Drug-metabolizing enzymes: role in drug resistance in cancer.

Although continuous researches are going on for the discovery of new chemotherapeutic agents, resistance to these anticancer agents has made it really difficult to reach the fruitful results. There are many causes for this resistance that are being studied by the researchers across the world, but still, success is far because there are several factors that are going along unattended or have been studied less. Drug-metabolizing enzymes (DMEs) are one of these factors, on which less study has been conducted. DMEs include Phase I and Phase II enzymes. Cytochrome P450s (CYPs) are major Phase I enzymes while glutathione-S-transferases (GSTs), UDP-glucuronosyltransferases (UGTs), dihydropyrimidine dehydrogenases are the major enzymes belonging to the Phase II enzymes. These enzymes play an important role in detoxification of the xenobiotics as well as the metabolism of drugs, depending upon the tissue in which they are expressed. When present in tumorous tissues, they cause resistance by metabolizing the drugs and rendering them inactive. In this review, the role of these various enzymes in anticancer drug metabolism and the possibilities for overcoming the resistance have been discussed.

Therapeutic potential of immune privileged Sertoli cells

Sertoli Cells (SCs) in the testes have evolved to possess unique immune privileged properties to protect the developing germ cells from immunological attack. These immune privileged properties are not restricted to the testis, as SCs survive when transplanted across immunological barriers as allo- and xeno-grafts. Here we discuss the therapeutic potential of transplanted SCs in protecting cells, tissues or organs, which could be paramount in the field of transplantation to treat life-threatening diseases. Similar to the testis, transplanted SCs inhibit and/or modulate the immune response locally (at the transplant site) or systemically. Protection of transplanted cells, present in close vicinity of SCs, along with reduction of inflammation at the transplant site support that SC can inhibit and/or modulate the immune response locally. While protection of skin, islets in the contralateral kidney, and organs by SCs support their role in inducing systemic tolerance. Additionally, amelioration of autoimmune diseases, specifically type 1 diabetes mellitus, further supports this notion. Studies exploring SCs role as a vehicle for the cell based gene therapy further widens the horizon of SCs therapeutic potential in transplantation.

Therapeutic potential of immune privileged Sertoli cells

Sertoli Cells (SCs) in the testes have evolved to possess unique immune privileged properties to protect the developing germ cells from immunological attack. These immune privileged properties are not restricted to the testis, as SCs survive when transplanted across immunological barriers as allo- and xeno-grafts. Here we discuss the therapeutic potential of transplanted SCs in protecting cells, tissues or organs, which could be paramount in the field of transplantation to treat life-threatening diseases. Similar to the testis, transplanted SCs inhibit and/or modulate the immune response locally (at the transplant site) or systemically. Protection of transplanted cells, present in close vicinity of SCs, along with reduction of inflammation at the transplant site support that SC can inhibit and/or modulate the immune response locally. While protection of skin, islets in the contralateral kidney, and organs by SCs support their role in inducing systemic tolerance. Additionally, amelioration of autoimmune diseases, specifically type 1 diabetes mellitus, further supports this notion. Studies exploring SCs role as a vehicle for the cell based gene therapy further widens the horizon of SCs therapeutic potential in transplantation.(AU)

Antibacterial efficacy of Nisin, Pediocin 34 and Enterocin FH99 against Listeria monocytogenes and cross resistance of its bacteriocin resistant variants to common food preservatives.

Antilisterial efficiency of three bacteriocins, viz, Nisin, Pediocin 34 and Enterocin FH99 was tested individually and in combination against Listeria mononcytogenes ATCC 53135. A greater antibacterial effect was observed when the bacteriocins were combined in pairs, indicating that the use of more than one LAB bacteriocin in combination have a higher antibacterial action than when used individually. Variants of Listeria monocytogenes ATCC 53135 resistant to Nisin, Pediocin 34 and Enterocin FH99 were developed. Bacteriocin cross-resistance of wild type and their corresponding resistant variants were assessed and results showed that resistance to a bacteriocin may extend to other bacteriocins within the same class. Resistance to Pediocin 34 conferred cross resistance to Enterocin FH 99 but not to Nisin. Similarly resistance to Enterocin FH99 conferred cross resistance to Pediocin 34 but not to Nisin. Also, the sensitivity of Nisin, Pediocin 34 and Enterocin FH99 resistant variants of Listeria monocytogenes to low pH, salt, sodium nitrite, and potassium sorbate was assayed in broth and compared to the parental wild-type strain. The Nisin, Pediocin 34 and Enterocin FH99 resistant variants did not have intrinsic resistance to low pH, sodium chloride, potassium sorbate, or sodium nitrite. In no case were the bacteriocin resistant Listeria monocytogenes variants examined were more resistant to inhibitors than the parental strains.

Testisimmune privilege - Assumptions versus facts.

The testis has long enjoyed a reputation as an immunologically privileged site based on its ability to protect auto-antigenic germ cells and provide an optimal environment for the extended survival of transplanted allo- or xeno-grafts. Exploration of the role of anatomical, physiological, immunological and cellular components in testis immune privilege revealed that the tolerogenic environment of the testis is a result of the immunomodulatory factors expressed or secreted by testicular cells (mainly Sertoli cells, peritubular myoid cells, Leydig cells, and resident macrophages). The blood-testis barrier/Sertoli cell barrier, is also important to seclude advanced germ cells but its requirement in testis immune privilege needs further investigation. Testicular immune privilege is not permanent, as an effective immune response can be mounted against transplanted tissue, and bacterial/viral infections in the testis can be effectively eliminated. Overall, the cellular components control the fate of the immune response and can shift the response from immunodestructive to immunoprotective, resulting in immune privilege.

Antibacterial efficacy of Nisin, Pediocin 34 and Enterocin FH99 against Listeria monocytogenes and cross resistance of its bacteriocin resistant variants to common food preservatives

Antilisterial efficiency of three bacteriocins, viz, Nisin, Pediocin 34 and Enterocin FH99 was tested individually and in combination against Listeria mononcytogenes ATCC 53135. A greater antibacterial effect was observed when the bacteriocins were combined in pairs, indicating that the use of more than one LAB bacteriocin in combination have a higher antibacterial action than when used individually. Variants of Listeria monocytogenes ATCC 53135 resistant to Nisin, Pediocin 34 and Enterocin FH99 were developed. Bacteriocin cross-resistance of wild type and their corresponding resistant variants were assessed and results showed that resistance to a bacteriocin may extend to other bacteriocins within the same class. Resistance to Pediocin 34 conferred cross resistance to Enterocin FH 99 but not to Nisin. Similarly resistance to Enterocin FH99 conferred cross resistance to Pediocin 34 but not to Nisin. Also, the sensitivity of Nisin, Pediocin 34 and Enterocin FH99 resistant variants of Listeria monocytogenes to low pH, salt, sodium nitrite, and potassium sorbate was assayed in broth and compared to the parental wild-type strain. The Nisin, Pediocin 34 and Enterocin FH99 resistant variants did not have intrinsic resistance to low pH, sodium chloride, potassium sorbate, or sodium nitrite. In no case were the bacteriocin resistant Listeria monocytogenes variants examined were more resistant to inhibitors than the parental strains.

Testis immune privilege - Assumptions versus facts

The testis has long enjoyed a reputation as a n immunologically privileged site based on its ability to protect auto - antigenic germ cells and provide an optimal environment for the extended survival of transplanted allo - or xeno - grafts. Exploration of the role of anatomical, physiological, immunologica l and cell ular components in testis immune privilege reveal ed that the tolerogenic environment of the test i s is a result of the immunomodulatory factors expressed or secreted by testicular cells (mainly Sertoli cells, peritubular myoid cells, Leydig cells , and resident macrophages ). The b lood - testis barrier/Sertoli cell barrier, is also important to seclude advanced germ cells but its requirement in testis immune privilege needs further investigation . T esticular immune privilege is not permanent , as an effe ctive immune response can be mounted against transplanted tissue , and bacterial/viral infections in the testis can be effectively eliminated . Overall, the cellular components control the fate of the immune response and can shift the response from immunodestructive to immunoprotective, resulting in immuneprivilege.

Antibacterial efficacy of Nisin, Pediocin 34 and Enterocin FH99 against Listeria monocytogenes and cross resistance of its bacteriocin resistant variants to common food preservatives

Antilisterial efficiency of three bacteriocins, viz, Nisin, Pediocin 34 and Enterocin FH99 was tested individually and in combination against Listeria mononcytogenes ATCC 53135. A greater antibacterial effect was observed when the bacteriocins were combined in pairs, indicating that the use of more than one LAB bacteriocin in combination have a higher antibacterial action than when used individually. Variants of Listeria monocytogenes ATCC 53135 resistant to Nisin, Pediocin 34 and Enterocin FH99 were developed. Bacteriocin cross-resistance of wild type and their corresponding resistant variants were assessed and results showed that resistance to a bacteriocin may extend to other bacteriocins within the same class. Resistance to Pediocin 34 conferred cross resistance to Enterocin FH 99 but not to Nisin. Similarly resistance to Enterocin FH99 conferred cross resistance to Pediocin 34 but not to Nisin. Also, the sensitivity of Nisin, Pediocin 34 and Enterocin FH99 resistant variants of Listeria monocytogenes to low pH, salt, sodium nitrite, and potassium sorbate was assayed in broth and compared to the parental wild-type strain. The Nisin, Pediocin 34 and Enterocin FH99 resistant variants did not have intrinsic resistance to low pH, sodium chloride, potassium sorbate, or sodium nitrite. In no case were the bacteriocin resistant Listeria monocytogenes variants examined were more resistant to inhibitors than the parental strains.(AU)