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)

This study is to investigate the effect of the C21 sterols on inducing apoptosis of hepatocellular cancer cells and its potential mechanism. The transplanted model of hepatoma substantiality (Heps) was established in mice, and the mice were divided into four groups: negative controls group and C21 sterols groups (10, 20, 40 mg x kg(-1)) , treated with drugs separately once a day for 9 days. Then the mice were sacrificed, the tumor growth inhibition rate (IR) was calculated and tumor tissue samples were taken and examined under electron microscope. The tumor cells were harvested and cell viability or apoptosis was analyzed by acridine orange and ethidium bromide (AO/EB) stain. B-cell lymphoma/leukemia-2 gene (bcl-2) in tumor cells was inspected by immunohistochemistry. After treatment with C21 sterols (10, 20, 40 mg x kg(-1)), inhibitory effect on the transplanted Heps was observed. The IR was 34.79%, 47.08% and 50.23%, respectively. Apoptosis induced by the C21 sterols was observed, low growth density and some apoptotic cells were observed in tumor under the electron microscope. The expression of bcl-2 gene on tumor cells decreased in the C21 sterols groups, but the percentage of positive area is higher in 40 mg x kg(-1) group than that in 20 mg x kg(-1) group, which differed from apoptosis results. Inhibiting the excessive expression of bcl-2 gene to promote apoptosis may be one of anti-tumor mechanisms for the C21 sterols in Baishouwu.
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PMID:[Apoptosis induced by the C21 sterols in Baishouwu and its mechanism of action in hepatoma]. 1763 1

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.
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PMID:Neural cell adhesion molecule (CD56)-positive B-cell lymphoma. 1763 42

Intravascular lymphoma or intravascular lymphomatosis (IVL) is an uncommon extranodal lymphoma, which gives rise to exclusively intravascular tumor growth. In 1/3 of the reported cases the disease debuts with involvement of the nervous system, which is particularly susceptible. Over the clinical course of the disease, 2/3 of the patients will present neurological symptoms. Owing to its characteristic growth pattern, IVL can give rise to very different central or peripheral nervous system neurological syndromes. Not infrequently a single patient will present more than one neurological syndrome. Moreover, the specificity of the neurological tests is low. All these factors explain the difficulties involved in diagnosing this entity and the fact that in most cases the diagnosis is established on autopsy study. This article presents the clinical, biological, radiological and post-mortem neuropathological findings in an immunocompetent patient with IVL. The onset was a cauda equina syndrome and showed multiple and varied neurological manifestations during the course of the disease, which progressed in the months before death. Spinal cord biopsy performed in life did not provide diagnostic findings because the vessels showed no neoplastic involvement. Immunohistochemical findings demonstrated large B-cell lymphoma. A review of the neurological features described in previously published cases of IVL is provided.
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PMID:Intravascular large B-cell lymphoma presenting with neurological syndromes: clinicopathologic study. 1770

IFN-alpha, a cytokine crucial for the innate immune response, also demonstrates antitumor activity. However, use of IFN-alpha as an anticancer drug is hampered by its short half-life and toxicity. One approach to improving IFN-alpha's therapeutic index is to increase its half-life and tumor localization by fusing it to a tumor-specific Ab. In the present study, we constructed a fusion protein consisting of anti-HER2/neu-IgG3 and IFN-alpha (anti-HER2/neu-IgG3-IFN-alpha) and investigated its effect on a murine B cell lymphoma, 38C13, expressing human HER2/neu. Anti-HER2/neu-IgG3-IFN-alpha exhibited potent inhibition of 38C13/HER2 tumor growth in vivo. Administration of three daily 1-microg doses of anti-HER2/neu-IgG3-IFN-alpha beginning 1 day after tumor challenge resulted in 88% of the mice remaining tumor free. Remarkably, anti-HER2/neu-IgG3-IFN-alpha demonstrated potent activity against established 38C13/HER2 tumors, with complete tumor remission observed in 38% of the mice treated with three daily doses of 5 microg of the fusion protein (p = 0.0001). Ab-mediated targeting of IFN-alpha induced growth arrest and apoptosis of lymphoma cells contributing to the antitumor effect. The fusion protein also had a longer in vivo half-life than rIFN-alpha. These results suggest that IFN-alpha Ab fusion proteins may be effective in the treatment of B cell lymphoma.
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PMID:Targeting IFN-alpha to B cell lymphoma by a tumor-specific antibody elicits potent antitumor activities. 1798 79

To determine the most robust and reproducible parameters for noninvasively estimating tumor cell burden in a murine model, we used real-time in vivo bioluminescent imaging to assess the growth kinetics and dissemination of luciferase-transfected Raji B-cell lymphoma. Bioluminescent signals were acquired every minute for 40 minutes after luciferin injection every other day post-tumor injection. The total 40-minute area under the curve (AUC) of photon intensity (photons/second) was calculated and compared with simplified fixed time point observations (every 5 minutes from 5 to 40 minutes after substrate injection). There was substantial variability in the shape of the time signal intensity curves at different stages of tumor growth in both the intravenous and subcutaneous models. The coefficient of variance in the AUC was 0.27 (intravenous) and 0.36 (subcutaneous) as values determined by fitting the curve, whereas the 20-minute time point measurement varied at 0.29 (intravenous) and 0.37 (subcutaneous). In both the subcutaneous and intravenous models, single time point measurements at 20 minutes had the highest correlation value with AUC. This simplified single time point measurement appears appropriate to estimate the total tumor burden in this model, but the substantial variance at each measurement must be considered in experimental designs.
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PMID:How reproducible is bioluminescent imaging of tumor cell growth? Single time point versus the dynamic measurement approach. 1809 16

This laboratory and others have shown that agents that inhibit the in vitro catalytic activity of methionine aminopeptidase-2 (MetAP2) are effective in blocking angiogenesis and tumor growth in preclinical models. However, these prototype MetAP2 inhibitors are clearly not optimized for therapeutic use in the clinic. We have discovered an orally active class of MetAP2 inhibitors, the anthranilic acid sulfonamides exemplified by A-800141, which is highly specific for MetAP2. This orally bioavailable inhibitor exhibits an antiangiogenesis effect and a broad anticancer activity in a variety of tumor xenografts including B cell lymphoma, neuroblastoma, and prostate and colon carcinomas, either as a single agent or in combination with cytotoxic agents. We also have developed a biomarker assay to evaluate in vivo MetAP2 inhibition in circulating mononuclear cells and in tumors. This biomarker assay is based on the N-terminal methionine status of the MetAP2-specific substrate GAPDH in these cells. In cell cultures in vitro, the sulfonamide MetAP2 inhibitor A-800141 caused the formation of GAPDH variants with an unprocessed N-terminal methionine. A-800141 blocked tumor growth and MetAP2 activity in a similar dose-response in mouse models, demonstrating the antitumor effects seen for A-800141 are causally connected to MetAP2 inhibition in vivo. The sulfonamide MetAP2 inhibitor and GAPDH biomarker in circulating leukocytes may be used for the development of a cancer treatment.
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PMID:Correlation of tumor growth suppression and methionine aminopetidase-2 activity blockade using an orally active inhibitor. 1825 27

An undifferentiated status and the epigenetic inactivation of tumor-suppressor genes are hallmarks of transformed cells. Promoter CpG island hypermethylation of differentiating genes, however, has rarely been reported. The Groucho homologue Transducin-like Enhancer of Split 1 (TLE1) is a multitasked transcriptional corepressor that acts through the acute myelogenous leukemia 1, Wnt, and Notch signaling pathways. We have found that TLE1 undergoes promoter CpG island hypermethylation-associated inactivation in hematologic malignancies, such as diffuse large B-cell lymphoma and AML. We also observed a mutual exclusivity of the epigenetic alteration of TLE1 and the cytogenetic alteration of AML1. TLE1 reintroduction in hypermethylated leukemia/lymphoma cells causes growth inhibition in colony assays and nude mice, whereas TLE1-short hairpin RNA depletion in unmethylated cells enhances tumor growth. We also show that these effects are mediated by TLE1 transcriptional repressor activity on its target genes, such as Cyclin D1, Colony-Stimulating Factor 1 receptor, and Hairy/Enhancer of Split 1. These data suggest that TLE1 epigenetic inactivation contributes to the development of hematologic malignancies by disrupting critical differentiation and growth-suppressing pathways.
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PMID:Epigenetic inactivation of the Groucho homologue gene TLE1 in hematologic malignancies. 1851 70

Maspin is a serine protease inhibitor with tumor suppressor activity. Maspin can suppress tumor growth and metastasis in vivo and tumor cell motility and invasion in vitro. Maspin also modulates apoptosis of tumor cells, possibly by modulating the expression of the B-cell lymphoma-2 family member. p53 regulates the expression of the tumor suppressor gene maspin. Breast cancer is known for its propensity to recur even after decades. The biology behind this phenomenon of tumor dormancy is poorly understood. This study was conducted to clarify the role of maspin and B-cell lymphoma-2 in early and late recurring breast cancer. The expression of maspin, B-cell lymphoma-2, p53, and estrogen receptor was studied by immunohistochemistry in 73 primary breast cancers and in their metastatic relapses detected within 2 years, or 5 or 10 years after primary surgery. The cytoplasmic expression of maspin was significantly higher in the primary tumors of the early metastasizing breast cancers (first tumor relapse within 2 years) and also in their metastases compared to late metastasizing cancers. An opposite activity was observed in the expression of B-cell lymphoma-2. The level of B-cell lymphoma-2 staining was lower in the early relapsing cancers and significantly lower in their metastases, compared to tumors which metastasized 5 or 10 years after primary surgery. High cytoplasmic expression of maspin and low expression of B-cell lymphoma-2 in primary breast cancer predict early tumor relapse.
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PMID:High expression of maspin is associated with early tumor relapse in breast cancer. 1942 67

beta-glucans are biological response modifiers with activatory effects on macrophages, dendritic cells (DC), granulocytes and NK cells. In this study, we investigated the effect of a soluble yeast-derived beta-(1-3), (1-6)-D-glucan on prophylactic peptide vaccination against the B cell lymphoma A20 in syngeneic Balb/c mice. We found that repeated immunizations with two MHC class-I restricted peptides derived from the tumor antigen survivin combined with oral co-administration of beta-glucan could significantly diminish intradermal tumor growth, whereas peptide vaccination alone failed to control tumor growth. beta-glucan as single agent induced only a weak but non-significant growth inhibitory effect. To determine whether the tumor inhibitory effect of the combined treatment was associated with the induction of a tumor-specific immune response we quantified splenic DC and macrophages, analyzed the maturation of DC and measured the frequency of peptide-specific CD8+ and CD4+ T cells. Treated mice showed significantly increased numbers of splenic macrophages and mature DC compared to untreated tumor-bearing mice. After restimulation with both peptides in vitro elevated levels of interferon (IFN)-gamma-secreting CD8+ T cells were found in two of four tested mice following treatment and one of four mice showed a strong increase of interleukin (IL)-4-secreting CD4+ T cells. Our data reveal a beneficial effect of beta-(1-3), (1-6)-D-glucan in tumor growth inhibition by tumor-specific peptide vaccination which may rely on a function of the polymeric sugar as immunological adjuvant.
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PMID:Oral administration of a soluble 1-3, 1-6 beta-glucan during prophylactic survivin peptide vaccination diminishes growth of a B cell lymphoma in mice. 1966 25

Therapeutic vaccination holds great potential as complementary treatment for non-Hodgkin's lymphoma. Here, we report that a therapeutic whole cell vaccine formulated with IL-2 adsorbed onto aluminum hydroxide as cytokine-depot formulation elicits potent antitumor immunity and induces delayed tumor growth, control of tumor dissemination and longer survival in mice challenged with A20-lymphoma. Therapeutic vaccination induced higher numbers of tumor's infiltrating lymphocytes (CD4(+) and CD8(+) T cells and NK cells), and the production of IFN-gamma and IL-4 by intratumoral CD4(+) T cells. Further, strong tumor antigen-specific cellular responses were detected at systemic level. Both the A20-derived antigenic material and the IL-2 depot formulation were required for induction of an effective immune response that impacted on cancer progression. All mice receiving any form of IL-2, either as part of the vaccine or alone as control, showed higher numbers of CD4(+)CD25(+/high)Foxp3(+) regulatory T cells (Treg) in the tumor, which might have a role in tumor progression in these animals. Nevertheless, for those animals that received the cytokine as part of the vaccine formulation, the overall effect was improved immune response and less disseminated disease, suggesting that therapeutic vaccination overcomes the potential detrimental effect of intratumoral Treg cells. Overall, the results presented here show that a simple vaccine formulation, that can be easily prepared under GMP conditions, is a promising strategy to be used in B-cell lymphoma and may have enough merit to be tested in clinical trials.
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PMID:A B-cell lymphoma vaccine using a depot formulation of interleukin-2 induces potent antitumor immunity despite increased numbers of intratumoral regulatory T cells. 1976 58


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