Effects of adjuvant chemotherapy and radiation on overall survival in children with choroid plexus carcinoma

Choroid plexus carcinoma (CPCs) is a rare, malignant, primary brain tumor with a poor prognosis. Currently, there is no consensus on the use of adjuvant therapy, and few large-scale studies focus exclusively on the pediatric population. We performed a comprehensive systematic review of pediatric CPCs to determine the effects of various adjuvant therapy modalities on overall survival (OS). A literature search was performed to identify studies reporting children with CPC who underwent surgical resection. Only patients who had clearly received adjuvant therapy, or were described as not selected for adjuvant therapy were analyzed in our comparison groups. Kaplan–Meier and multivariate Cox regression survival analyses were performed to determine the effects of different types of adjuvant therapies on OS. A total of 135 children (age ≤ 18 years) with CPC who had known adjuvant therapy status and OS were identified from 53 articles. Kaplan–Meier analysis showed that while adjuvant therapy overall improved OS (p = 0.001), different modes of adjuvant therapies had varying effects on OS (p = 0.034). Specifically, combined chemo-radiotherapy as well as chemotherapy alone improved OS (p = 0.001), but radiation did not (p = 0.129). Multivariate Cox proportional hazard model adjusting for confounding factors showed that combined therapy was associated with better OS compared to chemotherapy alone (HR: 0.291, p = 0.027). Both chemotherapy alone and combined chemo-radiation improved OS independent of age, gender, tumor location and extent of resection, while radiation alone did not.     

Molecular and Immunological Characterization of Heat Shock Protein 70 (HSP70) Gene from Buffalo

Heat shock protein 70 (HSP70) is a predominant member of the HSP family of proteins, which play a variety of functions in the cells and are responsible for cytoprotection under stress conditions. The present study was characterized by HSP70 (orf) in buffalo (Buablus bubalis). Genomic DNA was isolated from lymphocytes and that was used for PCR amplification of HSP70 gene. Polymerase chain reaction product (1,926 bp) was cloned in pGEM-T easy vector and sequenced. Sequence analysis revealed 1,926 bp long open reading frame of HSP70 gene encoding 641 amino acids in buffalo. The amino acid sequence showed 98 % identity with Bos taurus, Bos indicus, Yak, Capra hircus and 90–95 % identity with Camelus dromedaries, Felis catus, Canis familiaris, Sus scrofa, and Homo sapiens. The expression of this gene was in prokaryotic expression vector pPRoExHTa producing a recombinant protein of ~70 kDa, which is detected by SDS-PAGE. The tagged protein purified by Ni-NTA affinity chromatography under denaturing conditions was confirmed by western blotting using Ni-NTA HRP conjugate and 4 chloro-1-naphthol as substrate. Recombinant HSP70 was injected in mice and antiserum contained polyclonal antibody, which was detected by western blot. The recombinant HSP70 protein obtained may be used for the development of an assay for detection of thermal stress.     

Nucleic acid based risk assessment and staging for clinical practice in multiple myeloma

The recently introduced Revised International Staging System (R-ISS) for multiple myeloma (MM) integrates albumin, β2 microglobulin, lactate dehydrogenase (LDH) with high-risk cytogenetic aberrations (CA), i.e., t(4;14) and t(14;16) and del17p using fluorescent in situ hybridization (FISH). We evaluated utility of nucleic acid-based tests of multiplex ligation-based probe amplification (MLPA) and quantitative real-time polymerase chain reaction (qRT-PCR) to define the CA and the R-ISS categories as per this approach were evaluated for their ability to predict outcome in terms of response, progression-free (PFS), and overall survival (OS). In this study (n?=?180), 17 (9.4%), 118 (65.6%), and 45 (25%) patients were assigned to R-ISS1, R-ISS2, and R-ISS3 categories with statistically significant differences in median PFS (p?=?0.02) and OS (p?<?0.001).On univariate analysis, serum creatinine, LDH, 17p deletion, chromosome 1q gain, and response after first induction therapy were associated with statistically significant differences (p?<?0.05) in PFS and in addition, age>?65 years and use of triplet therapy with OS. On multivariate analysis, only serum creatinine, LDH, and response after first induction therapy retained significance for predicting PFS and in addition, use of triplet therapy retained significance for the OS. The proposed nucleic acid-based algorithm using qRT-PCR and MLPA for R-ISS is resource-effective in terms of small quantities of sample required; feasibility of batch processing and reduced overall cost for the total number of regions evaluated and retained the prognostic significance of R-ISS, making it suitable for clinical practice for molecular characterization of MM.     

The 2016 revision of the WHO Classification of Central Nervous System Tumours: retrospective application to a cohort of diffuse gliomas

Journal of Neuro-Oncology - The classification of central nervous system tumours has more recently been shaped by a focus on molecular pathology rather than histopathology. We re-classified 82...     

Cellular immune response to Mycobacterium tuberculosis-specific antigen culture filtrate protein-10 in south India

The Mycobacterium tuberculosis (M. tuberculosis)-specific culture filtrate protein-10 (CFP-10) is highly recognized by M. tuberculosis infected subjects. In the present study, the proliferative response and IFN-γ secretion was found for C-terminal peptides of the protein (Cfp6_51–70, Cfp7_61–80, Cfp8_71–90, and Cfp9_81–100). The alleles HLA DRB1 *04 and HLA DRB1 *10 recognized the C-terminal peptides Cfp7, Cfp8, and Cfp9 in HHC. Cfp6 was predominantly recognized by the alleles HLA DRB1 *03 and HLA DRB1 *15 by PTB. The minimal nonameric epitopes from the C-terminal region were CFP-10_56–64 and CFP-10_76–84. These two peptides deserve attention for inclusion in a vaccine against tuberculosis in this region.     

Relationships among activities of extracellular enzyme production and virulence against Helicoverpa armigera in Beauveria bassiana

Extracellular enzymes produced by Beauveria bassiana, are believed to play a key role in cuticle hydrolysis. Enzyme production and pathogenicity has been found to be positively correlated. Twenty‐eight isolates of B. bassiana, collected from different geographical regions and host ranges were characterized by in vitro extracellular enzyme production and SDS–PAGE techniques for discerning biochemical basis for virulence among the different isolates. In vitro analysis of extracellular enzymes like protease, amylase, caseinase, chitinase and lipase was undertaken in an attempt to understand their relevance to virulence of the isolates. The different isolates of B. bassiana were evaluated for virulence to the second instar larvae of Helicoverpa armigera in laboratory bioassays. SDS–PAGE of total intracellular soluble proteins was also studied in order to understand affinities among the different isolates of B. bassiana. The relationship between enzyme production and pathogenicity and vice versa was nearly 50%. There was a 50% relationship associated with original insect host, pathogenicity and enzyme production. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Induction of protective CTL immunity against peptide transporter TAP-deficient tumors through dendritic cell vaccination

A large proportion of human cancers show deficiencies in the MHC class I antigen-processing machinery. Such defects render tumors resistant to immune eradication by tumoricidal CTLs. We recently identified a unique population of CTL that selectively targets tumor immune-escape variants through recognition of MHC-presented peptides, termed TEIPP (T cell epitopes associated with impaired peptide processing), expressed on cells lacking functional TAP-peptide transporters. Previously, we showed that vaccination with TEIPP peptides mediates protection against TAP-deficient tumors. Here, we further explored the concept of TEIPP-targeted therapy using a dendritic cell (DC)-based cellular vaccine. Impairment of TAP function in DC induced the presentation of endogenous TEIPP antigens by MHC class I molecules, and immunization with these DCs protected mice against the outgrowth of TAP-deficient lymphomas and fibrosarcomas. Immune analysis of vaccinated mice revealed strong TEIPP-specific CTL responses, and a crucial role for CD8(+) cells in tumor resistance. Finally, we show that TEIPP antigens could be successfully induced in wild-type DC by introducing the viral TAP inhibitor UL49.5. Our results imply that immune intervention strategies with TAP-inhibited DC could be developed for the treatment of antigen processing-deficient cancers in humans.