Interstitial Docetaxel (Taxotere), Carmustine and Combined Interstitial Therapy: a Novel Treatment for Experimental Malignant Glioma

Docetaxel (Taxotere) is a hemisynthetic, anti-cancer compound with good preclinical and clinical activity in a variety of systemic neoplasms. We tested its activity against malignant gliomas using local delivery methods. Antitumor activity was assessed in vitro against human (U87 and U80 glioma) and rat brain-tumor (9L gliosarcoma and F98 glioma) cell lines. For in vivo evaluation, we incorporated docetaxel into a biodegradable polymer matrix, determined associated toxicity in the rat brain, and measured efficacy at extending survival in a rat model of malignant glioma. Also, we examined the combined local delivery of docetaxel with carmustine (BCNU) against the experimental intracranial glioma. Rats bearing intracranial 9L gliosarcomas were treated 5 days after tumor implantation with various polymers (placebo, 5% docetaxel, 3.8% BCNU, or 5% docetaxel and 3.8% BCNU combination). Animals receiving docetaxel polymers (n = 15, median survival 39.1 days) had significantly improved survival over control animals (n = 12, median survival 22.5 days, P = 0.01). Similarly, animals receiving BCNU polymers (n = 15, median survival 39.3 days, 13.3% long-term survivors) demonstrated an increase in survival compared to the controls (P = 0.04). Animals receiving the combination polymers demonstrated a modest increase in survival compared to either chemotherapeutic agent alone (n = 14, median survival 54.9 days, 28.6% long-term survivors) with markedly improved survival over controls (P = 0.003). We conclude that locally delivered docetaxel shows promise as a novel anti-glioma therapy and that the combination of drug regimens via biodegradable polymers may be a great therapeutic benefit to patients with malignant glioma.     

Aberrant CBFA2T3B gene promoter methylation in breast tumors

Background  

The CBFA2T3 locus located on the human chromosome region 16q24.3 is frequently deleted in breast tumors. CBFA2T3 gene expression levels are aberrant in breast tumor cell lines and the CBFA2T3B isoform is a potential tumor suppressor gene. In the absence of identified mutations to further support a role for this gene in tumorigenesis, we explored whether the CBFA2T3B promoter region is aberrantly methylated and whether this correlates with expression.     

Calcium requirements for the athlete

There is oftentimes a notion of "the more, the better" with regard to vitamin and mineral intake among individuals, and especially among athletes. Although adequate calcium intake is necessary to promote bone health and prevent osteoporosis, increased physical activity alone does not necessarily demand an increased intake of dietary calcium or other micronutrients. Athletes may lose calcium via sweat, in which case replenishment is advocated either via dietary intake of calcium-rich foods or a commercial calcium supplement. The important message to athletes is to consume a diet adequate in energy, protein, fat, vitamins, minerals, and fluids to support the physical demands and replenish the physiologic losses incurred with physical training.     

Astroglia induce cytotoxic effects on brain tumors via a nitric oxide-dependent pathway both in vitro and in vivo

OBJECTIVE: In the central nervous system, astroglia produce nitric oxide (NO) in response to cytokines. We investigated whether cytokine stimulation of astroglia could inhibit brain tumor cell growth in vitro and prolong survival in vivo via an NO-dependent pathway. METHODS: Astroglia cultures were stimulated with the cytokines lipopolysaccharide and interferon-gamma and subsequently seeded with tumor cell lines. Wild-type mice and inducible NO synthase-knockout mice received in vivo cytokine stimulation followed by B16F10 murine melanoma challenge. RESULTS: Our in vitro studies demonstrate that astroglia stimulated to produce NO by the addition of cytokines dose-dependently inhibit the growth of one primary rat brain tumor cell line (9L) and three primary human brain tumor cell lines (H80, U87, and U373). This inhibition of tumor cell growth is also observed in metastatic cell lines (B16F10 melanoma, Lewis lung carcinoma, and CT26 colon). Cultured astrocytes from inducible NO synthase-knockout mice, which are incapable of induction of NO, are without the enhanced tumoricidal effect. Furthermore, when C57BL/6 mice are primed to produce NO through stereotactic intracranial administration of lipopolysaccharide plus interferon-gamma and subsequently challenged with B16F10 murine melanoma, survival is significantly prolonged, with a median survival of 26 days versus 16 days in the control group (P < 0.001). The addition of an NO synthase inhibitor (N(G)-nitro-l-arginine methyl ester) decreases this beneficial effect (median survival, 21 d). CONCLUSION: These findings suggest that NO may have an important role as a defense mechanism molecule against brain tumors; stimulation or modification of this mechanism may represent a new approach to the treatment of primary and metastatic brain tumors.     

Sacrococcygeal ganglioneuroma

Ganglioneuromas are benign slow-growing masses that can be treated with complete surgical extirpation without any adjuvant therapy. Such lesions involving the sacrococcygeal region are exceedingly rare. The authors present the case of a 70-year-old woman with a sacrococcygeal ganglioneuroma treated by total en bloc resection. This patient also had a previous coccygeal fracture. To the authors' knowledge, there are no other reports of ganglioneuroma in association with a history of trauma.     

Chronic smoke exposure alters the phenotype pattern and the metabolic response in human alveolar macrophages

Smoking induces a chronic inflammatory process in the lower respiratory tract, where the alveolar macrophages (AM) are the main phagocytes. In the present study, the expressions of different membrane glycoproteins (CD11abc, CD71, CD54, CD14 and CD16) were determined by flow cytometry in AM from smokers and non-smokers after quenching of the intracellular autofluorescence. The metabolic activity of the AM was quantified as a functional test. The expressions of CD11a, CD54 and CD71 were higher in non-smokers' AM than in smokers'. The expressions of CD11b and CD16 were similar between the groups, while the CD11c was higher in smokers' AM compared with non-smokers’. The expression of CD14 was weak in both groups, therefore there was no clear-cut difference between the background and positively labelled cell populations. The metabolic response after in vitro stimulation with the phorbol ester phorbol myristate acetate (PMA) was higher in non-smokers' than in smokers' AM. Our results indicate that chronic exposure to tobacco smoke influences both the expression of AM membrane antigens and the metabolic activity. AM from non-smokers express a phenotype more related to cell proliferation and an accessory function. In contrast, receptors reflecting adhesion and phagocytosis were unaltered or even increased in smokers' AM. The findings suggest a functional change in the AM population after chronic smoke exposure.     

Hyperactivation may assist human spermatozoa to detach from intimate association with the endosalpinx

The behaviour of human spermatozoa was observed during incubationwith epithelial cells isolated from the isthmic and ampullarysections of human uterine (Fallopian) tubes.During incubation,spermatozoa were observed to bind to the epithelial cells ofthe tube (the endosalpinx), and individual spermatozoa attachedand detached at intervals.The kinematic characteristics of spermatozoaduring these behaviour patterns were determined. The resultsshowed that detached spermatozoa typically had an increasedcurvilinear velocity and amplitude of lateral head displacement,accompaniedby a decrease in their linearity. Significantly (P<0.01)more of the detaching spermatozoa were hyperactivated than werespermatozoa prior to attachment for both isthmic (35.3 ±5.5 versus 4.0 ± 3.3%mean ± SEM) and ampullary(26.0 ± 7.0 versus 2.0 ±1.4%) regions. Incubationwith epithelial cells from either region produced no differencesin any category of sperm behaviour. Furthermore, there was nosignificant difference between regions in the amount of timespermatozoa spent bound (33.6 ± 12.9 and 20.6 ±3.0 s for isthmic and ampullary tissue respectively). Theseresults support the hypothesis that hyperactivation may assistspermatozoa in breaking connections with epithelial cells.     

Spine stereotactic radiosurgery for metastases from hepatobiliary malignancies: patient selection using PRISM scoring

Journal of Neuro-Oncology - Glioblastoma multiforme (GBM) is one of the most devastating brain malignancies worldwide and is considered to be incurable. However, the mechanisms underlying its...