hypoglycemia are largely unknown. In this paper, we report the case of patient with type B insulin resistance syndrome who presented with frequent severe fasting hypoglycemia and acanthosis nigricans.MethodsTo evaluate the mechanism of hypoglycemia, we measured the inhibition of insulin binding to erythrocytes and IM9 lymphocytes in a sample of the patient's dialyzed serum before and after immunosuppressive therapy.ResultsIn the patient's pre-treatment serum IgG, the binding of 125I-insulin to erythrocytes was markedly inhibited in a dose-dependent manner until the cold insulin level reached 10-9 mol/L. We also observed dose-dependent inhibition of insulin binding to IM9 lymphocytes, which reached approximately 82% inhibition and persisted even when diluted 1:20. After treatment with glucocorticoids, insulin-erythrocyte binding activity returned to between 70% and 80% of normal, while the inhibition of insulin-lymphocyte binding was reduced by 17%.ConclusionWe treated a patient with type B insulin resistance syndrome showing recurrent fasting hypoglycemia with steroids and azathioprine. We characterized the patient's insulin receptor antibodies by measuring the inhibition of insulin binding

Isolation and Characterization of Isofraxidin 7- O

Abnormalities in skin pigmentation can produce disorders such as albinism or melasma. There is a research need to discover novel compounds that safely and effectively regulate pigmentation. To identify novel modulators of pigmentation, we attempted to purify compounds from a bioactive fraction of the Korean medicinal plant Artemisia capillaris Thunberg. The novel compound isofraxidin 7-O-(6′-O-p-coumaroyl)-β-glucopyranoside (compound 1) was isolated and its pigmentation activity was characterized in mammalian melanocytes. Compound 1 stimulated melanin accumulation and increased tyrosinase activity, which regulates melanin synthesis. Moreover, compound 1 increased the expression of tyrosinase and the key melanogenesis regulator microphthalmia-associated transcription factor (MITF) in melanocytes. Compared to the parent compound, isofraxidin, compound 1 produced greater effects on these pigmentation parameters. To validate compound 1 as a novel hyperpigmentation agent in vivo, we utilized the zebrafish vertebrate model. Zebrafish treated with compound 1 showed higher melanogenesis and increased tyrosinase activity. Compound 1 treated embryos had no developmental defects and displayed normal cardiac function, indicating that this compound enhanced pigmentation without producing toxicity. In summary, our results describe the characterization of novel natural product compound 1 and its bioactivity as a pigmentation enhancer, demonstrating its potential as a therapeutic to treat hypopigmentation disorders

A Degenerative Intraspinal Cyst Mimicking a Nerve Root: A Case Report on an Intraoperative Challenge

Various intraspinal cysts have been described in the literature. Sometimes these cysts are difficult to recognize intraoperative and can place a surgeon in dilemma. We report a case of a degenerative intraspinal cyst with severe adhesion with dura, which was mimicking as a nerve root and posed a diagnostic dilemma during surgery. A Sixty-year-old man presented with insidious onset, gradually progressing lower back pain, right leg pain and neurological claudication of six months duration. The pain radiated to the right S1 dermatome. Right side straight leg raise test was positive at 45°. Sensations were diminished over the right L5 and S1 dermatomes. Motor function was normal. MRI showed a large cystic lesion at right L5-S1 level. The cyst appeared to compress the dural sac and traversing right S1 root at L5-S1 level. The lesion was isointense on T1-weighted image and hyperintense on T2-weighted image. While treating this condition using the uniportal full endoscopic technique the cyst appeared as nerve root. Meticulous dissection was required to separate the cyst from neural structures. Histology confirmed the diagnosis of a degenerative intraspinal cyst. The patient had significant improvement after surgery and at six months follow up he was completely asymptomatic. Various cysts can occur in the intraspinal canal, and careful attention should be paid to minimize the nerve injury in the presence of severe adhesions