Effects of combination drug therapy on the subcutaneous and pulmonary growth of a slow and a fast-growing C3H/He mammary carcinoma

Changes in susceptibility to treatment with Cytoxan, methotrexate, 5-fluorouracil, and Adriamycin, single or in combination, have been studied during the initial and progressive stages of s.c. and pulmonary (via tail vein injection) growth of two transplanted syngeneic C3H/He mammary carcinomas. One tumor was fast growing, reaching a size of 3 mm from a 1-mm s.c. implant in 7 days; the second tumor would grow to the same size in 30 days. The tumor with the slower growth rate was more susceptible to drug treatment, manifested by delayed growth as well as by prevented growth. The slower-growing tumor also remained susceptible longer, when treatment was delayed, than did the faster-growing tumor. Pulmonary growth was more often prevented by drug treatment than was s.c. growth. Tumor implants s.c. which had reached palpable size could be reduced temporarily to impalpable size by effective drug treatment but were rarely cured. The importance of early treatment relative to the time of tumor implantation was indicated when early treatment with a single drug proved more effective than did delayed treatment with a more potent combination of drugs

A systematic review of naturalistic interventions in refugee populations

Naturalistic interventions with refugee populations examine outcomes following mental health interventions in existing refugee service organisations. The current review aimed to examine outcomes of naturalistic interventions and quality of the naturalistic intervention literature in refugee populations with the view to highlight the strengths and limitations of naturalistic intervention studies. Database search was conducted using the search terms ‘refugee’, ‘asylum seeker’, ‘treatment’, ‘therapy’ and ‘intervention. No date limitations were applied, but searches were limited to articles written in English. Seven studies were identified that assessed the outcome of naturalistic interventions on adult refugees or asylum seekers in a country of resettlement using quantitative outcome measures. Results showed significant variation in the outcomes of naturalistic intervention studies, with a trend towards showing decreased symptomatology at post-intervention. However, conclusions are limited by methodological problems of the studies reviewed, particularly poor documentation of intervention methods and lack of control in the design of naturalistic intervention studies. Further examination of outcomes following naturalistic interventions is needed with studies which focus on increasing the rigour of the outcome assessment process

Prediction of martensite start temperature by neural network analysis

Commercial steels are nowadays sophisticated alloys formed by a large number of alloying elements. The martensite start ( Ms) temperature of such steels is of vital engineering importance, and its prediction through models allows us to enhance the design and development of industrial products. In the present work, Ms temperature dependence on chemical composition has been examined by neural network analysis. Neural networks represent powerful methods of non-linear regression modelling. The network is a mathematical function which is fitted to experimental data. The influence of alloying elements such as C, Mn, Si, Cr, Ni, Mo, V, Co, W, Al, Nb, Cu, B and N on Ms temperature was analysed. Finally, a new empirical equation for Ms temperature was derived based on the neural network results.Peer Reviewe

The effect of a low molecular weight inhibitor of lipid peroxidation on ultrastructural alterations to ischemia-reperfusion in the isolated rat heart

The effects of H290/51, a novel indenoindole derivative inhibitor of lipid peroxidation, on ultrastructural changes during cardiac ischemia-reperfusion injury were investigated. Langendorff-perfused rat hearts were exposed to 30 minutes of global ischemia followed by 20 minutes of reperfusion: Group A: Control hearts with standard buffer perfusion with vehicle added. Group B: H290/51 (10-6 mol/l) added to buffer throughout stabilisation and reperfusion. In an additional Group C, where hearts were given H290/51, but not subjected to ischemia, the ultrastructure was preserved till the end of reperfusion. Absolute volumes and calculated volume fractions (Vv) of tissue and subcellular components were assessed with quantitative stereologic morphometry. After ischemia the increase in volume of extracellular interstitium was inhibited by H290/51 (247±80 vs. 159±50ml, mean±SD, groups A and B, respectively, p<0.05). The Vv (interstitium/myocard) was higher in control hearts (0.318±0.062 vs. 0.206±0.067, p<0.05). Vv (cell edema/myocyte) was higher in the control group (0.144±0.07 vs. 0.083±0.033, p<0.05). Vv (myocyte/myocard) was higher in group B after ischemia than in the control group (0.622±0.071 vs. 0.707±0.052, p<0.05). The decreased Vv (capillary/myocard) after ischemia was inhibited by H290/51. After reperfusion there was no difference between groups. Treatment with H290/51 reduced edema and ensured better preserved sarcolemmal membrane structure during ischemia. The effect was no longer present after reperfusion.

Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial

BACKGROUND: The MITO-2 (Multicentre Italian Trials in Ovarian cancer) study is a randomized phase III trial comparing carboplatin plus paclitaxel to carboplatin plus pegylated liposomal doxorubicin in first-line chemotherapy of patients with ovarian cancer. Due to the paucity of published phase I data on the 3-weekly experimental schedule used, an early safety analysis was planned. METHODS: Patients with ovarian cancer (stage Ic-IV), aged < 75 years, ECOG performance status ≤ 2, were randomized to carboplatin AUC 5 plus paclitaxel 175 mg/m(2), every 3 weeks or to carboplatin AUC 5 plus pegylated liposomal doxorubicin 30 mg/m(2), every 3 weeks. Treatment was planned for 6 cycles. Toxicity was coded according to the NCI-CTC version 2.0. RESULTS: The pre-planned safety analysis was performed in July 2004. Data from the first 50 patients treated with carboplatin plus pegylated liposomal doxorubicin were evaluated. Median age was 60 years (range 34–75). Forty-three patients (86%) completed 6 cycles. Two thirds of the patients had at least one cycle delayed due to toxicity, but 63% of the cycles were administered on time. In most cases the reason for chemotherapy delay was neutropenia or other hematological toxicity. No delay due to palmar-plantar erythrodysesthesia (PPE) was recorded. No toxic death was recorded. Reported hematological toxicities were: grade (G) 3 anemia 16%, G3/G4 neutropenia 36% and 10% respectively, G3/4 thrombocytopenia 22% and 4% respectively. Non-haematological toxicity was infrequent: pulmonary G1 6%, heart rhythm G1 4%, liver toxicity G1 6%, G2 4% and G3 2%. Complete hair loss was reported in 6% of patients, and G1 neuropathy in 2%. PPE was recorded in 14% of the cases (G1 10%, G2 2%, G3 2%). CONCLUSION: This safety analysis shows that the adopted schedule of carboplatin plus pegylated liposomal doxorubicin given every 3 weeks is feasible as first line treatment in ovarian cancer patients, although 37% of the cycles were delayed due to haematological toxicity. Toxicities that are common with standard combination of carboplatin plus paclitaxel (neurotoxicity and hair loss) are infrequent with this experimental schedule, and skin toxicity appears manageable

Investigation into the Role of Tumor-Associated Macrophages in the Antitumor Activity of Doxil

Purpose. Our recent studies show specific localization of long-circulating liposomes (LCL) within the endosomal/lysosomal compartment of tumor-associated macrophages (TAM). Based on this finding, the present study aims to investigate whether clinically applied LCL formulations such as Doxil (LCLencapsulated doxorubicin), have alternative mechanisms of action additionally to direct drug-mediated cytotoxicity towards tumor cells. Methods. The antitumor activity of Doxil was evaluated in B16.F10 melanoma-bearing mice, in the presence and in the absence of TAM. To suppress TAM functions, liposomal clodronate (Lip-CLOD) was injected 24 h before the actual treatment. The effect of Doxil on the levels of angiogenic factors was determined using an angiogenic protein array. As positive control, the same experiments were conducted with LCL-encapsulated prednisolone phosphate (LCL-PLP), a tumor-targeted formulation with known strong anti-angiogenic/anti-inflammatory effects on TAM. Results. Our results show that the antitumor efficacy of Doxil was only partially attributed to the inhibition of TAM-mediated angiogenesis whereas LCL-PLP inhibited tumor growth through strong suppressive effects on pro-angiogenic functions of TAM. As described previously, the main mechanism of Doxil might be a cytotoxic effect on tumor cells. Conclusions. Our findings suggest that the antitumor activity of Doxil does not depend mainly on the presence of functional TAM in tumors