Delineation of a cellular hierarchy in lung cancer reveals an oncofetal antigen expressed on tumor-initiating cells

Poorly differentiated tumors in non-small cell lung cancer (NSCLC) have been associated with shorter patient survival and shorter time to recurrence following treatment. Here, we integrate multiple experimental models with clinicopathologic analysis of patient tumors to delineate a cellular hierarchy in NSCLC. We show that the oncofetal protein 5T4 is expressed on tumor-initiating cells and associated with worse clinical outcome in NSCLC. Coexpression of 5T4 and factors involved in the epithelial-to-mesenchymal transition were observed in undifferentiated but not in differentiated tumor cells. Despite heterogeneous expression of 5T4 in NSCLC patient-derived xenografts, treatment with an anti-5T4 antibody-drug conjugate resulted in complete and sustained tumor regression. Thus, the aggressive growth of heterogeneous solid tumors can be blocked by therapeutic agents that target a subpopulation of cells near the top of the cellular hierarchy.     

Seroprevalence of HCV and its co-infection with HBV and HIV among liver disease patients of South Tamil Nadu

AIM: To determine the seroprevalence of hepatitis C virus (HCV) and its co-infection with hepatitis B virus (HBV), hepatitis delta agent (HDV) and human immunodeficiency virus (HIV) among liver disease patients of south Tamil Nadu.METHODS: A total of 1012 samples comprising 512 clinically diagnosed cases of liver disease patients and 500 apparently healthy age and sex matched individuals were screened for Hepatitis C virus (anti HCV and HCV RNA), Hepatitis B virus (HBsAg), Hepatitis delta agent (anti HDV) and Human immuno virus (antibodies to HIV-1 and HIV-2) using commercially available enzyme linked immunosorbent assay kits. HCV RNA was detected by RT-PCR. Liver function tests like ALT, AST, GGT, ALP, bilirubin and albumin were also studied.RESULTS: The seroprevalence of HCV was found to be 5.6% among liver disease patients by ELISA. 27/512, 49/512 and 12/512 patients were positive for HIV, HBV & HDV respectively. Co-infection of HCV & HBV was found in 8 patients, with 6 for HCV & HIV and 4 for HCV, HBV & HIV co-infections. Sex-wise analysis showed that HIV, HCV & HBV and HCV & HIV co-infection was high among females whereas for HBV it was high in males. The mean ALT and AST in HCV positive cases were 42.1 ± 8.3 and 49 ± 10.1. In people co-infected with HCV & HBV or HCV & HIV or HCV, HBV & HIV the mean ALT of 58.0 ± 03.16, 56.78 ± 4.401 and 64.37 ± 4.01 respectively.CONCLUSION: We strongly recommend routine test of the blood for HCV in addition to HBV and HIV. We also recommend individualized counseling to identify those at risk and testing for those who want it. Improved surveillance and periodic epidemiological studies will have to be undertaken to monitor and prevent these blood-borne viruses.     

Seroepidemiological study on hantavirus infections in India

Hantaviruses are etiological agents of hemorrhagic fever with renal syndrome in many parts of Asia and Europe. There has been no documented case of hantavirus disease from India, although serological evidence exists. We investigated the prevalence of hantavirus in the Indian population and tried to identify potential risk groups for hantavirus infections. The presence of hantavirus-specific IgG antibodies was prospectively evaluated in 661 subjects belonging to different groups, i.e. patients with chronic renal disease, warehouse workers and tribal members engaged in rodent trapping. Healthy volunteer blood donors were included as a control group. Thirty-eight seropositive samples were found using a combination of a commercial ELISA followed by an indirect immunofluorescence assay. Western blot using recombinant Hantaan virus nucleocapsid antigen confirmed the presence of anti-hantavirus IgG in 28 (74%) of the 38 sera tested. This study confirms the presence of hantaviruses in India and warrants increasing awareness of the problems of emerging pathogens and the threats they may pose to the public health system.     

Phase II trial of bevacizumab and erlotinib in patients with recurrent malignant glioma

Vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) signaling are established contributors to malignant glioma (MG) biology. We, therefore, evaluated bevacizumab, a humanized anti-VEGF monoclonal antibody, in combination with the EGFR tyrosine kinase inhibitor erlotinib, in this phase 2 study for recurrent MG patients (www.ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT00671970","term_id":"NCT00671970"}}NCT00671970). Fifty-seven patients (n = 25, glioblastoma [GBM]; n = 32, anaplastic glioma [AG]) were enrolled. The primary endpoint was 6-month progression-free survival (PFS-6). Overall survival (OS), radiographic response, pharmacokinetics, and correlative biomarkers were the secondary endpoints. Patients were stratified based on the concurrent use of enzyme-inducing antiepileptic drugs (EIAEDs). Bevacizumab (10 mg/kg) was given intravenously every 2 weeks. Erlotinib was orally administered daily at 200 mg/day for patients not on EIAEDs and 500 mg/day for patients on EIAEDs. PFS-6 and median OS were 28% and 42 weeks for GBM patients and 44% and 71 weeks for AG patients, respectively. Twelve (48%) GBM patients and 10 (31%) AG patients achieved a radiographic response. Erlotinib pharmacokinetic exposures were comparable between EIAED and non-EIAED groups. Rash, mucositis, diarrhea, and fatigue were common but mostly grades 1 and 2. Among GBM patients, grade 3 rash, observed in 32%, was associated with survival benefit, whereas elevated hypoxia-inducible factor-2 alpha and VEGF receptor-2 levels were associated with poor survival. Bevacizumab plus erlotinib was adequately tolerated in recurrent MG patients. However, this regimen was associated with similar PFS benefit and radiographic response when compared with other historical bevacizumab-containing regimens.     

Pharmacogenomics in oral diseases

The availability of newer technologies for identification and characterization of the human genome has enabled our understanding of the genetic variations in a majority of human diseases. Human genomic sequence varies in less than 1% among the different population group and these differences known as gene polymorphisms are the primary reasons for differences in individuals’ response to various drug therapy. Also understanding the genetic changes may enable implementation of targeted therapy, thus providing for effective treatment strategies and minimizing the adverse side effects. Pharmacogenomics is a recent development in the field of personalized medicine which focuses on the genetic determinants of drug response at the levels of entire human genome. It primarily deals with tailoring of drug therapy for every individual based on their genetic make-up and identifying new target in various diseases for drug therapy. While the application of pharmacogenomics in systemic illness is well researched, its role in oral diseases needs documentation. Identifying specific targets in periodontitis, head and neck cancer, infections and genetic disorders can be beneficial in discovery of new drugs. This editorial provides an overview of basics of pharmacogenomics, its current role in disease management and its potential role in various head and neck diseases.     

Automated analysis of seizure semiology and brain electrical activity in presurgery evaluation of epilepsy: A focused survey

Epilepsy being one of the most prevalent neurological disorders, affecting approximately 50 million people worldwide, and with almost 30–40% of patients experiencing partial epilepsy being nonresponsive to medication, epilepsy surgery is widely accepted as an effective therapeutic option. Presurgical evaluation has advanced significantly using noninvasive techniques based on video monitoring, neuroimaging, and electrophysiological and neuropsychological tests; however, certain clinical settings call for invasive intracranial recordings such as stereoelectroencephalography (SEEG), aiming to accurately map the eloquent brain networks involved during a seizure. Most of the current presurgical evaluation procedures focus on semiautomatic techniques, where surgery diagnosis relies immensely on neurologists’ experience and their time‐consuming subjective interpretation of semiology or the manifestations of epilepsy and their correlation with the brain's electrical activity. Because surgery misdiagnosis reaches a rate of 30%, and more than one‐third of all epilepsies are poorly understood, there is an evident keen interest in improving diagnostic precision using computer‐based methodologies that in the past few years have shown near‐human performance. Among them, deep learning has excelled in many biological and medical applications, but has advanced insufficiently in epilepsy evaluation and automated understanding of neural bases of semiology. In this paper, we systematically review the automatic applications in epilepsy for human motion analysis, brain electrical activity, and the anatomoelectroclinical correlation to attribute anatomical localization of the epileptogenic network to distinctive epilepsy patterns. Notably, recent advances in deep learning techniques will be investigated in the contexts of epilepsy to address the challenges exhibited by traditional machine learning techniques. Finally, we discuss and propose future research on epilepsy surgery assessment that can jointly learn across visually observed semiologic patterns and recorded brain electrical activity.     

Comparison of two different methodologies for the detection of hepatitis B virus DNA in plasma

In this study, two different methodologies were compared for the detection of hepatitis B virus (HBV) DNA in the plasma of 28 patients and 36 controls. Method 1 was a nested polymerase chain reaction (PCR) followed by product detection in an ethidium bromide stained gel, whereas method II was a commercial single step PCR with digoxigenin labeled product captured by a probe and then detected in a digoxigenin-antidigoxigenin enzyme-linked immunosorbent assay (DIG ELISA). The results indicate that both methods are comparable showing a concordance of 98.4%, there was no statistically significant difference in the detection rates. We feel that any one of these assays may be suitable in a clinical laboratory setting, though the commercial assay may offer some advantages to laboratories without sufficient skilled staff in trouble-shooting PCR related problems.