PAHs: The Indiscriminate and Silent Carcinogens among us

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SONY DSC

Fig: Burning of garbage can be one of the most potent and common sources of Polycyclic Aromatic Hydrocarbons (Photo by Mark Williams courtesy of flickr.com/creativecommons).

Ever enjoyed a sumptuous meal of roasted meat? It is a delicious and sumptuous delicacy loaded with cancer- causing potential due to the presence of polycyclic aromatic hydrocarbons (PAHs).  Polycyclic Aromatic Hydrocarbons (PAHs) are a class of organic chemical compounds found generally everywhere in the environment. They are polycyclic derivatives of the Benzene ring (a six- carbon hexagonal compound which is cyclic in nature). Some of the most popular PAHs include naphthalene (used in disinfection in toilets) and phenanthrene.  They are usually found in the environment as a result of incomplete combustion of fuel from vehicle engines, incinerators, fossil fuels, forest fires, tobacco smoke and also high temperature cooking of foods such as meat and vegetables.

The International Association for Research on Cancer has classified a number of PAHs as carcinogens or potentially carcinogenic including naphthalene derivatives such as naphthylamines and pyrene derivatives such as benzo-pyrene. PAHs can be inhaled through the air or ingested through foods. They are not completely metabolized in the human body ending up as very reactive species capable of causing mutating changes in the DNA structure resulting into conditions such as cancer. PAHs have been known to be culpable of stomach, skin, lung and liver cancers. Due to their prevalence in everyday life, it is essential to appreciate the routes of exposure to them in order to find ways of minimizing their effects in our lives:

AIR POLLUTION

This is the most common way through which PAH exposure takes place. Populations living in urban areas or on the road sides have a high likelihood of exposure to PAHs due to the incomplete combustion of diesel in vehicle exhausts. Many vehicles emit a high amount of PAHs from their exhausts resulting into air pollution and exposing the population around to cancerous risks. Also, forest fires and the usage of fossil fuels such as charcoal for cooking may expose many people especially in the developing nations to higher risks of cancer due to exposure to PAHs. Populations living near industries, especially those using fossil fuels like coal, may also be exposed to high PAHs levels in the environment.

francesco falciani

Fig: Air pollution from industries. A major source of PAHs in urban areas (photo by Francesco Falciani through flickr.com/creativecommons)

DIET

Foods such as meats cooked under very high temperatures can result in the formation of several forms of PAHs. When foods are cooked over a low and regulated heat, the disintegration of the organic bonds in the food is gradual resulting into much more tender and healthier foods as opposed to when they are cooked under extremely high heat which results into incomplete breakdown of the chemical bonds in the foods producing some PAHs. Smoked or roasted foods are very big carriers of PAHs and if ingested regularly may increase the chances of development of several kinds of cancers.

marilyn acosta

Fig: Roasted meat on a grill. High temperature cooking methods such as roasting may end up elevating the levels of PAHs in foods leading to more instances of Cancer (Photo by Maryline Acosta through flickr.com/creativecommons)

TOBACCO SMOKING

Tobacco is composed of a cocktail of PAHs. It also contains other cancer causing substances such as Cadmium and benzene derivatives therefore making it one of the most potent causes of cancer of the lungs. Secondary smokers are also at the risk of interacting with the PAHs from tobacco which could result into cancer.

Polycyclic Aromatic Hydrocarbons are very potent carcinogens due to their metabolism in the body. They are usually completely broken down by some animals but are not fully metabolized in Humans leading to the formation of very reactive intermediates in the process. These reactive intermediates can alter the structure of DNA through bonding or transferring of important DNA bases leading to gene mutation and ultimately cancer. Some of the well known potentially cancer-causing PAHs include naphthalene and pyrene derivatives. Some enzymes have however been known to deter the cancer causing effects of these PAHs in a number of cases thus suppressing the occurrence of cancer.

PAHs are environmental pollutants which should be of concern at the local and national level. Monitoring of the levels of PAHs requires the usage of techniques such as liquid chromatography and mass spectrometry. These instruments could be stationed government environmental or quality control labs.

References and further reading

https://www.epa.gov/sites/production/files/2014-03/documents/pahs_factsheet_cdc_2013.pdf

https://www.dhs.wisconsin.gov/chemical/pah.htm

http://www.idph.state.il.us/envhealth/factsheets/polycyclicaromatichydrocarbons.htm

https://nepis.epa.gov/Exe/ZyNET.exe/30003UP9.TXT?ZyActionD=ZyDocument&Client=EPA&Index=1991+Thru+1994&Docs=&Query=&Time=&EndTime=&SearchMethod=1&TocRestrict=n&Toc=&TocEntry=&QField=&QFieldYear=&QFieldMonth=&QFieldDay=&IntQFieldOp=0&ExtQFieldOp=0&XmlQuery=&File=D%3A%5Czyfiles%5CIndex%20Data%5C91thru94%5CTxt%5C00000002%5C30003UP9.txt&User=ANONYMOUS&Password=anonymous&SortMethod=h%7C-&MaximumDocuments=1&FuzzyDegree=0&ImageQuality=r75g8/r75g8/x150y150g16/i425&Display=hpfr&DefSeekPage=x&SearchBack=ZyActionL&Back=ZyActionS&BackDesc=Results%20page&MaximumPages=1&ZyEntry=1&SeekPage=x&ZyPURL

https://uk-air.defra.gov.uk/networks/network-info?view=pah

https://en.wikipedia.org/wiki/Polycyclic_aromatic_hydrocarbon

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AFLATOXINS: A Cancerous Battalion hidden in Food

Aspergillus fungi twin and twin trading cdc

Fig: A microscopic view of the Aspergillus fungus (Photo by Twin and Twin Trading/ CDC through flickr.com/creativecommons)

Aflatoxins are poisonous chemicals released by a special kind of fungi called the Aspergillus species. These fungi dwell in dry foodstuffs such as maize, peanuts and groundnuts. Aflatoxins can also be found in livestock milk after the animals feed on pasture infected by these fungi. Aflatoxins have been known to cause liver cancer if ingested over time. Since maize and peanuts are staple foods in many parts of the African continent, there is a need to mitigate against Aflatoxin contamination of these foodstuffs to avoid a growing Cancer epidemic.

Aflatoxins are produced by two kinds of fungi called Aspergillus parasiticus and Aspergillus flavus. These fungi can be found in dry foodstuffs such as maize, peanuts, legumes, cereals and even in groundnuts. There are four major types of Aflatoxins produced which include B1, B2, G1 and G2 types. Aflatoxin B1 (AfB1) is the most potent type which has been classified by the International Agency for  Research on Cancer as a class 1 carcinogen. Aflatoxins can also occur in milk if the livestock feed on feeds that have been infested by the Aspergillus species fungi. They are metabolized and then converted to a different but potent form of Aflatoxins called either AfM1 or AfM2.

Intl Instut of Tropical Agric

Fig: Maize Infected by Aspergillus Fungi (Photo by International Institute of Tropical Agriculture through flickr.com/creativecommons)

Since the Aspergillus fungi grow on maize and peanuts, the likelihood of great exposure to aflatoxin poisoning exists for those populations which rely on maize and peanuts as major food sources. This puts many populations in the developing nations at risk of aflatoxin poisoning. In order to avoid the possibility of exposure, it is advisable to purchase foodstuffs like maize meal and peanuts from reputable retail outlets. Also, before purchasing, observe for signs like discoloration, mold or shriveling of nuts and maize. Storage of these foodstuffs must be in cool and dry conditions to avoid such contamination. It must be noted that Aflatoxins are extremely hard to remove due to the prevalence of fungi in many foodstuffs. Good food storage especially in cool and dry conditions is essential in reducing the possibility of aflatoxin poisoning. 

Aflatoxins have a variety of health effects in the body. Aflatoxicosis is a condition resulting from the poisoning of the human body due to the ingestion of Aflatoxins which may result into death. They can also be taken in the body through breathe especially by farmers or farm workers in fungi infested areas. Liver Cancer is the major ailment brought about by ingesting of Aflatoxins. Aflatoxins are also known as DNA mutating agents (substances that cause an alteration of the DNA pattern) which are some of the major causes of cancer in humans. The most potent of the Aflatoxins in its carcinogenicity is tge B1 type. 

The concentration of Aflatoxins in food stuffs can be determined using a technique called liquid chromatography. In this procedure, a portion of the foodstuffs is reacted with an organic liquid capable of dissolving the Aflatoxins from the foodstuffs. This aflatoxin solution is then subjected to a chromatographic column which detects its presence in solution and even quantifies it’s concentration in mg or ng/L. other more modern methods of aflatoxin quantification include the use of a High Performance liquid Chromatography and Enzyme Linked Immuno- Sorbent Assay or ELISA.

Aflatoxin contamination can be mitigated against by the use of substances that bind to the Aflatoxins thereby reducing their bio-availability in the body. Silicates (Sands) such as zeolites, montmorillonite and various clays have been used in reacting with Aflatoxins in cattle feeds. They are able to reduce their bio-availability thus reducing their toxicity to the animals’ bodies.

References and further reading/

http://poisonousplants.ansci.cornell.edu/toxicagents/aflatoxin/aflatoxin.html

https://www.cancer.gov/about-cancer/causes-prevention/risk/substances/aflatoxins

https://ec.europa.eu/food/safety/chemical_safety/contaminants/catalogue/aflatoxins_en

https://medlineplus.gov/ency/article/002429.htm

http://ajcn.nutrition.org/content/80/5/1106.full

LUNG CANCER: Nanotechnology and Treatment

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Fig. : Quantum Dots being used to label microorganisms in disease diagnostics. Courtesy of microbiologybytes.com. Through flickr.com/creativecommons.

The treatment of lung cancer is much more effective before it gets to its final stages (stage III and IV). The stages of cancer can be summarized in the following way according to Cancer Research UK: Stage I- Tumor localized in a specific location within the organ; Stage II- Tumor is still localized in the organ but has grown in size; Stage III- Tumor is larger and may have started spreading to other surrounding tissues; and Stage IV- Tumor has spread from where it had started to another body organ also known as metastasis.

Conventional treatment of lung cancer is dependent on whether is Small Cell or Non Small Cell Lung Cancer. Small Cell Lung Cancer is very aggressive in spreading so it may be hard to employ treatment methods such as Radiotherapy without destroying many healthy cells.

CONVENTIONAL TREATMENT METHODS

Chemotherapy

This involves the usage of drugs that have a toxic effect on the cancerous cells. They end up being taken up by the tumors and metabolized leading to the death of the cells. Research is going on in the area of targeted therapy where the destruction of healthy cells is drastically reduced by packaging the drugs in substances such as metal or polymeric nanoparticles which have an affinity for the cancer cells leading to targeted destruction of the tumors. Chemotherapy can be used for both SCLC and NSCLC.

Radiotherapy

This involves the usage of very high frequency radiation such as X-Rays in the destruction of cancerous cells. It is comfortably applicable in tumors which are localized and have not yet started spreading such as in Non Small Cell Lung Cancer (NSCLC). Research is ongoing to come up with much more target friendly ways to destroy cancer cells in order to reduce collateral damage using nanotechnology. Some of these research initiatives are being geared by the US National Cancer Institute’s Alliance for Nanotechnology in Cancer.

Surgery

This is one of the ways used to remove localized tumors especially before they start spreading. 

NANOTECHNOLOGY IN LUNG CANCER TREATMENT

Inhalation Nano-Chemotherapy

Nanotechnology offers a range of opportunities for research in the treatment of lung cancer. Being a disease affecting the respiratory organs, treatment of lung cancer can be carried out by the use of inhalation of cancer-toxic drugs which are carried by biodegradable nano-particles such as polymer(1). These nano-particles, some of which have an affinity for cancerous cells, can contain the drug substances within them or attached to them chemically then dispatched specifically to the lung cells using an asthma- type of inhaler. More research is still ongoing in this area.

Photodynamic Therapy

This technique is still under active research but has been employed in various hospitals in the UK and USA. It involves the usage of the unique light- interacting capabilities of some nano-particles such as those of Gold (AuNPs), Iron Oxide and quantum dots (QDs) in destroying cancer cells (26).  The nano-particles are taken up by the cancer cells then activated by light of a specific wavelength range in order to destroy the cancer cells by emitting radiation in the Near Infrared range (NIR).

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Fig: Iron Oxide Nanoparticles can be used in cancer diagnosis and treatment (through flickr.com/creativecommons)

Nano-structured Pharmaceuticals

The action of some anti- cancer drugs is usually impeded due to their fast secretion from the body, fast action of the body defenses against them or their low solubility in water (2,3,4). Fast secretion of the drugs from the body after marginal effect can be corrected by encapsulating the drugs in substances like polymeric nanoparticles which ensure slow and sustained release of the drugs to the specific targets while avoiding macrophages (body defenses). Some drugs which are not water soluble can be enclosed in water soluble nanoparticles for delivery to their targets for fast action.

 

DISCLAIMER: The information in this article is written for general information purposes and MUST NOT be used as a substitute for personalized medical care from a qualified medical practitioner. This blog platform will not be responsible for any injury or damage to persons or property arising from any errors or omissions.

 

References

1.      Javed Ahmad,1,* Sohail Akhter,2,3,* Md Rizwanullah,1 Saima Amin,1 Mahfoozur Rahman,4 Mohammad Zaki Ahmad,5Moshahid Alam Rizvi,6 Mohammad A Kamal,7 and Farhan Jalees Ahmad1,2. Nanotechnology-based inhalation treatments for lung cancer: state of the art. Nanotechnol Sci Appl. 2015; 8: 55–66.

  1. -M. Lü, X. Wang, C. Marin-Muller, et al. Current advances in research and clinical applications of PLGA-based nanotechnology Expert Rev Mol Diagn, 9 (2009), pp. 325–341
  1. A. Gabizon, H. Shmeeda, S. Zalipsky Pros and cons of the liposome platform in cancer drug targeting J Liposome Res, 16 (2006), pp. 175–183
  1. Wing-Hin Lee,   Ching-Yee Loo,   Daniela TrainiPaul M. Young. Inhalation of nanoparticle-based drug for lung cancer treatment: Advantages and challenges. Asian Journal of Pharmaceutical Sciences Volume 10, Issue 6, December 2015, Pages 481–489
  1. ipcrc.net/pdfs/Kenya-National-Cancer-Control-strategy.pdf
  1. or.ke/wp-content/uploads/2013/10/NAtional-CANCER-REGISTRY-.ppt)

7.      https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet

  1. https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet
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  1. https://www.cancer.gov/types/lung/patient/small-cell-lung-treatment-pdq
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  1. https://medlineplus.gov/ency/article/000122.htm
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  2. Horn L, Eisenberg R, Gius D, et al. Cancer of the lung. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds.Abeloff’s Clinical Oncology. 5th ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2014:chap 72.
  1. National Cancer Institute. PDQ Small cell lung cancer treatment.Bethesda, MD. http://www.cancer.gov. Date last modified January 23, 2015.
  1. http://www.cancer.gov/cancertopics/pdq/treatment/small-cell-lung/healthprofessional. Accessed October 7, 2015.
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  1. http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. Accessed October 7, 2015.
  1. Silvestri GA, Pastis NJ, Tanner NT, Jett JR. Clinical aspects of lung cancer. In: Broaddus VC, Mason RJ, Ernst JD, et al, eds.Murray and Nadel’s Textbook of Respiratory Medicine. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 53.
  1. https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lung-cancer.html
  1. http://www.ipcrc.net/pdfs/Kenya-National-Cancer-Control-strategy.pdf
  1. http://jme.endocrinology-journals.org/content/47/1/R11.full
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  1. https://www.mycancergenome.org/content/disease/lung-cancer/kras/
  1. Meyers JD1,Cheng Y2Broome AM1Agnes RS1Schluchter MD3Margevicius S3Wang X1Kenney ME2Burda C2Basilion JP Peptide-Targeted Gold Nanoparticles for Photodynamic Therapy of Brain Cancer. Part Part Syst Charact. 2015 Apr; 32(4): 448–457.Published online 2014 Oct 6. doi:  10.1002/ppsc.201400119

LUNG CANCER: Genetic Signatures

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Fig: A DNA Double Helix model (flickr.com/creativecommons)

Lung Cancer is a group of diseases which are not easily detected due to diverse the nature of their manifestation. There are no specific and dependable biomarkers (molecules that signify disease) present in the blood or tissues which could be used to confirm the existence of the disease in all of its manifestations. However, genetics is a very important tool that can be employed in the tracking, detecting and treatment of lung cancer especially at the early stages.

Genetics is the study of genes. Genes are codes on DNA which express characteristics of organisms. The DNA is a double strand formed out of molecules called nucleotide bases which complement each other on the opposite side of the strands. There are four nucleotides in the DNA strands: Guanine (G), Adenine (A), Cytosine (C) and Thymine (T). Guanine (G) usually complements with Cytosine (C) while Adenine (A) usually complements with Thymine (T). The different combinations of these nucleotide bases code for specific amino acids which in turn are joined together to form proteins which are the building blocks of life and are important in the formation of enzymes and hormones. A group of nucleotide bases arranged to code for a certain protein on a DNA strand is called a gene. The body manufactures proteins on a need to need basis as required by the cells and the tissues. For example, when one has an injury, the DNA in the cells around the injured area may code for the manufacture of specific proteins such as melanin (skin pigment) to be able to accelerate recovery from the wound.

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Fig: Representation of nucleotide base sequence as depicted (Photo by Miki Ashihito through flickr.com/creativecommons)

Sometimes however, genetic expressions on the DNA may be altered due to a person’s heritage (family line) or environmental factors e.g. chemicals such as aflatoxins, aromatic hydrocarbons and radioactivity which can alter the expression of certain genes, also known as gene mutation. When gene mutation occurs, the coding of some proteins can be exaggerated or suppressed leading to the development of diseases like cancer.

In lung cancer, some proteins which are located on the lung cell walls may be affected by this genetic disorder and are crucial in the understanding of the disease.

EGFR (Epidermal Growth Factor Receptor)

EGFR is a protein that doubles up as an enzyme. It is found on the surface of healthy cells and is crucial in the process of cell division. It is encoded in the EGFR gene on the DNA. Genetic mutations on the DNA strand may lead to an over-expression of this gene leading to the synthesis of excessive EGFR resulting into excessive and abnormal cell division. About 15% of patients with Non Small Cell Lung Cancer exhibit mutations of this gene (24). EGFR belongs to a group of enzymes known as Tyrosine Kinases which are very important in cell division. In Lung Cancer treatment, substances known as ‘Tyrosine Kinase Inhibitors’ or TKI are employed in the control of excessive and abnormal cell division.

ALK (Anaplastic Lymphoma Kinase)

ALK is also a protein which functions as an enzyme and is found on the cell surface and is also responsible for cell division belonging to the class enzymes called Tyrosine Kinases. It is coded by the ALK gene on the DNA. Gene mutation leads to an over- expression of its code leading to its excessive synthesis and promotion of rapid and abnormal cell division in the body. About 3-7% of lung cancer patients display this gene mutation especially among smokers and non- smokers who are young (25). Its cancerous nature can be suppressed by Tyrosine Kinase Inhibitor drugs.

KRAS (Kirsten Rat Sarcoma) Viral Oncogene Homolog

KRAS is a protein which functions as an enzyme in healthy cells. It belongs to a group of enzymes called the GTPases which are also very important in cell division. It is encoded by the KRAS gene on the DNA which is also known as an oncogene (genes expressing proteins that are very key in cell division). A mutation of this gene may lead to production of excessive KRAS in the cells leading to abnormal cell division and cancer. KRAS gene mutation is usually expressed in about 15- 20% of Non Small Cell Lung Cancer (NSCLC) patients with the Adenocarcinoma variety.

Genetic mutations of can be detected in a biotechnological or biochemistry lab by using methods such as FISH (Fluorescent In- Situ Hybridization) as approved by the US Food and Drug Administration. It involves the labeling of specific genes on DNA extracted from a patient with light- emitting substances and reacting them with healthy DNA in order to mark out the over-expressed or missing genes for disease diagnosis.

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Fig: Fluorescent In-Situ Hybridization (FISH) technique displaying genetic mutations as emitted light (Photo by Wellcome Images through flickr.com/creativecommons)

DISCLAIMER: The information in this article is written for general information purposes and MUST NOT be used as a substitute for personalized medical care from a qualified medical practitioner. This blog platform will not be responsible for any injury or damage to persons of property arising from any errors or omissions.

 

References

1.      Javed Ahmad,1,* Sohail Akhter,2,3,* Md Rizwanullah,1 Saima Amin,1 Mahfoozur Rahman,4 Mohammad Zaki Ahmad,5Moshahid Alam Rizvi,6 Mohammad A Kamal,7 and Farhan Jalees Ahmad1,2. Nanotechnology-based inhalation treatments for lung cancer: state of the art. Nanotechnol Sci Appl. 2015; 8: 55–66.

  1. -M. Lü, X. Wang, C. Marin-Muller, et al. Current advances in research and clinical applications of PLGA-based nanotechnology Expert Rev Mol Diagn, 9 (2009), pp. 325–341
  1. A. Gabizon, H. Shmeeda, S. Zalipsky Pros and cons of the liposome platform in cancer drug targeting J Liposome Res, 16 (2006), pp. 175–183
  1. Wing-Hin Lee,   Ching-Yee Loo,   Daniela TrainiPaul M. Young. Inhalation of nanoparticle-based drug for lung cancer treatment: Advantages and challenges. Asian Journal of Pharmaceutical Sciences Volume 10, Issue 6, December 2015, Pages 481–489
  1. ipcrc.net/pdfs/Kenya-National-Cancer-Control-strategy.pdf
  1. or.ke/wp-content/uploads/2013/10/NAtional-CANCER-REGISTRY-.ppt)

7.      https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet

  1. https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet
  1. https://www.cancer.gov/types/lung/patient/non-small-cell-lung-treatment-pdq
  1. https://www.cancer.gov/types/lung/patient/small-cell-lung-treatment-pdq
  1. https://www.cancer.org/cancer/small-cell-lung-cancer/about/what-is-small-cell-lung-cancer.html
  1. https://medlineplus.gov/ency/article/000122.htm
  1. http://www.cancerresearchuk.org/about-cancer/lung-cancer/treatment
  1. knh.or.ke/wp-content/uploads/2013/10/NAtional-CANCER-REGISTRY-.ppt
  2. Horn L, Eisenberg R, Gius D, et al. Cancer of the lung. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds.Abeloff’s Clinical Oncology. 5th ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2014:chap 72.
  1. National Cancer Institute. PDQ Small cell lung cancer treatment.Bethesda, MD. http://www.cancer.gov. Date last modified January 23, 2015.
  1. http://www.cancer.gov/cancertopics/pdq/treatment/small-cell-lung/healthprofessional. Accessed October 7, 2015.
  1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Small cell lung cancer. Version 1.2016.http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf.Accessed October 7, 2015.National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Small cell lung cancer. Version 1.2016.
  1. http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. Accessed October 7, 2015.
  1. Silvestri GA, Pastis NJ, Tanner NT, Jett JR. Clinical aspects of lung cancer. In: Broaddus VC, Mason RJ, Ernst JD, et al, eds.Murray and Nadel’s Textbook of Respiratory Medicine. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 53.
  1. https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lung-cancer.html
  1. http://www.ipcrc.net/pdfs/Kenya-National-Cancer-Control-strategy.pdf
  1. http://jme.endocrinology-journals.org/content/47/1/R11.full
  1. http://www.cancer.net/research-and-advocacy/asco-care-and-treatment-recommendations-patients/epidermal-growth-factor-receptor-egfr-testing-advanced-non-small-cell-lung-cancer
  1. https://www.mycancergenome.org/content/disease/lung-cancer/kras/

LUNG CANCER: Unmasking the Killer

Lung Cancer diagnosis can take several forms in hospitals. Sometimes the cancer may be discovered accidentally while aggressively progressing forms may trigger symptoms in an individual leading to diagnosis. This is a brief analysis of some of the diagnostic methods and tools employed the detection of lung cancer in the body:

CT SCAN

The CT Scan is a computerized image produced by the penetrative capabilities of X-Rays in  body organs and tissues. This is one of the most used procedures in the detection of lung cancer since it can be able to draw images of the cell tissues in the lungs and related organs helping in detecting the presence of tumors by contrasting their images in relation to the other healthy cells.

yale rosen ct

Fig: A CT Scan of the lungs showing a tumor on the top right (Photo by Yale Rosen through flickr.com/creativecommons)

SPUTUM TESTING

One of the symptoms of lung cancer is the removal of sputum after coughing. Some forms of lung cancers can develop among cells which produce mucus leaving their remnants in the removed sputum. The sputum can be extracted and taken to a lab where it can be observed for the presence of cancerous cells and tissues.

BIOPSY

A biopsy involves the removal of a tissue of an infected area in order to analyze it in a lab for infection. In lung cancer diagnosis, removal of the lung tissue can be carried out in one of the following ways:

Fine Needle Aspiration (FNA) Biopsy: Here, a very fine needle is inserted into the lung and used to extract lung fluid or tissue which can be inspected by a pathologist for cancerous cells under a microscope.

Bronchoscopy: In this procedure, a tube fitted with a camera is inserted into the trachea and then the bronchi of the patient and used to scan for possible signs of tumor development. It can also possess a small scalpel which can be used in the removal of some tissue if need be for further examination in a lab.

Thoracentesis: This is the removal of the fluid between the lungs and the chest for observation of the signs of tumor cell development.

ELECTRON MICROSCOPY

Electron microscopy is a technique employed in physical sciences and also in medicine. It involves the usage of a high level of magnification lenses to draw up an extremely fine details of the surface or contents of an object such as a body organ in order to understand it. In cancer diagnostics, it can be used to highlight the surface of the lungs (areas of interest) in order to check if there is tumor development.

Zeiss microscopy- skin cancer cells

Fig: High resolution micro-graph of rapidly dividing skin cancer cells (photo by Zeiss Microscopy through flickr.com/creativecommons)

BIOMARKER ANALYSIS

A biomarker is a substance such as a protein produced by a disease which can be used to ascertain its existence. It could be present in the blood or in body tissues. In lung cancer two major biomarkers are of utmost importance in mapping the disease: ALK (Anaplastic Lymphoma Kinase) and EGFR (Epidermal Growth Factor Receptor). These biomarkers, which are proteins, are usually located on the surfaces of cells of interest in the lungs. They have the capability to alter the cell division process of the cells after binding unique substances called ligands, leading to increased and abnormal cell division and ultimately cancer.They are useful in monitoring the patient’s response to lung cancer treatment. Since DNA is responsible for the coding and manufacture of proteins in the body, the abnormal production of these biomarkers can be assessed by the mapping of the DNA genes of interest which can be done in a biochemistry or biotechnology lab.

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Fig: A gene sequence in DNA represented by the different colors. The alteration of these sequences can lead to the over- expression of a certain gene and ultimately over production of proteins such as ALK and EGFR which are important in Lung Cancer Diagnosis (Photo by Andy Leppard through flickr.com/creativecommons)

DISCLAIMER: The information contained in this article is written for general information purposes and MUST NOT be used as a substitute for personalized medical care from a qualified medical practitioner. This blog platform will not be responsible for any injury or damage to persons of property arising from any errors or omissions.

References and further reading

1.      Javed Ahmad,1,* Sohail Akhter,2,3,* Md Rizwanullah,1 Saima Amin,1 Mahfoozur Rahman,4 Mohammad Zaki Ahmad,5Moshahid Alam Rizvi,6 Mohammad A Kamal,7 and Farhan Jalees Ahmad1,2. Nanotechnology-based inhalation treatments for lung cancer: state of the art. Nanotechnol Sci Appl. 2015; 8: 55–66.

 

  1. -M. Lü, X. Wang, C. Marin-Muller, et al. Current advances in research and clinical applications of PLGA-based nanotechnology Expert Rev Mol Diagn, 9 (2009), pp. 325–341

 

 

  1. A. Gabizon, H. Shmeeda, S. Zalipsky Pros and cons of the liposome platform in cancer drug targeting J Liposome Res, 16 (2006), pp. 175–183

 

  1. Wing-Hin Lee,   Ching-Yee Loo,   Daniela Traini,  Paul M. Young. Inhalation of nanoparticle-based drug for lung cancer treatment: Advantages and challenges. Asian Journal of Pharmaceutical Sciences Volume 10, Issue 6, December 2015, Pages 481–489

 

 

  1. www.ipcrc.net/pdfs/Kenya-National-Cancer-Control-strategy.pdf

 

  1. knh.or.ke/wp-content/uploads/2013/10/NAtional-CANCER-REGISTRY-.ppt)

7.      https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet

 

  1. https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet

 

  1. https://www.cancer.gov/types/lung/patient/non-small-cell-lung-treatment-pdq

 

  1. https://www.cancer.gov/types/lung/patient/small-cell-lung-treatment-pdq

 

  1. https://www.cancer.org/cancer/small-cell-lung-cancer/about/what-is-small-cell-lung-cancer.html

 

  1. https://medlineplus.gov/ency/article/000122.htm

 

  1. http://www.cancerresearchuk.org/about-cancer/lung-cancer/treatment

 

  1. or.ke/wp-content/uploads/2013/10/NAtional-CANCER-REGISTRY-.ppt
  2. Horn L, Eisenberg R, Gius D, et al. Cancer of the lung. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds.Abeloff’s Clinical Oncology. 5th ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2014:chap 72.

 

  1. National Cancer Institute. PDQ Small cell lung cancer treatment.Bethesda, MD. http://www.cancer.gov. Date last modified January 23, 2015.

 

  1. http://www.cancer.gov/cancertopics/pdq/treatment/small-cell-lung/healthprofessional. Accessed October 7, 2015.

 

  1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Small cell lung cancer. Version 1.2016.http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf.Accessed October 7, 2015.National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Small cell lung cancer. Version 1.2016.

 

  1. http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. Accessed October 7, 2015.

 

  1. Silvestri GA, Pastis NJ, Tanner NT, Jett JR. Clinical aspects of lung cancer. In: Broaddus VC, Mason RJ, Ernst JD, et al, eds.Murray and Nadel’s Textbook of Respiratory Medicine. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 53.

 

  1. https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lung-cancer.html

 

  1. http://www.ipcrc.net/pdfs/Kenya-National-Cancer-Control-strategy.pdf

 

  1. http://jme.endocrinology-journals.org/content/47/1/R11.full

LUNG CANCER: Cryptic but Crushing

 

 

SONY DSC

Fig: Air Pollution from burning waste material. A couple of cancer- causing substances are released through polluted air such as Cadmium and Poly-Cyclic Aromatic Hydrocarbon (PAHs) compounds (through flickr.com/creativecommons)

Lung Cancer refers to a collection of diseases that can affect the lungs and the areas that are related to the respiratory system such as the bronchi, trachea and the larynx. It accounts for about 1.3 million deaths worldwide (5). Its prevalence in Kenya is about 7.9% of the population (6). The disease can cause difficulty in the functioning of the respiratory system but could also spread to other parts of the body such as the liver, brain and bones.

The respiratory system functions by letting air through the nose which is passed into the lungs through the larynx, the trachea then the bronchi. The trachea is the main tube which divides into two bronchi before ending up in the lungs. The right lung is usually slightly larger than the left lung due to space displacement on the left side by the heart. The bronchi (singular- bronchus) divides into many small tubes called the bronchioles which deliver the air to small sacs called alveoli where gaseous exchange takes place. Here the lungs absorbs the oxygen and releases the Carbon dioxide for exhalation.

Lung cancer is categorized by the American Cancer Society into either Small Cell Lung Cancer or SCLC (affects about 10-15% of people) and Non- Small Cell Lung Cancer or NSCLC (affects about 80-85% of people).

Small Cell Lung Cancer (SCLC) or Oat Cell Cancer is most common among tobacco smokers and is very aggressive in its growth and spread (metastatic). It begins in the lungs but moves rapidly to other organs such as the liver, brain and bones. It is referred to this way because the cells it affects are small, flat cells in the lungs.

Yale Rosen Small cell carcinoma

Fig: Small Cell Lung Carcinoma Cells seen through a microscope (Photo by Yale Rosen through flickr.com/creativecommons)

Non- Small Cell Lung Cancer (NSCLC) is a much less aggressive form of lung cancer but most common type. One of the most common forms of NSCLC is known as Adenocarcinoma which accounts for about 40% of all cases of lung cancer. It affects younger people, non- smokers and smokers alike and is found in the areas of the lungs that secrete mucus mostly on the lung- lining. It is also most common form of Lung cancer among women.  Another form of NSCLC affects the flat cells lining the air passageways of the lungs also called squamous cells. It accounts for about 30% of all lung cancer cases. A much less common form of NSCLC is called the Large Cell Carcinoma which is very aggressive in its growth and spread but less specialized in location thus can be found anywhere in the lungs. These facts make it very difficult to identify and treat.

Ed Uthman nsclc

Fig: Non Small Cell Cancer Cells seen using a microscope (Photo by Ed Uthman through flickr.com/creativecommons)

The main cause of lung cancer is tobacco smoking. However, tobacco can be considered with other relevant risk factors which together or individually can accelerate the occurrence of lung cancer.

TOBACCO SMOKING

Tobacco smoking is the best known cause of lung cancer. Some of the substances present in tobacco are well- known carcinogens such as Cadmium, aromatic organic compounds such as benzene and tar. The risk of contracting lung cancer increases with the length of time one has been smoking tobacco and even their age. Tobacco smoking is such a potent cause of lung cancer that even people who have stopped smoking could still be exposed to the risk of cancer later on in their lives. Secondary smoking has also been known to cause lung cancer. Some nations like Kenya have legislated laws to confine tobacco smoking to specific areas so as to reduce instances of secondary smoking.

RADON

Radon is a gas produced due to the radioactive decay of Uranium. It is not a very common substance in the environment but could be present especially near Uranium mines and people exposed to radio activity especially occupationally such as radiologists in the hospitals. The concentrations of the gas especially in residential areas near Uranium mines needs to be checked to reduce the occurrence of lung cancer among the population.

ASBESTOS AND RELATED SUBSTANCES

Asbestos is a very fine silicate substance that is used in construction. The danger it poses to those exposed to it is its very fine nature which can lead to it accumulating in the lungs without removal leading to respiratory infections and later cancer. Construction workers, cement factory workers and people working in mines are very much at risk from asbestos and other related and fine materials which could put them in at risk of contracting lung cancer.

GENETICS

A family history of lung cancer is an important factor to consider when assessing the risk factors. Genes are fragments of the DNA which express certain characteristics of an individual passed down to them by the parents. Lung cancer can be caused by abnormal expression of certain inherited genes which might trigger excessive and abnormal cell division (onco-genes) while suppressing genes which control or stop rapid cell division (suppressor genes). It is therefore essential to note any family member with a history of lung cancer in order to assess it as a risk factor.

AIR POLLUTION

In most industrialized cities, the air is polluted by toxic gases such as motor vehicle exhaust, nitrogen oxides, sulfur oxides, carbon monoxide, cadmium, Polycyclic Aromatic Hydrocarbons such as benzene derivatives like styrene,  naphthalene,  phenanthrene etc.  and soot among others. This is also dependent on the location of the cities and the industrial activities around it. Some of these pollutants are well known carcinogens such as Cadmium and benzene. Exposure to highly polluted air in cities has been known to be one of the risk factors that could trigger contracting of lung cancer.

HIV/ AIDS

HIV/ AIDS being a condition which breaks down the body immune system could also expose the body to the risk of contracting an opportunistic disease like lung cancer. Due to the degradation of the body’s immune system, there is a breakdown of its ability to regulate activities such as cell division which could proceed abnormally leading to various forms of cancer.

The symptoms of lung cancer are varied depending on the nature and the location of the disease in the respiratory tract. However, some common features include: Chest pain and discomfort; Persistent Coughing; Wheezing; Weight- loss; Swelling in the Face; Sputum in the blood; and trouble while breathing.

DISCLAIMER: The information contained in this article is written for general information purposes and MUST NOT be used as a substitute for personalized medical care from a qualified medical practitioner. This blog platform will not be responsible for any injury or damage to persons of property arising from any errors or omissions.

References and Further Reading

1.      Javed Ahmad,1,* Sohail Akhter,2,3,* Md Rizwanullah,1 Saima Amin,1 Mahfoozur Rahman,4 Mohammad Zaki Ahmad,5Moshahid Alam Rizvi,6 Mohammad A Kamal,7 and Farhan Jalees Ahmad1,2. Nanotechnology-based inhalation treatments for lung cancer: state of the art. Nanotechnol Sci Appl. 2015; 8: 55–66.

  1. -M. Lü, X. Wang, C. Marin-Muller, et al. Current advances in research and clinical applications of PLGA-based nanotechnology Expert Rev Mol Diagn, 9 (2009), pp. 325–341
  1. A. Gabizon, H. Shmeeda, S. Zalipsky Pros and cons of the liposome platform in cancer drug targeting J Liposome Res, 16 (2006), pp. 175–183
  1. Wing-Hin Lee,   Ching-Yee Loo,   Daniela Traini,  Paul M. Young. Inhalation of nanoparticle-based drug for lung cancer treatment: Advantages and challenges. Asian Journal of Pharmaceutical Sciences Volume 10, Issue 6, December 2015, Pages 481–489
  1. www.ipcrc.net/pdfs/Kenya-National-Cancer-Control-strategy.pdf
  1. knh.or.ke/wp-content/uploads/2013/10/NAtional-CANCER-REGISTRY-.ppt)

7.      https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet

 8.https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet

  1. https://www.cancer.gov/types/lung/patient/non-small-cell-lung-treatment-pdq

 

  1. https://www.cancer.gov/types/lung/patient/small-cell-lung-treatment-pdq

 

  1. https://www.cancer.org/cancer/small-cell-lung-cancer/about/what-is-small-cell-lung-cancer.html

 

  1. https://medlineplus.gov/ency/article/000122.htm

 

  1. http://www.cancerresearchuk.org/about-cancer/lung-cancer/treatment

 

  1. or.ke/wp-content/uploads/2013/10/NAtional-CANCER-REGISTRY-.ppt
  2. Horn L, Eisenberg R, Gius D, et al. Cancer of the lung. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds.Abeloff’s Clinical Oncology. 5th ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2014:chap 72.

 

  1. National Cancer Institute. PDQ Small cell lung cancer treatment.Bethesda, MD. http://www.cancer.gov. Date last modified January 23, 2015.

 

  1. http://www.cancer.gov/cancertopics/pdq/treatment/small-cell-lung/healthprofessional. Accessed October 7, 2015.

 

  1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Small cell lung cancer. Version 1.2016.http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf.Accessed October 7, 2015.National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Small cell lung cancer. Version 1.2016.

 

  1. http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. Accessed October 7, 2015.

 

  1. Silvestri GA, Pastis NJ, Tanner NT, Jett JR. Clinical aspects of lung cancer. In: Broaddus VC, Mason RJ, Ernst JD, et al, eds.Murray and Nadel’s Textbook of Respiratory Medicine. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 53.

 

  1. https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lung-cancer.html

 

  1. http://www.ipcrc.net/pdfs/Kenya-National-Cancer-Control-strategy.pdf

 

  1. http://jme.endocrinology-journals.org/content/47/1/R11.full

PROSTATE CANCER: Nanotechnology- Aided Diagnostics and Treatment

B0007784 Lung cancer cells

Fig: Fast dividing Lung Cancer cells (photo by Wellcome Images through flickr.com/creativecommons)

Prostate cancer treatment involves the use of both radiotherapy and chemotherapy. Radiotherapy involves the usage of radioactive energy in the destruction of the cancerous cells while chemotherapy or hormonal therapy involves the usage of medicine and hormones in the suppression of the spread of the disease. One of the major side-effect in the usage of such methods has been the indiscriminate targeting of cells leading to the destruction of healthy cells. This collateral damage on many occasions leads to the weakening of the patient.

Nanotechnology is a multi disciplinary field concerned with the manipulation of matter at nano-scale in order to draw out unique characteristics useful for applications in medicine, engineering, pharmaceuticals, environment and agriculture among others.  Nanotechnology is a very fast growing area in the field of cancer research since a number of nano-materials have been used for both the diagnosis and treatment of cancer diseases such as prostate cancer. Since these nano-materials have the ability to identify and bind to cancerous cells, they can simultaneously be activated  to destroy them in the process. This process of combining both the diagnostics and the therapeutic steps in cancer treatment is known as thera-nostics. These materials also have the capability to deliver drugs to the cancer cells specifically avoiding damage to the healthy cells, a phenomenon known as targeted drug delivery.

Two very significant nano materials which are still under active research in the field of cancer diagnostics and therapy are Gold Nano-particles (AuNPs) and Quantum Dots (QDs).

GOLD NANOPARTICLES (AuNPs)

gold

Fig: Gold Nanoparticles (AuNPs) used in targeting and destruction of cancerous cells ( Flickr.com/creativecommons)

Targeted Radioactive Thera-nostics

Gold nano-particles (AuNPs) are today’s wonder substance in cancer diagnostics and treatment. AuNPs are capable of identifying and binding onto cancerous cells easily thereby helping in their isolation. Cancer cells are known for their rapid metabolism and lack of specialization which might be the reasons why AuNPs are attracted to them. Also, due to their high metabolic rate, cancer cells end up absorbing the AuNPs into their cell fluid (cytoplasm) easily. Magnetically enabled AuNPs can be used in the identification of cancer cells through enhanced imaging especially in procedures like the MRI scans. The high affinity cancerous cells have for AuNPs mean that a ‘Trojan Horse’ strategy could be used to destroy them specifically without damaging the other health cells. This can be done by radiating the tumor after uptake of the AuNPs with light of a specific wavelength. Since the AuNPs have surface electrons, they end up absorbing the radiation, getting excited then releasing the excess energy as heat in the Near Infra Red (NIR) range. The NIR wavelength range of light is known to be quite destructive to animal tissues thus can end up destroying the cancerous cells rendering them inactive. This procedure also known as Seed Implantation Therapy is used in some UK hospitals in treating some localized forms of prostate cancer(1).

 Targeted Chemotherapy

Targeted chemotherapy(10) is an area that is still under active research. AuNPs can be used this way by being attached to a specific chemical agent toxic to the tumor and getting absorbed specifically into cancerous cells for targeted destruction. Also, AuNPs could be coated with a special dye which is able to absorb light at a specific wavelength emitting the rest as NIR thereby destroying the cancerous cells. Healthy cells do not take in the dye- laced nanoparticles thus enabling the targeting to be specific for cancerous cells. The light activation of the dye can take place using a laser beam.

QUANTUM DOTS (QDs)

3360754104_c944ca47e3_o

Fig: Colloidal Quantum Dots (QD Solutions) used in identification and targetting of Cancerous Cells (Photo by Evident Technologies through flickr.com/creativecommones)

Drug delivery and tracking

Quantum dots or QDs are semi-conductor nano-particles. Due to their small sizes, they are capable of confining their electrons into smaller spaces leading to them exhibiting very unique light absorbing characteristics. Depending on the sizes of the QDs, the absorbance of energy by their electrons is different leading to them emmiting light in different colors also known as fluorescing. Due to their ability to radiate different colors, QDs can be employed in tracking the visible movement and action of drugs in cancerous cells (3). Because of their affinity to the cancerous cells also, they can also be attached to some specific cancer drugs and used to deliver them to the specific cells for targeted action.

Phyto-dynamic Therapy (3)

Because of their unique interactions with visible light and their affinity for cancerous cells, QDs can be used for attachment to the cells followed by activation for their destruction using light. Some QDs absorb and emit light in the Near IR (NIR) range which is very significant in the destruction of cell tissue. Therefore, QDs of unique shapes can be synthesized and used in the targeted destruction of cancerous cells without damage to healthy cells.

DISCLAIMER: The information contained in this article is written for general information purposes and MUST NOT be used as a substitute for personalized medical care from a qualified medical practitioner. This blog platform will not be responsible for any injury or damage to persons of property arising from any errors or omissions.

 References and further reading

  1. http://www.cancerresearchuk.org/about-cancer/prostate-cancer/treatment/radiotherapy/internal-radiotherapy/seed-implantation-radiotherapy
  1. Ajita Pathak, Tanya. Use of Nanotechnology in Cancer Diagnosis and Treatment. International Journal of Engineering Science and Innovative Technology (IJESIT) Volume 5, Issue 3, May 2016
  2. Luo G1,Long JZhang BLiu CJi SXu JYu XNi Q. Quantum dots in cancer therapy. Expert Opin Drug Deliv. 2012 Jan;9(1):47-58. doi: 10.1517/17425247.2012.638624. Epub 2011 Dec 16.
  1. http://prostatecanceruk.org/prostate-information/are-you-at-risk
  1. http://www.nhs.uk/Conditions/Cancer-of-the-prostate/Pages/Causes.aspx
  1. https://www.cancer.gov/types/prostate
  1. https://www.cancer.gov/types/prostate/psa-fact-sheet
  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621223/
  1. http://www.iraj.in/journal/journal_file/journal_pdf/1-120-142815338131-35.pdf
  1. DEEPTHI N, CLINTON LEWIS, A ARUNKUMAR. A NANOELECTRONIC APPROACH FOR EARLY DETECTION AND TREATMENT OF PROSTATE CANCER. IJEEDC, ISSN (P): 2320-2084, (O) 2321–2950, COE, Bharti Vidyapeeth, Deemed University, Pune, Special Issue-1 April-2015.
  1. https://www.ncbi.nlm.nih.gov/pubmed/20524513
  1. http://www.ijesit.com/Volume%205/Issue%203/IJESIT201603_11.pdf
  1. Dev Kumar Chatterjee,1,*Tatiana Wolfe,1,* Jihyoun Lee,1,2,* Aaron P Brown,1,* Pankaj Kumar Singh,1,* Shanta Raj Bhattarai,1,* Parmeswaran Diagaradjane,1 and Sunil Krishnan Convergence of nanotechnology with radiation therapy—insights and implications for clinical translation. Transl Cancer Res. 2013 Aug 23; 2(4): 256–268.doi:  10.3978/j.issn.2218-676X.2013.08.10.

14.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4179207/