https://novaprd-lb.newcastle.edu.au/vital/access/manager/Index ${session.getAttribute("locale")} 5 https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:24157 Wed 11 Apr 2018 14:20:24 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:24380 Thu 24 Mar 2022 11:34:21 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:7152 Sat 24 Mar 2018 08:34:15 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:1259 Sat 24 Mar 2018 08:32:47 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:989 Sat 24 Mar 2018 08:29:49 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:2497 1.1, additivity by a CI between 0.9 and 1.1, and synergism by a CI<0.9. Results: Both cell lines were equally sensitive to cantharidin alone (GI50 values 5.4 and 7.3 mgrM), which induced a significant increase in the S-phase population of both cell lines within 6 h with a concomitant increase in DNA synthesis. This response culminated in G2/M cell cycle arrest within 24 h and subsequent cell death. In response to nolatrexed alone, HT29 cells were more sensitive than HCT116 cells (GI50 1.9 mgrM vs 9.8 mgrM), with G1/S-phase cell cycle arrest occurring within 24 h in both cell lines. In HT29 cells, this was followed by cell death, whereas in HCT116 cells, a proportion of cells died following arrest but the predominant event was re-entry into the cell cycle. The simultaneous exposure of HT29 cells to the combination of nolatrexed and cantharidin in drug molar ratios of 1:1 and 1:2.5 for 72 h was synergistic producing composite CIs of 0.88 and 0.87, respectively. The sequence of nolatrexed followed by cantharidin 24 h later resulted in greater synergism (CI values of 0.75, 0.52, 0.55, 0.68 for molar ratios of 10:1, 1:1, 1:2.5, 1:10), whereas the reverse sequence was antagonistic, suggesting that the point of interaction is downstream of TS inhibition. In HCT116 cells only additive and antagonistic interactions were observed for any of the treatment combinations. The lack of synergism in these cells may be caused by the reduced sensitivity of these cells to nolatrexed as a single agent. Conclusion: The effect of TS inhibition can be enhanced by the inhibition of serine/threonine protein phosphatases.]]> Sat 24 Mar 2018 08:27:43 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:1773 1000 μM. Analogues possessing good PP1 and/or PP2A inhibition also returned moderate to good anti-cancer activity. Analogues with substituents directly attached to the intact bicyclo[2.2.1]heptane skeleton were poor to moderate anti-cancer agents. This correlates well with their lack of PP1 or PP2A activity. Analogues capable of undergoing a facile ring opening of the anhydride or with a single carboxylate were good PP1 and PP2A inhibitors, largely correlating to the observed anti-cancer activity in all cases, except 11. Analogue 11, whist neither a PP1 nor a PP2A inhibitor shows anti-cancer activity comparable to 1 and 2. We believe that intracellular esterases generate the corresponding dicarboxylate, which is a potent PP1 and PP2A inhibitor, and that it is this species which is responsible for the observed anti-cancer activity.]]> Sat 24 Mar 2018 08:27:36 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:12336 Sat 24 Mar 2018 08:15:52 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:12335 Sat 24 Mar 2018 08:15:52 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:13278 2 twice daily for 14 of every 21 days; n = 107) or continuously (650 mg/m² twice daily for 21 of every 21 days; n = 107), or to classical CMF (oral cyclophosphamide 100 mg/m² days 1 to 14 with intravenous methotrexate 40 mg/m² and fluorouracil 600 mg/m² on days 1 and 8 every 28 days; n = 109). The primary end point was quality-adjusted progression-free survival (PFS); secondary end points included PFS, overall survival (OS), objective tumor response, and adverse events. Intermittent and continuous capecitabine were to be compared first and, if similar (P > .05), combined for definitive comparisons versus CMF. Results: Quality-adjusted PFS (P = .2), objective tumor response rate (20%; P = .8), and PFS (median, 6 months; hazard ratio [HR], 0.86; 95% CI, 0.67 to 1.10; P = .2) were similar in women assigned capecitabine versus CMF. OS was longer in women assigned capecitabine rather than CMF (median, 22 v 18 months; HR, 0.72; 95% CI, 0.55 to 0.94; P = .02). Febrile neutropenia, infection, stomatitis, and serious adverse events were more common with CMF; hand-foot syndrome was more common with capecitabine. Conclusion: Capecitabine improved OS by being similarly active, less toxic, and more tolerable than CMF. Capecitabine is a good first-line chemotherapy option for women with advanced breast cancer who are unsuited to more intensive regimens.]]> Sat 24 Mar 2018 08:15:16 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:12304 50 values between 0.23 and 7.6 μM. Addition of pyridoxine at concentrations of 1–25 μM does not affect OHP cytotoxicity. Conclusions: Administration of pyridoxine, at concentrations extending across possible therapeutic plasma levels in humans, does not antagonise OHP antitumour effects in a range of relevant tumour cell lines. This study provides a foundation for clinical studies to test whether pyridoxine can minimise OHP-related neurotoxicity, and clinicians can be confident that pyridoxine is very unlikely to reverse the antitumour effects of OHP, as seems to be the case with Ca/Mg infusions. This could prove to be a cost-effective way to minimise OHP-related neurotoxicity, allowing more effective less toxic treatment and better outcomes in patients.]]> Sat 24 Mar 2018 08:11:35 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:10494 Sat 24 Mar 2018 08:08:58 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:5130 Sat 24 Mar 2018 07:48:56 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:3264 Sat 24 Mar 2018 07:21:22 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:3263 Sat 24 Mar 2018 07:21:22 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:3265 Sat 24 Mar 2018 07:21:21 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:22369 Sat 24 Mar 2018 07:09:29 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:26139 Mon 23 Sep 2019 13:37:57 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:48509 2 with filgrastim support every 3 weeks for 3 cycles (HDEC) or standard dose epirubicin 75 mg/m² and cyclophosphamide 750 mg/m² every 3 weeks for 6 cycles (SDEC). Primary outcomes were time to progression, overall survival and quality of life. Results: In 118 patients allocated HDEC 90% of the planned dose was delivered, compared to 96% in the 117 participants allocated SDEC. There were no significant differences in the time to disease progression (5.7 vs. 5.8 months, P = 0.19) or overall survival (14.5 vs. 16.5 months, P = 0.29) between HDEC and SDEC, respectively. Patients on HDEC reported worse quality of life during therapy, but scores improved after completion to approximate those reported by patients allocated SDEC. Objective tumour response was recorded in 33 (28%) on HDEC and 42 patients (36%) on SDEC. HDEC produced more haematologic toxicity. Conclusion: For women with metastatic breast cancer, disease progression, survival or quality of life were no better with high-dose intensity compared to standard dose EC chemotherapy. Australian Clinical Trials Registry registration number ACTRN12605000478617.]]> Mon 20 Mar 2023 16:24:14 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:20065 Fri 21 Aug 2015 13:38:26 AEST ]]>