Animal models of hepatocellular carcinoma prevention

Hepatocellular carcinoma (HCC) is a deadly disease and therapeutic efficacy in advanced HCC is limited. Since progression of chronic liver disease to HCC involves a long latency period of a few decades, a significant window of therapeutic opportunities exists for prevention of HCC and improve patient prognosis. Nonetheless, there has been no clinical advancement in instituting HCC chemopreventive strategies. Some of the major challenges are heterogenous genetic aberrations of HCC, significant modulation of tumor microenvironment and incomplete understanding of HCC tumorigenesis. To this end, animal models of HCC are valuable tools to evaluate biology of tumor initiation and progression with specific insight into molecular and genetic mechanisms involved. In this review, we describe various animal models of HCC that facilitate effective ways to study therapeutic prevention strategies that have translational potential to be evaluated in a clinical context © 2019 by the authors. Licensee MDPI, Basel, Switzerland

Poboljšan postupak sinteze nekih novih 1,3-diaril-2-propen-1-ona koristeći PEG-400 kao reciklirajuće otapalo i njihovo antimikrobno vrednovanje

A simple and convenient route is described for the synthesis of novel hetero 1,3-diaryl-2-propen-1-ones (chalcones) by using recyclable poly PEG-400 as an alternative reaction solvent. The reaction is clean with excellent yield, shorter reaction time and reduces the use of volatile organic compounds (VOCs). All the synthesized compounds were evaluated for their antimicrobial activities against several pathogenic representatives.Opisana je jednostavna i pogodna metoda sinteze novih hetero 1,3-diaril-2-propen-1-ona (kalkona) koristeći poli(etilenglikol) (PEG-400) kao alternativno otapalo. Reakcija je jednoznačna, a uporaba hlapljivih organskih otapala je smanjena. Iskorištenja na produktima su visoka, a reakcijska vremena kraća. Svi sintetizirani spojevi testirani su na antimikrobno djelovanje na nekoliko patogenih mikroorganizama

Combination of a six microRNA expression profile with four clinicopathological factors for response prediction of systemic treatment in patients with advanced colorectal cancer

Background First line chemotherapy is effective in 75 to 80% of patients with metastatic colorectal cancer (mCRC). We studied whether microRNA (miR) expression profiles can predict treatment outcome for first line fluoropyrimidine containing systemic therapy in patients with mCRC. Methods MiR expression levels were determined by next generation sequencing from snap frozen tumor samples of 88 patients with mCRC. Predictive miRs were selected with penalized logistic regression and posterior forward selection. The prediction co-efficients of the miRs were re-estimated and validated by real-time quantitative PCR in an independent cohort of 81 patients with mCRC. Results Expression levels of miR-17-5p, miR-20a-5p, miR-30a-5p, miR-92a-3p, miR-92b-3p and miR-98-5p in combination with age, tumor differentiation, adjuvant therapy and type of systemic treatment, were predictive for clinical benefit in the training cohort with an AUC of 0.78. In the validation cohort the addition of the six miR signature to the four clinicopathological factors demonstrated a significant increased AUC for predicting treatment response versus those with stable disease (SD) from 0.79 to 0.90. The increase for predicting treatment response versus progressive disease (PD) and for patients with SD versus those with PD was not significant. in the validation cohort. MiR-17-5p, miR-20a-5p and miR-92a-3p were significantly upregulated in patients with treatment response in both the training and validation cohorts. Conclusion A six miR exp

Animal Models of Hepatocellular Carcinoma Prevention

Hepatocellular carcinoma (HCC) is a deadly disease and therapeutic efficacy in advanced HCC is limited. Since progression of chronic liver disease to HCC involves a long latency period of a few decades, a significant window of therapeutic opportunities exists for prevention of HCC and improve patient prognosis. Nonetheless, there has been no clinical advancement in instituting HCC chemopreventive strategies. Some of the major challenges are heterogenous genetic aberrations of HCC, significant modulation of tumor microenvironment and incomplete understanding of HCC tumorigenesis. To this end, animal models of HCC are valuable tools to evaluate biology of tumor initiation and progression with specific insight into molecular and genetic mechanisms involved. In this review, we describe various animal models of HCC that facilitate effective ways to study therapeutic prevention strategies that have translational potential to be evaluated in a clinical context

The importance of microRNAs in RAS oncogenic activation in human cancer

microRNAs (miRNAs) regulate gene expression by modulating the translation of protein-coding RNAs. Their aberrant expression is involved in various human diseases, including cancer. Here, we summarize the experimental pieces of evidence that proved how dysregulated miRNA expression can lead to RAS (HRAS, KRAS, or NRAS) activation irrespective of their oncogenic mutations. These findings revealed relevant pathogenic mechanisms as well as mechanisms of resistance to target therapies. Based on this knowledge, potential approaches for the control of RAS oncogenic activation can be envisioned

Non-coding RNAs in the reprogramming of glucose metabolism in cancer

Proliferating cancer cells reprogram their metabolic circuitry to thrive in an environment deficient in nutrients and oxygen. Cancer cells exhibit a higher rate of glucose metabolism than normal somatic cells, which is achieved by switching from oxidative phosphorylation to aerobic glycolysis to meet the energy and metabolites demands of tumour progression. This phenomenon, which is known as the Warburg effect, has generated renewed interest in the process of glucose metabolism reprogramming in cancer cells. Several regulatory pathways along with glycolytic enzymes are responsible for the emergence of glycolytic dependence. Non-coding (nc)RNAs are a class of functional RNA molecules that are not translated into proteins but regulate target gene expression. NcRNAs have been shown to be involved in various biological processes, including glucose metabolism. In this review, we describe the regulatory role of ncRNAsâ\u80\u93specifically, microRNAs and long ncRNAsâ\u80\u93in the glycolytic switch and propose that ncRNA-based therapeutics can be used to inhibit the process of glucose metabolism reprogramming in cancer cells

MicroRNAs in Animal Models of HCC

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality. Molecular heterogeneity and absence of biomarkers for patient allocation to the best therapeutic option contribute to poor prognosis of advanced stages. Aberrant microRNA (miRNA) expression is associated with HCC development and progression and influences drug resistance. Therefore, miRNAs have been assayed as putative biomarkers and therapeutic targets. miRNA-based therapeutic approaches demonstrated safety profiles and antitumor efficacy in HCC animal models; nevertheless, caution should be used when transferring preclinical findings to the clinics, due to possible molecular inconsistency between animal models and the heterogeneous pattern of the human disease. In this context, models with defined genetic and molecular backgrounds might help to identify novel therapeutic options for specific HCC subgroups. In this review, we describe rodent models of HCC, emphasizing their representativeness with the human pathology and their usefulness as preclinical tools for assessing miRNA-based therapeutic strategies

Chemoselective Aromatic Azido Reduction With Concomitant Aliphatic Azide Employing Al/gd Triflates/nal And Esi-ms Mechanistic Studies

Aluminium and gadolinium inflates catalyze the chemoselective reduction of aromatic azides to the corresponding amines in combination with sodium iodide. This mild chemoselective method has been applied to the synthesis of various aryl amines, C2azido-substituted pyrrolo[2,1-c]-[1,4]benzodiazepines, and fused[2,1b]quinazolinones by an intramolecular azido reduction tandem cyclization reaction. Interestingly, this methodology selectively reduces aryl azides with enhanced yields and proceeds in shorter reaction times than previous strategies. The mechanistic aspects have been investigated and the intermediates associated with this selective transformation have been intercepted and characterized by online monitoring of the reaction by ESI-MS. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.152972157224Scriven, E.F.V., Turnbull, R., (1988) Chem. Rev, 88, pp. 297-368Bräse, S., Gil, C., Knepper, K., Zimmermann, V., (2005) Angew. Chem, 117, pp. 5320-5374(2005) Angew. Chem. Int. Ed, 44, pp. 5188-5240(1971) The Chemistry of the Azido Group, , Ed, S. Patai, Wiley, New York(1984) Azides and Nitrenes: Reactivity and Utility, , Ed, E. F. V. Scriven, Academic Press, New YorkLarock, R.C., (1989) Comprehensive Organic Transformations: A Guide to Functional Group Preparations, p. 409. , VCH, WeinheimLiu, Q., Tor, Y., (2003) Org. Lett, 5, pp. 2571-2572Rodrigues, J.A.R., Abramovitch, R.A., de Souse, J.D.F., Leiva, G.C., (2004) J. Org. Chem, 69, pp. 2920-2928(1971) The Chemistry of the Azido Group, , Ed, S. Patai, Wiley, New York(1983) The Chemistry of Halides, Pseudo-halides and Azides, Supplement D, , Eds, S. Patai, Z. Rappoport, Wiley, New York(1995) Chemistry of Halides, Pseudo-Halides and Azides, Parti, , Ed, S. Patai, Wiley, New York(1995) Chemistry of Halides, Pseudo-Halides and Azides, Part 2, , Ed, S. Patai, Wiley, New YorkKolb, H.C., Finn, M.G., Sharpless, K.B., (2001) Angew. Chem, 113, pp. 2056-2075(2001) Angew. Chem. Int. Ed, 40, pp. 2004-2021Moses, J.E., Moorhouse, A.D., (2007) Chem. Soc. Rev, 36, pp. 1249-1262Kamal, A., Prabhakar, S., Shankaraiah, N., Reddy, C.R., Reddy, P.V., (2008) Tetrahedron Lett, 49, pp. 3620-3624Kamal, A., Shankaraiah, N., Devaiah, V., Reddy, K.L., Juvekar, A., Sen, S., Kurian, N., Zingde, S., (2008) Bioorg. Med. Chem. Lett, 18, pp. 1468-1473Kumar, H.M.S., Reddy, B.V.S., Anjaneyulu, S., Yadav, J.S., (1999) Tetrahedron Lett, 40, pp. 8305-8306Dove, A., (2001) Nat. Biotechnol, 19, pp. 913-917Mizuno, M., Muramoto, I., Kobayashi, K., Yaginuma, H., Inazu, T., (1999) Synthesis, pp. 162-165Ranu, B.C., Sarkar, A., Chakraborty, R., (1994) J. Org. Chem, 59, pp. 4114-4116. , and references therein;Hays, D.S., Fu, G.C., (1998) J. Org. Chem, 63, pp. 2796-2797Peters, R.G., Warner, B.P., Burns, C.J., (1999) J. Am. Chem. Soc, 121, pp. 5585-5586Boyer, J.H., (1951) J. Am. Chem. Soc, 73, pp. 5865-5866Boyer, J.H., Canter, F.C., (1954) Chem. Rev, 54, pp. 1-57Kyba, E.P., John, A.M., (1977) Tetrahedron Lett, 18, pp. 2737-2740Rao, H.S.P., Siva, P., (1994) Synth. Commun, 24, pp. 549-555Alvarez, S.G., Fisher, G.B., Singavam, B., (1995) Tetrahedron Lett, 36, pp. 2567-2570Molina, P., Diaz, I., Tarraga, A., (1995) Tetrahedron, 51, pp. 5617-5630Kunz, H., Unverzagt, C., (1988) Angew. Chem, 100, pp. 1763-1765(1988) Angew. Chem. Int. Ed. Engl, 27, pp. 1697-1699Corey, E.J., Nicolaou, K.C., Balanson, R.D., Machida, Y., (1975) Synthesis, p. 590591Benati, L., Bencivenni, G., Leardini, R., Minozzi, M., Nanni, D., Scialpi, R., Spagnolo, P., Zanardi, G., (2006) J. Org. Chem, 71, pp. 434-437Benati, L., Bencivenni, G., Leardini, R., Minozzi, M., Nanni, D., Scialpi, R., Spagnolo, P., Zanardi, G., (2006) J. Org. Chem, 71, pp. 5822-5825. , references thereinBalicki, R., (1990) Chem. Ber, 123, pp. 647-648Olah, G.A., Farooq, O., Farnia, S.M.F., Olah, J.A., (1988) J. Am. Chem. Soc, 110, pp. 2560-2565Borujeni, K.P., Massah, A.R., (2006) React. Funct. Polym, 66, pp. 1126-1131Williams, D.B.G., Lawton, M., (2005) Org. Biomol. Chem, 3, pp. 3269-3272Williams, D.B.G., Lawton, M., (2006) Tetrahedron Lett, 47, pp. 6557-6560Terblans, Y.M., Huyser, J., Huyser, M., Green, M.J., Yound, D.A., Sibiya, M.S., (2005) Can. J. Chem, 83, pp. 854-861Firouzabadi, H., Iranpoor, N., Kohmareh, G., (2003) Synth. Commun, 33, pp. 167-173Firouzabadi, H., Iranpoor, N., Sobhani, S., Ghassamipour, S., (2005) Synthesis, pp. 595-599Kunioka, M., Inuzuka, Y., Ninomiya, F., Funabashi, M., (2006) Macromol. Biosci, 6, pp. 517-523Kamal, A., Khan, M.N.A., Reddy, K.S., Srikanth, Y.V.V., Krishnaji, T., (2007) Tetrahedron Lett, 48, pp. 3813-3818Kamal, A., Ramana, K.V., Ankati, H.B., Ramana, A.V., (2002) Tetrahedron Lett, 43, pp. 6861-6863Bartoli, G., Antonio, G.D., Giovannini, R., Giuli, S., Lanari, S., Paoletti, M., Marcantoni, E., (2008) J. Org. Chem, 73, pp. 1919-1924Whitehouse, C.M., Dreyer, R.N., Yamashita, M., Fenn, J.B., (1985) Anal. Chem, 57, pp. 675-679Fenn, J.B., Mann, M., Meng, C.K., Wong, S.F., Whitehouse, C.M., (1989) Science, 246, pp. 64-71Cole, R.B., (1997) Electrospray Ionization Mass Spectroscopy, , Wiley, New YorkCooks, R.G., Zhang, D.X., Koch, K.J., Gozzo, F.C., Eberlin, M.N., (2001) Anal. Chem, 73, pp. 3646-3655Takats, Z., Nanita, S.C., Cooks, R.G., (2003) Angew. Chem, 115, pp. 3645-3647(2003) Angew. Chem. Int. Ed, 42, pp. 3521-3523Santos, L.S., DaSilveira, B.A., Consorti, C.S., Pavam, C.H., Almeida, W.P., Coelho, F., Dupont, J., Eberlin, M.N., (2006) J. Phys. Org. Chem, 19, pp. 731-736Koch, K.J., Gozzo, F.C., Nanita, S.C., Takats, Z., Eberlin, M.N., Cooks, R.G., (2002) Angew. Chem, 114, pp. 1797-1800(2002) Angew. Chem. Int. Ed, 41, pp. 1721-1724Meurer, E.C., Sabino, A.A., Eberlin, M.N., (2003) Anal. Chem, 75, pp. 4701-4709Cooks, R.G., Zhang, D.X., Koch, K.J., Gozzo, F.C., Eberlin, M.N., (2001) Anal. Chem, 73, pp. 3646-3655Griep-Raming, J., Meyer, S., Bruhn, T., Metzger, J.O., (2002) Angew. Chem, 114, pp. 2863-2866(2002) Angew. Chem. Int. Ed, 41, pp. 2738-2742Sabino, A.A., Machado, A.H.L., Correia, C.R.D., Eberlin, M.N., (2004) Angew. Chem, 116, pp. 2568-2572(2004) Angew. Chem. Int. Ed, 43, pp. 2514-2518Meyer, S., Metzger, J.O., (2003) Anal. Bioanal. Chem, 377, pp. 1108-1114Domingos, J.B., Longhinotti, E., Brandão, T.A.S., Santos, L.S., Eberlin, M.N., Bunton, C.A., Nome, F., (2004) J. Org. Chem, 69, pp. 7898-7905Domingos, J.B., Longhinotti, E., Brandão, T.A.S., Bunton, C.A., Santos, L.S., Eberlin, M.N., Nome, F., (2004) J. Org. Chem, 69, pp. 6024-6033Santos, L.S., (2008) Eur. J. Org. Chem, pp. 235-253Santos, L.S., Knaack, L., Metzger, J.O., (2008) Int. J. Mass Spectrom, 246, pp. 84-104Chen, P., (2003) Angew. Chem, 115, pp. 2938-2954(2003) Angew. Chem. Int. Ed, 42, pp. 2832-2847Kamal, A., Shankaraiah, N., Markandeya, N., Reddy, S.C., (2008) Synlett, pp. 1297-1300Kamal, A., Shankaraiah, N., Markandeya, N., Reddy, K.L., Reddy, S.C., (2008) Tetrahedron Lett, 49, pp. 1465-1468Kamal, A., Shankaraiah, N., Reddy, K.L., Devaiah, V., (2006) Tetrahedron Lett, 47, pp. 4253-4257Kamal, A., Reddy, K.L., Reddy, G.S.K., Reddy, B.S.N., (2004) Tetrahedron Lett, 45, pp. 3499-3501Kamal, A., Reddy, P.S.M.M., Reddy, D.R.S., (2002) Tetrahedron Lett, 43, pp. 6629-6631Kamal, A., Prasad, B.R., Khan, M.N.A., (2007) J. Mol. Catal. A, 274, pp. 133-136Kamal, A., Ramana, K.V., Rao, M.V., (2001) J. Org. Chem, 66, pp. 997-1001Hurley, L.H., (1977) J. Antibiot, 30, pp. 349-370Hurley, L.H., (1989) J. Med. Chem, 32, pp. 2027-2033Thurston, D.E., Thompson, A.S., (1990) Chem. Ber, 123, pp. 767-772Konishi, M., Ohkuma, H., Naruse, N., Kaqaguchi, H., (1984) J. Antibiot, 37, p. 200Takeuchi, T., Miyanoto, M., Ishizuka, M., Naganawa, H., Kondo, S., Hamada, M., Umezawa, H., (1976) J. Antibiot, 29, p. 93Hochlowski, J.E., Andres, W.W., Theriault, R.J., Jackson, M., MeAlpine, J.B., (1987) J. Antibiot, 40, p. 145Arima, K., Kohsaka, M., Tamura, G., Imanaka, H., Sakai, H., (1972) J. Antibiot, 25, p. 437Kamal, A., Reddy, K.L., Devaiah, V., Shankaraiah, N., Reddy, G.S.K., Raghavan, S., (2007) J. Comb. Chem, 9, pp. 29-42Kamal, A., Reddy, K.L., Devaiah, V., Shankaraiah, N., Rao, M.V., (2006) Mini-Rev. Med. Chem, 6, pp. 69-87Kamal, A., Shankaraiah, N., Prabhakar, S., Reddy, R.C., Markandeya, N., Reddy, K.L., Devaiah, V., (2008) Bioorg. Med. Chem. Lett, 18, pp. 2434-2439Kamal, A., Shankaraiah, N., Reddy, K.L., Devaiah, V., Juvekar, A., Sen, S., (2007) Lett. Drug Des. Discovery, 4, pp. 596-604Kamal, A., Khan, N.A., Reddy, K.S., Ahmed, S.K., Kumar, M.S., Juvekar, A., Sen, S., Zingde, S., (2007) Bioorg. Med. Chem. Lett, 17, pp. 5345-5348Shoji, E., Toshio, S., Tomohiro, O., Yuji, M., (1996) J. Org. Chem, 61, pp. 7316-7319Tadamasa, O., (1971) Tetrahedron Lett, 12, pp. 4387-4389Thurston, D.E., Bose, D.S., (1994) Chem. Rev, 94, pp. 433-465Kamal, A., Rao, M.V., Reddy, B.S.N., (1998) Khim. Getero. Seod, p. 1588Kamal, A., Rao, N.V., (1996) Chem. Commun, pp. 385-386Kamal, A., Shankaraiah, N., Devaiah, V., Reddy, K.L., (2006) Tetrahedron Lett, 47, pp. 9025-9028Kamal, A., Devaiah, V., Shankaraiah, N., Reddy, K.L., (2006) Synlett, 2, pp. 2609-2612Amin, A.H., Mehta, D.R., (1959) Nature, 184, p. 1317Al-Shamma, A., Drake, S., Flynn, D.L., Mitscher, L.A., Park, Y.H., Rao, G.S.R., Simpson, A., Wu, S.T.S., (1981) J. Nat. Prod, 44, pp. 745-747Grange, J.M., Snell, N.J., (1996) J/. Ethnopharmacol, 49, p. 5091Santos, L.S., Pavam, C.H., Almeida, W.P., Coelho, F., Eberlin, M.N., (2004) Angew. Chem, 116, pp. 4430-4433(2004) Angew. Chem. Int. Ed, 43, pp. 4330-4333Ferraz, H.M.C., Pereira, F.L.C., Goncalo, E.R.S., Santos, L.S., Eberlin, M.N., (2005) J. Org. Chem, 70, p. 110114Dalmazio, I., Santos, L.S., Lopes, R.P., Eberlin, M.N., Augusti, R., (2005) Environ. Sci. Technol, 39, pp. 5982-5988Moura, F.C.C., Araujo, M.H., Dalmazio, I., Alves, T.M.A., Santos, L.S., Eberlin, M.N., Augusti, R., Lago, R.M., (2006) Rapid Commun. Mass Spectrom, 20, pp. 1859-1863Milagre, C.D.F., Milagre, H.M.S., Santos, L.S., Lopes, M.L.A., Moran, P.J.S., Eberlin, M.N., Rodrigues, J.A.R., (2007) J. Mass Spectrom, 42, pp. 1287-1293Meurer, E.C., Santos, L.S., Pilli, R.A., Eberlin, M.N., (2003) Org. Lett, 5, pp. 1391-1394Meurer, E.C., Rocha, L.L., Pilli, R.A., Eberlin, M.N., Santos, L.S., (2006) Rapid Commun. Mass Spectrom, 20, pp. 2626-2629Santos, L.S., Metzger, J.O., (2006) Angew. Chem, 118, pp. 991-995(2006) Angew. Chem. Int. Ed, 45, pp. 977-981Raminelli, C., Prechtl, M.H.G., Santos, L.S., Eberlin, M.N., Comasseto, J.V., (2004) Organometallics, 23, pp. 3990-3996Santos, L.S., Cunha, R.L.O.R., Comasseto, J.V., Eberlin, M.N., (2007) Rapid Commun. Mass Spectrom, 21, pp. 1479-1484Santos, L.S., Rosso, G.B., Pilli, R.A., Eberlin, M.N., (2007) J. Org. Chem, 72, pp. 5809-5812Abella, C.A.M., Benassi, M., Santos, L.S., Eberlin, M.N., Coelho, F., (2007) J. Org. Chem, 72, pp. 4048-4054Cenini, S., La Monica, G., (1976) Inorg. Chim. Acta, 18, p. 279Kwart, H., Khan, A.A., (1967) J. Am. Chem. Soc, 89, p. 1951It has been demonstrated that either ArSO2N=IPh-metal or nitrenoid-metal species participates in the sulfimidation using ArSO 2N= IPh as the precursor: C. Ohta, T. Katsuki, Tetrahedron Lett. 2001, 42, 3885-3888Zdilla, M.J., Abu-Omar, M.M., (2006) J. Am. Chem. Soc, 128, pp. 16971-16979Cenini, S., Tollari, S., Penoni, A., Cereda, C., (1999) J. Mol. Catal. A, 137, pp. 135-146Ragaini, F., Penoni, A., Gallo, E., Tollari, S., Gotti, C.L., Lapadula, M., Mangioni, E., Cenini, S., (2003) Chem. Eur. J, 9, pp. 249-259Lai, T.-S., Kwong, H.-L., Che, C.-M., Peng, S.-M., (1997) Chem. Commun, pp. 2373-2374Thurston, D.E., Murty, V.S., Langley, D.R., Jones, G.B., (2009) Synthesis, pp. 81-8