A novel component from citrus, ginger, and mushroom family exhibits antitumor activity on human meningioma cells through suppressing the Wnt/ß-catenin signaling pathway.

Recurrent meningiomas constitute an uncommon but significant problem after standard (surgery and radiation) therapy failure. Current chemotherapies (hydroxyurea, RU-486, and interferon-α) are only of marginal benefit. There is an urgent need for more effective treatments for meningioma patients who have failed surgery and radiation therapy. Limonin, Tangeritin, Zerumbone, 6-Gingerol, Ganoderic Acid A, and Ganoderic Acid DM are some of the plant derivatives that have anti-tumorgenic properties and cause cell death in meningioma cells in vitro. Due to its ease of administration, long-term tolerability, and low incidence of long-term side effects, we explored its potential as a therapeutic agent against meningiomas by examining their efficacy in vitro against meningioma cells. Treatment effects were assessed using MTT assay, Western blot analysis, caspases assay, and DNA fragmentation assay. Results indicated that treatments of IOMM-Lee and CH157MN meningioma cells with Limonin, Tangeritin, Zerumbone, 6-Gingerol, Ganoderic Acid A, and Ganoderic Acid DM induced apoptosis with enhanced phosphorylation of glycogen synthase kinase 3 ß (GSK3ß) via inhibition of the Wnt5/ß-catenin pathway. These drugs did not induce apoptosis in normal human neurons. Other events in apoptosis included downregulation of tetraspanin protein (TSPAN12), survival proteins (Bcl-XL and Mcl-1), and overexpression apoptotic factors (Bax and caspase-3). These results provide preliminary strong evidence that medicinal plants containing Limonin, Tangeritin, 6-Gingerol, Zerumbone, Ganoderic Acid A, and Ganoderic Acid DM can be applied to high-grade meningiomas as a therapeutic agent, and suggests that further in vivo studies are necessary to explore its potential as a therapeutic agent against malignant meningiomas.

Mechanisms and clinical significance of histone deacetylase inhibitors: epigenetic glioblastoma therapy.

Glioblastoma is the most common and deadliest of malignant primary brain tumors (Grade IV astrocytoma) in adults. Current standard treatments have been improving but patient prognosis still remains unacceptably devastating. Glioblastoma recurrence is linked to epigenetic mechanisms and cellular pathways. Thus, greater knowledge of the cellular, genetic and epigenetic origin of glioblastoma is the key for advancing glioblastoma treatment. One rapidly growing field of treatment, epigenetic modifiers; histone deacetylase inhibitors (HDACis), has now shown much promise for improving patient outcomes through regulation of the acetylation states of histone proteins (a form of epigenetic modulation) and other non-histone protein targets. HDAC inhibitors have been shown, in a pre-clinical setting, to be effective anticancer agents via multiple mechanisms, by up-regulating expression of tumor suppressor genes, inhibiting oncogenes, inhibiting tumor angiogenesis and up-regulating the immune system. There are many HDAC inhibitors that are currently in pre-clinical and clinical stages of investigation for various types of cancers. This review will explain the theory of epigenetic cancer therapy, identify HDAC inhibitors that are being investigated for glioblastoma therapy, explain the mechanisms of therapeutic effects as demonstrated by pre-clinical and clinical studies and describe the current status of development of these drugs as they pertain to glioblastoma therapy.

Molecular Targets and Treatment of Meningioma.

Meningiomas are by far the most common tumors arising from the meninges. A myriad of aberrant signaling pathways involved with meningioma tumorigenesis, have been discovered. Understanding these disrupted pathways will aid in deciphering the relationship between various genetic changes and their downstream effects on meningioma pathogenesis. An understanding of the genetic and molecular profile of meningioma would provide a valuable first step towards developing more effective treatments for this intracranial tumor. Chromosomes 1, 10, 14, 22, their associated genes, and other potential targets have been linked to meningioma proliferation and progression. It is presumed that through an understanding of these genetic factors, more educated meningioma treatment techniques can be implemented. Future therapies will include combinations of targeted molecular agents including gene therapy, si-RNA mediation, proton therapy, and other approaches as a result of continued progress in the understanding of genetic and biological changes associated with meningiomas. This review provides an overview of the current knowledge of the genetic, signaling and molecular profile of meningioma and possible treatments strategies associated with such profiles.

Current Studies of Immunotherapy on Glioblastoma.

Glioblastoma is a form of brain tumor with a very high morbidity and mortality. Despite decades of research, the best treatments currently in clinical practice only extend survival by a number of months. A promising alternative to conventional treatment for glioblastomas is immunotherapy. Although proposed over a century ago, the field of cancer immunotherapy has historically struggled to translate it into effective clinical treatments. Better understanding is needed of the various regulatory and co-stimulatory factors in the glioblastoma patient for more efficient immunotherapy treatments. The tumor microenvironment is anatomically shielded from normal immune-surveillance by the blood-brain barrier, irregular lymphatic drainage system, and it's in a potently immunosuppressive environment. Immunotherapy can potentially manipulate these forces effectively to enhance anti-tumor immune response and clinical benefit. New treatments utilizing the immune system show promise in terms of targeting and efficacy. This review article attempts to discuss current practices in glioblastoma treatment, the theory behind immunotherapy, and current research into various clinical trials.

Growth factor use in medication-induced hematologic toxicity.

Myelosuppression is a dose-limiting adverse effect with antineoplastic therapy and nonchemotherapy medications. Clinicians have data and guidelines to provide direction for the management of neutropenia and thrombocytopenia in patients with malignancies. Clinical situations outside oncology extrapolate these data along with limited data sets for those patients who demonstrate myelosuppressive effects from medications that are not traditionally considered cytotoxic. Pharmacological treatments can be used to help ameliorate the myelosuppressive toxicities. Recombinant technology has provided growth factors to counteract or lessen the degree of toxicity from myelosuppressive medications including chemotherapy. Clinical strategies and future trends on how to mitigate medication-related myelosuppression are discussed.

Retrospective review of hemoglobin and/or hematocrit levels with occurrence of thrombosis in cancer patients treated with erythropoiesis stimulating agents.

BACKGROUND: No data exists that directly compares hemoglobin and hematocrit levels between cancer patients with and without occurrence of thrombosis during treatment with erythropoiesis stimulating agents (ESAs). OBJECTIVE: To determine the association of hemoglobin and hematocrit levels with the occurrence of thrombosis in cancer patients treated with ESAs. METHODS: A retrospective case-control study approved by the Institutional Review Board was conducted on cancer patients billed for epoetin or darbepoetin between 1 July 2002 and 30 June 2007. Cases were defined as patients billed for thrombosis while controls were defined as patients not billed for thrombosis. RESULTS: Sixteen patients had an occurrence of thrombosis (cases) and were matched to 16 patients that did not have an occurrence of thrombosis (controls) based on age, sex, and cancer type. The mean peak hemoglobin levels for cases and controls were 12.6 +/- 1.2 g/dL versus 12.6 +/- 1.4 g/dL (p = 0.9). The mean peak hematocrit levels for cases and controls were 37.3 +/- 3.8% versus 37.9 +/- 4.3% (p = 0.8). For the 16/586 (2.7%) patients with thrombosis, the mean hemoglobin and hematocrit at time of thrombosis were 9.6 +/- 1.0 g/dL and 28.9 +/- 3.1%. A significant identifiable risk factor for thrombosis between the cases and controls was history of thrombosis 31.3% versus 0% (p = 0.04). CONCLUSION: There was no statistical difference in peak hemoglobin and hematocrit levels between patients with thrombosis and those without thrombosis. Further study is warranted to determine if these levels are true risk factors for thrombosis.

Hypersensitivity reactions to oxaliplatin: what nurses need to know.

Colorectal cancer (CRC) is the third-leading cause of cancer death in the United States. With the advent of new chemotherapy drugs, such as oxaliplatin, for CRC, disease-free and long-term survival has improved in this patient population. As oxaliplatin use increases, more hypersensitivity reactions may be expected. The etiology of these reactions is unclear but may be a combination of immunologic responses. Pretreatment, treatment, and desensitization protocols are available to prevent and treat hypersensitivity reactions. Nurses' rapid assessment and management of infusion-related hypersensitivity reactions are vital to ensuring the safe administration of oxaliplatin.

Pain and personality profiles in burning mouth syndrome.

The McGill Pain Questionnaire (MPQ) and the Minnesota Multiphasic Personality Inventory (MMPI) were administered to 72 subjects with burning mouth syndrome (BMS) who were also requested to match the levels of their clinical pain to line lengths on a visual analogue scale (VAS) and to experimentally induced warm and painful thermal stimuli. The responses of 102 toothache pain subjects and 43 asymptomatic age- and sex-matched control subjects were used to compare the responses of the BMS subjects on the MPQ and MMPI, respectively. The results indicated that BMS pain is quantitatively similar to, but qualitatively different from, toothache pain, that self-reports of BMS pain appear to be valid, that when compared to the asymptomatic control subjects, BMS subjects show elevations in certain personality characteristics which are similar to those seen in other chronic pain patients, and that these personality disturbances tend to increase with increased pain. Therefore, our findings indicate that the pain of BMS is more severe than has previously been suggested and that the severity of this pain may explain some of the personality changes which occur in the BMS subjects.