Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ocular adnexal lymphomas represent the malignant end of the spectrum of lymphoproliferative lesions that occur in these locations. The Revised European and American Lymphoma (REAL) Classification and the new World Health Organization Classification of Tumors of Hemopoietic and Lymphoid Tissues are the most suitable for subdividing the ocular adnexal lymphomas, whereby the extranodal marginal zone B-cell lymphoma represents the most common lymphoma subtype. This review is based on five cases subtyped according to the above classifications-three "typical" lymphomas (an extranodal marginal zone B-cell lymphoma, a diffuse large cell B-cell lymphoma arising from an extranodal marginal zone B-cell lymphoma, and a follicular lymphoma) and two "atypical" lymphomas (a non-endemic Burkitt lymphoma in an immune competent elderly patient, and a primary Hodgkin lymphoma of the eyelid) of the ocular adnexa. Management of patients with ocular adnexal lymphomas includes a thorough systemic medical examination to establish the clinical stage of the disease. The majority of patients with ocular adnexal lymphoma have stage IE disease. Current recommended therapy in stage IE tumors is radiotherapy, while disseminated disease is treated with chemotherapy. Despite usually demonstrating an indolent course, extranodal marginal zone B-cell lymphomas are renowned for recurrence in extranodal sites, including other ocular adnexal sites. Long-term follow-up with 6-month examinations are therefore recommended. Major prognostic criteria for the ocular adnexal lymphomas include anatomic location of the tumor; stage of disease at first presentation; lymphoma subtype as determined using the REAL classification; immunohistochemical markers determining factors such as tumor growth rate; and the serum lactate dehydrogenase level.
 ...
PMID:Ocular adnexal lymphomas: five case presentations and a review of the literature. 1243 95

Overexpression of Bcl-2/Bcl-X(L) protein has been observed in more than 80% of B-cell lymphomas. Diffuse large cell lymphoma (DLCL) is the most common subtype of non-Hodgkin's lymphoma. (-)-Gossypol, a natural product isolated from cottonseeds, was discovered as a potent small-molecule inhibitor of Bcl-2 and Bcl-X(L) proteins, with a Ki value in the nanomole per liter range for both. In vitro, (-)-gossypol showed significant growth inhibition effect against WSU-DLCL2 lymphoma cell line and fresh cells obtained from a lymphoma patient with no effect on normal peripheral blood lymphocytes. As expected (-)-gossypol induced complete cytochrome c release from mitochondria, increased caspases-3 and -9 activity, and caused apoptotic death without affecting protein levels of Bcl-2, Bcl-X(L), Bax, and Bak. The addition of cyclophosphamide-Adriamycin-vincristine-prednisolone (CHOP) regimen to lymphoma cells preexposed to (-)-gossypol enhanced killing significantly. The maximum tolerated dose of (-)-gossypol in severe combined immunodeficient (SCID) mice was 40 mg/kg for three i.v. injections when given alone and 20 mg/kg x 3 when given in combination with CHOP. Using WSU-DLCL2-SCID mouse xenograft model, the tumor growth inhibition, the tumor growth delay, and the log10 kill of mice treated with (-)-gossypol + CHOP were better than CHOP or (-)-gossypol alone. We conclude that adding Bcl-2/Bcl-X(L) small-molecule inhibitor to standard chemotherapy may prove an effective strategy in lymphoma therapy.
 ...
PMID:Preclinical studies of a nonpeptidic small-molecule inhibitor of Bcl-2 and Bcl-X(L) [(-)-gossypol] against diffuse large cell lymphoma. 1565 49

Lymphomas and leukemias, neoplasms of hematopoetic lineage, pose unique challenges that require novel treatment paradigms. The inter-relationship between the immune system and the neoplastic lesion in these diseases dictates that, to evaluate novel therapies, models are needed that mimic human disease in an immunocompetent host. In the present study, we describe a disseminated, syngeneic model of B-cell lymphoma in the Balb/c mouse based upon the A20 cell line. This model mimics aspects of diffuse large B-cell lymphomas in humans, and recapitulates para-spinous tumor growth, bone destruction and nerve root compression, which may complicate disseminated disease. Furthermore, this tumor expresses a key marker of interest, CD40, which is a candidate for tumor-specific vector targeting via current modalities. The present study therefore describes a high-fidelity model of disseminated lymphoma with implications for novel targeted therapeutics. Lymphomas and leukemias, neoplasms of hematopoetic lineage, pose unique challenges that require novel treatment paradigms. The inter-relationship between the immune system and the neoplastic lesion in these diseases dictates that, to evaluate novel therapies, models are needed that mimic human disease in an immunocompetent host. In the present study, we describe a disseminated, syngeneic model of B-cell lymphoma in the Balb/c mouse based upon the A20 cell line. This model mimics aspects of diffuse large B-cell lymphomas in humans, and recapitulates para-spinous tumor growth, bone destruction and nerve root compression, which may complicate disseminated disease. Furthermore, this tumor expresses a key marker of interest, CD40, which is a candidate for tumor-specific vector targeting via current modalities. The present study therefore describes a high-fidelity model of disseminated lymphoma with implications for novel targeted therapeutics.
 ...
PMID:The natural history of a novel, systemic, disseminated model of syngeneic mouse B-cell lymphoma. 1633 7

Nonmyeloablative allogeneic transplantation provides a valuable therapeutic option for patients with relapsed non-Hodgkin lymphomas, particularly those that have recurred after autologous transplantation. However, the absence of an intensive conditioning regimen renders this approach less effective for patients with aggressive or bulky lymphoma because rapid tumor growth may outpace the evolution of the graft-versus-lymphoma effect. Radioimmunotherapy provides an attractive, minimally toxic modality to safely prevent early progression of B-cell lymphomas and induce remissions without incurring the risks of traditional intensive therapy. This approach provides a time window during which a robust graft-versus-lymphoma effect may be established before tumor progression, thereby providing more effective long-term disease control. The rationale for incorporation of radioimmunotherapy into reduced intensity allogeneic transplantation regimens for non-Hodgkin lymphoma is discussed, as are current study designs, preliminary results, and future directions.
 ...
PMID:Improving the efficacy of reduced intensity allogeneic transplantation for lymphoma using radioimmunotherapy. 1678 58

Diffuse large B-cell lymphoma is the most common lymphoid malignancy in adults. It is a heterogeneous disease with variability in outcome. Genomic instability of a subset of proto-oncogenes, including c-MYC, BCL6, RhoH, PIM1, and PAX5, can contribute to initial tumor development and has been correlated with poor prognosis and aggressive tumor growth. Lymphomas in which these proto-oncogenes are unstable derive from germinal center B cells that express activation-induced deaminase (AID), the B-cell-specific factor that deaminates DNA to initiate immunoglobulin gene diversification. Proto-oncogene instability is evident as both aberrant hypermutation and translocation, paralleling programmed instability which diversifies the immunoglobulin loci. We have asked if genomic sequence correlates with instability in AID-positive B-cell lymphomas. We show that instability does not correlate with enrichment of the WRC sequence motif that is the consensus for deamination by AID. Instability does correlate with G-richness, evident as multiple runs of the base guanine on the nontemplate DNA strand. Extending previous analysis of c-MYC, we show experimentally that transcription of BCL6 and RhoH induces formation of structures, G-loops, which contain single-stranded regions targeted by AID. We further show that G-richness does not characterize translocation breakpoints in AID-negative B- and T-cell malignancies. These results identify G-richness as one feature of genomic structure that can contribute to genomic instability in AID-positive B-cell malignancies.
 ...
PMID:G-rich proto-oncogenes are targeted for genomic instability in B-cell lymphomas. 1736 77

Expression of neural cell-adhesion molecule CD56 is a rare event in B-cell lymphoma. We described four cases of CD56-positive B-cell lymphoma, including follicular lymphoma and diffuse large B-cell lymphoma. These lymphoma cells expressed CD10 and bcl-6, which suggests germinal center-stage phenotype. Immunohistochemistry showed that CD56-positive cells aggregated and displayed a cohesive growth pattern, indicating that homotypic adhesion through the molecules might affect the manner of tumor growth and expansion. Although CD56 expression level varies among the cases, this molecule might play some roles in the manner of growth and expansion of CD56-positive B-cell lymphomas.
 ...
PMID:Neural cell adhesion molecule (CD56)-positive B-cell lymphoma. 1763 42

WWOX is a putative tumor suppressor gene encoded within common chromosomal fragile site region FRA16D, in chromosome band 16q23. Multiple studies have demonstrated that WWOX expression is often reduced or lost in various tumor types. WWOX tumor suppressor activity was suggested by re-expressing WWOX in breast, ovarian, and lung tumor cell lines leading to tumor growth inhibition in vivo. To determine whether loss of Wwox gene expression has a role in tumorigenesis, we generated a mouse strain containing a Wwox gene mutated by a gene-trap vector. Homozygous Wwox gene-trap mice (Wwox(gt/gt)) had no detectable Wwox protein in most tissues examined, although, a low level could be detected in a minority of tissues. Because of these observations, we concluded that these mice are Wwox hypomorphs. Remarkably, Wwox hypomorphic mice are viable in contrast to the recently reported postnatal lethality of Wwox knockout mice. Testes from Wwox(gt/gt) males had high numbers of atrophic seminiferous tubules and reduced fertility when compared with wild-type counterparts. We observed that the Wwox(gt/gt) mice had a significantly shorter lifespan, and female hypomorphs had a higher incidence of spontaneous B-cell lymphomas. In conclusion, we describe a novel Wwox hypomorphic mouse model that overcomes postnatal lethality that was recently observed in Wwox knockout mice. Therefore, tumorigenesis studies using this model more closely recapitulates the loss of WWOX expression observed in human cancers. Importantly, our observation that Wwox hypomorphs had an increased incidence of B-cell lymphomas supports a role of Wwox as a tumor suppressor.
 ...
PMID:WWOX hypomorphic mice display a higher incidence of B-cell lymphomas and develop testicular atrophy. 1782 27

Hedgehog-mediated signaling has been shown to promote growth and dissemination of solid cancers, most prominently basal cell carcinomas and medulloblastoma. Recent findings indicate that hedgehog signals are also important for tumor growth in hematologic malignancies. Hedgehog ligands secreted by stromal cells could elicit Patched/Smoothened-mediated antiapoptotic signaling in mouse B-cell lymphomas. Inhibition of hedgehog signaling induced apoptosis in lymphoma cells and prolonged survival of lymphoma-bearing mice. Depletion of tumor cells proceeded in the absence of p53 via the mitochondrial apoptotic pathway. These and other recently published data on hedgehog inhibition in cancer cells and their implications will be discussed.
 ...
PMID:Stroma-initiated hedgehog signaling takes center stage in B-cell lymphoma. 1828 68

LMO2 is a transcription regulator involved in human T-cell leukemia, including some occurring in X-SCID gene therapy trials, and in B-cell lymphomas and prostate cancer. LMO2 functions in transcription complexes via protein-protein interactions involving two LIM domains and causes a preleukemic T-cell development blockade followed by clonal tumors. Therefore, LMO2 is necessary but not sufficient for overt neoplasias, which must undergo additional mutations before frank malignancy. An open question is the importance of LMO2 in tumor development as opposed to sustaining cancer. We have addressed this using a peptide aptamer that binds to the second LIM domain of the LMO2 protein and disrupts its function. This specificity is mediated by a conserved Cys-Cys motif, which is similar to the zinc-binding LIM domains. The peptide inhibits Lmo2 function in a mouse T-cell tumor transplantation assay by preventing Lmo2-dependent T-cell neoplasia. Lmo2 is, therefore, required for sustained T-cell tumor growth, in addition to its preleukemic effect. Interference with LMO2 complexes is a strategy for controlling LMO2-mediated cancers, and the finger structure of LMO2 is an explicit focus for drug development.
 ...
PMID:Targeting LMO2 with a peptide aptamer establishes a necessary function in overt T-cell neoplasia. 1948 90

The functional development of tumor-specific CD4(+) T cells has a critical impact on the outcome of antitumor immune responses. Adoptive immunotherapy involving tumor-specific CD4(+) T cells has shown encouraging clinical benefits in some cancer patients. To mount an effective antitumor immunity, it is desirable to elicit activated type 1 T helper cells. Here, we report that type 1 T helper cell-like effector cells that arose in tumor-bearing hosts progressively expressed programmed death 1 during tumor growth. The programmed death 1(hi) effector cells displayed a dysfunctional phenotype, characterized by selective down-regulation of interleukin-7 receptor, heightened apoptosis, and poor antitumor efficacy. This tumor-driven aberrant T-cell response could be prevented by a single dose of the widely used chemotherapy agent cyclophosphamide. We show that chemotherapy conditioned the host environment, creating a transient window for optimal effector differentiation for adoptively transferred CD4(+) T cells. This robust effector differentiation, which was antigen-driven and mechanistically dependent on an intact host response to type I interferon, gave rise to activated polyfunctional T helper cells with high interleukin-7 receptor, rapid clonal expansion, and potent antitumor activity against established B-cell lymphomas. We hypothesize that prevention of tumor-induced effector cell dysfunction is a major mechanism contributing to the efficacy of combined chemoimmunotherapy.
 ...
PMID:Chemotherapy rescues tumor-driven aberrant CD4+ T-cell differentiation and restores an activated polyfunctional helper phenotype. 2011 5


<< Previous 1 2 3 4 5 Next >>