| 1. |
- Booy, Evan P., et al.
(author)
-
Monoclonal and bispecific antibodies as novel therapeutics
- 2006
-
In: Archivum Immunologiae et Therapiae Experimentalis. - : Birkhäuser-Verlag. - 0004-069X .- 1661-4917. ; 54:2, s. 85-101
-
Journal article (peer-reviewed)abstract
- Gene amplification, over-expression, and mutation of growth factors, or the receptors themselves, causes increased signaling through receptor kinases, which has been implicated in many human cancers and is associated with poor prognosis. Tumor growth has been shown to be decreased by interrupting this process of extensive growth factor-mediated signaling by directly targeting either the surface receptor or the ligand and thereby preventing cell survival and promoting apoptosis. Monoclonal antibodies have long been eyed as a potential new class of therapeutics targeting cancer and other diseases. Antibody-based therapy initially entered clinical practice when trastuzumab/Herceptin became the first clinically approved drug against an oncogene product as a well-established blocking reagent for tumors with hyperactivity of epidermal growth factor signaling pathways. In the first part of this review we explain basic terms related to the development of antibody-based drugs, give a brief historic perspective of the field, and also touch on topics such as the "humanization of antibodies" or creation of hybrid antibodies. The second part of the review gives an overview of the clinical usage of bispecific antibodies and antibodies "armed" with cytotoxic agents or enzymes. Further within this section, cancer-specific, site-specific, or signaling pathway-specific therapies are discussed in detail. Among other antibody-based therapeutic products, we discuss: Avastin (bevacizumab), CG76030, Theragyn (pemtumomab), daclizumab (Zenapax), TriAb, MDX-210, Herceptin (trastuzumab), panitumumab (ABX-EGF), mastuzimab (EMD-72000), Erbitux (certuximab, IMC225), Panorex (edrecolomab), STI571, CeaVac, Campath (alemtuizumab), Mylotarg (gemtuzumab, ozogamicin), and many others. The end of the review deliberates upon potential problems associated with cancer immunotherapy.
|
|
| 2. |
- Ghavami, Saeid, et al.
(author)
-
Brevinin-2R semi-selectively kills cancer cells by a distinct mechanism, which involves the lysosomal-mitochondrial death pathway
- 2008
-
In: Journal of Cellular and Molecular Medicine. - : Wiley-Blackwell. - 1582-1838 .- 1582-4934. ; 12:3, s. 1005-1022
-
Journal article (peer-reviewed)abstract
- Brevinin-2R is a novel non-hemolytic defensin that was isolated from the skin of the frog Rana ridibunda. It exhibits preferential cytotoxicity towards malignant cells, including Jurkat (T-cell leukemia), BJAB (B-cell lymphoma), HT29/219, SW742 (colon carcinomas), L929 (fibrosarcoma), MCF-7 (breast adenocarcinoma), A549 (lung carcinoma), as compared to primary cells including peripheral blood mononuclear cells (PBMC), T cells and human lung fibroblasts. Jurkat and MCF-7 cells overexpressing Bcl2, and L929 and MCF-7 over-expressing a dominant-negative mutant of a pro-apoptotic BNIP3 (ΔTM-BNIP3) were largely resistant towards Brevinin-2R treatment. The decrease in mitochondrial membrane potential (ΔΨm), or total cellular ATP levels, and increased reactive oxygen species (ROS) production, but not caspase activation or the release of apoptosis-inducing factor (AIF) or endonuclease G (Endo G), were early indicators of Brevinin-2R-triggered death. Brevinin-2R interacts with both early and late endosomes. Lysosomal membrane permeabilization inhibitors and inhibitors of cathepsin-B and cathepsin-L prevented Brevinin-2R-induced cell death. Autophagosomes have been detected upon Brevinin-2R treatment. Our results show that Brevinin-2R activates the lysosomalmitochondrial death pathway, and involves autophagy-like cell death.
|
|
| 3. |
- Ghavami, Saeid, et al.
(author)
-
Role of BNIP3 in TNF-induced cell death - TNF upregulates BNIP3 expression
- 2009
-
In: Biochimica et Biophysica Acta. Molecular Cell Research. - : Elsevier. - 0167-4889 .- 1879-2596. ; 1793:3, s. 546-560
-
Journal article (peer-reviewed)abstract
- Tumor necrosis factor alpha (TNF) is a cytokine that induces caspase-dependent (apoptotic) and caspase-independent (necrosis-like) cell death in different cells. We used the murine fibrosarcoma cell line model L929 and a stable L929 transfectant over-expressing a mutated dominant-negative form of BNIP3 lacking the C-terminal transmembrane (TM) domain (L929-ΔTM-BNIP3) to test if TNF-induced cell death involved pro-apoptotic Bcl2 protein BNIP3. Treatment of cells with TNF in the absence of actinomycin D caused a rapid fall in the mitochondrial membrane potential (ΔΨm) and a prompt increase in reactive oxygen species (ROS) production, which was significantly less pronounced in L929-ΔTM-BNIP3. TNF did not cause the mitochondrial release of apoptosis inducing factor (AIF) and Endonuclease G (Endo-G) but provoked the release of cytochrome c, Smac/Diablo, and Omi/HtrA2 at similar levels in both L929 and in L929-ΔTM-BNIP3 cells. We observed TNF-associated increase in the expression of BNIP3 in L929 that was mediated by nitric oxide and significantly inhibited by nitric oxide synthase inhibitor N5-(methylamidino)-l-ornithine acetate. In L929, lysosomal swelling and activation were markedly increased as compared to L929-ΔTM-BNIP3 and could be inhibited by treatment with inhibitors to vacuolar H+-ATPase and cathepsins −B/−L. Together, these data indicate that TNF-induced cell death involves BNIP3, ROS production, and activation of the lysosomal death pathway.
|
|
| 4. |
- Naidu, Sreus A.G., et al.
(author)
-
COVID-19 during Pregnancy and Postpartum:: I) Pathobiology of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) at Maternal-Fetal Interface
- 2020
-
In: Journal of dietary supplements. - : Informa UK Limited. - 1939-0211 .- 1939-022X.
-
Research review (peer-reviewed)abstract
- Coronavirus Disease 2019 (COVID-19) triggered by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection has been declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Oxidative stress and its related metabolic syndromes are potential risk factors in the susceptibility to, and severity of COVID-19. In concert with the earliest reports of COVID-19, obstetricians started to diagnose and treat SARS-CoV-2 infections during pregnancy (“COVID-19-Pregnancy”). High metabolic demand to sustain normal fetal development increases the burden of oxidative stress in pregnancy. Intracellular redox changes intertwined with acute phase responses at the maternal-fetal interface could amplify during pregnancy. Interestingly, mother-to-fetus transmission of SARS-CoV-2 has not been detected in most of the COVID-19-Pregnancy cases. This relative absence of vertical transmission may be related to the presence of lactoferrin in the placenta, amniotic fluid, and lacteal secretions. However, the cytokine-storm induced during COVID-19-Pregnancy may cause severe inflammatory damage to the fetus, and if uncontrolled, may later result in autism spectrum-like disorders and brain development abnormalities in neonates. Considering this serious health threat to child growth and development, the prevention of COVID-19 during pregnancy should be considered a high priority. This review summarizes the intricate virulence factors of COVID-19 and elucidate its pathobiological spectrum during pregnancy and postpartum periods with a focus on the putative and complex roles of endogenous and exogenous lactoferrin in conferring immunological advantage to the host.
|
|
