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Identifying Melanoma by Scent

Author: Tilda Barliya PhD

Researchers from the Monell Chemical Center developed a nano-sensor constructed of nano-size carbon nanotubes coated with DNA that could identify melanoma cells by scent (1).

The smell of cancer_MIT Technology

Currently, early detection of skin carcinoma is accomplished primarily through a visual exam,imaging techniques and biopsy of any suspected areas (1).

The biopsy is invasive and usually requires examination by a pathologist,  and the use of reflectance confocal microscopy and dermoscopy in situ for diagnosis of primary melanoma and other skin diseases, require specialized training.  Additionally, proteomics of caner-related biomarkers has also emerged in recent years. The discovery of cancer-related biomarkers using proteomic techniques has primarily focused on prognostic indicators of melanoma, i.e., examining the serum and plasma proteome for biomarkers indicative of metastases to distant sites (2,3).

Volatile cue however, such as those use to detect lung cancer (I), diabetes, COPD etc, have not yet been exploit in detecting melanoma. Rather volatile chemicals are released from melanoma tissues that can be differentiated from those of normal skin, posed a very interestingscientific questions.

Electronic nose that can sniff out cancer

It was no surprising that Dogs can identify by olfaction,melanoma on the skin of patients or melanoma samples hidden on healthy subjects, suggesting that volatile organic compounds (VOCs) from melanoma differ from those of normal skin. (4, 5).

D‘Amico et al. [6] employed gas chromatography/mass spectrometry (GC–MS) and a gas sensor array to investigate whether skin lesions of melanoma and nevi can be differentiated. In his paper, D’Amico had very promising results in which electronic nose sensors have been shown to have good sensitivity (with 80% accuracy) towards volatile organic compounds emitted by skin lesions, and the method seems to be effective for malign lesions identification (6).

Other attempts have been carried out to identify more closely the different VOCs of melanoma lesions compared to normal skin, however, environmental contamination rather than compounds from skin metabolism have failed to yield good detection methodology.

Kwak J et al, created an electronic nose (e-nose)  device employing functionalized DNA-coated carbon nanotube sensors, capable of sensitive and selective detection of compounds emitted from skin (1). These “single walled carbon nanotube field effect transistors (CNT FET’s), functionalized with single stranded DNA (DNACNT), have been shown to respond through a change in source drain current when exposed to VOCs” (7).

“The sensors show rapid response and recovery (seconds), very low signal drift, and chemical responses that are single strand DNA (ss-DNA) base sequence dependent. Single stranded-DNA is chosen for functionalization of the CNTs because it displays recognition for chemical vapors”.

The authors employed SPME and GC–MS to identify the VOCs that differentiate between human melanoma and normal melanocyte cells cultured in vitro, which may provide a model for in vivo human melanomas.  Same analysis were later conducted using GC–MS and DNACNT. Analysis of different normal melanocytes and melanoma cancer cell lines revealed: the growth media for normal melanocytes and cancer cells differed from each other in relative abundance of several compounds:

• 3-hydroxy-2-butanone (acetoin),
• 1-hexanol,
• acetophenone,
• phenylethyl alcohol
• phenol

They also noted that dimethylsulfone, which has been reported, in preliminary fashion, as a significant indicator of basal cell carcinoma, was seen in significantly greater amounts in metastatic melanoma cells vs. normal cells.

Summary

It is well known that cancer cells have altered metabolisms, which are expected to yield a different profile of metabolites.The authors presented here suggest significant differences in the “volatile metabolome” of melanoma cells vs. normal melanocytes.

The authors posit that successful development of rapid screening techniques incorporating new e-nose technologies, fitted with nanosensors with high selectivity for endogenous melanoma biomarkers, may effectively scan the complex volatile fingerprints acquired from suspicious lesions and quickly provide an evaluation for the physician, regardless of their geographic location”.

Smelling a disease has also been examined in bladder cancer (8), ovarian cancer (9) as well as Parkinson and Alzheimer disease (10) and it may potentially be used to enable easy, fast and accurate method to scenting a disease.

Ref:

1. Kwak J, Gallagher M, Ozdener MH, Wysocki CJ, Goldsmith BR, Isamah A, Faranda A, Fakharzadeh SS, Herlyn M, Johnson AT, Preti G. Volatile biomarkers from human melanoma cells. Journal of Chromatography B, 931 (2013) 90–96. http://www.ncbi.nlm.nih.gov/pubmed/23770738

2. S.A. Hoffman, W.A. Joo, L.A. Echan, D.W. Speicher, Higher dimensional (Hi-D) separation strategies dramatically improve the potential for cancer biomarker detection in serum and plasma.  J. Chromatogr. B: Analyt. Technol. Biomed. Life Sci. 849 (2007) 43. http://www.ncbi.nlm.nih.gov/pubmed/17140865

3.  J. Solassol, A. Du-Thanh, T. Maudelonde, B. Guillot,  Serum proteomic profiling reveals potential biomarkers for cutaneous malignant melanoma. Int. J. Biol. Markers 26 (2011) 82. http://www.ncbi.nlm.nih.gov/pubmed/21607923

4. H. Williams, A. Pembroke, SNIFFER DOGS IN THE MELANOMA CLINIC? Lancet 333 (1989) 734.  http://www.sciencedirect.com/science/article/pii/S0140673689922575
5. J. Church, H. Williams, Another sniffer dog for the clinic?  Lancet 358 (2001) 930.  http://www.sciencedirect.com/science/article/pii/S0140673601060652

6. D’Amico A, Bono R, Pennazza G, Santonico M, Mantini G, Bernabei M, Zarlenga M, Roscioni C, Martinelli E, Paolesse R, Di Natale C.  Identification of melanoma with a gas sensor array. Skin Res Technol. 2008 May;14(2):226-36.  http://www.ncbi.nlm.nih.gov/pubmed/18412567

7. C. Staii, A.T. Johnson Jr., M. Chen, A. Gelperin, DNA-Decorated Carbon Nanotubes for Chemical Sensing. Nano Lett. 5 (2005) 1774. http://pubs.acs.org/doi/abs/10.1021/nl051261f

8. Written By: Ian Anglin. SMELLING CANCER: DEVICE DETECTS BLADDER CANCER FROM ODOR OF URINE. http://singularityhub.com/2013/07/31/smelling-cancer-device-detects-bladder-cancer-from-odor-of-urine/

9. Horvath G, Chilo J, Lindblad T. Different volatile signals emitted by human ovarian carcinoma and healthy tissue.Future Oncol. 2010 Jun;6(6):1043-1049. http://www.ncbi.nlm.nih.gov/pubmed/?term=Volatile+biomarkers+from+ovarian+cacner

10. Ulrike Tisch, Ilana Schlesinger, Radu Ionescu, Maria Nassar, Noa Axelrod, Dorina Robertman, Yael Tessler, Faris Azar, Abraham Marmur, Judith Aharon-Peretz and Hossam Haick. Detection of Alzheimer’s and Parkinson’s disease from exhaled breath using nanomaterial-based sensors. Nanomedicine January 2013, Vol. 8, No. 1, Pages 43-56   http://www.futuremedicine.com/doi/abs/10.2217/nnm.12.105?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed&

Other open access article in Pharmaceutical Inteliigence

I. By: Tilda Barliya PhD. Diagnosing lung cancer in exhaled breath using gold nanoparticles.  http://pharmaceuticalintelligence.com/2012/12/01/diagnosing-lung-cancer-in-exhaled-breath-using-gold-nanoparticles/