Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor progression is substantially dependent on network of multiple factors, including adhesion and homing molecules, which support the malignant metastatic spread. CD44, one of the adhesion/homing molecules, has attracted much attention not only because it is expressed on many types of tumors, but also owing to its numerous functions, such as supporting cell migration and transmitting survival signals, thereby being pro-oncogenic by nature. We have used the mouse malignant LB lymphoma cell line as a model for comprehensive in vitro and in vivo analyses of the interaction between CD44 and hyaluronic acid (HA), and its relevance to tumor dissemination. The in vitro studies revealed that LB cells could not bind HA, either under static or dynamic (i.e., shear flow) conditions, unless their CD44 is activated by phorbol ester, deglycosylated (to increase the CD44 positive net charge) or transfected with CD44 variants. In parallel, in vivo experiments showed that LB cell dissemination could be controlled by injection of anti-CD44 monoclonal antibodies or hyaluronidase. Furthermore, LB cells transfected with CD44v4-v10 variant, rather than standard CD44, displayed enhanced invasion of the peripheral lymph nodes. This effect was completely lost if the HA binding site of CD44 were mutated. LB cell accumulation in the lymph nodes is caused by enhanced migration via the afferent lymphatics rather than by accelerated proliferation within the lymph node. This information can be exploited to tailor a "therapeutic suit" that should be maximally effective in inducing tumor resistance, while minimizing destructive side effects.
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PMID:Involvement of CD44, a molecule with a thousand faces, in cancer dissemination. 1846 23

Follicular mucinosis is recognized as one of the histopathological reaction patterns characterized by the accumulation of mucin within follicular epithelium. It is induced by various causes including inflammatory diseases, and more than half of the cases are associated with malignant lymphoma, mainly mycosis fungoides. Herein, we describe the third documented case of adult T-cell leukemia/lymphoma (ATLL) accompanying follicular mucinosis. A 72-year-old Japanese male presented with persistent erythema in his arm and neck. Laboratory tests demonstrated positivity for human T-cell leukemia virus (HTLV)-1 antibodies. Histopathological study of the biopsy specimen from the neck revealed superficial perivascular, nodular, and intrafollicular lymphocytic infiltrations. These lymphocytes were small- to medium-sized and had convoluted nuclei. Mucoid material deposition was observed within the hair follicles, and it was digested by hyaluronidase. Immunohistochemically, these lymphocytes were positive for CD3, CD4, CD25, and Foxp3. Accordingly, an ultimate diagnosis of ATLL accompanying follicular mucinosis was made. The skin is the most common extralymphatic site of involvement of ATLL. The present case clearly demonstrated that albeit extremely rare, ATLL can cause follicular mucinosis. Therefore, ATLL should be included in the differential diagnostic consideration of follicular mucinosis.
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PMID:Adult T-cell leukemia/lymphoma accompanying follicular mucinosis: a case report with review of the literature. 2429 93

Cell-based immunotherapy for the treatment of hematologic malignancies, such as leukemia and lymphoma, has seen much success and played an increasingly important role in clinical studies. Nevertheless, the efficacy of immunotherapy in solid tumors still needs improvements due to the immunosuppressive properties of tumor cells and the microenvironment. To overcome these limitations, we prepared a novel tumor-targeting delivery system based on the underlying mechanism of immune-targeted cell death that encapsulated granzyme B protein within a porous polymeric nanocapsule. Methods: A cell-penetrating peptide TAT was attached onto granzyme B (GrB) to enhance its transmembrane transport efficiency and potency to induce cell apoptosis. The endocytosis and internalization pathways of GrB-TAT (GrB-T) were analyzed in comparison with perforin by confocal microscopy and flow cytometry. Furthermore, the positively charged GrB-T was wrapped into nanoparticles by p-2-methacryloyloxy ethyl phosphorylcholine (PMPC)-modified HA (hyaluronic acid). The nanoparticles (called TCiGNPs) were characterized in terms of zeta potential and by transmission electron microscopy (TEM). The in vitro anti-tumor effects of GrB-T were examined by cell apoptosis assay and Western blotting analysis. The in vivo anti-tumor therapeutic efficacy of TCiGNPs was evaluated in a mouse tumor model. Results: The TAT peptide could play a role similar to perforin to mediate direct transmembrane transfer of GrB and improve GrB-induced cell apoptosis. The TCiGNPs were successfully synthesized and accumulated in the solid tumor through enhanced permeability and retention (EPR) effect. In the tumor microenvironment, TCiGNPs could be degraded by hyaluronidase and triggered the release of GrB-T. The TAT peptide enabled the translocation of GrB across the plasma membrane to induce tumor cell apoptosis in vivo. Conclusion: We successfully developed a granzyme B delivery system with a GrB-T core and a PMPC/HA shell that simulated CTL/NK cell-mediated cancer immunotherapy mechanism. The GrB delivery system holds great promise for cancer treatment analogous to the CTL/NK cell-induced immunotherapy.
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PMID:A novel Granzyme B nanoparticle delivery system simulates immune cell functions for suppression of solid tumors. 3169 90

Common variable immunodeficiency (CVID) is the most common clinically significant primary antibody deficiency diagnosed in adults. The early symptoms are not specific. They include common infections, mainly of the respiratory tract, caused by typical microorganisms, so cases can be missed in primary care. In the majority of patients increased susceptibility to infections coexists with signs or symptoms of autoimmunity, inflammation or polyclonal lymphoproliferation, which can divert diagnosis from immune deficiency. The overall incidence of malignancy is increased in CVID and certain cancers are significantly more common. Lymphomas and gastric carcinoma are the most frequently reported malignancies in CVID, so a high index of suspicion is recommended. Diagnostic delay in CVID is seen worldwide. The main goal of this paper is to increase the awareness about CVID among health care professionals. We aim to present features which can be helpful in CVID diagnosis in order to shorten the "latency" of proper management of CVID patients. We review clinical symptoms, complications and laboratory abnormalities of CVID. Immunoglobulin replacement therapy is regarded as the cornerstone of pharmacological intervention. New modes of Ig application, mainly subcutaneously and via the hyaluronidase-facilitated subcutaneous route, help to adjust therapy to patients' needs and preferences. Still there remain unmet needs. It remains to be seen whether CVID complications can be avoided by earlier diagnosis, treatment and thorough monitoring in the context of increased risk of malignancy. Development of patient tailored protocols depending on the clinical phenotype and risk factors might be more appropriate. The most important consideration is to diagnose suspected cases and stratify patients in a precise and timely way. Work is needed to define features predictive of unfavorable prognosis.
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PMID:From infections to autoimmunity: Diagnostic challenges in common variable immunodeficiency. 3302 51


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