Complete immunological tolerance to sheep cells can be induced in mice when cyclophosphamide is injected together with sheep cells or up to 72 hr before or 48 hr after the antigen. As is true for radiation-induced immune suppression, the drug is most effective when given in the 24 hr prior to antigen. Complete cyclophosphamide-induced immunological suppression requires large doses of sheep cell...

objective(s):gemifloxacin is a broad spectrum antibiotic and has shown excellent coverage against a wide variety of microorganisms. in this study, an attempt was made to evaluate the immunomodulatory potential of gemifloxacin in male swiss albino mice in vivo. materials and methods: three doses of gemifloxacin 25 mg/kg, 50 mg/kg and 75 mg/kg were used intraperitoneally (ip) for the evaluation o...

Extensive research into mechanisms of cytotoxic drug resistance and subsequent clinical trials of drug resistance modifiers have produced few encouraging results. In this report, we analyze 4,400+ ex vivo Differential Staining Cytotoxicity (DiSC) assay drug response results from patients with chronic lymphocytic leukemia (CLL) to investigate the development of drug resistance during treatment. ...

The tumor vasculature delivers nutrients, oxygen, and therapeutic agents to tumor cells. Unfortunately, the delivery of anticancer drugs through tumor blood vessels is often inefficient and can constitute an important barrier for cancer treatment. This barrier can sometimes be circumvented by antiangiogenesis-induced normalization of tumor vasculature. However, such normalizing effects are tran...

The 0-24-h urinary metabolic profile of cyclophosphamide was investigated in a series of 14 patients with various malignancies receiving combination chemotherapy including i.v. cyclophosphamide. This was accomplished using combined thin-layer chromatography-photography-densitometry, which can quantitate cyclophosphamide and its four principal urinary metabolites (4-ketocyclophosphamide, nor-nit...

Spermatogenesis is sensitive to the chemotherapeutic drug cyclophosphamide, which decreases the patients' sperm count. Since the recovery of fertility is dependent on regeneration from stem cells, in the present study we evaluated the ability of cyclophosphamide-exposed stem spermatogonia from mice to regenerate spermatogenesis in situ and after transplantation. When seven doses of cyclophospha...

In the design of sequential high-dose chemotherapy regimens, the selection of antitumor alkylating agents to be included in each intensification and the interval between the intensifications are critical to the design of the therapy. The tumor cell survival assay and tumor growth delay assay using the murine EMT-6 mammary carcinoma were used as a solid tumor model in which to address these issu...

The promising but still limited efficacy of angiogenesis inhibitors as monotherapies for cancer treatment indicates a need to integrate these agents into existing therapeutic regimens. Presently, we investigate the antitumor activity of the small-molecule angiogenesis inhibitor axitinib (AG-013736) and its potential for combination with metronomic cyclophosphamide. Axitinib significantly inhibi...

The 0-24-h urinary metabolic profile of cyclophosphamide was inves tigated in a series of 14 patients with various malignancies receiving combination chemotherapy including i.v. cyclophosphamide. This was accomplished using combined thin-layer chromatography-photographydensitometry, which can quantitate cyclophosphamide and its four prin cipal urinary metabolites (4-ketocyclophosphamide, nor-ni...

Given the bulky nature of nanotherapeutics relative to small molecules, it is hypothesized that effective tumor delivery and penetration are critical barriers to their clinical activity. HER2-targeted PEGylated liposomal doxorubicin (MM-302, HER2-tPLD) is an antibody-liposomal drug conjugate designed to deliver doxorubicin to HER2-overexpressing cancer cells while limiting uptake into nontarget...