J L Arbiser

..Thus, overall, our results indicate that NF-kappaB and NF-kappaB-regulated gene expression inhibited by honokiol enhances apoptosis and suppresses osteoclastogenesis and invasion...

..Epstein-Barr virus (EBV) is associated with the malignant transformation of B, T, and NK lymphocytes in humans, especially in immunosuppressed individuals...

..Collectively, we conclude that c-FLIP down-regulation is a key event for honokiol to modulate the death receptor-induced apoptosis...

..Our findings provide a rationale for the combined use of rapamycin and imatinib, both FDA approved drugs, for the treatment of TS...

..Discontinuation of oral clioquinol use led to elimination of SMON, however, the mechanism of how clioquinol induces neurotoxicity is unclear...

..Progressive growth and malignant transformation of brain and kidney lesions constitute the major cause of morbidity and mortality in adults with tuberous sclerosis. In addition, growth of skin lesions may be disfiguring to patients...

..Fumarate, a natural product that is generated internally in humans during the Krebs cycle, is an attractive alternative to these therapies. However, the mechanism for fumarate's activity in psoriasis remains unknown...

..Thus, we describe a novel but simple method of determining the functional tyrosine kinase profile of a neoplastic cell and our results suggest that STI571 might be useful in the treatment of neoplasms commonly seen in patients with TS...

..We wished to determine whether virally- induced endothelial tumors are rejected by CD4 and CD8 lymphocytes, and whether there are differences in requirements for costimulation in the rejection of these tumors by lymphocyte subsets...

..This knowledge is important because inhibitors of VEGF, including bevacizumab (anti-VEGF antibodies) and sorafenib (Braf/VEGFR2 kinase inhibitor), have already entered the clinic. These agents may "remodel" tumor signaling...

..This is the first description of specific abnormalities in tumor suppressor genes in RDEB associated SCC, and demonstrates that alterations in both p53 and p16ink4a can contribute to RDEB associated SCC...

..Based upon these findings, preclinical and clinical trials of topical cinnamate esters as proteasome inhibitors are warranted for psoriasis and other inflammatory disorders...

..These strategies may be useful in the design of prevention and treatment strategies for cancer...

..I hypothesize that hemangiomas, angiosarcomas, and vascular malformations represent the extremes of signaling abnormalities seen in pathogenic angiogenesis...

..They then studied pharmacologic COX inhibition in mice and humans with loss of patch, finding a trend in humans toward decreased BCC burden. This finding has implications for public health...

..Nox1 induction of VEGF is eliminated by coexpression of catalase, indicating that hydrogen peroxide signals part of the switch to the angiogenic phenotype...

..Currently, a major focus of pharmaceutical companies is to develop ever more potent and specific tyrosine kinases. The results presented here suggest that this approach may not be successful...

..Endothelial malignancies, such as angiosarcoma and hemangioendothelioma, are often resistant to chemotherapy and surgery, and may result in death. Improved means of therapy are needed for these disorders...

..This method allows rapid isolation of stromal cells and should facilitate biochemical and genetic analysis of tumor-stromal interactions...

..3-fold over control) and tumor growth (5-fold over control). Peripheral corticotropin-releasing hormone may thus enhance local angiogenesis, which may provide clues to its function outside of the nervous system...

..These results suggest that high level expression of VEGF in endothelial cells may result in malignant transformation. This transformation process likely involves both autocrine and paracrine pathways...

..Activation of mitogen-activated protein kinase (MAPK) is an important signal transduction mechanism that may predict response of a tumor to chemotherapy...

..These cells should serve as a valuable tool to elucidate signal transduction pathways underlying renal angiomyolipomas...

..Interestingly, solenopsin also inhibited Akt-1 activity in an ATP-competitive manner in vitro without affecting 27 of 28 other protein kinases tested...

..Given its antiangiogenic and anti-inflammatory activities, carbazole is likely a major component of the antipsoriatic activity of coal tar. Carbazole and derivatives may be useful in the therapy of human psoriasis...

..These ulcers cause significant morbidity through pain and interference with eating. Thalidomide, an angiogenesis inhibitor, is efficacious for the treatment of aphthous ulcers...

..The genetic changes in carcinogenesis in these organs involve different genes, but curcumin is effective in preventing carcinogenesis in both organs. A possible explanation for this finding is that curcumin may inhibit angiogenesis...

..Our model allows the assessment of epigenetic changes that occur during human carcinogenesis. In addition, these studies provide insight into the clinical failure of tyrosine kinase inhibitors as monotherapy for advanced malignancy...

..Activation of MAP kinase signaling may be an important pathway involved in melanoma transformation. Inhibition of MAP kinase signaling may be useful in the prevention and treatment of melanoma...

..Inhibition of MAP kinase leads to decreased tumor growth in vivo. Pharmacological inhibition of MAP kinase may be a therapeutic target in the prevention and treatment of TS-related tumors...

..Our preclinical data suggests that honokiol is a systemically available and non-toxic inhibitor of angiogenesis and should be further evaluated as a potential chemotherapeutic agent...

..Our data are the first to demonstrate that specific signaling abnormalities underlie specific hamartomas in a model of a human genetic disorder...

..The distribution of these growth factors in skin disease has not been determined...

..Infection of cultured endothelium with B. bacilliformis also resulted in induction of angiopoetin-2 in vitro. These findings imply a collaboration between infected endothelium and overlying epidermis to induce angiogenesis...

..In addition, occupational exposure to nickel has been shown to result in an increased risk of carcinogenesis. The molecular mechanisms of foreign body-induced carcinogenesis are not fully understood...

..Knowledge of the dual activities of honokiol can assist with the development of honokiol derivatives and the design of clinical trials that will maximize the potential benefit of honokiol in the patient setting...

..Use of this stain may facilitate detection of micrometastases in sentinel lymph nodes...

..We report a case of a young woman whose disorder responded to isotretinoin. Our findings have potential relevance to the treatment of skin disorders in which ulceration is a prominent feature...

..5x10(6)M(-1)s(-1)). Therefore, honokiol is an effective scavenger of both superoxide and peroxyl radicals, which may be important for physiological activity of honokiol...

..A separation of honokiol 1 from the closely structurally related magnolol 2 was developed. Honokiol demonstrated weak activity against HIV-1 in human lymphocytes...

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..Akt thus serves as a molecular switch that increases angiogenesis and the generation of superoxide, fostering more aggressive tumor behavior. Targeting Akt and ROS may be of therapeutic importance in treatment of advanced melanoma...

..has been shown to induce apoptosis in malignant cells. The effect of honokiol and the combined therapy with docetaxel on prostate cancer (PCa) growth and bone metastasis was investigated in experimental models...

..Curcumin's effect on the overall process of angiogenesis compounds its enormous potential as an antiangiogenic drug...

..Given their low cost, ease of application, and favorable side effect profile, triphenylmethanes must be considered legitimate treatment options for pyodermas, particularly in the face of continued and emerging bacterial resistance...

..Several of the plaques, including one on his right flank, had overlying deep ulcerations (Figure 1A and 1B). Bilateral inguinal lymphadenopathy was present...

..CONCLUSIONS: Infection with Treponema pallidum results in increased angiogenesis in secondary syphilis. The mechanism for increased angiogenesis may involve elaboration of angiogenic cytokines, such as VEGF and epidermal growth factor...

..In this review, we highlight our experience with a group of existing and novel, small molecules that combine several modes of action against angiogenesis in addition to other properties--triarylmethane dyes and fulvene derivatives...

..The association of increased proliferation and tumor type may prove to be clinically useful and shed light on the role of sequential oncogenic alterations in NLT...

..Mediators such as VEGF and angiopoietin-2 play significant roles in the pathophysiology and may even account for the maintenance of the chronic inflammatory state. Targets in this shared pathway may offer alternative avenues for therapy...

..Certain compounds exhibited specific anti-proliferation activity against SVR cells and moderate anti-HIV-1 activity in primary human lymphocytes. Compound 5h was the most potent compound and its anti-tumor activity was evaluated in vivo...

..CONCLUSIONS: Our findings implicate MAPK activation as an early event in melanoma progression, and MAPK may be a potential target for pharmacologic intervention...

..Currently, no entirely satisfactory method of treatment exists for these lesions. Recently, a patient who was enrolled in a clinical trial of topical tacrolimus for atopic dermatitis applied this drug to a keloid and noted clearing...

..While a cure is not yet within grasp, the picture on the horizon is less hazy and the next decade promises to yield exciting new therapeutic discoveries...

..These results support a novel histogenesis of angiomyolipoma as a defect in differentiation of stem cell precursors...

..In conclusion, the present study establishes Nox4 as a critical regulator of hemangioma growth and identifies fulvenes as a potential class of candidate inhibitor to therapeutically interfere with Nox function...

..Studies were carried out to determine the mechanism of action of Tris DBA...

..Use of antidepressants that decrease Akt may improve the efficacy of interferon and other therapies against melanoma. Further studies are needed to elucidate whether sertraline acts as an Akt inhibitor in melanoma...

..Topical antiangiogenic therapy, directed at either down-regulating epidermal VEGF or inhibiting keratinocyte-derived VEGF activity on its endothelial receptors, may be useful in the treatment of keloids...

..Our findings imply that inhibition of ROS may be useful in the treatment of EBV-induced neoplasia...

..The occurrences of arteriovenous malformations in territories susceptible to increased remodeling also point towards epigenetic events in the development of vascular malformations...

..Pachyonychia congenita (PC) is a rare keratin disorder that typically presents with nail dystrophy and focal plantar keratoderma. We present seven cases of PC with transgrediens involvement of the dorsal feet...

..The phenotype of the reactive oxygen driven tumor can be monitored using available markers already in use in most hospital laboratories...

..To examine the potential role of angiogenesis in leprosy...

..However, it has been correlated with malignant behavior in pancreatic and ovarian cancer. The role of maspin in malignant melanoma (MM) has not yet been systematically examined...

..This expression pattern may serve as a marker for cell cycle inhibition during peripheral nerve tumorigenesis...

..Akt1 is a serine-threonine protein kinase, which is a key mediator of resistance to programmed cell death. Our objective was to determine whether sustained activation of Akt1 could lead to vascular malformation in mice...

..CONCLUSION: We found that Wilms tumor 1 is expressed in most melanomas but is nearly absent in nevi. Immunohistochemical analysis for Wilms tumor 1 may be clinically useful in distinguishing nevi from melanoma...

..These findings provide a rationale for clinical trials of inhibitors of gli-1 signaling, including tacrolimus and sizolimus, for the treatment of cutaneous sarcoidosis and other granulomatous disorders of the skin...

..Inhibitors of matrix metalloproteinases may be useful in the prevention and treatment of calciphylaxis...

..Since there are no Akt inhibitors approved for clinical use, we examined phosphorylated S6 expression, a downstream target of Akt. Phosphorylated S6 indicates potential sensitivity to rapamycin...

..We observed rapid improvement in skin stiffness and mobility. Our results provide the rationale for larger clinical trials of rapamycin in scleroderma and other fibrotic disorders...

..However, this activity must be tightly regulated as aberrant activity can disturb the ability of endothelial cells to undergo differentiation...

..Phosphatidylinositol 3-(PI 3)-kinase and reactive oxygen species (ROSs) were involved in the PSK-induced activation of monocytes. Restimulation of the cultures with EBV-transformed B cells generated specific cytotoxic activity...

..These compounds were screened for antiangiogenic properties via an in vitro SVR assay and were found to inhibit cell proliferation...

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..These results suggest that TRAIL can induce apoptosis in premalignant cells and suggests a novel therapy for the treatment of premalignant lesions in vivo...

..Our data suggest that HNK is a systemically available, non-toxic inhibitor of breast cancer growth and should be examined for clinical applications...

..Due to both their commercial availability and their fairly straightforward synthetic preparation, these low molecular weight compounds are attractive leads for developing future angiogenic inhibitors...

..We anticipate that this cysteinyl-labeling enrichment strategy can be applied broadly to study reversible oxidation as a mechanism of harnessing PTP catalytic activity in a variety of signaling pathways...

..Honokiol is a compound that suppresses tumor growth in mouse models. The purpose of this study was to investigate the effect of honokiol on PLD survival signals and the Ras dependence of these signals...

..These promising findings suggest that the nontoxic anti-inflammatory properties of HNK could be valuable for blocking the autoimmune response...

..It is concluded that Shb regulates apoptosis and cell shape in tumor endothelial cells via FAK, and that Shb is a potential target for inhibition of angiogenesis...

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..However, time-lapse photography showed a significant increase in random motility in MAE-Amot cells. We conclude that angiomotin may promote angiogenesis by both stimulating invasion as well as stabilizing established tubes...

..Interestingly, exogenously added C(4)-homoserine lactone (HSL), but not 3-oxo-C(12)-HSL, restored P. aeruginosa QS signaling, suggesting that solenopsin A targets the C(4)-HSL-dependent rhl QS system...

..Specific Aim 3. To determine whether dysregulation of p16ink4a and PTCH (patched) acts as a modifier of theTS phenotype in transgenic mice expressing dominant negative tuberin. ..

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