Systemic antitumor effect by regional hyperthermia combined with low-dose chemotherapy and immunologic correlates in an adolescent patient with rhabdomyosarcoma - a case report.

Introduction: An abscopal effect is a clinical observation whereby a local treatment is associated with regression of metastatic cancer at a site distant from the primary location of treatment. Here, we describe the clinical systemic effect induced by regional hyperthermia combined with low-dose chemotherapy and provide immunologic correlates.Case presentation: A 15-year-old patient had been diagnosed with alveolar rhabdomyosarcoma (ARMS). All previous treatment options failed in the patient including haploidentical stem cell transplantation and donor lymphocyte infusion. The patient presented with local and metastatic disease, and upon admission, underwent regional hyperthermia combined with low-dose chemotherapy. Immediately following therapy severe skin reactions were observed. Skin biopsies revealed an intraepithelial lymphocytic infiltration dominated by CD3+/CD8+ T cells with a regular network of dendritic cells. Clinical images compared before and during sequential treatment cycles showed complete metabolic response of the local tumor for more than 10 months of therapy. In addition, metastases completely regressed although they were not direct targets of regional hyperthermia. The systemic effect was associated with enhanced frequency of NK cells and T cells expressing the lectin-like natural-killer group 2 D activating receptor (NKG2D), an increase of the CD56bright subset of NK cells, as well as an increase of effector/memory and effector CD8+ and CD4+ T cells in the blood while the percentage of CD25+FOXP3+ regulatory T cells declined.Conclusions: Regional hyperthermia combined with low-dose chemotherapy had the potential to create a systemic effect which was associated with activation of NK cells and T cells.

Neuroprotection and enhanced neurogenesis by extract from the tropical plant Knema laurina after inflammatory damage in living brain tissue.

Inflammatory reactions in the CNS, resulting from a loss of control and involving a network of non-neuronal and neuronal cells, are major contributors to the onset and progress of several major neurodegenerative diseases. Therapeutic strategies should therefore keep or restore the well-controlled and finely-tuned balance of immune reactions, and protect neurons from inflammatory damage. In our study, we selected plants of the Malaysian rain forest by an ethnobotanic survey, and investigated them in cell-based-assay-systems and in living brain tissue cultures in order to identify anti-inflammatory and neuroprotective effects. We found that alcoholic extracts from the tropical plant Knema laurina (Black wild nutmeg) exhibited highly anti-inflammatory and neuroprotective effects in cell culture experiments, reduced NO- and IL-6-release from activated microglia cells dose-dependently, and protected living brain tissue from microglia-mediated inflammatory damage at a concentration of 30 microg/ml. On the intracellular level, the extract inhibited ERK-1/2-phosphorylation, IkB-phosphorylation and subsequently NF-kB-translocation in microglia cells. K. laurina belongs to the family of Myristicaceae, which have been used for centuries for treatment of digestive and inflammatory diseases and is also a major food plant of the Giant Hornbill. Moreover, extract from K. laurina promotes also neurogenesis in living brain tissue after oxygen-glucose deprivation. In conclusion, extract from K. laurina not only controls and limits inflammatory reaction after primary neuronal damage, it promotes moreover neurogenesis if given hours until days after stroke-like injury.

A combination of peppermint oil and caraway oil attenuates the post-inflammatory visceral hyperalgesia in a rat model.

OBJECTIVE: Visceral hyperalgesia plays a pivotal role in manifestation of symptoms in patients with functional gastrointestinal disorders. In clinical studies combined treatment of peppermint- and caraway oil significantly reduced symptoms. Thus, the aim of this study was to characterize the effects of peppermint- and caraway oil, individually and in combination, on visceral nociception in a rat model of post-inflammatory visceral hyperalgesia. MATERIAL AND METHODS: On day 28, male Lewis rats (n=80) were randomized to treatment with a rectal administration of trinitrobenzene sulphonic acid (TNBS)/ethanol or physiological saline solution. To quantify the visceromotor response to a standardized colorectal distension, bipolar electrodes were implanted into the external oblique musculature, just superior to the inguinal ligament for electromyographic recordings on day 3. On day 0, baseline measurement was performed. Thereafter, oral treatment with peppermint- or caraway oil or combination treatment was started and continued for 14 consecutive days. After 7 and 14 days of treatment a colorectal distension was performed. Colonic tissue samples were obtained on days 0, 7 and 14 to assess histological alterations due to the different treatment groups and the influence of different compounds. RESULTS: After a single instillation of TNBS/ethanol persistent elevation of the visceromotor response at all different time-points was observed, although colonic mucosa was completely normal. After 14 days of combined treatment with peppermint- and caraway oil, a reduced visceromotor response of up to 50% compared to placebo was detected in TNBS/ethanol pretreated animals. In contrast, neither peppermint- nor caraway oil had a significant effect on post-inflammatory visceral hyperalgesia. In saline-treated controls there was no significant difference in the visceromotor response. CONCLUSIONS: These data show that combined treatment with peppermint- and caraway oil modulates post-inflammatory visceral hyperalgesia synergistically. The exact mechanisms have to be further investigated.