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Biomedical subjects

Anil Sehgal

Publications and source records attributed to Anil Sehgal.

9 recordsLinked to original sources
PubMed2006

In silico prediction of clinical efficacy.

Drug development is a high risk and costly process, and the ability to predict clinical efficacy in silico (in a computer) can save the pharmaceutical industry time and resources. Additionally, such an approach will result in more targeted, personalized therapies. To date, a number of in silico strategies have been developed to provide better information about the human response to novel therapies earlier in the drug development process. Some of the most prominent include physiological modeling of disease and disease processes, analytical tools for population pharmacodynamics, tools for the analysis of genomic expression data, Monte Carlo simulation technologies, and predictive biosimulation. These strategies are likely to contribute significantly to reducing the failure rate of drugs entering clinical trials.

Clinical Trials as Topic↗
PubMed2003

Anticancer drug discovery using chemical genomics.

Cancer is the leading cause of death in United States and World wide. Drug discovery and development for cancer therapeutics takes several years before a patient is benefited from a new drug. The average time length from start to finish is approximately 15 years. This time length includes 4-5 years of basic research, discovery, preclinical development and validation studies. Next, it takes approximately 7-10 years for a drug to go through human clinical trials. This time length is too long and need to be shortened to benefit patients quickly from new technologies and product development ideas. Furthermore, with the recent explosion of genomics and proteomics information, it is now becoming difficult to make rapid and logical decisions on hundreds of potential drug targets available. Thus, there is immediate need to develop and integrate tools and technologies that will not only reduce the time length but also the risk of late clinical drug failure. Chemical Genomics is an emerging field in which tools and technologies from biology and chemistry are utilized in a parallel and cyclic fashion very early in the development process. In addition chemical genomics proposes to integrate latest developments in tools and technologies from a variety of modern fields such as combinatorial chemistry, informatics, synthesis chemistries, cell based assays, microarrays, genomics and proteomics tools to accelerate drug discovery and development. Thus, in cancer therapeutics the aim of chemical genomics is not only to reduce the time length of pre-clinical development but also the risk of late clinical failure by making smart decisions early in the process.

Animals↗
PubMed2002

Recent developments in peptide-based cancer therapeutics.

Peptides make up only a fraction of therapeutically beneficial pharmaceutical molecules that are either in clinical testing or in the market. Despite the initially low number and impact of peptides on therapeutics, their potential has just intensified with new developments in modifications, stability, delivery and preclinical success. With the completion of the human genome sequence and developments in the proteomics field, peptides are emerging as important molecules for cancer therapy. Several peptides with exciting preclinical results have now entered into clinical trial for the treatment of human cancers. In this review, some of the recent advances in peptide-based cancer therapeutics will be discussed.

Animals↗
PubMed2002

Drug discovery and development using chemical genomics.

Now that the human genome is completely sequenced, it is important to convert this wealth of knowledge to therapeutic drugs. It is documented that there are approximately 30,000 genes in the human genome that may code for approximately 100,000 proteins. Traditionally, the drug development process starts with a protein target, taking approximately eight to ten years for a drug to pass all the critical steps of testing before reaching the market. If this situation continues it will take several decades before all potential drug targets are tested and developed. Chemical genomics is a new paradigm in which chemistry is utilized early in the development process along with other tools such as genomics, proteomics, combinatorial chemistry and cell-based screening to accelerate the drug development process. Utilizing chemical genomics not only reduces the risk of drug failure but it can increase the number of potential targets for drug development.

Animals↗
PubMed2002

Genomic Partnering - Fifth Annual CHI Meeting: emerging and early-stage companies. Genome Tri-Conference. 23-24 February 2002, Santa Clara, CA, USA.

The 2002 Genome Tri-Conference was a medium-sized meeting, with an approximate attendance of 400 to 500 delegates. This event held three conferences back to back, addressing three different aspects of current developments in the area of genomics, ie, genomic partnering, human genome discovery and gene functional analysis. Several new aspects of genomics, such as clinical genomics and chemical genomics, were discussed.

Journal Article↗
PubMedDate not supplied

Molecular characterization of a novel BR-2 gene that is down-regulated in human low grade glioma tumors.

Using the technique of differential hybridization of a human fetal brain library, we have identified a novel gene, brain 2 (BR-2). This gene is expressed in normal brain but has low or no expression in human oligodendrogliomas and other brain tumor samples. We have cloned and sequenced the full-length cDNA corresponding to this gene. A data base search for the nucleotide sequence homology was performed for BR-2. BR-2 sequence showed strong homolog to a human genomic clone from chromosome 2. Moderate sequence homology was observed between BR-2 and an EST from a human placenta library. Multiple tissue dot blot analysis indicated that the BR-2 gene is expressed in a number of tissues including brain, heart, lung, placenta, lymph node, trachea and kidney. The BR-2 gene is also expressed in fetal heart, spleen and lung tissue. An extremely high level of BR-2 expression is observed in the left atrium of the heart. Low or no expression of BR-2 expression is observed in sixteen human cancer cell lines. RT-PCR analysis indicated that the BR-2 gene is expressed at high levels in two of the five normal brain tissue samples analyzed. Except for low expression in one oligodendroglioma, no expression of BR-1 gene was observed in eight anaplastic astrocytomas and glioblastoma multiforme tissue samples. Four of nine glioblastoma tumor cell lines did show a low level of BR-2 expression. On the basis of its expression and sequence, we conclude that BR-2 is a novel gene with unique expression properties in human brain tumors.

Amino Acid Sequence↗
PubMedDate not supplied

Cloning, sequencing and expression analysis of a novel gene BR-1 that is expressed in normal human brain tissue but not in glioma tumor samples.

Using the technique of differential hybridization of a human fetal brain library, we identified a novel gene, brain 1 (BR-1). This gene is expressed in normal brain but has low or no expression in human gliomas. We have cloned and sequenced the full-length cDNA corresponding to this gene. A data base search for the nucleotide sequence homology was performed for BR-1. The BR-1 sequence showed strong homology to a human genomic clone from chromosome 2. Moderate sequence homology was observed between BR-1 and an expressed sequence tag (EST) from a human placenta library. Three different regions of BR-1 also showed homology to a mouse EST that is similar to EL-10 gene. Sequence analysis indicated that the protein sequence for BR-1 has one tyrosine kinase phosphorylation site and two N-myristoylation sites. Northern blot analysis indicated that the BR-1 gene is expressed in heart, placenta, lung, liver, skeletal muscle, kidney and pancreas. A low level of expression of BR-1 is observed in the cerebellum, cerebral cortex, spinal cord, occipital lobe and putamen. The BR-1 gene is also expressed in fetal brain, liver and kidney. Low expression of BR-1 gene was observed in a number of non-brain tumor cell lines. RT-PCR analysis indicated that the BR-1 gene was expressed in non-neoplastic (epilepsy specimens) but not in six oligodendrogliomas and three oligoastrocytoma tumor samples analyzed. BR-1 was not expressed in either seven low grade gliomas or eight grade IV glioblastoma tumor tissue samples analyzed. Three glioblastoma cell lines did show low expression of the BR-1 gene. On the basis of its expression properties, we conclude that BR-1 is a potential novel tumor suppressor gene.

Base Sequence↗
PubMedDate not supplied

Molecular characterization of a novel human brain tumor-associated gene BR-3.

Using the technique of differential hybridization of a human fetal brain library, we have identified a novel gene, brain 3 (BR-3). This gene is not expressed in normal human brain tissue samples but is expressed at high levels in human low-grade glioma tissue samples. We have cloned and sequenced the full-length cDNA corresponding to this gene. Data base search analysis indicated that the BR-3 gene has strong homology to a genomic sequence present on chromosome 1 but no homology to expressed genes. Open reading frame analysis has indicated the presence of a 71 amino acids long protein sequence. A data base search for the protein sequence homology showed no similarity to known sequences. Expression analysis of BR-3 indicated that it is expressed at high level in six out of seven low-grade glioma samples analyzed. In addition low levels of BR-3 gene expression was observed in six out of seven anaplastic astrocytoma tissue samples analyzed. BR-3 expression was observed in four of eight glioblastoma samples analyzed. Expression analysis of normal human tissues indicated that it is expressed in kidney, skeletal muscle, lung, spleen and heart. No expression of the BR-3 gene was observed in brain, liver or testes tissue. To understand the role of the BR-3 gene in cancer in general, we studied its expression in other cancer cell lines. Except for lung and ovarian carcinoma, the BR-3 gene is expressed in breast carcinoma, colon adenocarcinoma, prostatic adenocarcinoma, and pancreatic adenocarcinoma tissue samples. On the basis of its sequence, unique expression pattern, we conclude that BR-3 gene product may play a critical role in the genesis of human gliomas tumors.

Adult↗