AIM To investigate the therapeutic potential of two recombinant proteins, Survivin and luteinizing hormone-releasing hormone (LHRH) fusion protein [LHRH(6 leu)-LTB] for immunotherapy of breast cancer.METHODS Murine 4 ...AIM To investigate the therapeutic potential of two recombinant proteins, Survivin and luteinizing hormone-releasing hormone (LHRH) fusion protein [LHRH(6 leu)-LTB] for immunotherapy of breast cancer.METHODS Murine 4 T-1 breast cancer model was used to evaluate the efficacy of recombinant proteins in vivo. Twenty four Balb/c mice were divided into 4 groups of 6 mice each. Recombinant Survivin and LHRH fusion protein, alone or in combination, were administered along with immunomodulator Mycobacterium indicus pranii (MIP) in Balb/c mice. Unimmunized or control group mice were administered with phosphate buffer saline. Each group was then challenged with syngeneic 4 T-1 cells to induce the growth of breast tumor. Tumor growth was monitored to evaluate the efficacy of immune-response in preventing the growth of cancer cells.RESULTS Preventive immunization with 20 μg recombinant Survivin and MIP was effective in suppressing growth of 4 T-1 mouse model of breast cancer (P = 0.04) but 50 μg dose was ineffective in suppressing tumor growth. However, combination of Survivin and LHRH fusion protein was more effective in suppressing tumor growth (P = 0.02) as well as metastasis in vivo in comparison to LHRH fusion protein as vaccine antigen alone.CONCLUSION Recombinant Survivin and MIP suppress tumor growth significantly. Combining LHRH fusion protein with Survivin and MIP enhances tumor suppressive effects marginally which provides evidence for recombinant Survivin and LHRH fusion protein as candidates for translating the combination cancer immunotherapy approaches.展开更多
Dengue is amongst the most prevalent viral diseases which globally affects millions of individuals annually and renders billions at risk,particularly in tropical and sub-tropical nations.WHO estimated 100-400 mil-lion...Dengue is amongst the most prevalent viral diseases which globally affects millions of individuals annually and renders billions at risk,particularly in tropical and sub-tropical nations.WHO estimated 100-400 mil-lion infections each year and reported 4.2 million active cases in 2019 worldwide.The infection is caused by arthropod-transmitted dengue virus which is known to have 5 serotypes(DENV1-5).Most of the cases show mild clinical symptoms;though others may develop severe forms viz;dengue hemorrhagic fever and dengue shock syndrome.Though limited literature suggests the population-specific genetic influence on susceptibility and the clinical course of dengue;the genetic propensity of dengue is largely unknown in most ethnicities.In this context,the human leukocyte antigen(HLA)system represents the most polymorphic region of the human genome and is crucial for the initiation of an appropriate immune response.In most of the genome-wide association studies,the HLA complex is the most significantly linked genetic region with susceptibility or protection towards vari-ous infectious and noninfectious diseases.Killer immunoglobulin-like receptors represent another highly variable system present on the surface of natural killer(NK)cells which regulate the activity of NK cells through inter-actions with their cognate HLA ligands.It is conceivable that the interaction of HLA-Killer immunoglobulin-like receptors systems influences the host susceptibility towards dengue infection as well the disease outcome.Here we attempt to review these parameters in dengue infection and disease outcome.Further detailed investigations are warranted towards the identification of novel susceptibility markers and targeted therapeutic interventions.展开更多
Activation of specific sets of protein kinases by intracellular signal molecules has become more and more apparent in the past decade. Phosphorylation, one of key posttranslational modification events, is activated by...Activation of specific sets of protein kinases by intracellular signal molecules has become more and more apparent in the past decade. Phosphorylation, one of key posttranslational modification events, is activated by kinase or regulatory protein and is vital for controlling many physiological functions of eukaryotic cells such as cell proliferation, differentiation, malignant transformation,and signal transduction mediated by external stimuli. Moreovers, the reversible modification of phosphorylation and dephosphorylation can result in different features of the target substrate molecules including DNA binding, protein-protein interaction, subcellular location and enzymatic activity, and is often hijacked by viral infection. Epstein-Barr virus(EBV) and Kaposi's sarcomaassociated herpesvirus(KSHV), two human oncogenic gamma-herpesviruses, are shown to tightly associate with many malignancies. In this review, we summarize the recent progresses on understanding of molecular properties and regulatory modes of cellular and viral proteins phosphorylation influenced by these two tumor viruses, and highlight the potential therapeutic targets and strategies against their related cancers.展开更多
The dynamic interplay between tumor cells and immune cells in the microenvironment plays a crucial role in determining disease severity and therapeutic outcome in cancer.Myeloid cells are the most abundantly available...The dynamic interplay between tumor cells and immune cells in the microenvironment plays a crucial role in determining disease severity and therapeutic outcome in cancer.Myeloid cells are the most abundantly available cell population in the tumor microenvironment.Myeloid cells have been shown to exist in diverse phenotypes and play both antitumoral and protumoral roles in cancer.Understanding the biology of myeloid cells can lay the foundation for the development of therapeutic strategies aimed at enhancing the antitumoral role of myeloid cells.This article presents an overview of the role of myeloid cells in tumor development and various mechanisms by which myeloid cells aid tumor progression.Existing drugs against cancer that utilize myeloid cells and the role of myeloid cells in drug resistance are also discussed.展开更多
文摘AIM To investigate the therapeutic potential of two recombinant proteins, Survivin and luteinizing hormone-releasing hormone (LHRH) fusion protein [LHRH(6 leu)-LTB] for immunotherapy of breast cancer.METHODS Murine 4 T-1 breast cancer model was used to evaluate the efficacy of recombinant proteins in vivo. Twenty four Balb/c mice were divided into 4 groups of 6 mice each. Recombinant Survivin and LHRH fusion protein, alone or in combination, were administered along with immunomodulator Mycobacterium indicus pranii (MIP) in Balb/c mice. Unimmunized or control group mice were administered with phosphate buffer saline. Each group was then challenged with syngeneic 4 T-1 cells to induce the growth of breast tumor. Tumor growth was monitored to evaluate the efficacy of immune-response in preventing the growth of cancer cells.RESULTS Preventive immunization with 20 μg recombinant Survivin and MIP was effective in suppressing growth of 4 T-1 mouse model of breast cancer (P = 0.04) but 50 μg dose was ineffective in suppressing tumor growth. However, combination of Survivin and LHRH fusion protein was more effective in suppressing tumor growth (P = 0.02) as well as metastasis in vivo in comparison to LHRH fusion protein as vaccine antigen alone.CONCLUSION Recombinant Survivin and MIP suppress tumor growth significantly. Combining LHRH fusion protein with Survivin and MIP enhances tumor suppressive effects marginally which provides evidence for recombinant Survivin and LHRH fusion protein as candidates for translating the combination cancer immunotherapy approaches.
文摘Dengue is amongst the most prevalent viral diseases which globally affects millions of individuals annually and renders billions at risk,particularly in tropical and sub-tropical nations.WHO estimated 100-400 mil-lion infections each year and reported 4.2 million active cases in 2019 worldwide.The infection is caused by arthropod-transmitted dengue virus which is known to have 5 serotypes(DENV1-5).Most of the cases show mild clinical symptoms;though others may develop severe forms viz;dengue hemorrhagic fever and dengue shock syndrome.Though limited literature suggests the population-specific genetic influence on susceptibility and the clinical course of dengue;the genetic propensity of dengue is largely unknown in most ethnicities.In this context,the human leukocyte antigen(HLA)system represents the most polymorphic region of the human genome and is crucial for the initiation of an appropriate immune response.In most of the genome-wide association studies,the HLA complex is the most significantly linked genetic region with susceptibility or protection towards vari-ous infectious and noninfectious diseases.Killer immunoglobulin-like receptors represent another highly variable system present on the surface of natural killer(NK)cells which regulate the activity of NK cells through inter-actions with their cognate HLA ligands.It is conceivable that the interaction of HLA-Killer immunoglobulin-like receptors systems influences the host susceptibility towards dengue infection as well the disease outcome.Here we attempt to review these parameters in dengue infection and disease outcome.Further detailed investigations are warranted towards the identification of novel susceptibility markers and targeted therapeutic interventions.
基金supported by the National Natural Science Foundation of China (NO. 81471930, 81402542, 81672015, 81772166)National Key Research and Development Program of China (2016YFC1200400)
文摘Activation of specific sets of protein kinases by intracellular signal molecules has become more and more apparent in the past decade. Phosphorylation, one of key posttranslational modification events, is activated by kinase or regulatory protein and is vital for controlling many physiological functions of eukaryotic cells such as cell proliferation, differentiation, malignant transformation,and signal transduction mediated by external stimuli. Moreovers, the reversible modification of phosphorylation and dephosphorylation can result in different features of the target substrate molecules including DNA binding, protein-protein interaction, subcellular location and enzymatic activity, and is often hijacked by viral infection. Epstein-Barr virus(EBV) and Kaposi's sarcomaassociated herpesvirus(KSHV), two human oncogenic gamma-herpesviruses, are shown to tightly associate with many malignancies. In this review, we summarize the recent progresses on understanding of molecular properties and regulatory modes of cellular and viral proteins phosphorylation influenced by these two tumor viruses, and highlight the potential therapeutic targets and strategies against their related cancers.
文摘The dynamic interplay between tumor cells and immune cells in the microenvironment plays a crucial role in determining disease severity and therapeutic outcome in cancer.Myeloid cells are the most abundantly available cell population in the tumor microenvironment.Myeloid cells have been shown to exist in diverse phenotypes and play both antitumoral and protumoral roles in cancer.Understanding the biology of myeloid cells can lay the foundation for the development of therapeutic strategies aimed at enhancing the antitumoral role of myeloid cells.This article presents an overview of the role of myeloid cells in tumor development and various mechanisms by which myeloid cells aid tumor progression.Existing drugs against cancer that utilize myeloid cells and the role of myeloid cells in drug resistance are also discussed.