Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chick embryo chorioallantoic membrane (CAM) is commonly used as an experimental in vivo assay to study both angiogenesis and antiangiogenesis in response to tissues, cells or soluble factors. This article summarizes literature data about the use of the CAM in the study of tumor angiogenesis and particularly our experimental data concerning the study of angiogenesis in multiple myeloma and in neuroblastoma.
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PMID:The chick embryo chorioallantoic membrane in the study of tumor angiogenesis. 1851 17

The aim of our study was to investigate whether the defective function of osteogenic cells induced by neuroblastoma might play a role in the development of skeletal metastases. This mechanism has been extensively demonstrated for multiple myeloma, in which the blockage of osteoblast differentiation has been ascribed to the inhibitors of canonical Wingless pathway (Wnt), namely Dickkopf 1 (Dkk1). Our purpose was to verify if neuroblastoma cells derived from bone marrow metastases (SH-SY5Y, LAN1) or primaries (NB100, CHP212) hamper the differentiation of mesenchymal stem cells (hMSCs) into osteoblasts in a paracrine manner, and to test whether this ability depends on Dkk1 activity. We found that all neuroblastoma cells increased the proliferation of hMSCs collected from pediatric-aged donors, with a corresponding decrease in osteoblast differentiation markers, including alkaline phosphatase (ALP), analyzed as gene expression, enzymatic activity and number of ALP-positive colony forming units, osteoprotegerin (OPG) release, OPG and osteocalcin gene-expression. Dkk1 mRNA and protein were detectable in all cell lines, and the use of neutralizing anti-Dkk1 antibody reversed the effects induced by SH-SY5Y cells. Taken together, our results confirm that neuroblastoma hinders osteoblastogenesis, and that Dkk1 release seems to play a crucial role in blocking the differentiation of osteoprogenitor cells, though the ability to promote osteoclast activation remains an essential requirement for the development of skeletal metastases. Finally, our findings suggest that strategies regulating Wnt signaling and Dkk1 activity could be considered for adjuvant therapies in neuroblastoma metastasizing to the skeleton.
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PMID:Paracrine inhibition of osteoblast differentiation induced by neuroblastoma cells. 1862 32

The chick embryo chorioallantoic membrane (CAM) is an extraembryonic membrane mediating gas and nutrient exchanges until hatching. Since it has a dense capillary network, it has been commonly used in vivo to study both angiogenesis and antiangiogenesis in response to normal tissues and cells, to tumor bioptic specimens and cells, or to soluble factors. During the last 8 years, this assay has been used in over 550 published works. This chapter summarizes current knowledge about the embryological origin of the CAM, morphology of its blood and lymphatic vessels, the use of CAM in the study of tumor angiogenesis and metastasis, angiogenic and antiangiogenic substances. The angiogenic response of CAM to multiple myeloma and neuroblastoma cells and bioptic specimens and their responses to antiangiogenic molecules and the role played by fibroblast growth factor-2 in CAM vascularization have been analyzed in detail. Finally, advantages and limitations of CAM as an experimental model to study angiogenesis and antiangiogenesis are discussed.
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PMID:Chick embryo chorioallantoic membrane as a useful tool to study angiogenesis. 1908 37

From March 1991 through 31st December 2007, 2042 patients underwent stem cell transplantation at the Hematology-Oncology and Stem Cell Transplantation Research Center, affiliated to Tehran University of Medical Sciences. These transplantations included 1405 allogeneic stem cell transplantation, 624 autologous stem cell transplantation, and 13 syngeneic stem cell transplantation. Stem cell transplantation was performed for various diseases including acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic lymphoblastic leukemia, thalassemia major, sickle cell thalassemia, sickle cell disease, multiple myeloma, myelodysplasia, mucopolysaccharidosis, paroxysmal nocturnal hemoglobinuria, non-Hodgkin's lymphoma, Hodgkin's disease, severe aplastic anemia, plasma cell leukemia, Niemann-Pick disease, Fanconi anemia, severe combine immunodeficiency, congenital neutropenia, leukocyte adhesion deficiencies, Chediak-Higashi syndrome, osteopetrosis, histiocytosis X, Hurler syndrome, amyloidosis, systemic sclerosis, breast cancer, Ewing's sarcoma, testicular cancer, germ cell tumors, neuroblastoma, medulloblastoma, renal cell carcinoma, nasopharyngeal carcinoma, ovarian cancer, Wilms' tumor, rhabdomyosarcoma, pancreatoblastoma, and multiple sclerosis. We had 105 cellular therapies for postmyocardial infarction, multiple sclerosis, cirrhosis, head of femur necrosis, and renal cell carcinoma. About 30 patients were retransplanted in this center. About 74.9% of the patients (1530 of 2042) remained alive between one to 168 months after stem cell transplantation. Nearly 25.1% (512 of 2042) of our patients died after stem cell transplantation. The causes of deaths were relapse, infections, hemorrhagic cystitis, graft versus host disease, and others.
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PMID:Stem cell transplantation; Iranian experience. 1911 Oct 33

Emerging evidence suggests a role for glutamate and its receptors in the biology of cancer. This study was designed to systematically analyze the expression of ionotropic and metabotropic glutamate receptor subunits in various human cancer cell lines, compare expression levels to those in human brain tissue and, using electrophysiological techniques, explore whether cancer cells respond to glutamate receptor agonists and antagonists. Expression analysis of glutamate receptor subunits NR1-NR3B, GluR1-GluR7, KA1, KA2 and mGluR1-mGluR8 was performed by means of RT-PCR in human rhabdomyosarcoma/medulloblastoma (TE671), neuroblastoma (SK-NA-S), thyroid carcinoma (FTC 238), lung carcinoma (SK-LU-1), astrocytoma (MOGGCCM), multiple myeloma (RPMI 8226), glioma (U87-MG and U343), lung carcinoma (A549), colon adenocarcinoma (HT 29), T cell leukemia cells (Jurkat E6.1), breast carcinoma (T47D) and colon adenocarcinoma (LS180). Analysis revealed that all glutamate receptor subunits were differentially expressed in the tumor cell lines. For the majority of tumors, expression levels of NR2B, GluR4, GluR6 and KA2 were lower compared to human brain tissue. Confocal imaging revealed that selected glutamate receptor subunit proteins were expressed in tumor cells. By means of patch-clamp analysis, it was shown that A549 and TE671 cells depolarized in response to application of glutamate agonists and that this effect was reversed by glutamate receptor antagonists. This study reveals that glutamate receptor subunits are differentially expressed in human tumor cell lines at the mRNA and the protein level, and that their expression is associated with the formation of functional channels. The potential role of glutamate receptor antagonists in cancer therapy is a feasible goal to be explored in clinical trials.
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PMID:Expression of glutamate receptor subunits in human cancers. 1952 64

Betulin is a pentacyclic triterpene found in many plant species, among others, in white birch bark. The aim of the study was in vitro characterization of the anticancer activity of betulin in a range of human tumour cell lines (neuroblastoma, rhabdomyosarcoma-medulloblastoma, glioma, thyroid, breast, lung and colon carcinoma, leukaemia and multiple myeloma), and in primary tumour cultures isolated from patients (ovarian carcinoma, cervical carcinoma and glioblastoma multiforme). In this study, we demonstrated a remarkable anti-proliferative effect of betulin in all tested tumour cell cultures. Neuroblastoma (SK-N-AS) and colon carcinoma (HT-29) were the most sensitive to the anti-proliferative effect of betulin. Furthermore, betulin altered tumour cells morphology, decreased their motility and induced apoptotic cell death. These findings demonstrate the anti-cancer potential of betulin and suggest that they may be applied as an adjunctive measure in cancer treatment.
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PMID:Betulin elicits anti-cancer effects in tumour primary cultures and cell lines in vitro. 1982 31

Plitidepsin (Aplidin) is a novel antitumor agent, derived from the mediterranean tunicate Aplidium albicans, and is currently in phase ii clinical trials with evidence of activity in heavily pretreated multiple myeloma, renal cell carcinoma, melanoma and neuroblastoma patients. As compared to its parental compound didemnin B, plitidepsin has shown a better therapeutic index with less bone marrow toxicity, cardiotoxicity and neurotoxicity in patients and a more potent cytotoxic effect in several tumor cell lines. As sensitivity to the drug varies between cell lines and fresh leukemia samples, we performed studies on transport of plitidepsin in leukemia and lymphoma cell lines to determine the mechanism of uptake. The drug is taken up by an active transport process, i.e. the process is temperature and energy dependent, and has a high-affinity binding site with Kt =212 nM and Vmax = 15 pmoles/min. Importantly, once inside the cell, efflux of plitidepsin is minimum, suggesting that the drug is bound to intracellular macromolecules. Further work showed that plitidepsin binds to G-Protein Coupled Receptors (GPCRs), since GPCR and GRK (GPCR kinases) inhibitors suramin and heparin respectively, markedly reduce the drug uptake and its cytotoxic activity. Signaling via Jak/Stat pathway is inhibited by pharmacological concentrations of plitidepsin, further confirming the relationship between plitidepsin and GPCRs.
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PMID:Heparin and suramin alter plitidepsin uptake via inhibition of GPCR coupled signaling. 1993 47

BMS-754807 is a potent and reversible inhibitor of the insulin-like growth factor 1 receptor/insulin receptor family kinases (Ki, <2 nmol/L). It is currently in phase I development for the treatment of a variety of human cancers. BMS-754807 effectively inhibits the growth of a broad range of human tumor types in vitro, including mesenchymal (Ewing's, rhabdomyosarcoma, neuroblastoma, and liposarcoma), epithelial (breast, lung, pancreatic, colon, gastric), and hematopoietic (multiple myeloma and leukemia) tumor cell lines (IC50, 5-365 nmol/L); the compound caused apoptosis in a human rhabdomyosarcoma cell line, Rh41, as shown by an accumulation of the sub-G1 fraction, as well as by an increase in poly ADP ribose polymerase and Caspase 3 cleavage. BMS-754807 is active in vivo in multiple (epithelial, mesenchymal, and hematopoietic) xenograft tumor models with tumor growth inhibition ranging from 53% to 115% and at a minimum effective dose of as low as 6.25 mg/kg dosed orally daily. Combination studies with BMS-754807 have been done on multiple human tumor cell types and showed in vitro synergies (combination index, <1.0) when combined with cytotoxic, hormonal, and targeted agents. The combination of cetuximab and BMS-754807 in vivo, at multiple dose levels, resulted in improved clinical outcome over single agent treatment. These data show that BMS-754807 is an efficacious, orally active growth factor 1 receptor/insulin receptor family-targeted kinase inhibitor that may act in combination with a wide array of established anticancer agents.
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PMID:BMS-754807, a small molecule inhibitor of insulin-like growth factor-1R/IR. 1999 72

In neuroblastoma LAN-1 cells harboring an amplified MycN gene, disruption of cooperation between Ras and MycN proteins by the Ras inhibitor farnesylthiosalicylic acid (FTS, Salirasib) reportedly arrests cell growth. Our aim was to establish whether this is a general phenomenon. We examined the effects of FTS on gene-expression profiles, growth and death of NCIH929 myeloma cells and K562 leukemia cells, which-like LAN-1 cells-exhibit Myc gene amplification and harbor active Ras. Under specified conditions, FTS reduced Ras and Myc and induced cell growth arrest and death in all Myc-amplified cell lines but not in SHEP, a neuroblastoma cell line without Myc gene amplification. Gene-expression analysis revealed a common pattern of FTS-induced endoplasmic reticulum (ER) stress, known as the unfolded protein response (UPR), in Myc-amplified cells, but not in SHEP. Thus, Ras negatively regulates ER stress in cells with amplified Myc. ER stress was also inducible by dominant-negative (DN)-Ras or shRNA to Ras isoforms, all of which induced an increase in BIP (the master regulator of ER stress) and its downstream targets Nrf2 and eIF2alpha, both regulated by active p-PERK. FTS also induced an increase in p-PERK, while small interfering RNA to PERK reduced Nrf2 and ATF4 and rescued cells from FTS-induced death. BIP and its downstream targets were also increased by inhibitors of MAPK p38 and MEK. Ras, acting through MAPK p38 and MEK, negatively regulates the ER stress cascades BIP/PERK/Nrf2 and eIF2alpha/ATF4/ATF3. These findings can explain the Ras-dependent protection of Myc-amplified cells from ER stress-associated death.
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PMID:Ras inhibits endoplasmic reticulum stress in human cancer cells with amplified Myc. 1999 34

Bone tumors are fortunately rare, but small cell tumors of bone are a relatively common subset of these lesions. They comprise of a diverse group of primary and metastatic neoplasms in both children and adults. The most common small cell tumors of bone include Ewing sarcoma/primitive neuroectodermal tumor, small cell osteosarcoma, multiple myeloma, lymphoma, leukemia, neuroblastoma, rhabdomyosarcoma, and Langerhans cell histiocytosis. Although each entity has its distinctive features, the differential diagnosis of this group of tumors is still challenging because they are all "small, blue, and round cell tumors", histologically. The correct diagnosis of small cell tumors of bone depends on an evaluation of clinical, radiologic, pathologic, and genetic features. Patients' age and sex are very important, as are the signs and symptoms at presentation. Radiologically, which bone is involved, the specific portion of the bone (epiphysis, metaphysis, or diaphysis; cortex vs. medulla) involved, and the radiographic manifestations (lytic, blastic, or mixed lytic and blastic) are also often critical parameters for the diagnosis. In recent years, with a better understanding of the molecular and cytogenetic background of several small cell tumors, more accurate diagnoses have been supported by the clinicopathologic criteria and by a panel of immunohistochemical studies. In this review we will provide an overview of the clinical, radiologic, pathologic, and genetic characteristics of these tumors.
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PMID:Small cell tumors of bone. 2003 33


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