Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration

Background: Colorectal cancer (CRC) is the 3rd most common type of cancer worldwide. New anti-cancer agents are needed for treating late stage colorectal cancer as most of the deaths occur due to cancer metastasis. A recently developed compound, 3c has shown to have potent antitumor effect; however the mechanism underlying the antitumor effect remains unknown. Methods: 3c-induced inhibition of proliferation was measured in the absence and presence NAC using MTT in HT-29 and SW620 cells and xCELLigence RTCA DP instrument. 3c-induced apoptotic studies were performed using flow cytometry. 3c-induced redox alterations were measured by ROS production using fluorescence plate reader and flow cytometry and mitochondrial membrane potential by flow cytometry; NADPH and GSH levels were determined by colorimetric assays. Bcl2 family protein expression and cytochrome c release and PARP activation was done by western blotting. Caspase activation was measured by ELISA. Cell migration assay was done using the real time xCELLigence RTCA DP system in SW620 cells and wound healing assay in HT-29. Results: Many anticancer therapeutics exert their effects by inducing reactive oxygen species (ROS). In this study, we demonstrate that 3c-induced inhibition of cell proliferation is reversed by the antioxidant, N-acetylcysteine, suggesting that 3c acts via increased production of ROS in HT-29 cells. This was confirmed by the direct measurement of ROS in 3c-treated colorectal cancer cells. Additionally, treatment with 3c resulted in decreased NADPH and glutathione levels in HT-29 cells. Further, investigation of the apoptotic pathway showed increased release of cytochrome c resulting in the activation of caspase-9, which in turn activated caspase-3 and −6. 3c also (i) increased p53 and Bax expression, (ii) decreased Bcl2 and BclxL expression and (iii) induced PARP cleavage in human colorectal cancer cells. Confirming our observations, NAC significantly inhibited induction of apoptosis, ROS production, cytochrome c release and PARP cleavage. The results further demonstrate that 3c inhibits cell migration by modulating EMT markers and inhibiting TGFβ-induced phosphorylation of Smad2 and Samd3. Conclusions: Our findings thus demonstrate that 3c disrupts redox balance in colorectal cancer cells and support the notion that this agent may be effective for the treatment of colorectal cancer

Poesie und Essay. Ein Interview mit Durs Gru\u308nbein

Durs Gr\ufcnbein reflektiert \ufcber die Verflechtungen lyrischen und essayistischen Schreibens und fokussiert zum ersten Mal die Form seines "poetischen Essay[s]"

Soil-Moisture Estimation Using Hybrid Polarimetric SAR Data of RISAT-1

In this paper, the capabilities of hybrid polarimetric synthetic aperture radar are investigated to estimate soil moisture on bare and vegetated agricultural soils. A new methodology based on a compact polarimetric decomposition, together with a surface component inversion, is developed to retrieve surface soil moisture. A model-based compact decomposition technique is applied to obtain the surface scattering component under the assumption of a randomly oriented vegetation volume. After vegetation removal, the surface scattering component is inverted for soil moisture (under vegetation) by comparison with a surface component modeled by two physics-based scattering models: The integral equation method (IEM) and the extended Bragg model (X-Bragg). The developed algorithm, based on a two-layer (random volume over ground) scattering model, is applied on a time series of hybrid polarimetric C-band RISAT-1 right circular transmit linear receive data acquired from April to October 2014 over the Wallerfing test site in Lower Bavaria, Germany. The retrieved soil moisture is validated against in situ frequency-domain reflectometry measurements. Including the entire growing season (all acquired dates) and all crop types, the estimated soil moisture values indicate an overall rmse of 7 vol.% using the X-Bragg model and 10 vol.% using the IEM model. The proposed hybrid polarimetric soil-moisture inversion algorithm works well for bare soils (rmse = 3.1-8.9 vol.%) with inversion rates of around 30-70%. The inversion rate for vegetation-covered soils ranges from 5% to 40%, including all phenological stages of the crops and different soil moisture conditions

On the security and usability of dynamic cognitive game CAPTCHAs

Existing CAPTCHA solutions are a major source of user frustration on the Internet today, frequently forcing companies to lose customers and business. Game CAPTCHAs are a promising approach which may make CAPTCHA solving a fun activity for the user. One category of such CAPTCHAs - called Dynamic Cognitive Game (DCG) CAPTCHA - challenges the user to perform a game-like cognitive (or recognition) task interacting with a series of dynamic images. Specifically, it takes the form of many objects floating around within the images, and the user's task is to match the objects corresponding to specific target(s), and drag/drop them to the target region(s). In this paper, we pursue a comprehensive analysis of DCG CAPTCHAs. We design and implement such CAPTCHAs, and dissect them across four broad but overlapping dimensions: (1) usability, (2) fully automated attacks, (3) human-solving relay attacks, and (4) hybrid attacks that combine the strengths of automated and relay attacks. Our study shows that DCG CAPTCHAs are highly usable, even on mobile devices and offer some resilience to relay attacks, but they are vulnerable to our proposed automated and hybrid attacks