The oncogenic roles of bacterial infections in development of cancer.

Initiation of cancer is interconnected with different factors like infections. It has been estimated that infections, particularly viruses, participate in about 20% of all cancers. Bacteria as the most common infectious agents are also reported to be emerging players in the establishment of malignant cells. Microbial infections are able to modulate host cell transformation for promoting malignant features through the production of carcinogenic metabolites participating in inflammation responses, disruption of cell metabolism, and integrity and also genomic or epigenetic manipulations. It seems that the best example of the role of bacteria in cancer promotion is Helicobacter pylori infection, which is related to gastric cancer. World Health Organization (WHO) describes bacterium as class I carcinogens. Several bacterial infections have been reported in association with prevalent cancers. In this review, we will summarize the role of known bacterial infections in the initiation of the main common cancers, which show high mortality in the world. Examining the microbiomes in cancer patients is important and necessary to better understand the pathogenesis of this disease and also to plan therapeutic interventions.

Isolation and characterization of a novel scFv antibody fragments specific for Hsp70 as a tumor biomarker.

Many studies have shown that more than 50% of tumors express heat shock protein 70 kDa (Hsp70) at the plasma membrane surface while not seen in normal cells, therefore it is a promising therapeutic target in human cancers. Hence, we used phage display technology to produce a single-chain fragment variable (scFv) antibody against human Hsp70. For this, a target peptide from human Hsp70 was designed using bioinformatics studies and was chemically synthesized. Then, the selection was performed using four rounds of biopanning with a stepwise decreased amount of the target peptide. Fourteen positive scFv clones were selected using monoclonal phage enzyme-linked immunosorbent assay screening, which was further characterized by means of the polymerase chain reaction and DNA sequencing. Among them, the G6 clone was selected to express scFv into the Escherichia coli. Expression and purification of the scFv shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and confirmed by Western blot analysis. In silico analysis confirmed specific binding of the scFv to Hsp70 in CDR regions. The specificity of the scFv measured by surface plasmon resonance and immunofluorescence of the A549 human lung carcinoma cell line confirmed the in vitro function of the scFv. Based upon these findings, we propose a novel anti-human Hsp70 scFv as potential immunotherapy agents that may be translated into preclinical/clinical applications.

Hsp70 in Cancer: Partner or Traitor to Immune System.

Heat shock protein 70.1 (Hsp70.1), also known as Hsp70, is a highly conserved member of the heat shock protein family that exists in all living organisms and determines the protein fate as molecular chaperones. Hsp70 basal expression is undetectable or low in most unstressed normal cells, however, its abundant presence in several types of human cancer cells is reported. Several studies support upregulated Hsp70 involved in tumor progression and drug resistance through modulation of cell death pathways and suppresses anticancer immune responses. However, numerous studies have confirmed that Hsp70 can also induce anticancer immune responses through the activation of immune cells in particular antigen-presenting cells (APCs). Regarding the significant and the promising role of vaccines in cancer immunotherapy, identification and characterization of the overexpressed Hsp70 as a potential immune stimulatory factor can pave the path for development of highly effective anticancer vaccines. In this review, we will discuss the interactions of Hsp70 with components of the immune system in cancers as well as possible strategies to harness Hsp70 for eliciting anticancer immune responses.