Four different copolymers, of acrylamide and acrylic acid, acrylamide and 2-acrylamido-2-methyl propane sulfonic acid, N,N-dimethylacrylamide and acrylic acid, and N,N-dimethylacrylamide and 2-acrylamido-2-methyl propane sulfonic acid (sodium salts), were prepared. The copolymers were characterized by their intrinsic viscosities and monomer ratios and with IR, 1 H-NMR, and X-ray diffraction (XRD) spectroscopy. No crystallinity was observed by differential thermal analysis, and this was well supported by XRD. All the polymers showed low decomposition temperatures. A number of decomposition temperatures were observed in differential thermogravimetry thermograms because of the elimination of gases such as CO 2 , SO 2 , CO, and NH 3 . The replacement of the acrylate group with a sulfonate group produced polymers that were more compatible with brine, whereas the replacement of acrylamide with a more hydrophobic group such as N,Ndimethylacrylamide produced a more shear-resistant polymer. A N,N-dimethylacrylamide-co-sodium-2-acrylamido-2-methyl propane sulfonate copolymer was better with respect to thermal stability when the polymer solution was aged at 120°C for a period of 1 month.

BackgroundDespite recent advances in outlining the mechanisms involved in pancreatic carcinogenesis, precise molecular pathways and cellular lineage specification remains incompletely understood.ResultsWe show here that Cyr61/CCN1 play a critical role in pancreatic carcinogenesis through the induction of EMT and stemness. Cyr61 mRNA and protein were detected in the early precursor lesions and their expression intensified with disease progression. Cyr61/CCN1 expression was also detected in different pancreatic cancer cell lines. The aggressive cell lines, in which the expressions of mesenchymal/stem cell molecular markers are predominant; exhibit more Cyr61/CCN1 expression. Cyr61 expression is exorbitantly higher in cancer stem/tumor initiating Panc-1-side-population (SP) cells. Upon Cyr61/CCN1 silencing, the aggressive behaviors are reduced by obliterating interlinking pathobiological events such as reversing the EMT, blocking the expression of stem-cell-like traits and inhibiting migration. In contrast, addition of Cyr61 protein in culture medium augments EMT and stemness features in relatively less aggressive BxPC3 pancreatic cancer cells. Using a xenograft model we demonstrated that cyr61/CCN1 silencing in Panc-1-SP cells reverses the stemness features and tumor initiating potency of these cells. Moreover, our results imply a miRNA-based mechanism for the regulation of aggressive behaviors of pancreatic cancer cells by Cyr61/CCN1.ConclusionsIn conclusion, the discovery of the involvement of Cyr61/CCN1 in pancreatic carcinogenesis may represent an important marker for PDAC and suggests Cyr61/CCN1 can be a potential cancer therapeutic target.

Although previous in vitro studies predicted that CCN5/ WISP-2 may act as an anti-invasive gene in breast cancer, the distribution pattern of CCN5 in breast cancer samples is conflicting. Thus, we systematically investigated the CCN5 expression profile in noninvasive and invasive breast tumor samples and its functional relevance in breast cancer progression. The studies showed that CCN5 expression is biphasic, such that in normal samples CCN5 expression is undetectable, whereas its expression is markedly increased in noninvasive breast lesions, including atypical ductal hyperplasia and ductal carcinoma in situ. Further, CCN5 mRNA and protein levels are significantly reduced as the cancer progresses from a noninvasive to invasive type. Additionally, we showed that CCN5 mRNA and protein level was almost undetectable in poorly differentiated cancers compared with the moderately or well-differentiated samples and its expression inversely correlated with lymph node positivity. The result was further supported by evaluating the RNA expression profile in microdissected sections using real-time PCR analysis. Therefore, our data suggest a protective function of CCN5 in noninvasive breast tumor cells. This hypothesis was further supported by our in vitro studies illuminating that CCN5 is a negative regulator of migration and invasion of breast cancer cells, and these events could be regulated by CCN5 through the modulation of the expression of genes essential for an invasive front. These include Snail-E-cadherin signaling and matrix metalloproteinase (MMP)-9 and MMP-2. Collectively, these studies suggest that the protective effect of CCN5 in breast cancer progression may have important therapeutic implications. [Cancer Res 2008;68(18):7606-12]

A high molecular weight (>10 6 ) copolymer of N,N-dimethyl acrylamide with Na-2-acrylamido-2-methylpropanesulfonate (NNDAM-NaAMPS) was prepared and characterized. The efficacy of the copolymer as an enhanced oil recovery (EOR) chemical was studied. Core flood tests using 72-150 mesh size unconsolidated sand having a porosity of 42% were carried out at different brine concentrations and temperatures. Initially, a crude oil fraction (150-300 °C) and, finally, the crude itself were used as the oils to be recovered. The copolymer was brine compatible. After a water flood, about 5.6% original oil in place (OIP) could be recovered by injecting 2000 ppm polymer solution to the sand pack containing oil fraction and 5000 ppm NaCl brine. The polymer solution was found to be thermally stable at 120 °C at least for a period of 1 month. It was further confirmed that the residual oil recovery increased with the increase of temperature. About 11% of OIP could be recovered as additional oil by injecting a 2000 ppm polymer solution to the unconsolidated sand pack containing one of the Indian crude oils and brine consisting of monoand bivalent metal ions at 90 °C.

Earlier studies have reported that trimethylamine Noxide (TMAO), a naturally occurring osmolyte, is a universal stabilizer of proteins because it folds unstructured proteins and counteracts the deleterious effects of urea and salts on the structure and function of proteins. This conclusion has been reached from the studies of the effect of TMAO on proteins in the pH range 6.0 -8.0. In this pH range TMAO is almost neutral (zwitterionic form), for it has a pK a of 4.66 ؎ 0.10. We have asked the question of whether the effect of TMAO on protein stability is pH-dependent. To answer this question we have carried out thermal denaturation studies of lysozyme, ribonuclease-A, and apo-␣-lactalbumin in the presence of various TMAO concentrations at different pH values above and below the pK a of TMAO. The main conclusion of this study is that near room temperature TMAO destabilizes proteins at pH values below its pK a , whereas it stabilizes proteins at pH values above its pK a . This conclusion was reached by determining the T m (midpoint of denaturation), ⌬H m (denaturational enthalpy change at T m ), ⌬C p (constant pressure heat capacity change), and ⌬G D°( denaturational Gibbs energy change at 25°C) of proteins in the presence of different TMAO concentrations. Other conclusions of this study are that T m and ⌬G D°d epend on TMAO concentration at each pH value and that ⌬H m and ⌬C p are not significantly changed in the presence of TMAO.Many organisms are known to accumulate low molecular weight organic molecules (osmolytes) in their tissues in response to harsh environmental stresses. These osmolytes are generally categorized into three groups, namely amino acids and their derivatives, polyhydric alcohols, and methylamines (1). Molecules of the first two groups are "compatible osmolytes," which means that cells accumulate these osmolytes to high concentrations without significantly perturbing protein functions under physiological conditions (1-4). Molecules of the third group, which reverse the perturbations caused by urea, are known as "counteracting osmolytes" (2, 5). One such counteracting osmolyte is trimethylamine N-oxide (TMAO), 1 which is present in high concentrations in coelacanth (sharks) and marine elasmobranchs (rays) (6). The effect of TMAO on protein stability and enzyme activity has been widely studied. This osmolyte has been shown in vitro to do the following: (i) increase the melting temperature as well as the unfolding free energy of proteins (7-11); (ii) offset the destabilizing effects of urea (8, 10, 11); (iii) restore the enzyme activity that is lost upon urea treatment (12, 13); (iv) force the folding of unstructured proteins (4, 12-15); (v) favor the protein self-association and polymerization of microtubules (16 -18); (vi) correct temperature-sensitive folding defects (19); and (vii) interfere with the formation of scrape prion protein (20). TMAO has been shown in vivo to counteract the damaging effects of salts (21), hydrostatic pressure (22, 23), and urea (24, 25) on proteins.TMAO is a compou...

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Patients with ovarian cancer (OC) may be treated with surgery, chemotherapy and/or radiation therapy, although none of these strategies are very effective. Several plant-based natural products/dietary supplements, including extracts from Emblica officinalis (Amla), have demonstrated potent anti-neoplastic properties. In this study we determined that Amla extract (AE) has anti-proliferative effects on OC cells under both in vitro and in vivo conditions. We also determined the anti-proliferative effects one of the components of AE, quercetin, on OC cells under in vitro conditions. AE did not induce apoptotic cell death, but did significantly increase the expression of the autophagic proteins beclin1 and LC3B-II under in vitro conditions. Quercetin also increased the expression of the autophagic proteins beclin1 and LC3B-II under in vitro conditions. AE also significantly reduced the expression of several angiogenic genes, including hypoxia-inducible factor 1α (HIF-1α) in OVCAR3 cells. AE acted synergistically with cisplatin to reduce cell proliferation and increase expression of the autophagic proteins beclin1 and LC3B-II under in vitro conditions. AE also had anti-proliferative effects and induced the expression of the autophagic proteins beclin1 and LC3B-II in mouse xenograft tumors. Additionally, AE reduced endothelial cell antigen – CD31 positive blood vessels and HIF-1α expression in mouse xenograft tumors. Together, these studies indicate that AE inhibits OC cell growth both in vitro and in vivo possibly via inhibition of angiogenesis and activation of autophagy in OC. Thus AE may prove useful as an alternative or adjunct therapeutic approach in helping to fight OC.

Background: Because CCN5 is an anti-invasive gene, present studies were designed to determine whether CCN5 exerts its anti-invasive function through controlling microRNA-10b expression. Results: Up-regulation of TWIST1, a miR-10b activator, can be achieved by CCN5 silencing through the activation of HIF-1␣ JNK signaling. Conclusion: CCN5 is a negative regulator of miR-10b in breast cancer cells. Significance: The reactivation of CCN5 could be a unique therapeutic strategy for Triple negative breast cancer.