Background:Prostate cancer is biologically and clinically a heterogeneous disease that makes imaging evaluation challenging. One of the important challenges in this cancer is to detect recurrent disease. Biochemical response using Prostate Specific Antigen (PSA) and Imaging using several PET tracers have poor sensitivity and specificity. Therefore, we analyse the role of Ga68-PSMA (Prostate Specific Membrane Antigen) imaging in prostate cancer, which is a new PET tracer.Methods:In this study, we evaluated PET scans of 262 patients with diagnosis of prostate cancer. These patients were scanned using Ga68-PSMA for either staging or response evaluation.Results:336 PSMA scans were performed. Ga68-PSMA scan resulted in the detection of extra-prostatic disease in 53.2% of cases when done at baseline before commencing any treatment. The sensitivity of Ga68-PSMA at baseline with histopathological diagnosis was 95% with 95% CI ranging from 86% to 98%. The positive predictive value was high at 98% with 95% CI ranging from 91% to 99%. In 26 (10%) patients who had surgical castration, Ga68-PSMA scan was able to detect disease progression / castration resistance in 100% of cases. The outcome of castration-resistant prostate cancer was compared with other cases where castration was not done. In those who did not undergo castration, there was a significantly better response by hormone therapy (p = 0.03) and radiotherapy (p = 0.01) on Ga68-PSMA. The sensitivity of Ga68-PSMA response with biochemical response was 66.7% with 95% CI ranging between 46 %- 82.7%. Ga68-PSMA response did not correlate with biochemical response.Conclusion:Ga68-PSMA has good sensitivity for diagnosis, staging, restaging, evaluation of therapy response and prognostication in prostate cancer.

Epimorphic regeneration is a process allowing the animal to regain its lost structure which depends on the resident pluripotent stem cells as well as de-differentiation of existing cells to form multi-potent stem cells. Many studies have been done to understand the appendage regeneration mechanism. The animal model used since decades is an urodele amphibian the axolotl. However, this ability is also seen in some members of reptiles, mainly lizards which on autotomy of tail regain the same by forming a replica of its lost tail. Lizards being closer to mammals are of greater interest and cannot be neglected. Hence, a stage specific protein profiling was undertaken in order to find the peptides playing a major role in epimorphosis. 2-DGE being basic tool for creating a protein profile was used. With advent of newer modern technology, label-free analysis which uses MS/MS was also performed. The study reports the peptides involved in apoptosis, inflammation and ECM remodelling across the stages of lizard tail regeneration for the first time. Apart from these peptides, structural protein, enzymes involved in metabolism have also been highlighted in the current study to give a bigger picture of the processes and the specific peptides required for tail regeneration.

Lizards are unique in having both-regeneration competent (tail) as well as non-regenerating appendages (limbs) in adults. They therefore present an appropriate model for comparing processes underlying regenerative repair and nonregenerative healing after amputation. In the current study, we use northern house gecko Hemidactylus flaviviridis to compare major cellular and molecular events following amputation of the limb and of the tail. Although the early response to injury in both cases comprises apoptosis, proliferation, and angiogenesis, the temporal distribution of these processes in each remained obscure. In this regard, observations were made on the anatomy and gene expression levels of key regulators of these processes during the healing phase of the tail and limb separately. It was revealed that cell proliferation markers like fibroblast growth factors were upregulated early in the healing tail, coinciding with the growing epithelium. The amputated limb, in contrast, showed weak expression of proliferation markers, limited only to fibroblasts in the later stage of healing. Additionally, apoptotic activity in the tail was limited to the very early phase of healing, as opposed to that in the limb, wherein high expression of caspase-3 was observed throughout the healing process. Early rise in VEGF-α expression reflected an early onset of angiogenesis in the tail, while it was seen to occur at a later stage in case of the limb. Moreover, the expression pattern of transforming growth factor beta members points toward a pro-fibrotic response being induced very early in the amputated limb. Collectively, these results explain why regenerating appendages are able to heal without scars and if we are to induce scar-free healing in nonregenerating limbs, what interventions can be envisaged. This is crucial to the field of regenerative medicine since it is the initial stages of repair following amputation, which decide whether the appendage will be restored or only covered with a scab.

Epimorphic regeneration in vertebrates involves the restoration of lost tissue or organs through the formation of a regeneration blastema and occurs through a complex interaction of a number of molecular signaling pathways. Of the many effectors of successful tail regeneration in the lizard Hemidactylus flaviviridis, one crucial pathway is the cyclooxygenase-2 (COX-2) mediated PGE 2 signaling pathway. The current study was aimed at understanding whether COX-2 signaling plays any role in the expression of Wnt/b-Catenin signaling components during regenerative outgrowth in H. flaviviridis. Etoricoxib-selective inhibitor of the inducible isoform of COX-2-was administered to lizards orally. We tested the expression of b-Catenin during wound epidermis and blastema stages in the regenerating tail and found a reduction in its expression in response to drug treatment. Further, it was observed that the expression of canonical Wnt ligands was greatly altered due to COX-2 inhibition. Our results provide evidence of a cross-talk between the COX-2 induced PGE 2 pathway and Wnt/b-Catenin signaling in the regenerating lizard tail. An understanding of the interaction among various signaling pathways will help elucidate the mechanism underlying epimorphosis in lizards, the only amniotes capable of appendage regeneration.

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Caudal fin regeneration in sailfin molly, Poecilia latipinna (Lesueur 1821) involves an initial wound healing stage, followed by blastema that is formed of fast proliferating cells. In order to replicate the lost fin, correct differentiation of the blastemal cells into various tissues is the prime essence. Among the molecular signals governing proper differentiation of blastemal cells, members of the bone morphogenetic protein (BMP) family are crucial. Herein, we investigated the specific effects of inhibition of BMP signaling using LDN193189 on skeletal and connective tissue formation in the regenerating tail fin of P. latipinna during early differentiation phase. It was observed that BMP inhibition leads to reduction in the length of regeneration, which can be correlated with compromised proliferation of blastemal cells. Decreased expression of cell proliferation marker like pcna together with reduced BrdU positive cells consolidate the above observation. Further, histological analysis revealed stunted progression of skeletal tissues and this correlated with the reduced expression of sox9, runx2 and dlx5, Osc and Osn genes in response to BMP inhibition. Also, defective bone patterning was observed due to BMP inhibition, which was associated with diminished levels of shh, ptc-1, gli2 and other BMP ligands. Moreover, histochemical analysis revealed that collagen, one of the most prominent components of connective tissue, was formed below par in treated fin tissues which was subsequently confirmed by biochemical and transcript level analyses. Overall our results highlight the importance of the BMP pathway in proper differentiation of skeletal and connective tissues during the differentiation stage of regenerating caudal fin.

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