Biomedical microelectromechanical systems (BioMEMS): Revolution in drug delivery and analytical techniques

Advancement in microelectromechanical system has facilitated the microfabrication of polymeric substrates and the development of the novel class of controlled drug delivery devices. These vehicles have specifically tailored three dimensional physical and chemical features which together, provide the capacity to target cell, stimulate unidirectional controlled release of therapeutics and augment permeation across the barriers. Apart from drug delivery devices microfabrication technology’s offer exciting prospects to generate biomimetic gastrointestinal tract models. BioMEMS are capable of analysing biochemical liquid sample like solution of metabolites, macromolecules, proteins, nucleic acid, cells and viruses. This review summarized multidisciplinary application of biomedical microelectromechanical systems in drug delivery and its potential in analytical procedures.     

Cytologic grade independently predicts survival of patients with pancreatic adenocarcinoma

Our objectives were to devise a cytologic grading system and determine whether it would predict survival of patients with solid-type pancreatic adenocarcinoma. We evaluated 116 consecutive patients from July 2000 to November 2002; they were followed up until September 2003. We scored the following features on rapid Romanowsky-stained endoscopic ultrasound-guided fine-needle aspiration smears: cell group architecture, single cells, nuclear grade, mucus, bizarre cells, and necrosis. A cytologic grade (low vs high) was assigned. The Kaplan-Meier estimate of 6-month survival was 76% (SE, 7%) for patients with low-grade tumors vs 50% (SE, 6%) for patients with high-grade carcinoma. The median survival for patients with low-grade vs high-grade tumors was 1 year vs 6 months, respectively (chi2 = 4.45; P = .035). Cox proportional hazards regression showed tumor stage, cancer-specific treatment, and cytologic grade to be independent predictors of survival (P = .001). No other factors (age, mass location, placement of stent, presence of concomitant chronic pancreatitis, race, sex) predicted survival. We devised a grading system that independently predicted survival in patients with pancreatic adenocarcinoma.     

Mandibular invasion in oral cancers

Mandibular resection for oral cancers has significant aesthetic and functional sequelae. A reliable preoperative predictor of mandibular invasion is required to guide the need for and extent of mandibular resection. An orthopantomogram of the mandible is an accurate, reliable, cost-effective predictor of bony involvement except for central arch lesions. The feasibility of outer table rim mandibulectomy alone in patients with floor of mouth tumors needs to be examined carefully. Received: 11 December 1998 / Accepted: 7 October 1999     

MUC1 and MUC2 expression in pancreatic ductal carcinoma obtained by fine-needle aspiration

BACKGROUND: Mucins are high molecular weight glycoproteins that are produced by various epithelial cells including those found in the pancreas. MUC1 and MUC2 are two well characterized mucin antigens. The objective of the current study was to examine the pattern of phenotypic expression of MUC1 and MUC2 in pancreatic lesions obtained by fine-needle aspiration biopsy (FNA) and to determine the utility of MUC1 and MUC2 as markers for pancreatic ductal carcinoma. METHODS: Thirty-nine cell blocks of pancreatic FNA obtained under endoscopic ultrasound guidance were retrieved from the archives and immunostained with a monoclonal antibody directed against MUC1 and MUC2. These cell blocks were taken from 39 patients (16 females and 23 males) who had a median age of 64 years. Eleven FNAs were taken from patients with reactive/inflammatory conditions. The remaining 28 FNAs included 24 ductal carcinomas, 2 neuroendocrine tumors, 1 lymphoma sample, and 1 sarcoma sample. The presence of immunoreactivity, irrespective of the level of intensity or the percentage of cells, was considered as positive for MUC1 and MUC2 expression. Follow-up included correlation with pathology materials obtained at surgery and review of medical records. RESULTS: Twenty-three of 24 pancreatic ductal carcinomas (96%) demonstrated positive staining with MUC1. Twenty-one positive cases demonstrated either apical or diffuse membranous staining with variable cytoplasmic staining. The remaining two positive cases showed only cytoplasmic staining. One of the 11 cases of chronic pancreatitis and benign conditions demonstrated weak apical membranous MUC1 staining in the acinic cells. The difference between the two groups was statistically significant (P < 0.001, using the Fisher exact test). Three pancreatic ductal carcinomas and one chronic pancreatitis specimen demonstrated cytoplasmic staining with MUC2; the difference between the two groups was not found to be statistically significant. None of the nonductal neoplasms demonstrated expression of either MUC1 or MUC2. The sensitivity and specificity of MUC1 as a marker for pancreatic ductal carcinomas were 96% and 94%, respectively. CONCLUSIONS: MUC1 is overexpressed in pancreatic ductal carcinoma with a predominantly membranous and variable cytoplasmic staining pattern. The results of the current study suggest that the phenotypic expression of MUC1 can be used as an ancillary marker for diagnosing pancreatic ductal carcinoma in cytologic preparations. Conversely, MUC2 does not appear to be a useful marker for recognizing pancreatic ductal carcinoma in FNA specimens.     

Prevalence of poliovirus antibodies in healthy children of Ahmedabad

Antibodies against polioviruses were estimated in 258 healthy children upto 3 years of age in Ahmedabad. Fifty per cent of the children were negative for all three poliovirus antibodies before immunisation. Only 7.8 per cent of children had antibodies against all the three types of poliovirus. Prevalence of poliovirus type 1, type 2 and type 3 antibodies were 32.3, 31.8 and 15.5 per cent respectively. In the 3–6 months age group 39.6 per cent children were having poliovirus antibodies against one or more type but the per cent positivity increased in the age group 25–36 months to 78.6 per cent children. There was no difference in the prevalence of polio antibodies between the two sexes. About 92.0 per cent of children upto 3 years of age were lacking in one or more types of poliovirus antibodies in their blood, and would be susceptible for paralytic poliomyelitis if not immunised. Financed by a grant from the Indian Council of Medical Research, New Delhi. This paper was presented in the 28th Annual Conference of Indian Association of Pathologists and Microbiologists heald at Chandigarh in December, 1979.     

Tamoxifen enhances therapeutic effects of gemcitabine on cholangiocarcinoma tumorigenesis

Cholangiocarcinoma is a highly malignant tumor with limited therapeutic options. We have previously reported that tamoxifen (TMX) induces apoptosis of cholangiocarcinoma cells and reduces cholangiocarcinoma tumorigenesis in mice. In the present studies, we determined the effect of combination therapy of TMX and gemcitabine (GMT), another chemotherapeutical reagent for many cancers, on cholangiocarcinoma tumorigenesis and investigated the responsible mechanisms. GMT inhibited cell growth and induced apoptosis of cholangiocarcinoma cells in a concentration-dependent manner. TMX enhanced GMT-induced apoptosis of cholangiocarcinoma cells. Consistently, GMT (15?mg/kg) inhibited cholangiocarcinoma tumorigenesis in nude mice by 50%. TMX (15?mg/kg) enhanced the inhibitory effect of GMT on tumorigenesis by 33%. The inhibition of tumor growth correlated with enhanced apoptosis in tumor tissues. To elucidate the mechanisms underlying the additive effects of TMX on GMT-induced apoptosis, we determined the activation of caspases in cholangiocarcinoma cells exposed to GMT, TMX, or both. Activation of caspases 9 and 3, as well as cytochrome c release to the cytosol, was demonstrated in cells exposed to both reagents. In contrast, TMX activated caspase 2, whereas GMT had no effect. Inhibition of caspase 2 activation decreased TMX-, but not GMT-, induced activation of caspase 3 and apoptosis of cholangiocarcinoma cells. Similarly, activation of caspase 2 was found in tumors from TMX-treated mice, but not GMT-treated mice. Therefore, the enhanced effect of TMX on GMT-induced cholangiocarcinoma cell death is partially mediated by activation of caspase 2. TMX and GMT both induce apoptosis and inhibit cholangiocarcinoma tumorigenesis, which may be attributed to the activation of distinct apoptosis signals by TMX and GMT. Our studies provide in vivo evidence and molecular insight to support the use of TMX and GMT in combination as an effective therapy for cholangiocarcinoma.