Current Medicinal Chemistry - Volume 11, Issue 4, 2004

Paclitaxel has been proven to be effective against different types of cancer. A delivery system loaded with paclitaxel at tumor site should provide a high local concentration of the drug detrimental to malignant cells, which prevents the re-growth and metastasis of tumor. In this review, paclitaxel formulations for systemic and for intratumoral administration are discussed.

Paclitaxel (Taxol™), a naturally occurring antimitotic agent, has shown significant cell-killing activity against tumor cells through induction of apoptosis. The mechanism by which paclitaxel induces cell death is not entirely clear. Recent studies in our laboratory discovered that glucocorticoids selectively inhibited paclitaxel-induced apoptosis without affecting the ability of paclitaxel to induce microtubule bundling Read More

Paclitaxel is one of the best antineoplastic drugs found from nature in the past decades, which has been found effective against a wide spectrum of cancers including ovarian cancer, breast cancer, small and non small cell lung cancer, colon cancer, head and neck cancer, multiple myeloma, melanoma, and Kaposi's sarcoma. Like many other anticancer drugs, it has difficulties in clinical administration due to its poor solubility i Read More

Ovarian cancer patients with paclitaxel-resistance have been reported to respond to a weekly schedule of the same drug. In this report, two cases with long progression free interval by weekly paclitaxel (T) are presented. Case 1. A 41-year-old Japanese woman, gravida 2, para 0, was referred to our hospital in September 16, 1998, because of abdominal mass accompanying large amount of ascites with elevated CA125 (8400 U Read More

The basic principle of the targeted delivery approach is that the conjugation of a drug to a tumorspecific molecule renders the drug inactive until it reaches the target site. Monoclonal antibodies (mAbs), which have shown high binding specificity for tumor-specific antigens, could be used as targeting agents. Paclitaxel has brought significant impact on the current cancer chemotherapy, but seriously suffers from the lack of tu Read More

Antibodies and anticancer drug-antibody conjugates used in experimental cancer research or clinically must be freeze-dried for preserving the activity and storage at room temperature. This often results in some denaturation and loss of activity . We describe a recovery of the cytotoxic activity of a paclitaxel-mAb immunoconjugate after freeze-drying. The paclitaxel-antibody conjugate specific for ovarian cancer was test Read More

All types of thymic cells are able to produce cytokines either spontaneously or after stimulation. The main producers of cytokines in the thymus are thymic epithelial cells (TEC) and thymocytes. Thymic cytokines act at short distance and their effects are limited by the internal space of the organ. The spectrum of biological effects of thymic cytokines is determined by the expression of cytokine receptors on the thymic cell surface. Read More

Sorbitol dehydrogenase (SDH), a member of the medium-chain dehydrogenase / reductase protein family and the second enzyme of the polyol pathway of glucose metabolism, converts sorbitol to fructose strictly using NAD+ as coenzyme. SDH is expressed almost ubiquitously in all mammalian tissues. The enzyme has attracted considerable interest due to its implication in the development of diabetic complications Read More

Many immune responses are dependent on the four members of the leukocyte integrin family of surface receptors. Organ transplantation triggers a range of immune responses aimed at rejecting the donor tissue. Engagement of cells of the immune system including T cells, B cells, and antigen presenting cells with each other or with the donor organ is an essential element of the rejection cascade, and this engagement is media Read More

Conformational change plays an important role in the life of all proteins, starting from when they fold, through their function and often their fate. For an increasing number of proteins inappropriate conformational change leads to a chain of events, which culminate in the deposition of proteinacious aggregates and disease. In this review we consider the current literature on a number of proteins which form part of the Read More

Bile formation is an osmotic process driven by the vectorial transport of actively transferred biliary components across the basolateral (sinusoidal) and apical (canalicular) hepatocyte membranes, the latter being the rate-limiting step of the overall blood-to-bile transfer. The ATP-binding cassette (ABC) superfamily of membrane transporters comprises novel ATP-dependent carriers that mediate canalicular transfer of several endo Read More