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A Phase I Clinical Study on the Hepatic Uptake, Pharmacokinetics, Safety and Tolerance of a New Oral Pentamidine Formulation in Hepatocellular Carcinoma Subjects Undergoing Thermal Ablation

The purpose of this study is to investigate on the Hepatic Uptake, Pharmacokinetics, Safety and Tolerance of a New Oral Pentamidine Formulation in Hepatocellular Carcinoma Subjects Undergoing Thermal Ablation

开始日期2014-08-01

申办/合作机构

Verlyx Pharma, Inc.

EUCTR2012-001812-50-PL / Not yet recruitingN/A

A Phase IIa Exploratory Study of OCZ103-OS in Combination with Platinum-Gemcitabine based Doublet First Line Therapy in Stage IV Non-Small Cell Lung Cancer (NSCLC) Patients

开始日期2012-09-18

申办/合作机构

Verlyx Pharma, Inc.

NCT01844791 / Completed临床2期

A Phase IIa Exploratory Study of OCZ103-OS in Combination With Platinum-Gemcitabine Based Doublet First Line Therapy in Stage IV Non-Small Cell Lung Cancer (NSCLC) Patients

The purpose of this study is to investigate the safety and efficacy of the use of OCZ103-OS in combination with Platinum-Gemcitabine based doublet first line therapy in stage IV non-small cell lung cancer (NSCLC) patients.

开始日期2012-09-01

申办/合作机构

Verlyx Pharma, Inc.

100 项与 Verlyx Pharma, Inc. 相关的临床结果

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0 项与 Verlyx Pharma, Inc. 相关的专利（医药）

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4

项与 Verlyx Pharma, Inc. 相关的文献（医药）

2015-07-01·International Journal of Pharmaceutics2区 · 医学

Development of a liposome formulation for improved biodistribution and tumor accumulation of pentamidine for oncology applications

2区 · 医学

Article

作者: De Souza, Raquel ; Allen, Christine ; Ekdawi, Sandra N ; Dou, Yannan ; Ravenelle, François ; Mérian, Juliette

Pentamidine isethionate, widely used for the treatment of parasitic infections, has shown strong anticancer activity in cancer cells and models of melanoma and lung cancer. Systemic administration of pentamidine is associated with serious toxicities, particularly renal, affecting as many as 95% of patients (O'Brien et al., 1997). This work presents the development of a liposome pentamidine formulation for greater tumor accumulation and lower drug exposure to vulnerable tissues. Liposomes formulated with saturated/unsaturated phospholipids of different chain lengths, varying cholesterol content, and surface PEG were explored to understand the effects of such variations on drug release, encapsulation efficiency, stability and in vivo performance. Saturated phospholipids with longer chain lengths, higher cholesterol content and PEG resulted in greater stability. The optimal formulation obtained showed significantly lower clearance rate (3.6 ± 1.2 mL/h/Kg) and higher AUC0-inf (348 ± 31 μmol/L × h) in vivo when compared to free drug (414 ± 138 mL/h/Kg and 2.58 ± 0.74 μmol/L × h, respectively). In tumor-bearing mice, liposomal delivery decreased kidney drug levels by up to 5-fold at 6 and 24h post-administration. Tumor drug exposure was up to 12.7-fold greater with liposomal administration compared to free drug. Overall, the liposomal pentamidine formulation developed has significant potential for the treatment of solid tumors.

2005-04-01·Future Oncology4区 · 医学

DNA Repair Protein: Endo-Exonuclease as a new Frontier in Cancer Therapy

4区 · 医学

Review

作者: Chow, Terry Y-K ; Choudhury, Sibgat A

DNA repair mechanisms are essential for cellular survival in mammals. A rapid repair of DNA breaks ensures faster growth of normal cells as well as cancer cells, making DNA repair machinery, a potential therapeutic target. Although efficiency of these repair processes substantially decrease the efficacy of cancer chemotherapies that target DNA, compromised DNA repair contributes to mutagenesis and genomic instability leading to carcinogenesis. Thus, an ideal target in DNA repair mechanisms would be one that specifically kills the rapidly dividing cancer cells without further mutagenesis and does not affect normal cells. Endo-exonucleases play a pivotal role in nucleolytic processing of DNA ends in different DNA repair mechanisms especially in homologous recombination repair (HRR) which mainly repairs damaged DNA in S and G2 phases of the cell cycle in rapidly dividing cells. HRR machinery has also been implicated in cell signaling and regulatory functions in response to DNA damage that is essential for cell viability in mammalian cells where as the predominant nonhomologous end-joining pathway is constitutive. Although HRR is thought to be involved at other stages of the cell cycle, it is predominant in growing phases (S and G2) of the cell cycle. The faster growing cells are believed to carryout more HRR in replicative stages of the cell cycle where homologous DNA is available for HRR. Targeting endo-exonucleases specifically involved in HRR will make the normal cells less prone to mutagenesis, rendering the fast growing tumor cells more susceptible to DNA-damaging agents, used in cancer chemotherapy.

2004-12-01·Molecular Cancer Therapeutics2区 · 医学

Erythropoietin induces cancer cell resistance to ionizing radiation and to cisplatin

2区 · 医学

Article

作者: Belenkov, Alexandre I. ; Chow, Terry Y.K. ; Rizhevskaya, Ekatarina ; Cournoyer, Denis ; Belzile, Jean-Philippe ; Devic, Slobodan ; Shenouda, George ; Souhami, Luis

AbstractRecent studies suggest that erythropoietin plays an important role in the process of neoplastic transformation and malignant phenotype progression observed in malignancy. To study the role of erythropoietin and its receptor (EPOR) on the response of cancer cells in vitro, we used two solid tumor cell lines, namely the human malignant glioma cell line U87 and the primary cervical cancer cell line HT100. All experiments were done with heat-inactivated fetal bovine serum in order to inactivate any endogenous bovine erythropoietin. The expression of the EPOR in these cells was confirmed with immunoblot techniques. The addition of exogenous recombinant human erythropoietin (rhEPO) induces the cancer cells to become more resistant to ionizing radiation and to cisplatin. Furthermore, this rhEPO-induced resistance to ionizing radiation and to cisplatin was reversed by the addition of tyrphostin (AG490), an inhibitor of JAK2. Our findings indicate that rhEPO result in a significant, JAK2-dependent, in vitro resistance to ionizing radiation and to cisplatin in the human cancer cells lines studied in this report.

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100 项与 Verlyx Pharma, Inc. 相关的转化医学

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