Cancer Science & Therapy

Immunotoxins composed of monoclonal antibodies linked to bacterial or plant protein toxins have been studied during the past 30 years as a potential targeted therapy for cancer. A series of refinements in the design of immunotoxins containing the bacterial toxin Pseudomonas exotoxin A (PE) led to the development of the current smaller, more selective, and more stable recombinant immunotoxins that are composed of a truncated form of PE fused to the variable domain of a monoclonal antibody. Immunotoxins targeting CD22, an antigen commonly expressed on B-cell malignancies, including BL22 (also known as CAT-3888) and its improved, higher affinity derivative, moxetumomab pasudotox (also known as HA22 or CAT-8015) are being evaluated in patients with hematologic malignancies. BL22 induced complete remissions in the majority of patients with chemoresistant hairy cell leukemia (HCL) during phase 1 and 2 studies, and showed promising antitumor activity in patients with chronic lymphocytic leukemia (CLL). Moxetumomab pasudotox is currently undergoing phase 1 testing in refractory HCL, as well as in CLL, non-Hodgkin lymphoma, and pediatric acute lymphoblastic leukemia (ALL). Thus far, clinical activity has been observed in approximately 80% of adult patients with HCL and complete remissions have been reported in 25% of children with ALL. No dose-limiting toxicities have been reported in the adult study in patients with HCL or in patients in the pediatric study who also received dexamethasone.

Phospholipids are potential antineoplastic agents that are abundant constituents of the cell membrane of eukaryotes and are supposed to be involved in specific intracellular signaling such as cell death. The aim of this study was to assess the in vitro and in vivo antitumor effects of synthetic phosphoethalomanine (PHO-S) on B16F10 murine melanoma cells and normal human fibroblasts. The cytotoxicty was evaluated by MTT assay and PHO-S was cytotoxic in melanoma cells but not in fibroblasts with IC50% of 1.4 mg/ml to melanoma cells. In vivo antitumor activity was evaluated in a mice model subcutaneously injected with B16F10 melanoma cells. The mice treated with PHO-S in all concentrations showed a decrease of the tumor growth and metastasis. Cytometry analysis showed that the PHO-S blocked DNA synthesis, decreased number of melanoma cells in S phase and G2/M, besides increasing number of apoptotic cells, inducing caspase-3 activity and decreasing Bad/Bax protein expression. Histologically, the dorsal tumors in the control group showed pigmented nodular masses with high vascularization and pleomorphic tumor cells. In the treated group, PHO-S reduction vascularization intratumoral with increased of collagen fibers and infiltrates neutrophils. The data indicate that PHO-S is a lipid compound potential with proapoptotic and antiproliferative effects but further work will be necessary to elucidate the antitumor mechanisms.

Prostate cancer is one of the most prevalent cancers in men in Western countries, increasing in frequency with age through the most advanced years. Patients with localized prostate cancer are generally treated with radical prostectomy or radiation therapy. However, treatment of more malignant stages of the disease is problematic. Docetaxel-based chemotherapy in men with androgen-independent prostate cancer has been shown to have survival benefits but hormonal manipulation and other chemotherapeutic regimens, especially for androgen-independent lesions, have uncertain value. While research into the complex pathophysiology of advanced prostate cancer has led to identification of mechanisms and target molecules, it nevertheless remains necessary to develop new anticancer drugs. Cell culture models that mimic the structure and features of prostate cancer in vivo are necessary for research on tumor biology and design of novel anticancer therapies. In this context, 3-dimensional cultures of prostate cancer cells, including multicellular spheroid (MCS) cultures, started attracting increasing attention. The present review provides up-to-date information regarding the significance of MCS culture for identification of mechanisms underlying human malignancies, including prostate cancer, and possible targets for prostate cancer therapies.

Background: Breast cancer survivors increasingly experience long-term side effects that influence their quality of life. The current study was carried out to asses the Quality of life of women with breast cancer at the time of diagnosis. Methods: This is a descriptive study; a case series of patients studied. The study was conducted at Lok Nayak Hospital, New Delhi, India; from January 2006 to May 2007. 172 women with new primary breast cancer were included in the study. Quality of Life - Cancer Survivor's (QOL-CS) instrument was used. Results: The mean score of overall QOL was 6.04. The mean score of the social well-being was 4.61 and was the lowest among all the domains. The mean score of spiritual well-being was 7.34, and physical well-being 7.24 and psychological well-being 4.98. Conclusion: Among all the domains the mean score was the lowest in the social well-being. The mean score of spiritual well-being was highest.