Bortezomib

Source: www.ncbi.nlm.nih.gov --- 1 day ago
Related Articles The combination of Bortezomib, melphalan, dexamethasone and intermittent thalidomide is an effective regimen for relapsed/refractory myeloma and is associated with improvement of abnormal bone metabolism and angiogenesis. Leukemia. 2008 Sep 4; Authors: Terpos E, Kastritis E, Roussou M, Heath D, Christoulas D, Anagnostopoulos N, Eleftherakis-Papaiakovou E, Tsionos K, Croucher P, Dimopoulos MA This phase 2 study aimed to determine the efficacy and safety of the combination of Bortezomib, melphalan, dexamethasone and intermittent thalidomide (VMDT) and its effect on bone remodeling and angiogenesis in relapsed/refractory myeloma. Bortezomib (1.0 mg/m(2)) was given on days 1, 4, 8, 11, oral melphalan (0.15 mg/kg) on days 1-4, whereas thalidomide (100 mg per day) and dexamethasone (12 mg/m(2)) were administered on days 1-4 and 17-20 of a 28-day cycle, for four cycles. Patients without disease progression continued for up to eight cycles. VMDT effect on bone remodeling was evaluated by measuring osteoclast regulators (soluble receptor activator of nuclear factor-kappa B ligand/osteoprotegerin ratio, osteopontin, macrophage inflammatory protein-1alpha), dickkopf-1 protein, bone resorption and formation markers, whereas its effect on angiogenesis was assessed by measuring serum vascular endothelial growth factor, angiogenin, angiopoietin-2 and basic fibroblast growth factor, after four cycles and at the study end. A total of 62 ...

Source: www.ncbi.nlm.nih.gov --- 14 days ago
Related Articles [Clinical study of Bortezomib in combination with dexamethasone for the treatment of multiple myeloma.] Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008 Aug;16(4):943-5 Authors: Wang LX, Lu H, Shen WY, Qian SX, Qiu HX, Wu HX, Zhang JF, Wu YJ, Li JY The objective of study was to evaluate the efficiency and safety of Bortezomib for the treatment of multiple myeloma. Bortezomib in combination with dexamethasone was administered as first-line treatment in all 7 newly diagnosed patients with multiple myeloma. The patients with refractory myeloma were treated with Bortezomib in combination with dexamethasone or with other traditional agents such as mitoxantrone and thalidomide. The results showed that according to the EMBT criteria, out of 7 patients one achieved complete response (CR), five achived partial response (PR) and one achived minor response (MR). The 3 patients with refractory/relapsed myeloma achieved PR (2/3) and MR (1/3). The overall response rate (CR + PR) was 80%. The most frequent adverse events observed were thrombocytopenia in three patients, diarrhea and peripheral neuropathy in one respectively. In conclusion, Bortezomib demonstrates efficiency in the treatment of new-diagnosed and refractory/relapsed multiple myeloma, and the side effects from treatment are acceptable and manageable. PMID: 18718096 [PubMed - in process] ...

Source: www.ncbi.nlm.nih.gov --- 12 days ago
Related Articles [Synergistic effects of arsenic trioxide and proteasome inhibitor Bortezomib on apoptosis induction in raji cell line.] Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008 Aug;16(4):794-8 Authors: He Y, Yang JM, Wang JM, Zhou H, Lü SQ, Hu XX The aim of this study was to explore the synergistic effect of arsenic trioxide and Bortezomib on apoptosis of Raji cell line. The cells were treated with arsenic trioxide, Bortezomib, low-dose arsenic trioxide combined with Bortezomib, respectively. The cell viability and proliferative curve were estimated by trypan blue dye exclusion. The cell apoptosis and cell cycle status were analyzed by flow cytometry. The apoptosis related elements such as caspase-3, BCL-2, BAX, JNK2 and IkappaB-alpha, were measured with Western blot. The results showed that compared with cells treated with mentioned above drugs alone, the proliferative potential of cells in combination group was significantly inhibited (p < 0.01), and apoptosis rate markedly increased (p = 0.001), while obvious cell cycle arrest was not observed. On the protein level, the expression of Caspase-3, BAX and IkappaB-alpha increased, while the expression of BCL-2, and JNK2 decreased. It is concluded that low-dose arsenic trioxide combined with Bortezomib synergistically induced apoptosis in Raji cell line which may be mediated by inhibiting NK-kappaB and JNK2 signaling. PMID: 18718063 [PubMed - in process] ...

Source: www.ncbi.nlm.nih.gov --- 34 days ago
Related Articles p38 mitogen-activated protein kinase inhibitor LY2228820 enhances Bortezomib-induced cytotoxicity and inhibits osteoclastogenesis in multiple myeloma; therapeutic implications. Br J Haematol. 2008 May;141(5):598-606 Authors: Ishitsuka K, Hideshima T, Neri P, Vallet S, Shiraishi N, Okawa Y, Shen Z, Raje N, Kiziltepe T, Ocio EM, Chauhan D, Tassone P, Munshi N, Campbell RM, Dios AD, Shih C, Starling JJ, Tamura K, Anderson KC The interaction between multiple myeloma (MM) cells and the bone marrow (BM) microenvironment induces proliferation and survival of MM cells, as well as osteoclastogenesis. This study investigated the therapeutic potential of novel p38 mitogen-activated protein kinase (p38MAPK) inhibitor LY2228820 (LY) in MM. Although cytotoxicity against MM cell lines was modest, LY significantly enhanced the toxicity of Bortezomib by down-regulating Bortezomib-induced heat shock protein 27 phosphorylation. LY inhibited interleukin-6 secretion from long term cultured-BM stromal cells and BM mononuclear cells (BMMNCs) derived from MM patients in remission. LY also inhibited macrophage inflammatory protein-1alpha secretion from patient MM cells and BMMNCs as well as normal CD14 positive osteoclast precursor cells. Moreover, LY significantly inhibited in vitro osteoclastogenesis from CD14 positive cells induced by macrophage-colony stimulating factor and soluble receptor activator of nuclear factor-kappaB ligand. Finall ...

Source: www.prnewswire.com --- 10 days ago
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Source: www.moreover.com --- 3 days ago
Checkbiotech Sep 3 2008 6:30PM GMT ...

Source: content.nejm.org --- 9 days ago
Patients with newly diagnosed multiple myeloma who were ineligible for treatment with high-dose chemotherapy plus hematopoietic stem-cell transplantation were randomly assigned to receive either melphalan and prednisone alone or melphalan and prednisone plus Bortezomib. The time to disease progression (the primary outcome) was longer in the Bortezomib group. The combination of Bortezomib, melphalan, and prednisone appears to be effective as initial treatment in patients with multiple myeloma who cannot withstand high-dose therapy. ...

Source: www.medpagetoday.com --- 10 days ago
SALAMANCA, Spain (MedPage Today) -- For multiple myeloma patients ineligible for high-dose chemotherapy, Bortezomib (Velcade) appears effective as a first-line therapy when added to standard melphalan (Alkeran) and prednisone, found a phase III trial. ...

Source: www.ad-hoc-news.de --- 23 days ago
Neuss (ots) - Das Committee for Medicinal Products for Human Use (CHMP) der European Medicines Agency (EMEA) hat eine Empfehlung für die Zulassung von Velcade® für die Primärtherapie des multiplen Myeloms in Kombination mit Melphalan und Prednison (VMP) abgegeben. Demnach können ... ...

Source: www.topix.com --- 8 days ago
In patients with multiple myeloma who are ineligible for high-dose therapy, addition of the proteasome inhibitor Bortezomib to melphalan plus prednisone improves response rate and survival, according to a ... ...

Source: www.biowizard.com --- 18 days ago
Cancer Res. 2008 Aug 15; 68(16):6698-707. Chen KF, Yeh PY, Yeh KH, Lu YS, Huang SY, Cheng AL ...

Source: www.anti-cancerdrugs.com --- 28 days ago
Page: 777 DOI: 10.1097/CAD.0b013e32830c236a Authors: Park, Juwon a; Ahn, Kwang-Sung a; Bae, Eun-Kyung e; Kim, Byung-Su a b; Kim, Byoung Kook a b c; Lee, Young-Yiul a d; Yoon, Sung-Soo a b c ...

Source: margaret.healthblogs.org --- 16 days ago
Sherlock (grazieeeee!) sent me a study titled “Dietary flavonoids inhibit the anti-cancer effects of the proteasome inhibitor Bortezomib” (see abstract: http://tinyurl.com/5pdxtu), published in the July 16 2008 issue of “Blood.” This is an important study for those who are taking Velcade (Bortezomib) and supplements at the same time, so I decided to read, and post about, [...] ...

Source: rarediseases.about.com --- 2 days ago
The standard treatment for multiple myeloma, a blood cell cancer, is taking the drugs Alkeran (melphalan) and prednisone. Velcade (Bortezomib) has also been shown to be an effective treatment. A... ...

Source: www.ncbi.nlm.nih.gov --- 4 days ago
Related Articles Treatment of Follicular Non-Hodgkin's Lymphoma: The Old and the New. Semin Hematol. 2008 Jul;45S2:S2-S6 Authors: Friedberg JW Despite remaining an incurable disease, overall survival improvements have been noted in patients with advanced-stage follicular lymphoma. The Follicular Lymphoma International Prognostic Index (FLIPI) is a robust prognostic index in this disease, and continues to provide prognostic information in the rituximab era. Rituximab has significantly changed the management of follicular lymphoma, and the most dramatic impact of rituximab is observed in combination with cytotoxic chemotherapy. However, resistance to rituximab remains a problem, and standard therapy in the rituximab-refractory setting includes radioimmunotherapy, autologous stem cell transplantation, and allogeneic stem cell transplantation. In addition, several novel agents show encouraging activity in follicular lymphoma, including bendamustine, lenalidomide, Bortezomib, and other proteasome inhibitors, and BCL2 inhibitors. PMID: 18760706 [PubMed - as supplied by publisher] ...

Source: www.ncbi.nlm.nih.gov --- 18 days ago
Related Articles Proteasome Inhibition Activates Epidermal Growth Factor Receptor (EGFR) and EGFR-Independent Mitogenic Kinase Signaling Pathways in Pancreatic Cancer Cells. Clin Cancer Res. 2008 Aug 15;14(16):5116-23 Authors: Sloss CM, Wang F, Liu R, Xia L, Houston M, Ljungman D, Palladino MA, Cusack JC PURPOSE: In the current study, we investigate the activation of antiapoptotic signaling pathways in response to proteasome inhibitor treatment in pancreatic cancer and evaluate the use of concomitant inhibition of these pathways to augment proteasome inhibitor treatment responses. EXPERIMENTAL DESIGN: Pancreatic cancer cell lines and mouse flank xenografts were treated with proteasome inhibitor alone or in combination with chemotherapeutic compounds (gemcitabine, erlotinib, and bevacizumab), induction of apoptosis and effects on tumor growth were assessed. The effect of Bortezomib (a first-generation proteasome inhibitor) and NPI-0052 (a second-generation proteasome inhibitor) treatment on key pancreatic mitogenic and antiapoptotic pathways [epidermal growth factor receptor, extracellular signal-regulated kinase, and phosphoinositide-3-kinase (PI3K)/AKT] was determined and the ability of inhibitors of these pathways to enhance the effects of proteasome inhibition was assessed in vitro and in vivo. RESULTS: Our data showed that proteasome inhibitor treatment activates antiapoptotic and mitogenic signaling pathways (epidermal growth fac ...

Source: www.ncbi.nlm.nih.gov --- 22 days ago
Related Articles Enhancing transduction of the liver by adeno-associated viral vectors. Gene Ther. 2008 Aug 14; Authors: Nathwani AC, Cochrane M, McIntosh J, Ng CY, Zhou J, Gray JT, Davidoff AM A number of distinct factors acting at different stages of the adeno-associated virus vector (AAV)-mediated gene transfer process were found to influence murine hepatocyte transduction. Foremost among these was the viral capsid protein. Self-complementary (sc) AAV pseudotyped with capsid from serotype 8 or rh.10 mediated fourfold greater hepatocyte transduction for a given vector dose when compared with vector packaged with AAV7 capsid. An almost linear relationship between vector dose and transgene expression was noted for all serotypes with vector doses as low as 1 x 10(7) vg per mouse (4 x 10(8) vg kg(-1)) mediating therapeutic levels of human FIX (hFIX) expression. Gender significantly influenced scAAV-mediated transgene expression, with twofold higher levels of expression observed in male compared with female mice. Pretreatment of mice with the proteasome inhibitor Bortezomib increased scAAV-mediated hFIX expression from 4+/-0.6 to 9+/-2 mug ml(-1) in female mice, although the effect of this agent was less profound in males. Exposure of mice to adenovirus 10-20 weeks after gene transfer with AAV vectors augmented AAV transgene expression twofold by increasing the level of proviral mRNA. Hence, optimization of individual steps in the AAV ge ...

Source: www.ncbi.nlm.nih.gov --- 57 days ago
Related Articles Bortezomib directly inhibits osteoclast function in multiple myeloma: Implications into the management of myeloma bone disease. Leuk Res. 2008 Jul 7; Authors: Terpos E PMID: 18614229 [PubMed - as supplied by publisher] ...

Source: www.medicalnewstoday.com --- 19 days ago
The Multiple Myeloma Research Consortium (MMRC) announced the initiation of a four-drug combination study with REVLIMID® (lenalidomide), VELCADE® (Bortezomib) for Injection, DOXIL® (doxorubicin HCl liposome injection) and dexamethasone for the treatment of multiple myeloma in patients who are previously untreated. ...

Source: www.medicalnewstoday.com --- 11 days ago
The Multiple Myeloma Research Consortium (MMRC) announced the initiation of a clinical trial with the oral immunomodulatory agent pomalidomide (CC-4047) in patients who have received at least two prior therapies including treatments with REVLIMID® (lenalidomide) and VELCADE® (Bortezomib) for Injection. ...