Sex hormonal milieus during the female fertility cycle modulate the tumor vascular permeability of breast cancer. It has been proposed that the liposomal formulated doxorubicin (ie, Doxil), given at the menstrual/estrous stage with the predicted highest tumor vascular permeability, allows significantly increased drug retention in the breast tumor. In the current study, syngeneic murine 4T1 mamm...

PURPOSE The efficacy of drug delivery systems can be enhanced by making them target specific via the attachment of various ligands. We attempted to enhance tumor accumulation and therapeutic effect of doxorubicin-loaded, long-circulating, polyethylene glycol-coated liposomes (Doxil, ALZA Corp.) by coupling to their surface the anticancer monoclonal antibody (mAb) 2C5 with nucleosome-restricted ...

The resistance of residual cancer cells after oncological resection to adjuvant chemoradiotherapies results in both high recurrence rates and high non-specific tissue toxicity, thus preventing the successful treatment of such cancers as head and neck squamous cell carcinoma (HNSCC). The patients' survival rate and quality of life therefore depend upon the efficacy, selectivity and low non-speci...

Using the photosensitizer 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a, we have determined that photodynamic therapy (PDT) can be used to facilitate the delivery of macromolecular agents. PDT regimens that use low fluences and fluence rates were the most successful. This effect was demonstrated for fluorescent microspheres with diameters ranging from 0.1 to 2 microm. Such treatment given im...

Polyethylene glycol-coated liposomal doxorubicin (Doxil) has a sustained release profile and a mild myelosuppressive effect that may enable a beneficial interaction with lymphocyte-activating cytokines, such as interleukin 2 (IL-2). Previous studies have shown that liposome entrapment of IL-2 potentiates its immunomodulatory effects and reduces the need for frequent dosing. We assessed the ther...

A cutaneous reaction termed palmar-plantar erythrodysesthesia (PPES) or hand-foot syndrome can be dose limiting for Doxil, a doxorubicin containing pegylated (Stealth) liposome. The objective of this study was to determine the ability of concomitant pyridoxine therapy to prevent the development of PPES during Doxil therapy. Forty-one dogs with non-Hodgkin's lymphoma were randomized in a double-...

Here, we investigate various factors affecting the therapeutic efficacy of free doxorubicin (Free-Dox) and polyethylene glycol (PEG)-coated (PEGylated) liposomal doxorubicm (referred to as Doxil) in the ascitic J6456 lymphoma model of BALB/c mice. Free drug and liposomal drug were affected differently by the tumor burden and route of treatment administration. A delay in start of treatment from ...

BACKGROUND The indications for pegylated liposomal doxorubicin (doxil) are expanding. We, therefore, wished to assess the safety of delivering doses exceeding 500 mg/m2 of doxil to patients with solid tumors. PATIENTS AND METHODS Subjects accrued to eight phase I and II protocol studies conducted at two institutions, were assessed for cardiac function at baseline and at specified intervals by...

PURPOSE Early assessment of tumor responses to chemotherapy could enhance treatment outcomes by ensuring that, from the beginning, treatments meet the individualized needs of patients. In this study, we applied multiple modality molecular imaging techniques to pre-clinical monitoring of early tumor responses to Doxil, focusing on imaging of apoptosis. METHODS Mice bearing UM-SCC-22B human hea...

Liposomal anticancer agents can effectively deliver drugs to tumor lesions, but their therapeutic effects are enhanced in only limited number of patients. Appropriate biomarkers to identify responder patients to these liposomal agents will improve their treatment efficacies. We carried out pharmacological and histopathological analyses of mouse xenograft models bearing human ovarian cancers (Ca...