No abstract

Three decades of research have revealed that cancer is easier to prevent than to treat and that consumption of certain fruits and vegetables can reduce the risk of cancer. Whereas chemotherapy is designed to destroy cancer after it appears, chemoprevention involves the abrogation or delay in the onset of cancer. Regardless of whether a chemopreventive or chemotherapeutic approach is taken, cancer is a multifactorial disease that requires modulation of multiple pathways and multiple targets. Various molecular targets of chemoprevention are also relevant to the therapy of cancer. These targets include the activation of apoptosis; suppression of growth factor expression or signalling; downregulation of antiapoptotic proteins; suppression of phosphatidylinositol-3'-kinase/Akt, NF-kappaB, Janus kinase-signal transducer and activator of transcription and activator protein-1 signalling pathways; and downregulation of angiogenesis through inhibition of vascular endothelial growth factor expression, cyclooxygenase-2, matrix metalloproteinase-9, urokinase-type plasminogen activator, adhesion molecules and cyclin D1. Pharmacologically safe phytochemicals that have been identified from plants or their variant forms can modulate these molecular targets. These phytochemicals include genistein, resveratrol, dially sulfide, S-ally cysteine, allicin, lycopene, capsaicin, curcumin, 6-gingerol, ellagic acid, ursolic acid, betulinic acid, flavopiridol, silymarin, anethol, catechins and eugenol. Recent work has shown that these phytochemicals also can reverse chemoresistance and radioresistance. Because of their pharmacological safety, these agents can be used alone to prevent cancer and in combination with chemotherapy to treat cancer.

Recent molecular phylogenetic studies indicate that the rafting Indian plate harboured several isolated vertebrate lineages between ca. 130 and 56 Myr ago that dispersed and diversified 'out of India' following accretion with Eurasia. A single family of the amphibian order Gymnophiona, the Ichthyophiidae, presently occurs on the Indian plate and across much of South East Asia. Ichthyophiid phylogeny is investigated in order to test competing out of India and out of South East Asia hypotheses for their distribution. Partial sequences of mitochondrial 12S and 16S rRNA and cytochrome b genes for 20 ichthyophiids and proximate outgroups were assembled. Parsimony, maximum-likelihood and distance analyses all recover optimum trees in which uraeotyphlids plus Ichthyophis cf. malabarensis are the sister taxa to all other Ichthyophis, among which the South East Asian taxa are monophyletic. Tree topology and branch lengths indicate that the Indian lineages are more basal and older, and thus are more consistent with the hypothesis that ichthyophiids dispersed from the Indian subcontinent into South East Asia. The estimated relationships also support monophyly of Sri Lankan Ichthyophis, and non-monophyly of striped and unstriped Ichthyophis species groups. Mitochondrial DNA sequences provide evidence that should assist current problematic areas of caecilian taxonomy.

India has a diverse caecilian fauna, including representatives of three of the six currently recognized families, the Caeciliidae, Ichthyophiidae, the endemic Uraeotyphlidae, but previous molecular phylogenetic studies of caecilians have not included sequences for any Indian caecilians. Partial 12S and 16S mitochondrial gene sequences were obtained for a single representative of each of the caecilian families found in India and aligned against previously reported sequences for 13 caecilian species. The resulting alignment (16 taxa, 1200 sites, of which 288 cannot be aligned unambiguously) was analyzed using parsimony, maximum-likelihood, and distance methods. As judged by bootstrap proportions, decay indices, and leaf stabilities, well-supported relationships of the Indian caecilians are recovered from the alignment. The data (1) corroborate the hypothesis, based on morphology, that the Uraeotyphlidae and Ichthyophiidae are sister taxa, (2) recover a monophyletic Ichthyophiidae, including Indian and South East Asian representatives, and (3) place the Indian caeciliid Gegeneophis ramaswamii as the sister group of the caeciliid caecilians of the Seychelles. Rough estimates of divergence times suggest an origin of the Uraeotyphlidae and Ichthyophiidae while India was isolated from Laurasia and Africa and are most consistent with an Indian origin of these families and subsequent dispersal of ichthyophiids into South East Asia. Ó

A few previous studies of skeletal and especially skull development in Gymnophiona often provided contradictory results. We studied the development of the skull and vertebral column of Gegeneophis ramaswamii, a direct-developing Indian caeciliid, based on 13 specimens. The chondrocranium forms at (Brauer in Zool Jahrb Anat 12:477-508,1899) stage 38. First dermal and perichondral ossifications occur at stage 40. The first dermal bones to form are the mentomeckelian, dentary, angular, vomer, and premaxillary. These are followed by the coronoid, palatine, pterygoid, maxillary, and the skull-roofing bones. The last occurring dermal ossifications are the parasphenoid and the squamosal. We present evidence for the occurrence of a lacrimal bone. No ectopterygoid, basioccipital, supraoccipital, pleurosphenoid, postorbital, or supratemporal elements were found. We assess the homology of the bones constituting the caecilian skull and discuss the above-mentioned terminologies. The phylogenetic implications of our findings are briefly discussed and we conclude that the evidence from developmental morphology is at present consistent with a monophyletic Lissamphibia of temnospondyl origin.