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  • 1
    Electronic Resource
    Electronic Resource
    PROTEASOME INHIBITION IN MULTIPLE MYELOMA: Therapeutic Implication (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 45 (2005), S. 465-476 
    Details
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: Normal cellular functioning requires processing of proteins regulating cell cycle, growth, and apoptosis. The ubiquitin-proteasome pathway (UBP) modulates intracellular protein degradation. Specifically, the 26S proteasome is a multienzyme protease that degrades misfolded or redundant proteins; conversely, blockade of the proteasomal degradation pathways results in accumulation of unwanted proteins and cell death. Because cancer cells are more highly proliferative than normal cells, their rate of protein translation and degradation is also higher. This notion led to the development of proteasome inhibitors as therapeutics in cancer. The FDA recently approved the first proteasome inhibitor bortezomib (VelcadeĐ?„), formerly known as PS-341, for the treatment of newly diagnosed and relapsed/refractory multiple myeloma (MM). Ongoing studies are examining other novel proteasome inhibitors, in addition to bortezomib, for the treatment of MM and other cancers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.pharmtox.45.120403.100037
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  • 2
    Electronic Resource
    Electronic Resource
    BORTEZOMIB: Proteasome Inhibition as an Effective Anticancer Therapy (2006)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Medicine 57 (2006), S. 33-47 
    Details
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Notes: VELCADE?℗ (bortezomib, Millennium Pharmaceuticals, Inc., Cambridge, MA, and Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Raritan, NJ) is a first-in-class proteasome inhibitor developed specifically for use as an antineoplastic agent. Inhibition of the proteasome results in disruption of homeostatic mechanisms within the cell that can lead to cell death. Bortezomib's first indication, for the treatment of relapsed myeloma in patients who have received at least two prior treatments and progressed on their previous treatment, was based in part on the magnitude of activity demonstrated in phase II trials. Bortezomib is currently indicated for patients who have received at least one prior therapy in the United States and European Union, although patients in the European Union must have already undergone bone marrow transplantation or be unsuitable for the procedure. A phase III trial demonstrated the superiority of bortezomib over high-dose dexamethasone in response rate, time to progression, and survival in patients with myeloma who had relapsed after 1Đ??3 prior therapies. Clinical development is ongoing to investigate its activity as monotherapy and in combination regimens for the treatment of non-Hodgkin's lymphoma, solid tumors, and earlier presentations of myeloma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.med.57.042905.122625
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  • 3
    Electronic Resource
    Electronic Resource
    THALIDOMIDE: Emerging Role in Cancer Medicine (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Medicine 53 (2002), S. 629-657 
    Details
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Notes: Abstract Thalidomide-removed from widespread clinical use by 1962 because of severe teratogenicity-has antiangiogenic and immunomodulatory effects, including the inhibition of tumor necrosis alpha factor. It has now returned to practice as an effective oral agent in the management of various disease states including erythema nodosum leprosum, for which it was approved by the U.S. Food and Drug Administration in 1998, and more recently certain malignancies, including multiple myeloma. Although thalidomide's mechanism of action remains incompletely understood, considerable insight has been generated by extensive preclinical studies in multiple myeloma. Moreover, clinical trials have confirmed benefit in relapsed disease, and the role of thalidomide in treating newly diagnosed patients is currently under study. Its use in other tumors is under evaluation, with promise in renal cell carcinoma, prostate cancer, glioma, and Kaposi's sarcoma. Activity has also been demonstrated in chronic graft-versus-host disease and in symptom relief as part of palliative care.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.med.53.082901.104043
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  • 4
    Electronic Resource
    Electronic Resource
    Novel therapeutic approaches for multiple myeloma (2003)
    Oxford, UK : Munksgaard International Publishers
    Immunological reviews 194 (2003), S. 0 
    Details
    ISSN: 1600-065X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary:  Multiple myeloma (MM) affects 15 000 new patients annually in the US, with 50 000 total patients, and remains incurable. Our preliminary in vitro and animal studies suggest a role for MM–host interactions in regulating MM cell growth, drug resistance, and migration in the bone marrow. Importantly, treatment strategies which target mechanisms whereby MM cells grow and survive in the bone marrow, including thalidomide and its potent immunomodulatory derivatives and proteasome inhibitor PS-341, can overcome classical drug resistance in preclinical and early clinical studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1600-065X.2003.00053.x
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  • 5
    Electronic Resource
    Electronic Resource
    The induction of cytotoxicity by a bispecific antibody against CEA positive cell line, in vitro (1996)
    Springer
    Surgery today 26 (1996), S. 83-88 
    Details
    ISSN: 1436-2813
    Keywords: cytotoxicity ; bispecific antibody ; CEA ; carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A mouse anti-human carcinoembryonic antigen (CEA) × anti-human CD3 bispecific antibody, AB5C10*UCHT1, was developed. This antibody-heteroconjugate was chemically prepared by cross-linking the AB5C10 monoclonal antibody reactive with human CEA with the monoclonal antibody, UCHT1, which binds to CD3 on human T-lymphocytes. The AB5C10*UCHT1 recognized both CEA expressed on the KATOIII cell line and CD3 expressed on T-lymphocytes, as determined using flowcytometry. Next, AB5C10*UCHT1-mediated cytolysis was analyzed by 51Cr-release assay. When 51Cr-labeled target KATOIII cells were incubated for 6 h with effector cells that had been pretreated with AB5C10*UCHT1 for 60 min at 4°C, the percentage specific lysis was significantly increased compared to that of untreated effector cells. Using peripheral blood mononuclear cells (PBMC) and lymphokine-activated killer (LAK) cells pretreated with AB5C10*UCHT1 for effector cells, the percentage specific lysis was determined to be 16.3% and 57.4% at effector:target (E:T) ratios of 100:1 and 12.5:1, respectively. On the other hand, the percentage specific lysis of untreated PBMC and LAK cells determined to be 3.0% and 35.8% at E:T ratios of 100:1 and 12.5:1, respectively. The minimum effective dose of AB5C10*UCHT1 required for antibody-mediated cytotoxicity was 0.1 μg/ml. The results of this study suggest that AB5C10*UCHT1 could be useful for augmenting the cytotoxicity of CD3-positive T-cells against CEA-positive target cells in vitro.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00311769
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  • 6
    Electronic Resource
    Electronic Resource
    Postoperative chylothorax following partial resection of mediastinal lymphangioma: Report of a case (1995)
    Springer
    Surgery today 25 (1995), S. 827-829 
    Details
    ISSN: 1436-2813
    Keywords: mediastinal tumor ; lymphangioma ; chylothorax
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report herein the rare case of a 20-year-old man in whom a mediastinal lymphangioma was incidentally detected by a chest roentgenogram taken during a routine health examination. Both computed tomography and magnetic resonance imaging confirmed a mass measuring 3×7 cm in diameter in the left anterior mediastinum. A thoracoscopic exploration was done, which confirmed a diagnosis of mediastinal lymphangioma, and 3 days later a sternotomy was performed. However, the tumor could not be completely extirpated due to partial invasion. Following the thoracoscopic procedure, a chylous discharge developed which was difficult to treat conservatively and he continued to drain 700–1,000 ml of chyle daily 2 weeks following the tumor extirpation. Therefore, a right thoracotomy with ligation of the thoracic duct was performed which resolved the chylothorax. The patient remains well without any regrowth of the regional tumor 9 months after his operation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00311461
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  • 7
    Electronic Resource
    Electronic Resource
    The unusual presentation of mucinous carcinoma in the colon making preoperative diagnosis difficult: Report of a case (1996)
    Springer
    Surgery today 26 (1996), S. 123-125 
    Details
    ISSN: 1436-2813
    Keywords: mucinous carcinoma ; colon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 51-year-old man was admitted to our hospital for investigation of fever, lower abdominal pain, and pain on micturition. Barium enema and endoscopic findings revealed an extracanal large cavity of the rectosigmoid colon, which suggested an abscess caused by penetration. Histological examination of the endoscopic biopsy specimen demonstrated no malignancy. A preoperative diagnosis of malignant lymphoma was strongly suspected from the imaging findings; however, intraoperative inspection revealed a large tumor invading the urinary bladder. An intraoperative incisional biopsy was performed and histological examination demonstrated mucinous carcinoma. The patient subsequently underwent pelvic exenteration about 1 week later followed by adjuvant chemotherapy and radiotherapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00311776
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