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Page 2 of 16                                                 Bhatia et al. Hepatoma Res 2018;4:9  I  http://dx.doi.org/10.20517/2394-5079.2018.04

               Conclusion: As evident by improved functional, hematological and biochemical markers, it may be inferred that LycT has
               the potential to delay HCC initiation.


               Keywords: Lycopene,  99m Tc-mebrofenin, hepatocellular carcinoma, hematology, oxidative stress, inflammation



               INTRODUCTION
               Environmental factors including exposure to chemical pollutants due to growing industrialization and
               adoption of unhealthy lifestyle choices like physical inactivity, imbalanced dietary regimen and smoking
               play a major role in the etiology of various ailments including cancer. The existing structural embodiment
               of our environment and surroundings makes impossible to evade the exposure from its pernicious clutches.
               Among various pollutants, N-nitrosodiethylamine (NDEA) is a potent environmental carcinogen found
               in air, soil, water and food . Metabolic activation of NDEA through hepatic biotransformation enzymes
                                      [1-3]
               renders liver as a target organ for carcinogenesis. Hepatocellular carcinoma (HCC) is figured to be the fifth
               most common tumors of liver across the globe and accounts for 2.5% increase of death rates every year .
                                                                                                        [4]
               Extremely high incidence rate, poor prognosis and asymptomatic behavior associated with HCC makes its
               diagnosis restrictable at initial stages. Furthermore, angiogenesis and malignant nature of tumorous tissue
               may also reduce the life expectancy of HCC patients at later stages.

               Early HCC diagnosis has become a priority in improving the survival among cancer patients. Despite the
               availability of various modalities for HCC treatment such as surgical resection, radiation and chemotherapy,
               the outcome of patient remains dismal. Additionally, various non-invasive modalities such as ultrasound,
               computed tomography, and magnetic resonance imaging are in use for early monitoring, diagnosis and
               stratification of HCC . But these provide only anatomical information not the functional status of the
                                  [5]
               tumorous tissue. Therefore, the development of non-invasive diagnostic techniques and identification of tumor
               specific serological markers linked to early stages of carcinogenesis would be of great clinical significance
               in the early management of HCC patients. This may be accomplished by  Tc-mebrofenin hepatobiliary
                                                                               99m
               functional test that mainly relies on functional perturbations in the tissue as functional alterations precede
               anatomical alterations . The main rationale behind the identification of candidate biomarkers relevant for
                                  [6]
               cancer risk is to find a link between biological alterations in nonspecific tissues, such as blood, and the
               occurrence of similar events in specific tissues involved in the carcinogenesis. Moreover, blood acts as a
               pathological reflector of the systemic status of an animal exposed to carcinogen .
                                                                                  [7]
               Hematological parameters are surrogate markers playing a key role in diagnosing the extent of damage to blood
               thus acting as a prognostic indicator of HCC patients . NDEA is also known to induce chronic inflammatory
                                                           [8]
               responses characterized by the upregulation of pro-inflammatory cytokines and recruitment of innate
               immune cells to liver tissue. Chronic inflammation further predisposes hepatic tissue to the development of
               HCC . Free radicals and reactive oxygen species (ROS) generation during NDEA metabolism further causes
                    [9]
               the oxidation of major cellular biomolecules thus may augment an oxidative stress which may be postulated
               as a major contributor in the genesis of cancer . Various reports support the relationship between the hepatic
                                                     [10]
               antioxidant system and development of hepatocarcinogenesis [11,12] . However, only few studies are available to
               evaluate the role of blood antioxidants in early diagnosis of HCC [13,14] . These observations emphasize the need
               for urgent implementation of efficient strategies to curb this disease. From the past few decades, preventive
               control approaches using the natural products derived from common dietary sources have been the main
               focus of scientific research to impede the induction of carcinogenesis .
                                                                         [15]
               Lycopene extracted from red tomatoes has found its widespread use in natural medicine because of its
               highest antioxidant and radical scavenging activity [3,16-18] . Consumption of lycopene enriched tomato extract
               has been revealed to be effective in alleviating cancer progression due to its increased bioavailability and
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