Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pseudomonas aeruginosa is an opportunistic pathogen whose adaptability, ubiquitousness, and pathogenicity are closely related. Both cell-associated and extracellular products of P. aeruginosa contribute to its virulence. Surface structures, including pili and the polysaccharide capsule or glycocalyx, appear to mediate the initial attachment of P. aeruginosa to its prospective host, thus permitting colonization. Extracellular enzymes such as alkaline protease, elastase, phospholipase C, and exotoxin A degrade infected tissues and promote bacterial invasion. When dissemination occurs, systemic disease results, often with fatal consequences. Although extracellular enzymes of P. aeruginosa figure prominently in local disease processes, exotoxin A and endotoxin are primarily responsible for systemic disease. The most protective antibodies presently known are directed toward the nontoxic portions of P. aeruginosa lipopolysaccharides that serve no known virulence function per se. However, there is preliminary evidence that the protective activity of these opsonic antibodies may be augmented by toxin-neutralizing antibodies directed toward the lipid A moiety of endotoxin and exotoxin A.
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PMID:The virulence of Pseudomonas aeruginosa. 644 64

Anaplastic large cell lymphoma (ALCL) is a biologic and clinically heterogenous subtype of T-cell lymphoma. Clinically, ALCL may present as localized (primary) cutaneous disease or widespread systemic disease. These two forms of ALCL are distinct entities with different clinical and biologic features. Both types share similar histology, however, with cohesive sheets of large lymphoid cells expressing the Ki-1 (CD30) molecule. Primary cutaneous ALCL (C-ALCL) is part of the spectrum of CD30+ lymphoproliferative diseases of the skin including lymphomatoid papulosis. Using conservative measures, 5-year disease-free survival rates are > 90%. The systemic ALCL type is an aggressive lymphoma that may secondarily involve the skin, in addition to other extranodal sites. Further, systemic ALCL may be divided based on the expression of anaplastic lymphoma kinase (ALK) protein, which is activated most frequently through the nonrandom t(2;5) chromosome translocation, causing the fusion of the nucleophosmin (NPM) gene located at 5q35 to 2p23 encoding the receptor tyrosine kinase ALK. Systemic ALK+ ALCLs have improved prognosis compared with ALK-negative ALCL, although both subtypes warrant treatment with polychemotherapy. Allogeneic and, to a lesser extent, autologous stem cell transplantation play a role in relapsed disease, while the benefit of upfront transplant is not clearly defined. Treatment options for relapsed patients include agents such as pralatrexate (Folotyn) and vinblastine. In addition, a multitude of novel therapeutics are being studied, including anti-CD30 antibodies, histone deacetylase inhibitors, immunomodulatory drugs, proteasome inhibitors, and inhibitors of ALK and its downstream signaling pathways. Continued clinical trial involvement by oncologists and patients is imperative to improve the outcomes for this malignancy.
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PMID:Primary cutaneous and systemic anaplastic large cell lymphoma: clinicopathologic aspects and therapeutic options. 2066 96

Since grey zone lymphoma (GZL) was originally included in the 2008 World Health Organization classification as a B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL), new biological and clinical knowledge have been learned. It is important to highlight that diagnosis of this entity is complex and involvement by haematopathologists with expertise in this disease is recommended. It is recognized now that patients with GZL may present clinically with primary mediastinal localization or systemic disease without mediastinal involvement. Regardless of clinical presentation, patients with GZL have relatively high relapse rates, especially compared with primary mediastinal DLBCL or cHL. Interestingly, relapsed/refractory GZL patients appear to be salvaged fairly successfully, especially with haematopoietic stem cell transplantation (HSCT). Off of a clinical trial, we recommend R-CHOP (rituximab, cyclophosphamide, doxorubicin, oncovin, prednisolone) or dose-adjusted EPOCH-R (etoposide, prednisolone, oncovin, cyclophosphamide, doxorubicin, rituximab) for frontline treatment of GZL. Additionally, we advocate use of consolidative radiotherapy for localized and/or bulky disease. For patients with relapsed/refractory GZL, salvage chemotherapy followed by consolidative autologous HSCT should be considered. Finally, continued biological and pathologic examination of this unique disease entity is warranted as well as exploration towards the integration of targeted therapeutic agents (e.g., brentuximab vedotin, programmed cell death 1inhibitors, B-cell receptor inhibitors, proteasome inhibitors, etc.) into the treatment paradigm of GZL.
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PMID:How I manage patients with grey zone lymphoma. 2730 70