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26


Circulating Memory T Cells Isolated from Hodgkin Lymphoma Patients Display Evidence of Exhaustion and Chronic Activation [Meeting Abstract]

Diefenbach, Catherine S; Raphael, Bruce G; Hymes, Kenneth B; Moskovits, Tibor; Kaminetzky, David; Martin, Peter; Ruan, Jia; Lauro, Stephanie; Banks, Danielle; Brown, Krysten; Bonakdar, Maryam; Abidoglu, Cem; Kozhaya, Lina; Leonard, John P; Unutmaz, Derya
ISI:000349233804059
ISSN: 1528-0020
CID: 1497562

Comparison of Graft Content and Efficiency of T Cell Depletion in Bone Marrow and Peripheral Blood Stem Cells Grafts After Manipulation by Three Negative or Positive CD34+Selection Strategies [Meeting Abstract]

Collins, Nancy H.; Kaminetzky, David; Koehne, Guenther; Maloy, Molly; Chen, Xiashe; Smith, Katherine; Bleau, Sharon; Tonon, Jo-ann; Meagher, Richard.; Papadopoulos, Esperanza; Young, James; Giralt, Sergio A.; O'Reilly, Richard; Jakubowski, Ann A.
ISI:000314441900408
ISSN: 1083-8791
CID: 227242

The Chemotherapy Regimen IVAC Is Highly Active for Multiply Relapsed and Refractory Hodgkin Lymphoma [Meeting Abstract]

Diefenbach, Catherine S.; Kaminetzky, David; Andersen, Shannon; Chin, Jane; MacGregor-Cortelli, Barbara; Zain, Jasmine M.
ISI:000314049604378
ISSN: 0006-4971
CID: 227432

Emerging role of epigenetic therapies in cutaneous T-cell lymphomas

Zain, Jasmine; Kaminetzky, David; O'Connor, Owen A
Cutaneous T-cell lymphomas (CTCLs) are rare lymphomas that arise primarily in the skin and are treated with skin-directed therapies in early-stage disease. Systemic therapy is indicated once skin-directed therapy is ineffective or for advanced-stage disease. CTCLs tend to be poorly responsive to chemotherapy and are incurable except for allogeneic stem cell transplantation. Recently, a new class of agents called histone deacetyalse inhibitors (HDACis) have shown remarkable activity in T-cell lymphomas in general and CTCLs in particular. Oral vorinostat and intravenous romidepsin are two HDACis that are now approved by the US FDA for use in patients with relapsed CTCLs. Several other HDACis are currently in clinical trials for CTCLs and other diseases and, although these agents vary by chemical structure and potency, the results of the ongoing clinical trials will eventually reveal if there are differences in clinical activity as well. The exact mechanism of action of these agents is unknown, but they are thought to affect the acetylation status of histones and other proteins in the cell and epigentically modulate transcription and other cellular activities. This leads to a myriad of downstream effects on cell cycle, apoptosis and differentiation. The following review summarizes the known biological mechanisms and clinical activity of various HDACis in the treatment of CTCLs and tries to define their role in the treatment paradigm of these unusual disorders
PMID: 21083462
ISSN: 1747-4094
CID: 114591

Denileukin diftitox for the treatment of cutaneous T-cell lymphoma

Kaminetzky, David; Hymes, Kenneth B
Cutaneous T-cell lymphoma/mycosis fungoides (CTCL/MF) is a rare lymphoproliferative disorder which can present as an indolent or as an aggressive process involving skin, lymph nodes, and blood. In stages IA, IB and IIA, it is usually managed with topical medications and phototherapy. If there is progression despite application of these treatments, or if the patient presents with a higher stage of disease, systemic chemotherapy or retinoids, rexinoids, biologic response modifiers are often necessary. Consequently, patients are often treated with a sequence of modalities and drugs. Denileukin diftitox (DD, Ontak(R)) is a targeted immunotoxin which has biological activity against malignancies expressing the IL-2 receptor. In addition to its unique mechanism of action, DD has a toxicity profile which does not overlap with most commonly used chemotherapeutic agents. CTCL/MF has been found be particularly susceptible to treatment with this agent. This review will describe the development DD, its proposed mechanism of action, the clinical trials which identified its utility in the treatment of CTCL/MF, the common toxicities encountered with this agent, and the management of these toxicities. In addition the incorporation of DD in the sequential treatment of CTCL/MF and data suggesting potential combination therapies employing this novel agent will be discussed
PMCID:2727893
PMID: 19707452
ISSN: 1177-5475
CID: 101902

Synergy in tumor suppression by direct interaction of neutral endopeptidase with PTEN

Sumitomo, Makoto; Iwase, Akira; Zheng, Rong; Navarro, Daniel; Kaminetzky, David; Shen, Ruoqian; Georgescu, Maria-Magdalena; Nanus, David M
We show in this study that endogenous NEP and PTEN associate in cells directly through electrostatic interactions between a highly basic residue stretch in the intracellular domain of NEP and the major phosphorylation site in PTEN's tail. NEP binds and engages in higher order complexes both phosphorylated and unphosphorylated PTEN. NEP recruits PTEN to the plasma membrane and enhances its stability and phosphatase activity. As a result, an enzymatically inactive NEP mutant preserves the ability to bind PTEN, inactivates the Akt/PKB kinase, and partially suppresses the growth of PC cells. This study demonstrates a molecular cooperation between NEP and PTEN tumor suppressors in which NEP constitutively recruits and activates PTEN to inhibit the PI3K/Akt oncogenic pathway
PMID: 14749127
ISSN: 1535-6108
CID: 135910