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Impact of relatively new chemotherapeutic agents on the outcome of Egyptian patients with advanced malignant pleural mesothelioma

Abstract

Purpose: Patients with malignant pleural mesothelioma (MPM) are well known to have poor response to chemotherapy. The aim of this work was to evaluate the efficacy and safety of new chemotherapeutic agents for the treatment of Egyptian MPM patients.

Patients and methods: The first study was a non-randomised, open-label trial. It included 34 eligible patients who were assigned to receive either cisplatin–pemetrexed or pemetrexed alone if cisplatin was contraindicated for a maximum of eight cycles. In the second trial, 21 chemo-naive patients with histologically proven advanced MPM were included. They received cisplatin and raltitrexed for a maximum of six cycles.

Results: In the first trial, the median age was 43.5 years (range 25–69), partial response (PR) was achieved in 37.5%, stable disease (SD) in 50%. Median time to progression (TTP) and overall survival (OS) were 7 and 14 months, respectively. Survival at 1 year was 64.7%. No toxicity was observed in 17.6% of patients and grade 3–4 toxicity was evident in 11.8% (neutropenia), 8.8% (anaemia) and 2.9% (vomiting and diarrhoea) of patients. In the second trial, median age was 46 years (range 19–71), PR was achieved in 23.2% and one CR was reported. SD was noticed in 61.9% of patients. Median TTP and OS were 6 and 12 months, respectively. Survival at 1 year was 51.6%.

Conclusion: Both cisplatin–pemetrexed and cisplatin–raltitrexed are effective and safe regimens in the treatment of MPM.

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In Vitro Antimicrobial Activities of 6-Substituted-3(2H)- pyridazinone-2-acetyl-2- (substituted/nonsubstitutedbenzal/ acetophenone) Hydrazone Derivatives

Abstract

Aim: In vitro antibacterial activity of 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(substituted/nonsubstitutedbenzal/ acetophenone) hydrazone derivatives were tested in common species causing hospital-acquired infections. Material and Method: Antimicrobial activities of the compounds were performed by determining minimum inhibitory concentration (MIC) value against four Gram-positive, five Gram-negative and four Candida species fungi. Modified serial microdilution method was carried out. Reference strains of American Type Culture Collection (ATCC) were used. Results: In general, eleven compounds exhibited considerable activity. Comparatively, compound 3 exhibited strong activity against Enterobacter hormaechei and 5, 11 were the most active against Acinetobacter baumannii at 31.25 μg/mL. Compounds 1,2,3,4,8 and 10 were found to be as active as positive control ampicillin trihidrate against Stenotrophomonas maltophilia. On the other hand, compounds 1,2,3,4,7,8,9,10 and 11 showed strong antifungal activitiy as much as fluconazole against Candida tropicalis. Compound 1 was mostly active against Candida albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis. It was also revealed that the antifungal activity of compounds 1, 6, 7, 8 and 9 were higher than the others. Compound 1 and 8 exhibited the best activity against Candida glabrata and Candida parapsilosis respectively. Conclusions: All tested compounds showed better activity against Gram-negative bacteria and yeast than Gram-positive bacteria. These compounds may be considered as alternative antimicrobial agents in the treatment of multiple drug resistant Gram-negative, Gram-positive bacteria and fungal pathogens. Especially, we suggested that Compound 1 and 8 might be a promising candidate of new antifungal agents

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Occurrence of Veterinary Antibiotics and Chemotherapeutics in Fresh Water, Sediment, and Fish of the Rivers and Lakes in Poland

Abstract

The occurrence of commonly used veterinary antimicrobial agents was investigated in 159 fresh water, 443 fish, and 150 sediment samples from Polish rivers and lakes. The agents included aminoglycosides, ß-lactams, diaminopyrimidines, fluoroquinolones, lincosamides, macrolides, pleuromutilins, sulfonamides, and tetracyclines. The analysis was performed by three different sample preparation procedures for each matrix and it was performed by liquid chromatography-tandem mass spectrometry with electrospray ionisation source in positive mode, under the same conditions. All analytical methods used were validated and showed good sensitivity, accuracy, and precision. The LOQ was in the range from 5 μg/kg to 125 μg/kg for fish samples, from 0.02 μg/L to 10 μg/L for fresh water samples, and from 1 μg/kg to 8 μg/kg for sediment samples.

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Osteonecrosis of the Jaws in Patients Receiving Anti-Angiogenic Drugs and Chemotherapeutics: Literature Review and Case Reports

Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is a relatively rare but serious pathology associated with the use of bisphosphonates (BPs) and antiresorptive drugs in patients with bone metastases, multiple myeloma and osteoporosis. Various cases of patients with jaw bone necrosis due to BPs have recently been reported in the literature. Anti-angiogenic drugs are novel anticancer agents prescribed to patients with renal carcinoma, lung carcinoma, soft tissue metastases, etc. Anti-angiogenic drugs target the vascular endothelial growth factor’s (VEGF) signaling pathways via different mechanisms and thus inhibit tumor cell proliferation, neoangiogenesis and tumor growth. Several reports have suggested a higher incidence of MRONJ in patients treated with BPs in combination with anti-angiogenic drugs. However, there is currently no sufficient data in the literature about the risk of ONJ in patients taking anti-angiogenic drugs or cancer chemotherapy alone. We present two clinical cases of osteonecrosis of the jaw in patients treated with chemotherapy, but no history of BPs. In the first case the necrosis is related to the anti-angiogenic agent sunitinib in a patient with lung metastases and in the second case- to complex chemotherapy in a patient with acute myeloid leukemia. We recommend conservative treatment with antibiotics in both cases, together with antiseptics and surgical removal of the necrotic bone following total demarcation of the sequesters.

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Electrochemotherapy in pancreatic adenocarcinoma treatment: pre-clinical and clinical studies

Introduction Pancreatic adenocarcinoma, despite extensive research, remains one of the deadliest cancers with high mortality rate. Surgical resection represents the only curative treatment for this pathology, but the majority of the patients are incurable at initial presentation with metastatic (stage IV) or surgically non-resectable disease (stage III disease). 1 – 3 At present gemcitabine and paclitaxel (Abraxane) are the best chemotherapeutic agents used for treatment of pancreatic cancer, however, patients develop drug resistance over the time. Thus

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Cisplatin-induced non-convulsive posterior reversible encephalopathy syndrome in a 41-year-old woman with metastatic malignant melanoma

References New PZ. Neurological complications of chemotherapeutic and biological agents. Continuum: lifelong learning in neurology. Neuro-Oncol 2005; 11(5): 116-152. Kaplan RS, Wiernik PH. Neurotoxicity of antineoplastic drugs. Sem Oncol 1982; 9: 103-30. Lyass O, Lossos A, Hubert A, Gips M, Peretz T. Cisplatin-induced non-convulzive encephalopathy. Anticancer Drugs 1998; 9: 100-4. Berman IJ, Mann MP. Seizures and transient cortical blindness

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Feasibility and safety of electrochemotherapy (ECT) in the pancreas: a pre-clinical investigation

, Büchler MW. Acquired resistance of pancreatic cancer cells towards 5-Fluorouracil and gemcitabine is associated with altered expression of apoptosis-regulating genes. Oncology 2002; 62: 354-62. 19. Arumugam T, Ramachandran V, Fournier KF, Wang H, Marquis L, Abbruzzese JL, et al. Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer. Cancer Res 2009; 69: 5820-8. 20. Tamburrin o A, Piro G, Carbone C, Tortora G, Melisi D. Mechanisms of resistance to chemotherapeutic and anti-angiogenic drugs as novel

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Enhanced cytotoxicity of bleomycin and cisplatin after electroporation in murine colorectal carcinoma cells

-13. Kuriyama S, Matsumoto M, Mitoro A, Tsujinoue H, Nakatani T, Fukui H, et al. Electrochemotherapy for colorectal cancer with commonly used chemotherapeutic agents in a mouse model. Dig Dis Sci 2000; 45: 1568-77. Kuriyama S, Tsujinoue H, Toyokawa Y, Mitoro A, Nakatani T, Yoshiji H, et al. A potential approach for electrochemotherapy against colorectal carcinoma using a clinically available alternating current system with bipolar snare in a mouse model. Scand J Gastroenterol 2001; 36: 297-302. Cemazar M, Miklavcic D

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Microsatellite instability in colorectal cancer

, Paterini P, et al. High tymidylate synthase expression in colorectal cancer with microsatellite instability: implications for chemotherapeutic strategies. Clin Cancer Res 2005; 11 : 4234-40. Tajima A, Hess MT, Cabrera BL, Kolodner RD, Carethers JM. The mismatch repair complex hMutS alpha recognizes 5-flourouracil modified DNA: implications for chemosensitivity and resistance. Gastroenterology 2004; 127 : 1678-84. Carethers JM, Chauhan DP, Fink D, Nebel S, Bresalier RS, Howell SB, et al. Mismatch repair proficiency

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Nanotechnology for treatment of glioblastoma multiforme

function that makes GBM highly aggressive. More importantly, these nanomaterials can be used to deliver chemotherapeutic agents specifically to the tumor tissues without causing systemic toxicity. BBB penetration through EPR effect The inability to cross the BBB in known standard chemotherapy options is the major obstacle in achieving remission after surgical resection followed by chemotherapy that is often combined with radiation. The BBB is formed by a single layer of endothelial cells that are bound by tight junctions and is the main defense of keeping exogenous

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