Dror Shalitin

Hebrew University of Jerusalem | HUJI

Based on the high density of plasmodesmata interconnecting the intermediary cells and their neighboring phloem parenchyma or bundle-sheath cells, and based on the insensitivity to the sucrose transport inhibitor p-chloromercuribenzenesulfonic acid (PCMBS), cucurbits have been concluded to be symplastic loaders. In the present study, we identified a...

1851 Poster Board I-877 Currently available drugs for multiple myeloma (MM) treatment show very little ability to distinguish MM cells from normal cells. This limits the dose of drugs with anti-MM activity that can be administered safely; and, thus, reduces their efficacy in eliminating the malignant plasma cell population. Therefore, novel strateg...

Examine the antitumor activity of the histone deacetylase inhibitor vorinostat's antitumor activity against multiple myeloma (MM) using cell lines and a murine xenograft model. RPMI8226, U266, and MM1S cells were cultured for 48 h in the presence of media, vorinostat, melphalan, or bortezomib alone, or combinations of vorinostat with melphalan or b...

Enhanced angiogenesis is a hallmark of cancer. Pleiotrophin (PTN) is an angiogenic factor that is produced by many different human cancers and stimulates tumor blood vessel formation when it is expressed in malignant cancer cells. Recent studies show that monocytes may give rise to vascular endothelium. In these studies, we show that PTN combined w...

Despite recent advances in the therapy of multiple myeloma (MM), the disease remains incurable. Current drugs for MM target not only MM but also normal cells. This limits the efficacy of these agents and may lead to significant morbidities for patients. Therefore, novel strategies are needed that allow targeting of tumor cells in these patients wit...

The mammalian target of rapamycin (mTOR) is an intracellular protein that acts as a central regulator of multiple signaling pathways (IGF, EGF, PDGF, VEGF, amino acids) that mediate abnormal growth, proliferation, survival and angiogenesis in cancer. mTOR is a critical component of the PI3K/Akt pathway, a key cell survival pathway that is dysregula...

Vascular endothelial growth factor (VEGF) is an important signaling protein that plays a critical role in vasculogenesis and angiogenesis, and serves as one of the contributors to physiological or pathological conditions that can stimulate the formation of new blood vessels. The uncontrolled growth of new blood vessels is an important contributor t...

Objective and Rationale Raf-1 kinase inhibitory protein (RKIP) is a modulator of cell signaling and survival that functions as an endogenous inhibitor of multiple kinases, including kinases involved in the Raf/MEK/ERK and NF-κB pathways. RKIP has been identified as a metastasis suppressor gene and an immune surveillance cancer gene, since loss of R...

Mammalian target of rapamycin (mTOR) is a central cell regulator involved in cell survival, growth and proliferation, and is being targeted for cancer therapy. There are two mTOR complexes, the rapamycin-sensitive mTORc1, and the rapamycin-insensitive mTORc2, both of which are downstream of the PI3K/Akt pathway. Protein Kinase C (PKC) refers to a f...

Recent studies suggest that zoledronic acid (ZOL) and other nitrogen-containing bisphosphonates (BPs) inhibit angiogenesis by reducing angiogenic factor production and signaling by these factors. However, few studies have addressed the potential role of BPs in blocking the formation of new vasculature or so-called vasculogenesis. Thus, we determine...

Deacetylase (DAC) inhibitors represent a new class of anti-cancer therapeutics that inhibit DAC enzymes and have been shown to have multiple effects in tumor cell lines including decreased oncoprotein expression (Bcr-Abl, HER-2), decreased angiogenesis, induction of apoptosis, induction of cell-cycle arrest, and decreased tumor cell motility and in...

We have recently shown that silencing of tumor necrosis factor receptor-associated factor 6 (TRAF6) with a C-terminal siRNA inhibits proliferation and increases apoptosis of multiple myeloma (MM) tumor cells. In addition, TRAF6 ubiquitin ligase is also essential for receptor activator of nuclear factor kappa B ligand (RANKL) signaling and osteoclas...

Angiogenesis is a hallmark of a variety of malignancies including multiple myeloma (MM). We have shown that MM patients express pleiotrophin (PTN), and this protein stimulates MM growth and prevents apoptosis. We have also demonstrated that PTN when combined with mCSF stimulates angiogenesis through the transdifferentiation (TD) of monocytes into e...

CRY2 is a blue light receptor regulating light inhibition of hypocotyl elongation and photoperiodic flowering in Arabidopsis thaliana. The CRY2 protein is found primarily in the nucleus, and it is known to undergo blue light-dependent phosphorylation and degradation. However, the subcellular location where CRY2 exerts its function or undergoes blue...

Arsenic trioxide (ATO) induces apoptosis of malignant plasma cells through multiple mechanisms, including inhibition of DNA binding by nuclear factor kappa-B, a key player in the development of chemoresistance in multiple myeloma (MM). This activity suggests that ATO may be synergistic when combined with other active antimyeloma drugs. To evaluate...

Pleiotrophin (PTN) is an important developmental cytokine that is highly expressed during embryogenesis but shows very limited expression in adult tissues, where it is largely restricted to the brain. High PTN serum levels are associated with a variety of solid tumors. We recently showed that patients with multiple myeloma (MM) also have elevated s...

Cryptochromes are blue light receptors that regulate photomorphogenesis in plants and the circadian clock in animals and plants. Arabidopsis cryptochrome 2 (CRY2) mediates blue light inhibition of hypocotyl elongation and photoperiodic control of floral initiation. CRY2 undergoes blue light-induced phosphorylation, which was hypothesized to be asso...

Histone deacetylase (HDAC) inhibitors represent a new mechanistic class of anti-cancer therapeutics that inhibit HDAC enzymes and have been shown to have anti-proliferative effects in cancer cells (including drug resistance subtypes), induce apoptosis, inhibit angiogenesis, and sensitize cancer cells when combined with other available anti-cancer t...

The peripheral benzodiazepine receptor (mPBR) appears to be a potential target to induce apoptosis in tumor cells. The expression of this receptor has been linked to a poor prognosis in cancer patients. PK11195 may represent a new, well-tolerated potent chemosensitizing agent that affects multiple resistance mechanisms within malignant cells. We ha...

Inorganic arsenics like arsenic trioxide (ATO) are novel anti-cancer drugs active in acute promyelocytic leukemia (APL) and multiple myeloma (MM). ATO induces apoptosis of plasma cells by several mechanisms including down-regulation of BCL-2 expression and inhibition of DNA-binding by NF-κB. The amount of ATO that can be safely given is low because...

Dominant negative inhibition is most commonly seen when a mutant subunit of a multi-subunit protein is co-expressed with the wild-type protein so that assembly of a functional oligomer is impaired. Studies have shown that TRAF6 plays a key role in the regulation of NF-κB through the IL-1R/TLR-TRAF6-TAK1-TAB1-TAB2-IkB-NF-κB pathway. We previously de...

We have discovered a novel mechanism leading to blood vessel formation involving transdifferentiation of monocytes into endothelial cells by tumor cell production of pleiotrophin (PTN), a protein highly produced by myeloma (H. Chen et al, Blood, 2005; Yeh et al BJH, 2006). Arsenic trioxide (ATO) induces apoptosis of cancer cells directly through a...

We have previously shown that multiple myeloma (MM) patients express pleiotrophin (PTN) and it is found at high levels in MM serum as well as PTN is a key factor in the transdifferentiation of monocytes into endothelial cells. We determined the level of PTN expression in myeloma and breast cancer and determined whether PTN produced by these tumor c...

Vascular endothelial growth factor (VEGF) is an important signaling protein that plays a critical role in vasculogenesis and angiogenesis, and serves as one of the contributors to physiological or pathological conditions that can stimulate the formation of new blood vessels. The uncontrolled growth of new blood vessels is an important contributor t...

The transition from vegetative growth to reproductive development in Arabidopsis is regulated by multiple floral induction pathways, including the photoperiodic, the autonomous, the vernalization, and the hormonal pathways. These pathways converge to regulate the expression of a small set of genes critical for floral initiation and different signal...

Expression of the Aspergillus nigerβ-glucosidase gene, BGL1, in Nicotiana tabacum plants (cv. Xanthi) had a profound effect on the volatile emissions of intact and crushed leaves. BGL1 was expressed under the control of the cauliflower mosaic virus (CaMV) 35S promoter and targeted to the cytoplasm, cell wall, lytic vacuole (LV), chloroplast or endo...

Cryptochromes are photolyase-like blue/UV-A light receptors that regulate various light responses in animals and plants. Arabidopsis cryptochrome 1 (cry1) is the major photoreceptor mediating blue light inhibition of hypocotyl elongation. The initial photochemistry underlying cryptochrome function and regulation remain poorly understood. We report...

Cryptochromes are photolyase-like blue/UV-A light receptors that regulate various light responses in animals and plants. Arabidopsis cryptochrome 1 (cry1) is the major photoreceptor mediating blue light inhibition of hypocotyl elongation. The initial photochemistry underlying cryptochrome function and regulation remain poorly understood. We report...

Cryptochromes are photosensory receptors mediating light regulation of growth and development in plants. Since the isolation of the Arabidopsis CRY1 gene in 1993, cryptochromes have been found in every multicellular eukaryote examined. Most plant cryptochromes have a chromophore-binding domain that shares similar structure with DNA photolyase, and...

In addition to its influence on plasmodesmal function, tobacco mosaic virus movement protein (TMV-MP) causes an alteration in carbon metabolism in source leaves and in resource partitioning among the various plant organs. The present study was aimed at characterizing the influence of cucumber mosaic virus (CMV)-MP on carbohydrate metabolism and tra...

Cryptochromes are blue/ultraviolet-A light receptors that mediate various light responses in plants and animals. But the initial photochemical reaction of cryptochrome is still unclear. For example, although most photoreceptors are known to undergo light-dependent protein modification such as phosphorylation, no blue-light dependent phosphorylation...

Cryptochromes are blue/ultraviolet-A light receptors that mediate various light responses in plants and animals1, 2. But the initial photochemical reaction of cryptochrome is still unclear. For example, although most photoreceptors are known to undergo light-dependent protein modification such as phosphorylation3, 4, no blue-light dependent phospho...

This paper originates from a presentation at the International Conference on Assimilate Transport and Partitioning, Newcastle, NSW, August 1999 Recent studies support the concept that long-distance signals are involved in the regulation of resource allocation among the various plant organs. Following the finding that viral movement proteins (MPs) c...

Viral infection often affects carbon assimilation and metabolism in host plants. To better understand the effect of cucumber mosaic virus (CMV) infection on sugar transport, carbohydrate levels and the amounts of the various sugars in the phloem sap were determined in infected melon (Cucumis melo L.) plants. Source leaves infected with CMV were cha...

Most plant viruses encode a protein(s) essential for movement from the site of replication to surrounding, uninfected cells. These movement proteins (MPs) can interact with plasmodesmata CPD) to elicit an increase in the molecular size exclusion limit (SEL) from 1.0 kDa to values ranging from 10 to 30 kDa. In recent years, we have established that...

Seven monoclonal antibodies (MAbs) showing homologous reactions with the VT strain of citrus tristeza virus (CTV) were tested against 21 CTV strains or isolates, representing the range of biological diversity and the geographical distribution of CTV in Israel. All the CTV strains gave positive reactions in ELISA with polyclonal antibodies and with...