Adenocarcinoma of the small bowel at a single Korean institute: management and prognosticators

Purpose  

Small bowel adenocarcinoma (SBA) is a rare malignancy with a poor outcome. We evaluated the natural history of SBA at a single Korean institute.     

Noninvasive Treatment Strategy for Swallowing Problems Related to Prolonged Nonoral Feeding in Spinal Muscular Atrophy Type II

A 25-year-old patient with spinal muscular atrophy (SMA) type II was referred due to swallowing problems related to prolonged nonoral feeding. Restriction of jaw movement, neck stiffness, absence of oral food intake, and weakness of the oropharyngeal and laryngeal muscles were considered to be the main factors contributing to the deterioration of his swallowing function. Treatment comprised exercises to improve flexibility of the neck and temporomandibular joint, tactile oral stimulation, passive and active oropharyngolaryngeal exercises, and supraglottic swallowing maneuvers. Treatment was performed for 30 min per day, three times a week, for 7 months. On initial videofluoroscopic examination, the patient was unable to safely tolerate any per-oral nutrition. After 7 months of treatment, the patient’s swallowing function had improved to the extent that he was able to resume oral intake of food under supervision, and aspiration was no longer evident. These findings suggest that noninvasive treatment is a possible strategy for enhancing the swallowing function of a patient with SMA type II presenting with swallowing difficulties related to prolonged nonoral feeding.     

Arsenic tolerance in Arabidopsis is mediated by two ABCC-type phytochelatin transporters

Arsenic is an extremely toxic metalloid causing serious health problems. In Southeast Asia, aquifers providing drinking and agricultural water for tens of millions of people are contaminated with arsenic. To reduce nutritional arsenic intake through the consumption of contaminated plants, identification of the mechanisms for arsenic accumulation and detoxification in plants is a prerequisite. Phytochelatins (PCs) are glutathione-derived peptides that chelate heavy metals and metalloids such as arsenic, thereby functioning as the first step in their detoxification. Plant vacuoles act as final detoxification stores for heavy metals and arsenic. The essential PC-metal(loid) transporters that sequester toxic metal(loid)s in plant vacuoles have long been sought but remain unidentified in plants. Here we show that in the absence of two ABCC-type transporters, AtABCC1 and AtABCC2, Arabidopsis thaliana is extremely sensitive to arsenic and arsenic-based herbicides. Heterologous expression of these ABCC transporters in phytochelatin-producing Saccharomyces cerevisiae enhanced arsenic tolerance and accumulation. Furthermore, membrane vesicles isolated from these yeasts exhibited a pronounced arsenite [As(III)]-PC(2) transport activity. Vacuoles isolated from atabcc1 atabcc2 double knockout plants exhibited a very low residual As(III)-PC(2) transport activity, and interestingly, less PC was produced in mutant plants when exposed to arsenic. Overexpression of AtPCS1 and AtABCC1 resulted in plants exhibiting increased arsenic tolerance. Our findings demonstrate that AtABCC1 and AtABCC2 are the long-sought and major vacuolar PC transporters. Modulation of vacuolar PC transporters in other plants may allow engineering of plants suited either for phytoremediation or reduced accumulation of arsenic in edible organs.     

Detection of sexually transmitted infection and human papillomavirus in negative cytology by multiplex-PCR

Background  

The aim of this study was to determine the prevalence of human papillomavirus (HPV) and 15 species that cause sexually transmitted infections (STIs) in negative cytology. In addition, we compared the diagnostic performance of multiplex polymerase chain reaction (PCR) with widely available techniques used to detect HPV.     

(3-Chloroacetyl)-indole, a novel allosteric AKT inhibitor, suppresses colon cancer growth in vitro and in vivo

Indole-3-carbinol (I3C) is produced in Brassica vegetables such as broccoli and cabbage and has been shown to inhibit proliferation and induce apoptosis in various cancer cells, including breast, prostate, colon, and leukemia. However, only high doses of I3C were shown to inhibit cell proliferation (IC(50) = 200-300 μmol/L). Our goal here was to develop a more potent antitumor agent by modifying the structure of I3C. We created I3C derivatives and found that (3-chloroacetyl)-indole (3CAI) more strongly inhibited colon cancer cell growth than I3C. In addition, by screening 85 kinases in a competitive kinase assay, we found that 3CAI was a specific AKT inhibitor. AKT is a serine/threonine kinase that plays a pivotal role in promoting transformation and chemoresistance by inducing proliferation and inhibiting apoptosis. Therefore, AKT is regarded as a critical target for cancer therapy. 3ICA, a derivative of I3C, is a potent and specific AKT inhibitor. This compound showed significant inhibition of AKT in an in vitro kinase assay and suppressed expression of AKT direct downstream targets such as mTOR and GSK3β as well as induced growth inhibition and apoptosis in colon cancer cells. In addition, oral administration of this potent AKT inhibitor suppressed cancer cell growth in an in vivo xenograft mouse model.     

A novel two-stage, transdisciplinary study identifies digoxin as a possible drug for prostate cancer treatment

Identification of novel indications for commonly prescribed drugs could accelerate translation of therapies. We investigated whether any clinically-used drugs might have utility for treating prostate cancer by coupling an efficient, high-throughput laboratory-based screen and a large, prospective cohort study. In stage 1, we conducted an in vitro prostate cancer cell cytotoxicity screen of 3,187 compounds. Digoxin emerged as the leading candidate given its potency in inhibiting proliferation in vitro (mean IC??=163 nM) and common use. In stage 2, we evaluated the association between the leading candidate drug from stage 1 and prostate cancer risk in 47,884 men followed 1986-2006. Regular digoxin users (versus nonusers: RR=0.76, 95% CI 0.61-0.95), especially users for ≥ 10 years (RR=0.54, 95% CI 0.37-0.79, P-trend<0.001), had a lower prostate cancer risk. Digoxin was highly potent in inhibiting prostate cancer cell growth in vitro and its use was associated with a 25% lower prostate cancer risk. SIGNIFICANCE: Our two-stage transdisciplinary approach for drug repositioning provides compelling justification for further mechanistic and possibly clinical testing of the leading nonchemotherapy candidate, digoxin, a cardiac glycoside, as a drug for prostate cancer treatment. Perhaps of equal importance, our study illustrates the power of the transdisciplinary approach in translational cancer research. By coupling laboratory and epidemiologic methods and thinking, we reduced the probability of identifying false-positive candidate drugs for the next steps in testing.     

Perioperative administration of pregabalin for pain after robot-assisted endoscopic thyroidectomy: a randomized clinical trial

Background  

Perioperative administration of pregabalin, which is effective for neuropathic pain, might reduce early postoperative and chronic pain. This randomized, double-blinded, placebo-controlled trial (Clinical Trials.gov ID NCT00905580) was designed to investigate the efficacy and safety of pregabalin for reducing both acute postoperative pain and the development of chronic pain in patients after robot-assisted endoscopic thyroidectomy.     

Tufting Enteropathy with EpCAM Mutations in Two Siblings

Tufting enteropathy is a rare autosomal recessive disorder presenting with early-onset severe intractable diarrhea. The epithelial cell adhesion molecule gene (EpCAM) has recently been identified as the gene responsible for tufting enteropathy. Based on histology, a diagnosis of tufting enteropathy was made in two Korean siblings. They developed chronic diarrhea and failure to thrive. They had a broad nasal bridge and micrognathia. Duodenal and colonic biopsies showed villous atrophy, disorganization of surface enterocytes, and focal crowding resembling tufts. Protracted diarrhea continued and so cyclic parenteral nutrition was supplied. The sister had juvenile rheumatoid arthritis. Mutation analysis of EpCAM identified two compound heterozygous mutations in these siblings: 1) a donor splicing site mutation in intron 5 (c.491+1G>A) and 2) a novel nonsense mutation in exon 3 (c.316A>T, Lys106X). Analysis of EpCAM will be useful for genetic counseling and prenatal diagnosis of tufting enteropathy.     

Complete endoscopic resection of very early stage gastric plasmacytoma

Gastric plasmacytomas are very rare, and most are not detected until the disease has progressed to an advanced stage. However, there have been recent reports of cases of early-stage gastric plasmacytoma, in which neoplastic cells are confined to the mucosa or submucosa. Here we report a case of a very early stage gastric plasmacytoma that was confined to the lamina propria of the gastric mucosa. The lesion was successfully and completely removed by endoscopic submucosal dissection, and the surveillance endoscopy showed no recurrence during the follow-up of 40 months. This report appears to be the first documented case of complete endoscopic removal of a primary gastric plasmacytoma.