CAG repeat length polymorphism in the androgen receptor gene and breast cancer risk: data on Indian women and survey from the world.

We analyzed the length of the CAG repeats of the androgen receptor gene in Indian women with breast cancer, and compared the data with that of other populations across the world in an attempt to find a potential pattern of association. The study was undertaken on 1,408 individuals comprising 747 breast cancer patients and 661 control individuals recruited from three southern states of India: Andhra Pradesh, Tamil Nadu, and Karnataka. The comparison revealed no difference in mean length of the repeat between cases and controls in any of the three groups or in the analysis of pooled data.

Balanced translocation in mother leading to interchange trisomy 21?

We report an unusual balanced translocation involving chromosomes 4 and 21 in a lady who had Down syndrome in her previous child. The most plausible explanation for this event is the 3:1 segregation of chromosomes at meiosis in her gametes leading to interchange trisomy 21.

Salivary IL-6 levels in oral leukoplakia with dysplasia and its clinical relevance to tobacco habits and periodontitis.

The development of oral cancer proceeds through discrete molecular changes that are acquired from loss of genomic integrity after continued exposure to environmental risk factors. It is preceded in the majority of cases by clinically evident oral potentially malignant disorders, the most common of which is leukoplakia. Early detection of these oral lesions by screening methods using suitable markers is critical as it mirrors molecular alterations, long before cancer phenotypes are manifested.

A novel human CRYGD mutation in a juvenile autosomal dominant cataract.

Purpose: Identification of causal mutation in the crystallin, connexin, and paired box gene 6 (PAX6) genes associated with childhood cataract in patients from India.

Methods: In this study, forty eight members from seventeen families and 148 sporadic cases of childhood cataract were evaluated. Clinical and ophthalmologic examinations were performed on available affected and unaffected family members.

Thiopurine S-methyltransferase alleles, TPMT(*)2, (*)3B and (*)3C, and genotype frequencies in an Indian population.

Thiopurine S-methyltransferase (TPMT) catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl compounds including thiopurine drugs such as 6-mercaptopurine, 6-thioguanine and azathioprine. TPMT activity exhibits genetic variation and shows tri-modal distribution with 89-94% of individuals possessing high activity, 6-11% intermediate activity and approximately 0.3% low activity.

Salivary proteins and early childhood caries: A gel electrophoretic analysis.

Background: Early childhood caries (ECC) is a common disease process that afflicts a large proportion of the child population worldwide. Extensive research in past indicates that it is the result of bacterial infection, also influenced by host and dietary factors. Current caries research seeks to identify risk factors as well as natural oral defenses that may protect against or prevent caries development.

Studies on Brahma rasayana in male swiss albino mice: Chromosomal aberrations and sperm abnormalities.

Ayurveda, the Indian holistic healthcare system encompasses traditional medicines with a principle of creating harmony and maintaining balance within the natural rhythms of the body. Rasayana is one of the branches of Ayurveda frequently used as rejuvenant therapy to overcome many discomforts and prevent diseases. It has been reported that rasayanas have immunomodulatory, antioxidant and antitumor functions.

Analysis of genotype and haplotype effects of ABCB1 (MDR1) polymorphisms in the risk of medically refractory epilepsy in an Indian population.

The transmembrane P-glycoprotein that functions as a drug-efflux transporter coded by ATP-binding cassette, subfamily B, member 1/Multidrug Resistance 1 (ABCB1/MDR1) gene is considered relevant to drug absorption and elimination, with access to the central nervous system. Effects of three ABCB1 single nucleotide polymorphisms (SNPs) in genotypic and haplotypic combination have been evaluated in a south Indian population for risk of pediatric medically refractory epilepsy. The study included age and sex matched medically refractory (N=113) cases and drug responsive epilepsy patients (N=129) as controls, belonging to the same ethnic population recruited from a tertiary referral centre, of Karnataka, Southern India.

MTHFR Gene variants C677T, A1298C and association with Down syndrome: A Case-control study from South India.

Background: The 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and low folate levels are associated with inhibition of DNA methyltransferase and consequently DNA hypomethylation. The expanding spectrum of common conditions linked with MTHFR polymorphisms includes certain adverse birth outcome, pregnancy complications, cancers, adult cardiovascular diseases and psychiatric disorders, with several of these associations remaining still controversial. Trisomy 21 or Down syndrome (DS) is the most common genetic cause of mental retardation.

The role of basic fibroblast growth factor in oral submucous fibrosis pathogenesis.

Background: Oral submucous fibrosis (OSF) is a chronic fibrotic disease of oral mucosa and oropharynx, induced by betel quid chewing often resulting in restricted mouth opening. The principal cells implicated as a source of extracellular matrix in areas of fibrosis are fibroblasts. Accumulation of connective tissue matrix is secondary to factors such as cytokines and growth factors.

Tissue microarray - a high-throughput molecular analysis in head and neck cancer.

With the identification of a number of novel markers having diagnostic, prognostic, and therapeutic significance, the application of tissue microarray (TMA) has become a valuable tool for validating candidate markers in cancer research. The TMA is a high-throughput technique, which allows large-scale analyses of hundreds of archival clinical tissue samples using the 'array' approach. This paper highlights briefly its robust technology, technical aspects of its construction, and the validity of the TMA results for oral pathology diagnostics by reviewing data from recent literature particularly with reference to head and neck cancer.

Thurston syndrome: report of a new case.

Thurston syndrome (oro-facial-digital syndrome type V) is an autosomal recessive condition characterized by median cleft of the upper lip, postaxial polydactyly of hands and feet, and oral manifestations. According to earlier reports, the syndrome is predominantly seen in subjects of Indian descent. We report a cast of Thurston syndrome in a 13-year-old south Indian boy who presented with oral features, incomplete median cleft of upper lip, and polydactyly of both hands and left foot.

Optical diagnosis of cervical cancer by fluorescence spectroscopy technique.

In the present work, we examine normal and malignant stage IIIB cervical tissue by laser induced fluorescence, with 2 different objectives. (i) Development of the fluorescence spectroscopy technique as a standard optical method for discrimination of normal and malignant tissue samples and, (ii) Optimization of the technique by the method of matching of a sample spectrum with calibration sets of spectra of pathologically certified samples. Laser-induced fluorescence spectra were measured using samples from 62 subjects at different excitation wavelengths.

The RAS/RAF/MEK/ERK and PI3K/AKT signaling pathways present molecular targets for the effective treatment of advanced melanoma.

Malignant melanoma is a highly aggressive tumor of the pigment-producing cells in the skin with a rapidly increasing incidence and a poor prognosis for patients with advanced disease that is resistant to current therapeutic concepts. Therefore, the development of novel strategies for treating melanoma are of utmost importance. In melanoma, both the Ras-Raf-MEK-ERK (MAPK) and the PI3K-AKT (AKT) signaling pathways are constitutively activated through multiple mechanisms, and thus exert several key functions in melanoma development and progression.

Microtubule-associated protein 2, a marker of neuronal differentiation, induces mitotic defects, inhibits growth of melanoma cells, and predicts metastatic potential of cutaneous melanoma.

Dynamic instability of microtubules is critical for mitotic spindle assembly and disassembly during cell division, especially in rapidly dividing tumor cells. Microtubule-associated proteins (MAPs) are a family of proteins that influence this property. We showed previously that MAP2, a neuron-specific protein that stabilizes microtubules in the dendrites of postmitotic neurons, is induced in primary cutaneous melanoma but is absent in metastatic melanomas.

Microarray analysis of phosphatase gene expression in human melanoma.

Background: Tyrosine phosphate is abnormally elevated in malignant melanoma, and this has been interpreted to reflect the activity of oncogenic protein tyrosine kinases. However, elevation may also arise due to decreased protein tyrosine phosphatase (PTP) expression.

Objectives: To survey phosphatase gene expression in melanoma cell lines, a benign naevus and normal melanocytes: we searched for downregulation of phosphatase gene expression in malignant cells that may indicate a role as melanoma suppressor genes.

Free radical reactions and antioxidant activities of sesamol: pulse radiolytic and biochemical studies.

Sesamol (from Sesamum indicum) is a dietary compound, which is soluble in aqueous as well as lipid phases. Free radical scavenging reactions of sesamol, 5-hydroxy-1,3-benzodioxole, have been studied using a nanosecond pulse radiolysis technique. Sesamol efficiently scavenges hydroxyl, one-electron oxidizing, organo-haloperoxyl, lipid peroxyl, and tryptophanyl radicals.

Induction of melanoma phenotypes in human skin by growth factors and ultraviolet B.

Exposure to UV radiation likely plays a key role in melanoma development, whereas other etiologic agents remain unknown. Here we show that in normal human skin an increased expression of a combination of three growth factors, basic fibroblast growth factor, stem cell factor, and endothelin-3, along with exposure to UVB can transform normal melanocytes into a melanoma phenotype within 4 weeks. Invasion of melanoma lesions was found in skin from newborn donors, whereas melanomas in adult skin were of a noninvasive in situ type only.

Detection of HLA class II-dependent T helper antigen using antigen phage display.

Major histocompatibility complex (MHC) class II-dependent antigens not only activate CD4+ T helper (Th) cells, but also cytolytic T lymphocytes and effector cells of the innate immune system. These antigens therefore are candidate vaccines against cancer and infectious agents. We have developed a novel approach using a model antigen, tetanus toxoid (TT), which provides the basis for the establishment of a novel strategy of cloning Th antigens.

Fibroblast growth factor-2 but not Mel-CAM and/or beta3 integrin promotes progression of melanocytes to melanoma.

A variety of melanoma-associated antigens have been identified that mediate adhesion, growth, proteolysis, and modulation of immune response. However, the mechanisms by which human normal melanocytes become malignant are not clearly understood. Among the most consistent observations is the up-regulation of fibroblast growth factor-2 (FGF-2) and of the adhesion molecules beta3 integrin and Mel-CAM during melanoma progression.

Function and regulation of melanoma-stromal fibroblast interactions: when seeds meet soil.

Melanoma development and progression not only involve genetic and epigenetic changes that take place within the melanocytic cells, but also involve processes that are determined collectively by contextual factors including intercellular adhesions and communications. In this review, we focus on melanoma-stromal fibroblast crosstalk by direct cell-cell contact and by growth factors/cytokines/chemokines interacting with their respective receptors. The interactions between melanoma cells and stromal fibroblasts create a context that promotes tumor growth, migration/invasion, and angiogenesis.

Stroma formation and angiogenesis by overexpression of growth factors, cytokines, and proteolytic enzymes in human skin grafted to SCID mice.

Reorganization of skin during wound healing, inflammatory disorders, or cancer growth is the result of expression changes of multiple genes associated with tissue morphogenesis. We wanted to identify proteins involved in skin remodeling and select those that may be targeted for agonistic or antagonist therapeutic approaches in various disease processes. Full-thickness human skin was grafted to severe combined immunodeficient mice and injected intradermally with 38 different adenoviral vectors inserted with 37 different genes coding for growth factors, cytokines, proteolytic enzymes and their inhibitors, adhesion receptors, oncogenes, and tumor suppressor genes.

Constitutive mitogen-activated protein kinase activation in melanoma is mediated by both BRAF mutations and autocrine growth factor stimulation.

Dysregulated activation of Ras or its downstream effectors such as mitogen-activated protein kinase kinase and ERK has been shown to play a critical role in tumorigenesis of many cancer types. However, in melanoma, activating mutations in Ras are rarely observed and are limited to N-Ras in UV-exposed cells. In this study, we identify constitutively activated ERK in almost all melanoma cell lines and in tumor tissues tested, which is in contrast to normal melanocytes and several early stage radial growth phase melanoma lines where ERK can be activated by serum or growth factors.