Immunotherapy and Chemotherapy Regimen May Prolong Survival in Advanced Cancers

In continuation of my update on interleukin and retinoic acid

Cancer patients who receive a combination of low-dose interleukin-2 and retinoic acid after conventional therapy seem to live longer than those who don't get the combination. 

Retinoic acid is derived from vitamin A. Interleukin-2, a compound that fortifies the immune system, is approved at high doses to treat "metastatic" melanoma and kidney cancer. Metastatic means that a cancer has spread.

The study showed that "these biological compounds may work at low doses. Bigger doses are not always better," said lead author Dr. Francesco Recchia, director of the oncology department at Civilian Hospital in Avezzano, Italy.

Recchia stumbled upon the possibility of using low-dose interleukin-2 (IL-2) when he switched a patient with metastatic melanoma who didn't tolerate high doses to a lower dose, and the patient had an extended response to the therapy.

This study involved 500 patients who had already responded well to chemotherapy. They had a variety of cancers, including ovarian, lung, colon, stomach, kidney, melanoma, breast and pancreatic.

Immunotherapy and Chemotherapy Regimen May Prolong Survival in Advanced Cancers

Synthetic derivative of Retinoic acid can induce cell death

Retinoic acid (RA), a natural derivative of vitamin A, is the basis of a number of treatments against cancer. Nevertheless, it has certain disadvantages, such as the possibility of the appearance of retinoic acid syndrome, present in 25 % of cases and which can lead to death. The development of 4-HPR (see structure -Fenretinide 4-hydroxy(phenyl)retinamide) a synthetic derivative of RA, has meant a considerable advance due to its greater efficacy compared to its predecessor. It is able to induce the death of tumour cells as the method for reducing their proliferation, in a precise manner and without serious damage to surrounding tissue. Moreover, it halts the referred-to retinoic acid syndrome and even functions with cells that resist RA. In vitro studies corroborate its effectiveness as a chemopreventive agent and also as a chemotherapeutic agent, both with leukaemias and with ovary, breast or brain tumour cells.

Biologist Ms Aintzane Apraiz studied the 4-HPR in depth, focusing on the causes that, according to previous research, give rise to this ability to induce cell death. To this end, she applied this synthetic derivative to acute lymphoblastic leukaemia T cells (LLA-T). Her PhD thesis, defended at the University of the Basque Country (UPV/EHU), is entitled Role of sphingolipids and oxidative stress in the antineoplasic activity of 4-HPR: study in a leucemia model.

Amongst the various processes that can induce cell death, in the case of 4-HPR, apoptosis is outstanding; a precise mechanism and without inflammatory processes or serious damage to surrounding tissue. According to Ms Apraiz, previous research on LLA-T undertaken by the team of which she is a member, showed that 4-HPR induced a massive accumulation of ceramides (lipids of the cell membrane) and of reactive oxygen species (ROS), both of which can cause cell death. 

More...

Retinoic acid may provide relief for ulcerative colitis !

We know that Retinoic acid is the oxidized form of Vitamin A. It functions in determining position along embryonic anterior/posterior axis in chordates. It acts through Hox genes, which ultimately control anterior/posterior patterning in early developmental stages. Retinoic acid acts by binding to heterodimers of the retinoic acid receptor (RAR) and the retinoid X receptor (RXR), which then bind to retinoic acid response elements (RAREs) in the regulatory regions of direct targets (including Hox genes), thereby activating gene transcription.

Recently when I was reading a paper, found this interesting fact that is "retinoic acid, could be a beneficial treatment for people suffering from ulcerative colitis and other irritable bowel diseases. Specifically the researchers found that retinoic acid helps suppress out-of-control inflammation, which is a hallmark of active ulcerative colitis.

Pharmaceutical strategies based on this research may offer a promising alternative to the current approaches of managing immune diseases including, IBD, arthritis, multiple sclerosis, and so on, Aiping Bai, a researcher involved in the work from Nanchang University in Nanchang City, China claimed.

The studies ultimately found that treatment with retinoic acid reduced the inflammation in the colon by increasing the expression of FOXP3, a gene involved with immune system responses, as well as decreasing the expression of IL-17, a cytokine believed to cause inflammation. Because many experts believe that IL-17 directly relates to the uncontrolled inflammation seen in ulcerative colitis and irritable bowel disease, the discovery that retinoic acid reduces IL-17's ability to cause inflammation could accelerate the development of treatments for these chronic diseases.

Ref : http://www.jleukbio.org/cgi/content/abstract/86/4/959?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Aiping+Bai&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT