Cancer cells perform their malicious activities through own cell membranes that screen and transmit inhibitory and stimulatory signals out of the cells and into them. This work is focused on changes of phospholipids content (PI-phosphatidylinositol, PS-phosphatidylserine, PE-phosphatidylethanolamine, PC-phosphatidylcholine) and electric charge that occur in cell membranes of colorectal cancer of pT 3 stage, various grades (G2, G3) and without/with metastasis. Qualitative and quantitative composition of phospholipids in the membrane was determined by HPLC (high-performance liquid chromatography). The surface charge density of colorectal cancer cell membranes was measured using electrophoresis. The measurements were carried out at various pH of solution. It was shown that the process of cancer transformation was accompanied by an increase in total amount of phospholipids as well as an increase in total positive charge at low pH and total negative charge at high pH. A malignant neoplasm cells with metastases are characterized by a higher PC/PE ratio than malignant neoplasm cells without metastases.
" . This parameter has been used not only for describing the surface electrostatics of cells in different environmental states  but also for assessing cellular phenomena such as adhesion and interaction with peptides [10,60–63]. Therefore, we next evaluated the zeta potential of live PC-3 and MOLT-4 cells in the presence of increasing concentrations of HNP-1. "
[Show abstract][Hide abstract] ABSTRACT: Cancer remains a major cause of morbidity and mortality worldwide. Although progress has been made regarding chemotherapeutic agents, new therapies that combine increased selectivity and efficacy with low resistance are still needed. In the search for new anticancer agents, therapies based on biologically active peptides, in particular, antimicrobial peptides (AMPs), have attracted attention for their decreased resistance development and low cytotoxicity. Many AMPs have proved to be tumoricidal agents against human cancer cells, but their mode of action is still controversial. The existence of common properties shared by the membranes of bacteria and tumor cells points to similar lipid-targeting mechanisms in both cases. On the other hand, anticancer peptides (ACPs) also induce apoptosis and inhibit angiogenesis. Human neutrophil peptide-1 (HNP-1) is an endogenous AMP that has been implicated in different cellular phenomena such as tumor proliferation. The presence of HNP-1 in the serum/plasma of oncologic patients turns this peptide into a potential tumor biomarker. The present work reveals the different effects of HNP-1 on the biophysical and nanomechanical properties of solid and hematological tumor cells. Studies on cellular morphology, cellular stiffness, and membrane ultrastructure and charge using atomic force microscopy (AFM) and zeta potential measurements show a preferential binding of HNP-1 to solid tumor cells from human prostate adenocarcinoma when compared to human leukemia cells. AFM also reveals induction of apoptosis with cellular membrane defects at very low peptide concentrations. Understanding ACPs mode(s) of action will certainly open innovative pathways for drug development in cancer treatment.
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 11/2014; 1853(2). DOI:10.1016/j.bbamcr.2014.11.006 · 5.02 Impact Factor
"It is this potential that is the underlying characteristic of the cell that could distinguish between normal and cancerous cells. It was been noted before that cancerous cell have a lower membrane potential, and it has been shown that the cell's membrane changes during cancer transformation, in particular the membrane's fluidity and charge 41-42. Therefore, by altering the cell membrane potential, one could possibly control the fate of the cell. "
[Show abstract][Hide abstract] ABSTRACT: Electrical properties of cells determine most of the cellular functions, particularly ones which occur in the cell's membrane. Manipulation of these electrical properties may provide a powerful electrotherapy option for the treatment of cancer as cancerous cells have been shown to be more electronegative than normal proliferating cells. Previously, we used an electrical impedance sensing system (EIS) to explore the responses of cancerous SKOV3 cells and normal HUVEC cells to low intensity (<2 V/cm) AC electric fields, determining that the optimal frequency for SKOV3 proliferation arrest was 200 kHz, without harming the non-cancerous HUVECs. In this study, to determine if these effects are cell type dependant, human breast adenocarcinoma cells (MCF7) were subjected to a range of frequencies (50 kHz-2 MHz) similar to the previously tested SKOV3. For the MCF7, an optimal frequency of 100 kHz was determined using the EIS, indicating a higher sensitivity towards the applied field. Further experiments specifically targeting the two types of cancer cells using HER2 antibody functionalized gold nanoparticles (HER2-AuNPs) were performed to determine if enhanced electric field strength can be induced via the application of nanoparticles, consequently leading to the killing of the cancerous cells without affecting non cancerous HUVECs and MCF10a providing a platform for the development of a non-invasive cancer treatment without any harmful side effects. The EIS was used to monitor the real-time consequences on cellular viability and a noticeable decrease in the growth profile of the MCF7 was observed with the application of the HER2-AuNPs and the electric fields indicating specific inhibitory effects on dividing cells in culture. To further understand the effects of the externally applied field to the cells, an Annexin V/EthD-III assay was performed to determine the cell death mechanism indicating apoptosis. The zeta potential of the SKOV3 and the MCF7 before and after incorporation of the HER2-AuNPs was also obtained indicating a decrease in zeta potential with the incorporation of the nanoparticles. The outcome of this research will improve our fundamental understanding of the behavior of cancer cells and define optimal parameters of electrotherapy for clinical and drug delivery applications.
" Similarly, elevated profiles of phosphatidylcholine and choline kinase activity have been demonstrated it colon cancers  and a high ratio of phosphatidylcholine to phosphatidy‐ lethanolamine has been used to differential metastatic colon cancers from localized ones.  Elevated levels of sphingomyelin have also been reported to characterize human colon cancer, based on nuclear magnetic resonance (NMR) studies , whilst cancer cell motility was shown to be down-regulated by the interaction between CD9 and sialoglycosphingolipid GM3 using CRC cell lines  and ceramides have been found to induce apoptosis in CRC cell lines (HT-29, LOVO, and HCT-116).    Urinary phospholipids analysis using nanoflow LC- ESI MS/MS has been previously used for the analysis of breast  ) and prostate cancer , but there is a dearth of literature on the application of this method to colorectal cancer. "
[Show abstract][Hide abstract] ABSTRACT: Themes
1. Brief history and evolution of –omics based molecular approach.
2. Diagnostic inaccuracies in colorectal cancer.
I. Reliability of Histopathology reports.
II. Tumour classification and staging.
III. Role of surgical pathology.
IV. Patient evaluation and therapeutic loop-holes.
3. Omics based techniques relevant to colorectal cancer management.
I. Genomics and Epigemomics
VI. Molecular imaging in cancer
VIII. Cancer nanothechnology
4. Prospects of –omics based approaches in a developing country: Cape Town case example.
5. Recommendations and conclusion.
1. Brief history and evolution of –omics based molecular approach
The fields of genomics, proteomics and lipidomics have classically been concerned with documentation of the identity, abundance and localization of DNA, RNA, protein and lipid biomolecules in a given cell, tissue or organism. These high throughput technologies have found considerable utility in many areas of human biology, particularly following the completion of the human genome sequence in 2003. More recently, clinical ‘omics approaches have become concerned with determination of disease-associated changes in the human genome, transcriptome, proteome, lipidome and metabolome with the aim of identifying disease-associated biomarkers for use in diagnostic tests, as well as with identifying underlying molecular mechanisms of disease. This review will focus on the potential for ‘omics technologies to impact on the diagnosis and treatment of colorectal cancer.
2. Diagnostic inaccuracies in colorectal cancer
The intricacies imbued in colorectal cancer are partly due to its multiple implicated aetiologies, and the heterogeneous nature of the tumour. This sometimes makes disease assessment complex and presents a diagnostic dilemma.
I. Reliability of Histopathology reports: Basic descriptive and morphologic histopathology has hitherto been of immense benefit for the diagnosis of colorectal cancer and continues to be so. However, newer molecular information suggests that these reports can be plagued with inaccuracies and that they therefore need to be supported with novel molecular and -omics based staging.
II. Tumour classification and staging: Newer and often more reliable molecular based assessment of tumour staging and prognosis have emerged and needs to be incorporated into routine diagnostic practice.
III. Role of Surgical Pathology: Early detection and prompt intervention is key in the effective management of colorectal cancer, including aiding in determining the type of adjuvant therapy a patient may benefit from. Surgical pathology is the interphase between surgery and pathologic specimen processing where the pathologist determines which area of the whole specimen to take samples from. Given recent molecular evidence on tumour heterogeneity, such sampling techniques are a potential minefield for diagnostic errors, even with the best mastery.
IV. Patient evaluation and therapeutic loop holes: The orthodox approach of prescribing a common therapeutic cancer regimen to all colorectal cancer patients treated at a given clinic has recently been a subject of debate in terms of its effectiveness and long term benefit to individual patients. Therapeutic focus is shifting towards personalized or individualized treatments based on individual genetic variability. For example, oncologists can now predict prognosis based on microsatellite instability (MSI) status, BRAF gene, and KRAS mutations, etc.
3. Omics based techniques relevant to colorectal cancer management
Omics based techniques in most instances are non- or minimally invasive and can assist in disease diagnosis, surveillance, treatment and prevention. A number of techniques relevant to colorectal cancer management will be highlighted as follows:
I. Genomics and Epigenomics
VI. Molecular imaging in cancer
VIII. Cancer nanotechnology
4. Prospects of –omics based approaches in a developing country: Cape Town case example.
Diagnosis and management of colorectal cancer in a developing country are characterized by problems typical to such economies, such as lack of routine health checks resulting in late presentation and advanced cancer stages. Other relevant factors include: cultural and religious beliefs; poverty; political unrest; educational level; infrastructure; maintenance culture; disease; nutrition; genetic variability; patient compliance; expertise; personnel; and many more. South Africa, being the largest economy in Africa, occupies a strategic location for treatment, research and enlightenment outreaches to the rest of Africa. Cape Town has relatively good access to modern molecular facilities and expertise and has the potential to be a major regional molecular and ‘omics centre in the near future.
5. Recommendations and Conclusion
We will recommend in this review that surgeons and clinicians should consider a more profound participation in basic medical researches to improve understanding and effectiveness of molecular approaches to cancer management. Education and health enlightenments are key to early diagnosis and management of colorectal cancer in the developing nations. The emergence of –omics based approaches may therefore be the much awaited future of cancer diagnosis and treatment.
Colorectal Cancer - Surgery, Diagnostics and Treatment, 1st edited by Jim S Khan, 03/2014: chapter 15: pages 1-40; INTECH., ISBN: 978-953-51-1231-0
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