No abstract

We investigated the effect of green tea (GT) in unilateral chronic constriction injury (CCI) to the rat scaitic nerve. Five groups (n = 6 rats/group) sham group: rats which underwent operation but with no ligation to the scaitic nerve, and received tap water for two weeks before and for five weeks after the surgery. Four experimental groups underwent CCI to the right sciatic nerve, divided randomly as follows: group E were given tap water throughout the study. Group B received GT before and after CCI. Group C was given GT following CCI. Group D received GT for two weeks prior to CCI. Groups which consumed GT showed significant improvement in the toe spread (P < 0.001) and foot positioning (P < 0.001) tests compared to the experimental control group. In addition, these groups showed a significant decrease in the behavioral mechanical hyperalgesia (P < 0.0001) and allodynia (P < 0.0002). Consumption of GT improves both reflexes and sensation which are often affected in the course of peripheral neuropathy.

Liposomal meso-tetrakis-phenylporphyrin (TPP) was tested for photodynamic therapy (PDT) of human amelanotic melanomas implanted in nude mice. After intratumoural TPP application (15 mg.kg -1 ) followed by PDT lamp irradiation (600 -700 nm, 635 nm peak), tumours retained their original volume up to the 23rd day post-PDT, whereas volumes increased 6 times in controls. PDT with intravenously (i. Key words: photodynamic therapy; meso-tetrakis-phenylporphyrin; meso-tetrakis-sulfonatophenylporphyrin; nude mice; liposomal drug delivery; human amelanotic melanoma A substantial difference was found in photodynamic therapy (PDT) of tumours between the effects of hydrophobic vs. hydrophilic photosensitizers. Although exceptions exist, hydrophilic photosensitizers frequently destroy the tumour bed microvasculature, which results in vascular stasis, anoxia and tumour necrosis, 1-3 whereas the hydrophobic photosensitizers can penetrate deeply into cells and might cause better disintegration of their membranes and organelles, thus directly killing the tumour cells. 2 Hydrophobic porphyrins, once administered to patients, are tightly bound by serum low-density lipoproteins, 4 -6 which are preferentially internalized by receptor-mediated endocytosis in the hyperprolife-rating cells. 7,8 Hydrophobic photosensitizers could be advantageous even for topical PDT, since they keep their direct cell-killing effect. Liposome-mediated delivery might increase the efficacy of PDT. It also overcomes problems caused by the water insolubility of hydrophobic compounds. In particular, the small unilamellar vesicles are significantly taken up by skin and intestine. 9 Hence, liposomal preparations of photosensitizers have been studied quite frequently and were developed commercially. 6,10 -21 We tried to develop a liposomal form of a hydrophobic photosensitizer for both topical and intravenous application. The compound of our choice was meso-tetrakisphenylporphy-rin (TPP), the nonsulfonated derivative of meso-tetrakis-sulfonatophenylporphyrin, TPPS 4 . 23 TPPS 4 has been abandoned in human medicine for some years due to the reported neurotoxicity after intraperitoneal application. 24 Later, these problems were solved by a better purification of the product. For example, Jirsa et al. 25 have synthesized pure TPPS 4 that did not delay motor nerve conduction velocity in rats or rabbits even in high doses. 26 Recently, we have also shown that hydrophobic TPP (nonsulfonated TPPS 4 ) in lipid environment is also the efficient singlet oxygen producer. 27 Even being shielded by lipid headgroups, TPP in a membrane interacts with the native oxygen solubilized in the surrounding aqueous space. Moreover, we have demonstrated the reducing decay rate of triplet-states of TPP in the membrane system, which can be due to an irreversible interaction of the singlet oxygen formed in the previous reaction cycle with the membrane lipids. 27 All these results demonstrated on the physicochemical basis a possible potential of the liposomal form of TPP to destroy the me...

To develop an effective pharmaceutical treatment for a disease, we need to fully understand the biological behavior of that disease, especially when dealing with cancer. The current available treatment for cancer may help in lessening the burden of the disease or, on certain occasions, in increasing the survival of the patient. However, a total eradication of cancer remains the researchers' hope. Some of the discoveries in the field of medicine relied on observations of natural events. Among these events is the spontaneous regression of cancer. It has been argued that such regression could be immunologically-mediated, but no direct evidence has been shown to support such an argument. We, hereby, provide compelling evidence that spontaneous cancer regression in humans is immunologically-mediated, hoping that the results from this study would stimulate the pharmaceutical industry to focus more on cancer vaccine immunotherapy. Our results showed that patients with>3 primary melanomas (very rare group among cancer patients) develop significant histopathological spontaneous regression of further melanomas that they could acquire during their life (P=0.0080) as compared to patients with single primary melanoma where the phenomenon of spontaneous regression is absent or minimal. It seems that such regression resulted from the repeated exposure to the tumor which mimics a self-immunization process. Analysis of the regressing tumors revealed heavy infiltration by T lymphocytes as compared to non-regressing tumors (P<0.0001), the predominant of which were T cytotoxic rather than T helper. Mature dendritic cells were also found in significant number (P<0.0001) in the regressing tumors as compared to the non regressing ones, which demonstrate an active involvement of the different arms of the immune system in the multiple primary melanoma patients in the process of tumor regression. Also, MHC expression was significantly higher in the regressing versus the non-regressing tumors (P <0.0001), which reflects a proper tumor antigen expression. Associated with tumor regression was also loss of the melanoma common tumor antigen Melan A/ MART-1 in the multiple primary melanoma patients as compared to the single primary ones (P=0.0041). Furthermore, loss of Melan A/ MART-1 in the regressing tumors significantly correlated with the presence of Melan A/ MART-1-specific CTLs in the peripheral blood of these patients (P=0.03), which adds to the evidence that the phenomenon of regression seen in these patients was immunologically-mediated and tumor-specific. Such correlation was also seen in another rare group of melanoma patients, namely those with occult primary melanoma. The lesson that we could learn from nature in this study is that inducing cancer regression using the different arms of the immune system is possible. Also, developing a novel cancer vaccine is not out of reach.

The incidence of cancer and its related morbidity and mortality remain on the increase in both developing and developed countries. Cancer remains a huge burden on the health and social welfare sectors worldwide and its prevention and cure remain two golden goals that science strives to achieve. Among the treatment options for cancer that have emerged in the past 100 years, cancer vaccine immunotherapy seems to present a promising and relatively safer approach as compared to chemotherapy and radiotherapy. The identification of different tumour antigens in the last fifteen years using a variety of techniques, together with the molecular cloning of cytotoxic T lymphocytes (CTLs)- and tumour infiltrating lymphocytes (TILs)-defined tumour antigens allowed more refining of the cancer vaccines that are currently used in different clinical trials. In a proportion of treated patients, some of these vaccines have resulted in partial or complete tumour regression, while they have increased the disease-free survival rate in others. These outcomes are more evident now in patients suffering from melanoma. This review provides an update on melanoma vaccine immunotherapy. Different cancer antigens are reviewed with a detailed description of the melanoma antigens discovered so far. The review also summarises clinical trials and individual clinical cases in which some of the old and current methods to vaccinate against or treat melanoma were used. These include vaccines made of autologous or allogenic melanoma tumour cells, melanoma peptides, recombinant bacterial or viral vectors, or dendritic cells.