Feedback within the Inter-Cellular Communication and Tumorigenesis in Carcinomas

The classical somatic mutation theory (SMT) of carcinogenesis and metastasis postulates that malignant transformation occurs in cells that accumulate a sufficient amount of mutations in the appropriate oncogenes and/or tumor suppressor genes. These mutations result in cell-autonomous activation of the mutated cell and a growth advantage relative to neighboring cells. However, the SMT cannot completely explain many characteristics of carcinomas. Contrary to the cell-centered view of the SMT with respect to carcinogenesis, recent research has revealed evidence that the tumor microenvironment plays a role in carcinogenesis as well. In this review, we present a new model that accommodates the role of the tumor microenvironment in carcinogenesis and complements the classical SMT. Our “feedback” model emphasizes the role of an altered spatiotemporal communication between epithelial and stromal cells during carcinogenesis: a dysfunctional intracellular signaling in tumorigenic epithelial cells leads to inappropriate cellular responses to stimuli from associated stromal or inflammatory cells. Thus, a positive feedback loop of the information flow between parenchymal and stromal cells results. This constant communication between the stromal cells and the tumor cells causes a perpetually activated state of tumor cells analogous to resonance disaster

The evaluation of acoustic characteristic performance on natural sound absorbing materials from cogon grass waste

In the past few decades, synthetic fibers are been used widely in the field of sound absorption due to their superior characteristics such as durable and chemical resistant. However, there are several disadvantages of synthetic fibers such as non-biodegradability and hazards to the health of human. In this research, the natural sound absorber from cogon grass was investigated. The objective of the research was to evaluate the performance of cogon grass physical characteristics on its acoustical behavior, to evaluate the effect of sodium hydroxide (NaOH) treatment times on physical and acoustical characteristics of cogon grass, to investigate the decay effects after it was left over for twelve months and lastly to compare and verify the acoustical results with theoretical models based on (Delany-Bazley and Miki Model). The measurement of acoustical characteristics which are sound absorption coefficient (SAC) and noise reduction coefficient (NRC) were done by using impedance tube method (ITM). The samples of cogon grass were tested in a way of the untreated and treated with NaOH in varied soaked hours which are one, two, three, four and five hours. Scanning electron microscope (SEM) and density kit were used to investigate physical characteristics. The research confirmed that physical characteristics of tortuosity and airflow resistivity values tend to increase with the increment of treatment times, but the density and porosity tend to decrease. Untreated samples were tested with varied thicknesses of 10, 20, 30, 40 and 50mm. The results show SAC value increases when the thickness of the sample was increased. Treated samples results show the least treated sample (1 hour) reached the maximum SAC value and indicated the highest value of NRC which is 0.50. The results also show a reduction in sound absorption value after the samples were left for twelve months. Verification parts demonstrated that Delany-Bazley and Miki Model can predict approximately pattern compared with ITM results because of the theoretical models are developed by a simple empirical model approach. Overall, cogon grass samples have the good characteristics to be an acoustic material component

p21(WAF1) (/Cip1) limits senescence and acinar-to-ductal metaplasia formation during pancreatitis

Trans-differentiation of pancreatic acinar cells into ductal-like lesions, a process defined as acinar-to-ductal metaplasia (ADM) is observed in the course of organ regeneration following pancreatitis. In addition, ADM is found in association with pre-malignant PanIN lesions and correlates with an increased risk of pancreatic adenocarcinoma (PDAC). Human PDAC samples show down-regulation of p21(WAF1) (/Cip1) , a key regulator of cell cycle and cell differentiation. Here we investigated whether p21 down-regulation is implicated in controlling the early events of acinar cell trans-differentiation and ADM formation. p21-mediated regulation of ADM formation and regression was analyzed in vivo during the course of cerulein-induced pancreatitis using wild type (WT) and p21 deficient (p21(-/-) ) mice. Biochemical and immunohistochemical methods were used to evaluate disease progression over two weeks of the disease and during a recovery phase. We found that p21 was strongly up-regulated in WT acinar cells during pancreatitis, while it was absent in ADM areas, suggesting that p21 down-regulation is associated with ADM formation. In support of this hypothesis, p21(-/-) mice showed a significant increase in number and size of metaplasia. In addition, p21 over-expression in acinar cells reduced ADM formation in vitro, suggesting that the protein regulates the metaplastic transition in a cell-autonomous manner. p21(-/-) mice displayed increased expression and re-localization of β-catenin during both pancreatitis and subsequent recovery phase. Finally, loss of p21 was accompanied by increased DNA damage and development of senescence. Our findings are consistent with a gate-keeper role of p21 in acinar cells to limit senescence activation and ADM formation during pancreatic regeneration