Safety of Therapeutic Fever Induction in Cancer Patients Using Approved PAMP Drugs.

William Coley, between 1895 and 1936, treated hundreds of cancer patients using infusions of fever inducing bacerial extracts. Similar experiments were done by Klyuyeva and co-workers in the 1940ies in Russia using trypanosoma extracts. Many remissions and cures were reported.

Coley's Lessons Remembered: Augmenting Mistletoe Therapy.

The following four observations point in the same direction, namely that there is an unleveraged potential for stimulating the innate immune system against cancer: (1) experimental treatments with bacterial extracts more than 100 years ago by Coley and contemporaries, (2) a positive correlation between spontaneous regressions and febrile infection, (3) epidemiological data suggesting an inverse correlation between a history of infection and the likelihood of developing cancer, and (4) our recent finding that a cocktail of pattern recognition receptor ligands (PRRLs) can eradicate solid tumors in cancer mice if applied metronomically. Because the main immunostimulating component of mistletoe extract (ME), mistletoe lectin, has been shown to be a PRRL as well, we suggest to apply ME in combination with additional PRRLs. Additional PRRLs can be found in approved drugs already on the market.

Mistletoe lectin has a shiga toxin-like structure and should be combined with other Toll-like receptor ligands in cancer therapy.

Mistletoe extract (ME) is applied as an adjuvant treatment in cancer therapy in thousands of patients each year in Europe. The main immunostimulating component of mistletoe extract, mistletoe lectin, recently has been shown to be a pattern recognition receptor ligand and hence is binding to an important class of pathogen-sensing receptors. Pattern recognition receptor ligands are potent activators of dendritic cells.

PDBselect 1992-2009 and PDBfilter-select.

PDBselect (http://bioinfo.tg.fh-giessen.

Toward general prophylactic cancer vaccination.

It is well established that chronic infections can lead to cancer. Almost unknown is that, in contrast, acute brief viral and bacterial infections may have beneficial effects in cases of established neoplastic disease, while exposure to pathogenic products by infection, vaccination, and inhalation can cause prophylactic effects. In the following I will align evidence from case studies of spontaneous regression and from epidemiological studies with recent immunology to conclude that pathogenic substances belonging to the group of "pathogen-associated molecular patterns" can trigger the innate immune system to establish anti-neoplastic immune responses.

Pathogen-associated molecular pattern in cancer immunotherapy.

Observations from different research frontiers--epidemiological data, case studies on spontaneous regressions from cancer, clinical studies, tumor immunology--indicate that exposure by vaccination or infection to pathogen-associated molecular patterns (PAMP) can have beneficial effects on neoplastic diseases, both prophylactically and therapeutically. These effects have not yet been harnessed to their full extent for the prophylaxis and therapy of cancer. Here, we summarize clinical, epidemiological, and experimental data and discuss the role of PAMP in cancer therapy.

ADP-ribosylation factor (ARF)-like 7 (ARL7) is induced by cholesterol loading and participates in apolipoprotein AI-dependent cholesterol export.

Here, we identify ADP-ribosylation factor (ARF)-like 7 (ARL7) as the only ARF- and ARL-family member whose mRNA-expression is induced by liver X-receptor/retinoid X-receptor agonists or cholesterol loading in human macrophages. Moreover, subcellular distribution of mutant and wild type ARL7-enhanced green fluorescent protein (EGFP) supports that ARL7 may be involved in a vesicular transport step between a perinuclear compartment and the plasma membrane. Therefore, we investigated the effect of ARL7 over-expression on the cholesterol secretory pathway.