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Dasanu C.A.,Saint Francis Medical Center College of Nursing | Alexandrescu D.T.,Georgetown Dermatology
Journal of Oncology Pharmacy Practice

Purpose. Retrospective analysis of two recent multiple myeloma (MM) clinical trials suggested that the use of bortezomib may be associated with an increased incidence of herpes zoster infections. Therefore, prophylactic use of antivirals has been advocated by some authors. This article explores the potential risks and pitfalls linked to routine acyclovir prophylaxis in bortezomib-treated MM. Summary. Use of antivirals can be associated with important nephro- and neurotoxicity. The nephrotoxicity induced by MM itself and its supportive therapies, superimposed to aging and inherent immunosuppression in myeloma, makes the development of renal impairment even more likely. On the other hand, sensory neuropathy is known to occur both during myeloma progression and in the setting of bortezomib therapy. Furthermore, preexisting nephropathy in MM patients can contribute to the occurrence of serious neurologic toxicity with acyclovir. Conclusions. Long-term acyclovir prophylaxis in MM patients treated with bortezomib may cause severe renal and neurological toxicity. Prevention of these complications can be achieved through either withholding of the antivirals or a very close monitoring of both neurologic status and renal function in this patient population. This highlights the importance of both clinician's and pharmacist's involvement in optimization of myeloma patient care. © The Author(s), 2010. Source

de Necochea-Campion R.,Loma Linda University | de Necochea-Campion R.,University of California at San Diego | Ghochikyan A.,Institute for Molecular Medicine | Josephs S.F.,University of California at San Diego | And 10 more authors.
Journal of Translational Medicine

BORIS, or CTCFL, the so called Brother of the Regulator of Imprinted Sites because of the extensive homology in the central DNA binding region of the protein to the related regulator, CTCF, is expressed in early gametogenesis and in multiple cancers but not in differentiated somatic cells. Thus it is a member of the cancer testes antigen group (CTAs). Since BORIS and CTCF target common DNA binding sites, these proteins function on two levels, the first level is their regulation via the methylation context of the DNA target site and the second level is their distinct and different epigenetic associations due to differences in the non-homologous termini of the proteins. The regulation on both of these levels is extensive and complex and the sphere of influence of each of these proteins is associated with vastly different cellular signaling processes. On the level of gene expression, BORIS has three known promoters and multiple spliced mRNAs which adds another level of complexity to this intriguing regulator. BORIS expression is observed in the majority of cancer tissues and cell lines analyzed up to today. The expression profile and essential role of BORIS in cancer make this molecule very attractive target for cancer immunotherapy. This review summarizes what is known about BORIS regarding its expression, structure, and function and then presents some theoretical considerations with respect to its genome wide influence and its potential for use as a vaccine for cancer immunotherapy. © 2011 de Necochea-Campion et al; licensee BioMed Central Ltd. Source

Alexandrescu D.T.,University of California at San Diego | Maslin B.,University of California at San Diego | Kauffman C.L.,Georgetown Dermatology | Ichim T.E.,Medistem Inc | Dasanu C.A.,Medical Center
Dermatologic Surgery

Background: Although the incidence of malignant melanoma in African Americans is considerably lower than in Caucasians, African Americans have a less-favorable prognosis related to later presentation and more deeply invasive lesions at diagnosis. Objective: To review the current literature addressing the specific clinical, histopathologic, and molecular features of melanoma in darkly pigmented individuals. Methods: We reviewed the most up-to-date literature pertaining to melanoma in this patient population, including data from clinical studies, epidemiologic analyses, and molecular and genetic studies. Results: Several studies have suggested differences between lightly and darkly pigmented populations with regard to clinicopathologic character and the underlying genetic processes affecting its pathogenesis. Conclusion: Further investigation is warranted to better elucidate the clinical and underlying biological differences in melanoma between Caucasians and African Americans. Such research may help to ameliorate the disparities in melanoma outcomes through improved screening, public health measures aimed at prevention, and potentially novel targeted therapeutic approaches. © 2013 by the American Society for Dermatologic Surgery, Inc. Source

Dasanu C.A.,Medical Center | Ichim T.,Medistem Inc | Alexandrescu D.T.,Georgetown Dermatology
Expert Opinion on Drug Safety

Importance of the field: T- and NK-cell abnormalities, decreased number and function of monocytes, neutrophils and dendritic cells, decreased production of certain cytokines and increased incidence of certain autoimmune conditions have been identified in untreated hairy cell leukemia (HCL) patients. These alterations are responsible for an increased rate of infections and additional malignancies in HCL. Areas covered in this review: The authors offer a focused review of the most relevant preclinical and clinical studies exploring the immune abnormalities in both untreated and treated HCL. What the reader will gain: The use of potent immunosuppressive agents such as cladribine and pentostatin in HCL therapeutics has generated increasing concerns about the likelihood of additional immune impairments in these patients. While the NK cells, monocytes and neutrophils were shown to recover shortly after complete responses are achieved with these agents, the CD4+ T-cell counts may require in excess of 2 - 3 years in order to re-enter the normal range. Take home message: Given the advent of new molecular, genetic and immunologic techniques, a comprehensive characterization of the immune abnormalities in untreated and treated HCL represents a reachable goal and could translate into improved outcomes in clinical practice. © 2010 Informa UK Ltd ISSN. Source

Dasanu C.A.,Medical Center | Alexandrescu D.T.,Georgetown Dermatology
Expert Opinion on Pharmacotherapy

Importance of the field: One of the feared events encountered in hairy cell leukemia (HCL) survivors is the subsequent development of a malignant neoplasm. The increased incidence of second cancers in HCL has been documented in large epidemiologic studies conducted in various locations on the globe. Areas covered in this review: The authors explore the current clinico-epidemiologic evidence, as well as the immune alterations, that link HCL and its therapies to the development of second cancers. Most relevant publications have been identified through the PubMed/Medline database search. What the reader will gain: Although HCL patients could develop both HCL and secondary malignancies because of a shared genetic predisposition, a common environmental carcinogen, or not yet identified infectious agents, multiple immune defects documented in HCL might play an important role in second carcinogenesis. Furthermore, the 'gold standards' of HCL therapy cladribine and pentostatin are associated with profound and prolonged suppression of the CD4 T-lymphocyte counts, often in excess of 2 3 years. And while there is no clear-cut evidence that pentostatin or interferon-alpha play an established role in generation of an excess of second cancers in HCL, the safety of cladribine, the preferred agent by a majority of clinicians worldwide, in this regard is a still largely unsettled issue. Take-home message: Therefore, it remains to be seen if the immune deficiencies induced by the HCL therapies and their consequences can be offset by the benefit conferred by controlling the leukemic process. Source

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