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American Journal of Translational Research (1)
Bone marrow transplantation (1)
Experimental and Therapeutic Medicine (1)
Bhutani, Manisha (2)
BHUTANI, MANISHA (1)
Babu, Dilip (1)
Chimento, Danielle (1)
Chung, David (1)
Devlin, Sean M. (1)
FAN, YOU H. (1)
Giralt, Sergio (1)
HONG, WAUN KI (1)
Hassoun, Hani (1)
KURIE, JONATHAN (1)
Koehne, Guenther (1)
LEE, J. JACK (1)
LIU, DIANE D. (1)
Landau, Heather (1)
Lendvai, Nikoletta (1)
Lesokhin, Alex (1)
MAO, LI (1)
MORICE, RODOLFO C. (1)
Mao, Li (1)
PATHAK, ASHUTOSH KUMAR (1)
Pathak, Ashutosh K. (1)
Riedel, Elyn (1)
Saintigny, Pierre (1)
TANG, HONGLI (1)
Zamarin, Dmitriy (1)
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Patterns of Relapse and Progression in Multiple Myeloma Patients after Autologous Stem Cell Transplantation: Implications for Patients’ Monitoring After Transplantation
Devlin, Sean M.
Bone marrow transplantation
Autologous stem cell transplantation (ASCT) is widely used in first-line treatment of multiple myeloma (MM). However, most patients eventually have relapse or progression of disease (R/POD). While precise knowledge of R/POD patterns would be important to generate evidence-based surveillance recommendations after ASCT, such data is limited in the literature, especially after introduction of the free light chain assay (FLCA). This retrospective study examined the patterns of R/POD after first-line ASCT in 273 patients, using established criteria. At time of R/POD, only 2% of patients had no associated serologic evidence of R/POD. Eighty five percent had asymptomatic R/POD first detected by serologic testing, while 15% had symptomatic R/POD with aggressive disease, early R/POD, and short survival, with poor cytogenetics and younger age identified as risk factors. While occult skeletal lesions were found in 40% of asymptomatic patients tested following serologic R/POD, yearly skeletal surveys and urine testing were poor at heralding R/POD. We found a consistent association between paraprotein types at diagnosis and R/POD allowing informed recommendations for appropriate serologic monitoring and propose a new needed criterion using FLCA for patients relapsing by FLC only. Our findings provide important evidence-based recommendations that strengthen current monitoring guidelines after first-line ASCT in MM.
Multiple Myeloma; Autologous Transplantation; Relapse; Free Light Chain Assay
Frequent expression of MAGE1 tumor antigens in bronchial epithelium of smokers without lung cancer
PATHAK, ASHUTOSH KUMAR
FAN, YOU H.
LIU, DIANE D.
LEE, J. JACK
MORICE, RODOLFO C.
HONG, WAUN KI
Experimental and Therapeutic Medicine
Melanoma antigens (MAGE) are frequently expressed in lung cancer and are promising targets of anticancer immunotherapy. Our preliminary data suggested that MAGE may be expressed during early lung carcinogenesis, raising the possibility of targeting MAGE as a lung cancer prevention strategy. The purpose of this study was to investigate MAGE activation patterns in the airways of chronic smokers without lung cancer. MAGE-A1, -A3 and -B2 gene expression was determined in bronchial brush cells from chronic former smokers without lung cancer by reverse transcription-PCR (RT-PCR). The results were correlated with clinical parameters. The 123 subjects had a median age of 57 years, a median of 40 pack-years smoking history, and had quit smoking for at least one year prior to enrollment. Among the subjects, 31 (25%), 38 (31%), and 46 (37%) had detectable MAGE-A1, -A3 and -B2 expression, respectively, in their bronchial brush samples. Expression of MAGE-A1 and -B2 positively correlated with pack-years smoking history (P=0.03 and 0.03, respectively). The frequency of expression did not decrease despite a prolonged smoking cessation period. In conclusion, MAGE-A1, -A3 and -B2 genes are frequently expressed in the bronchial epithelial cells of chronic smokers without lung cancer, suggesting that chronic exposure to cigarette smoke activates these genes even before the malignant transformation of bronchial cells in susceptible individuals. Once activated, the expression persists despite long-term smoking cessation. These data support the targeting of MAGE as a novel lung cancer prevention strategy.
melanoma antigens; airway; smokers; lung cancer; prevention
Heterotransplant mouse model cohorts of human malignancies: A novel platform for Systematic Preclinical Efficacy Evaluation of Drugs (SPEED)
Pathak, Ashutosh K.
American Journal of Translational Research
Advances in molecular biology demonstrate that cancer is heterogeneous disease necessitating a personalized management approach. This is introducing a paradigm shift in clinical trial designs where molecular characterization of cancers is assuming importance equal to (or even more than) the traditional histologic diagnosis as the eligibility criterion for randomized clinical trials of new therapies. Recommendations have been made to gather the molecular information from clinical phase II trials distinguishing responding from non responding tumors for subsequent planning of large scale phase III trials. However by the time we reach phase II level, more than a billion dollars apart from years of research have been invested. It would be therefore prudent to conceptualize laboratory based platforms to obtain the proof of concept as early as possible, even before embarking upon the pivotal clinical trials. In this regard, we hereby propose and detail a novel preclinical platform incorporating the existing mouse models to address the issue of tumor heterogeneity in a systematic manner through creation of a setting similar to phase II trials in human patients. By providing critical information about a drug's efficacy and the molecular determinants of response early on, this platform would potentially provide a solid foundation to build avant-garde clinical trials integrating recent advances in molecular medicine.
Cancer; heterotransplant; animal model; therapeutics; drug development
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