Protein Biomarkers in Cancers of the Digestive Tract - a Step Towards Personalized Medicine

Author(s):

Erno Duda, Elena Codrici, Daniela Ionela Popescu, Laura Necula and Radu AlbulescuPages 228-236 (9)

Abstract:

Digestive tract cancers – gastric-, colorectal-, pancreatic-, hepatocarcinoma- and esophageal are some of the most frequent cancers; they are characterized by invasivity, metastatic potential and bad outcomes. This group includes several of the most critical cancers (those ranked 2nd-4th in cancer related mortality), and, despite all efforts, they remain with low survival rates and lack of success of therapies. Discovery of novel biomarkers may improve disease characterization and make optimized or personalized therapies possible. The novel biomarkers are expected to provide, hopefully, less invasive or non-invasive diagnostic tools to make possible earlier detection of disease, and, also, they will provide more reliable selection in the drug discovery process, and provide guidance for personalized medicine.

Deregulation of protein expression and genetic alterations were demonstrated in various cancers, including digestive. Investigations in tissue samples provided a considerable amount of knowledge, identifying altered expressions of proteins associated with tumorigenesis and tumour progression. Over-expression of some tumour-inducing or tumour promoting proteins was demonstrated, as well as expression down-regulation of several tumor suppressor genes. Often mutated and polymorphic alleles were demonstrated to occur in various cancers with high incidence. Several protein biomarkers were also demonstrated to be differentially expressed in groups of patients showing different responsivities to therapies.

Both individual proteins and sets of multiple proteins were set up as candidate biomarkers for diagnostics or monitoring, offered relevant insights on the tumorigenic mechanisms. Proteins and other molecules (mRNAs, miRNAs, lncRNAs) are also providing potential candidates for multifactorial panels of biomarkers.

Keywords:

Biomarkers, colorectal cancer, gastric cancer, hepatocellular carcinoma, pancreatic cancer, protein biomarker.

Affiliation:

Institute of Pathology, 99-101 Spl. Independentei, Bucharest, Romania.

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Anti-cancer Therapies in High Grade Gliomas

Author(s):

Cristiana Pistol Tanase, Ana-Maria Enciu, Simona Mihai, Ana Iulia Neagu, Bogdan Calenic and Maria Linda CruceruPages 246-260 (15)

Abstract:

High grade gliomas represent one of the most aggressive and treatment-resistant types of human cancer, with only 1–2 years median survival rate for patients with grade IV glioma. The treatment of glioblastoma is a considerable therapeutic challenge; combination therapy targeting multiple pathways is becoming a fast growing area of research. This review offers an up-to-date perspective of the literature about current molecular therapy targets in high grade glioma, that include angiogenic signals, tyrosine kinase receptors, nodal signaling proteins and cancer stem cells related approaches. Simultaneous identification of proteomic signatures could provide biomarker panels for diagnostic and personalized treatment of different subsets of glioblastoma. Personalized medicine is starting to gain importance in clinical care, already having recorded a series of successes in several types of cancer; nonetheless, in brain tumors it is still at an early stage.

Keywords:

Antiangiogenic therapy, cancer stem cells, glioma, microRNA, personalized medicine, PI-3K.

Affiliation:

Victor Babes National Institute of Pathology, Dept. of Biochemistry-Proteomics, no 99-101 Splaiul Independentei, 050096 sect 5 Bucharest, Romania.

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A Simple Protein Extraction Method for Proteomic Analysis of Diverse Biological Specimens

Author(s):

Panga Jaipal Reddy, Aishwarya Anand Rao, Darpan Malhotra, Samridhi Sharma, Ravinder Kumar, Rekha Jain, Kishore Gollapalli, Namita Pendharkar, Srikanth Rapole and Sanjeeva SrivastavaPages 298-311 (14)

Abstract:

The success of a proteomic experiment largely depends on the quality and quantity of the protein extract. Currently, various protocols are available for extraction of proteins from different types of samples; however, further optimization is required for every new sample type. Hence, a common protein extraction protocol is desirable. In the present study, soluble proteins were extracted from six diverse samples using TRIzol without any additional clean-up step and subjected to 2-DE and 2D-DIGE analysis for global protein expression profiling. Image analysis using IMP7 and DeCyder showed good coverage, reproducibility and quality of the gel. MS analysis of 24 spots from all the six samples showed good score and coverage for the identified proteins. Additionally, this method facilitated the concurrent isolation of RNA from the same cell lysates with high integrity and quality, suitable for transcriptomic analysis. Thus, we demonstrate the use of a common protein extraction protocol involving TRIzol reagent for 2-DE, 2D-DIGE and MS analysis using six diverse samples and show its suitability for concomitant transcriptomic studies.

Keywords:

2-DE, 2D-DIGE, breast cancer, B. subtilis, glioblastoma cell line, mass spectrometry, protein extraction, S. coelicolor, TRIzol, yeast.

Affiliation:

Department of Biosciences and Bioengineering, IIT Bombay, Mumbai 400 076, India.

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Important Anti-Cancer Applications of Protein Based Nanoparticles

Author(s):

Mustafa Ergul, Merve Ergul and Yusuf TutarPages 334-340 (7)

Abstract:

Cancer is one of the most important health problems in the world and the treatment approaches are still challenging and generally not at desirable levels. Conventional anti-cancer agents may cause systemic toxicity, have poor solubility, and lack of selectivity. In order to overcome these hurdles, nanoparticle based therapeutics have been widely employed to enhance therapeutic efficacies and reduce systemic toxicity of pharmaceutical agents. In recent years, nanoparticulate carrier systems (NPCs) in medicine have attracted considerable scientific attention and interest in the worldwide because of their unique properties in the diagnosis and therapy of many diseases including cancer. One of the therapeutic strategies of NPCs is protein based nanoparticles. Human serum albumin (HSA) and bovine serum albumin (BSA) are the most frequently used materials for this purpose due to their remarkable advantages. In this review article, we focused on protein based nanoparticles and summarized their important applications including anti-cancer drug delivery, photodynamic therapy, and gene delivery.

Keywords:

Anti-cancer drug delivery, bovine serum albumin, gene delivery, human serum albumin, photodynamic therapy, protein based nanoparticles.

Affiliation:

Division of Biochemistry, Cumhuriyet University, 58140, Sivas, Turkey.

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B-factor Analysis and Conformational Rearrangement of Aldose Reductase

Author(s):

Ganesaratnam K. Balendiran, J. Rajendran Pandian, Evin Drake, Anubhav Vinayak, Malkhey Verma and Duilio CascioPages 151-160 (10)

Abstract:

The NADPH-dependent reduction of glucose reaction that is catalyzed by Aldose Reductase (AR) follows a sequential ordered kinetic mechanism in which the co-factor NADPH binds to the enzyme prior to the aldehyde substrate. The kinetic/structural experiments have found a conformational change involving a hinge-like movement of a surface loop (residues 213-224) which is anticipated to take place upon the binding of the diphosphate moiety of NADPH. The reorientation of this loop, expected to permit the release of NADP+, represents the rate-limiting step of the catalytic mechanism. This study reveals: 1) The Translation/Libration/Screw (TLS) analysis of absolute B-factors of apo AR crystal structures indicates that the 212-224 loop might move as a rigid group. 2) Residues that make the flexible loop slide in the AR binary and ternary complexes. 3) The normalized B-factors separate this segment into three differnt clusters with fewer residues.

Keywords:

Aldo-keto reductase, B-factor, clustering, crystal structure, statistical analysis, structural dynamics, TLS.

Affiliation:

Department of Chemistry, WBSH 6017, Youngstown State University, One University Plaza, Youngstown, OH 44555, USA.

Graphical Abstract:

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