Girish Maru - Academia.edu (original) (raw)
Papers by Girish Maru
Mini-Reviews in Medicinal Chemistry, 2010
Biomedical Research Journal
Majority of human cancers are caused, mediated and modified by environmental and lifestyle factor... more Majority of human cancers are caused, mediated and modified by environmental and lifestyle factors; and the multi-factorial, multi-step and multi-path process of carcinogenesis involves a series of genetic and epigenetic events. In spite of tremendous advancement in understanding of the molecular basis of cancer and identification of several environmental carcinogens, avoidance of exposure to carcinogens and early detection and/or successful treatment for most cancers have met with limited success. Based on the susceptibility to modulations of the multi-step process of carcinogenesis by a multitude of environmental compounds, lifestyle changes and host factors, and the demonstrated success of prevention of certain infectious diseases and cardiovascular events, cancer preventive interventions are receiving increasing attention. Several cancer preventive interventions such as vaccination, chemoprevention, weight control and lifestyle changes have been implemented. The current review focuses on several approaches and agents that have been scrutinized by way of randomized clinical trials in humans for their cancer prevention potential. Successful chemopreventive agents include selective oestrogen receptor modulators and aromatase inhibitors for breast cancer, the 5-α-reductase inhibitors for prostate cancer, non-steroidal antiinflammatory drugs (NSAIDs) for colorectal lesions and vaccines for viruses that are associated with cervical and liver cancers. Several experimentally proven chemopreventive agents have been observed to lack efficacy with and without toxicity. In spite of numerous chemoprevention trials, the number of successful agents is rather small. Identifying novel approaches and chemopreventives holds tremendous potential for reducing the burden of cancer.
Natural product research, Jan 11, 2017
Flowers of the plant Nyctanthes arbor-tristis (NAT) are widely used in the traditional medicinal ... more Flowers of the plant Nyctanthes arbor-tristis (NAT) are widely used in the traditional medicinal systems of several Asian countries. In the present study, potential genotoxicity and modulatory effects of ethanolic extract of NAT flower calyx (NAT FCE) and crocin, a carotenoid principle were evaluated employing standard Salmonella assay. Experiments evaluating the genotoxic potential of NAT FCE and crocin, with and without the S9-activation in TA 98, TA 100 and TA 102 showed a lack of increase in revertant mutants. Evaluation of modulatory effects of NAT FCE and crocin, without the S9, showed significant decrease in the number of 4-nitro-o-phenylenediamine-, sodium azide- and ethyl methanesulfonate-induced revertants. However, with S9, NAT FCE and crocin moderately increased the 2-aminoanthracene-induced revertants in TA 98; they moderately decreased revertants in TA 100 and TA 102. Both NAT FCE and crocin have been shown to be non-genotoxic and to be able to modulate responses of st...
Molecular Carcinogenesis, 2016
The aim of our study was to evaluate chemopreventive efficacy and possible mechanism of most abun... more The aim of our study was to evaluate chemopreventive efficacy and possible mechanism of most abundant polyphenolic fraction in black tea, polymeric black tea polyphenols (PBPs), in experimental lung carcinogenesis model. Effect of 1.5% black tea derived PBPs on benzo(a)pyrene [B(a)P] and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induced lung lesions were studied over 28 wks. Chemopreventive efficacy was studied using decrease in tumor incidence and/or multiplicity and/or delay in the latency period in A/J mice. Histopathological analysis of lung was carried out post-carcinogen treatment weeks to analyze the microscopic lung lesions. Inflammation, cell proliferation, and apoptosis markers along with signaling kinases like p38, Akt, and their phosphorylated forms were studied using immunoblotting and immunohistochemistry at 4th, 10th, and 18th wk post-carcinogen treatment. Administration of PBPs throughout the treatment period significantly decreased the multiplicity of surface tumors as well as microscopic lung lesions, including adenomas. Although tumor incidence and latency period remains unaffected, histopathological evaluation of lung at 6, 10, and 18 wks post- carcinogen treatment period showed decrease in tumor multiplicity which was also correlated with different molecular markers. Anti- inflammatory action of PBPs was demonstrated by reduced Cox-2 expression. PBPs down-regulated the B(a)P and NNK-induced cell proliferation (diminished PCNA expression, proliferation index, and Bcl-2 expression) and enhanced apoptosis (increased Bax expression and apoptotic index) potentially through phosphorylation of p38 and Akt. PBPs, most abundant polyphenolic component in the black tea, have chemopreventive effect through inhibition of inflammation, cellular proliferation, and induction of apoptosis possibly via modulation of signaling kinases. © 2016 Wiley Periodicals, Inc.
World journal of biological chemistry, Jan 26, 2016
Chemoprevention is one of the cancer prevention approaches wherein natural/synthetic agent(s) are... more Chemoprevention is one of the cancer prevention approaches wherein natural/synthetic agent(s) are prescribed with the aim to delay or disrupt multiple pathways and processes involved at multiple steps, i.e., initiation, promotion, and progression of cancer. Amongst environmental chemopreventive compounds, diet/beverage-derived components are under evaluation, because of their long history of exposure to humans, high tolerability, low toxicity, and reported biological activities. This compilation briefly covers and compares the available evidence on chemopreventive efficacy and probable mechanism of chemoprevention by selected dietary phytochemicals (capsaicin, curcumin, diallyl sulphide, genistein, green/black tea polyphenols, indoles, lycopene, phenethyl isocyanate, resveratrol, retinoids and tocopherols) in experimental systems and clinical trials. All the dietary phytochemicals covered in this review have demonstrated chemopreventive efficacy against spontaneous or carcinogen-ind...
Toxicol Appl Pharmacol, 2008
Arzneimittel-Forschung
Effect of isoniazid on nucleic acid biosynthesis was studied in Swiss mice. It was observed that ... more Effect of isoniazid on nucleic acid biosynthesis was studied in Swiss mice. It was observed that i.p. injection of isoniazid stimulated activities of nuclease. Isoniazid also inhibits RNA biosynthesis in lung and liver tissue of 3-weeks old mice but has no inhibitory effect on the same in 6 weeks old mice. It inhibits DNA biosynthesis in lung tissue of 3- and 6-week old mice. With the decrease in nucleic acid biosynthesis and increased activities of nucleases the nucleotide pool is increased. I.p. injection of ammonium chloride produces inhibition of nucleic acid biosynthesis to a similar extent. Administration of amino acids L-arginine or L-Na-glutamate or of vitamins pyridoxine or folic acid along with isoniazid prevents the inhibitory effect of isoniazid on nucleic acid biosynthesis.
Indian journal of physiology and pharmacology
Preliminary studies on the in vivo and in vitro interactions of ltC-metronidazole with macromolec... more Preliminary studies on the in vivo and in vitro interactions of ltC-metronidazole with macromolecules showed that the agent or its metabolite(s) can interac(with nucleic acids and proteins in vivo. In vitro studies suggest that in absence of DNA synthesis trace amount of metronidazole does bind to DNA/protein and addition of metabolic activation system (from mouse liver) generates more reactive species from metronidazole.
Journal of Biomedical Optics, 2015
The lung is one of the most common sites of metastases, with approximately 50% of patients with e... more The lung is one of the most common sites of metastases, with approximately 50% of patients with extrathoracic cancer exhibiting pulmonary metastases. Correct identification of the metastatic status of a lung lesion is vital to therapeutic planning and better prognosis. However, currently available diagnostic techniques, such as conventional radiography and low dose computed tomography (LDCT), may fail to identify metastatic lesions. Alternative techniques such as Raman spectroscopy (RS) are hence being extensively explored for correct diagnosis of metastasis. The current ex vivo study aims to evaluate the ability of a fiber optic-based Raman system to distinguish breast cancer metastasis in lung from primary breast and lung tumor in animal models. In this study, spectra were acquired from normal breast, primary breast tumor, normal lung, primary lung tumor, and breast cancer metastasis in lung tissues and analyzed using principal component analysis and principal component-linear discriminant analysis. Breast cancer metastasis in lung could be classified with 71% classification efficiency. Approximately 6% breast metastasis spectra were misclassified with breast tumor, probably due to the presence of breast cancer cells in metastasized lungs. Test prediction results show 64% correct prediction of breast metastasis, while 13% breast metastasis spectra were wrongly predicted as breast tumor, suggesting the possible influence of breast cancer cells. Thus, findings of this study, the first of such explorations, demonstrate the potential of RS in classifying breast metastasis in lungs from primary lung and primary breast tumor. Prospective evaluation on a larger cohort with better multivariate analysis, combined with LDCT and recently developed real-time in vivo probes, RS can play a significant role in nonsurgical screening of lesions, which can lead to individualized therapeutic regimes and improved prognoses.
Journal of cancer research and therapeutics
Technology in cancer research & treatment, Oct 13, 2015
Oral cancers suffer from poor 5-year survival rates, owing to late detection of the disease. Curr... more Oral cancers suffer from poor 5-year survival rates, owing to late detection of the disease. Current diagnostic/screening tools need to be upgraded in view of disadvantages like invasiveness, tedious sample preparation, long output times, and interobserver variances. Raman spectroscopy has been shown to identify many disease conditions, including oral cancers, from healthy conditions. Further studies in exploring sequential changes in oral carcinogenesis are warranted. In this Raman spectroscopy study, sequential progression in experimental oral carcinogenesis in Hamster buccal pouch model was investigated using 3 approaches-ex vivo, in vivo sequential, and in vivo follow-up. In all these studies, spectral changes show lipid dominance in early stages while later stages and tumors showed increased protein to lipid ratio and nucleic acids. On similar lines, early weeks of 7,12-dimethylbenz(a)anthracene-treated and control groups showed higher overlap and low classification. The classi...
Journal of Raman Spectroscopy, 2015
ABSTRACT Breast cancer is the most common cancer amongst women worldwide. Early detection of this... more ABSTRACT Breast cancer is the most common cancer amongst women worldwide. Early detection of this cancer results in better prognosis. Owing to the disadvantages of currently available screening tools for early detection of this cancer, rapid and sensitive alternatives such as optical spectroscopic techniques are being extensively explored. Detection of premalignant lesions using these techniques has been reported. However, premalignant lesions are risk indicators and may not be true predictors of tumor development. Therefore, the current study aims at correlation between spectral changes and tumor appearance. In this context, transcutaneous in vivo spectra were acquired from same carcinogen-induced rats immediately before carcinogen treatment, 3, 8–10, and 12–14 weeks after carcinogen treatment and from frank tumors. These were analyzed using multivariate statistical tools principal component analysis and principal component linear discriminant analysis. Further, a complex test data set consisting of spectra from rats of varying ages, tumor appearance times, and tumor induction protocols was used to test the feasibility of correctly identifying controls and pretumors using Raman spectroscopy. Results suggest feasibility of distinguishing pretumor spectra from controls. Taking into consideration the heterogeneity of afflicted breast, rat-wise analysis was performed wherein a rat was declared ‘will develop tumor’, even if one spectrum was found abnormal. Using this criterion, in vivo Raman spectroscopy could predict tumor appearance with 82% sensitivity and 95% specificity. Prospectively, combined with emerging technologies like deep Raman spectroscopy and fiber-probe-based whole sample imaging, Raman spectroscopy may prove as an invaluable adjunct to currently available breast cancer screening tools. Copyright
Indian journal of experimental biology, 1981
Mini-Reviews in Medicinal Chemistry, 2010
Biomedical Research Journal
Majority of human cancers are caused, mediated and modified by environmental and lifestyle factor... more Majority of human cancers are caused, mediated and modified by environmental and lifestyle factors; and the multi-factorial, multi-step and multi-path process of carcinogenesis involves a series of genetic and epigenetic events. In spite of tremendous advancement in understanding of the molecular basis of cancer and identification of several environmental carcinogens, avoidance of exposure to carcinogens and early detection and/or successful treatment for most cancers have met with limited success. Based on the susceptibility to modulations of the multi-step process of carcinogenesis by a multitude of environmental compounds, lifestyle changes and host factors, and the demonstrated success of prevention of certain infectious diseases and cardiovascular events, cancer preventive interventions are receiving increasing attention. Several cancer preventive interventions such as vaccination, chemoprevention, weight control and lifestyle changes have been implemented. The current review focuses on several approaches and agents that have been scrutinized by way of randomized clinical trials in humans for their cancer prevention potential. Successful chemopreventive agents include selective oestrogen receptor modulators and aromatase inhibitors for breast cancer, the 5-α-reductase inhibitors for prostate cancer, non-steroidal antiinflammatory drugs (NSAIDs) for colorectal lesions and vaccines for viruses that are associated with cervical and liver cancers. Several experimentally proven chemopreventive agents have been observed to lack efficacy with and without toxicity. In spite of numerous chemoprevention trials, the number of successful agents is rather small. Identifying novel approaches and chemopreventives holds tremendous potential for reducing the burden of cancer.
Natural product research, Jan 11, 2017
Flowers of the plant Nyctanthes arbor-tristis (NAT) are widely used in the traditional medicinal ... more Flowers of the plant Nyctanthes arbor-tristis (NAT) are widely used in the traditional medicinal systems of several Asian countries. In the present study, potential genotoxicity and modulatory effects of ethanolic extract of NAT flower calyx (NAT FCE) and crocin, a carotenoid principle were evaluated employing standard Salmonella assay. Experiments evaluating the genotoxic potential of NAT FCE and crocin, with and without the S9-activation in TA 98, TA 100 and TA 102 showed a lack of increase in revertant mutants. Evaluation of modulatory effects of NAT FCE and crocin, without the S9, showed significant decrease in the number of 4-nitro-o-phenylenediamine-, sodium azide- and ethyl methanesulfonate-induced revertants. However, with S9, NAT FCE and crocin moderately increased the 2-aminoanthracene-induced revertants in TA 98; they moderately decreased revertants in TA 100 and TA 102. Both NAT FCE and crocin have been shown to be non-genotoxic and to be able to modulate responses of st...
Molecular Carcinogenesis, 2016
The aim of our study was to evaluate chemopreventive efficacy and possible mechanism of most abun... more The aim of our study was to evaluate chemopreventive efficacy and possible mechanism of most abundant polyphenolic fraction in black tea, polymeric black tea polyphenols (PBPs), in experimental lung carcinogenesis model. Effect of 1.5% black tea derived PBPs on benzo(a)pyrene [B(a)P] and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induced lung lesions were studied over 28 wks. Chemopreventive efficacy was studied using decrease in tumor incidence and/or multiplicity and/or delay in the latency period in A/J mice. Histopathological analysis of lung was carried out post-carcinogen treatment weeks to analyze the microscopic lung lesions. Inflammation, cell proliferation, and apoptosis markers along with signaling kinases like p38, Akt, and their phosphorylated forms were studied using immunoblotting and immunohistochemistry at 4th, 10th, and 18th wk post-carcinogen treatment. Administration of PBPs throughout the treatment period significantly decreased the multiplicity of surface tumors as well as microscopic lung lesions, including adenomas. Although tumor incidence and latency period remains unaffected, histopathological evaluation of lung at 6, 10, and 18 wks post- carcinogen treatment period showed decrease in tumor multiplicity which was also correlated with different molecular markers. Anti- inflammatory action of PBPs was demonstrated by reduced Cox-2 expression. PBPs down-regulated the B(a)P and NNK-induced cell proliferation (diminished PCNA expression, proliferation index, and Bcl-2 expression) and enhanced apoptosis (increased Bax expression and apoptotic index) potentially through phosphorylation of p38 and Akt. PBPs, most abundant polyphenolic component in the black tea, have chemopreventive effect through inhibition of inflammation, cellular proliferation, and induction of apoptosis possibly via modulation of signaling kinases. © 2016 Wiley Periodicals, Inc.
World journal of biological chemistry, Jan 26, 2016
Chemoprevention is one of the cancer prevention approaches wherein natural/synthetic agent(s) are... more Chemoprevention is one of the cancer prevention approaches wherein natural/synthetic agent(s) are prescribed with the aim to delay or disrupt multiple pathways and processes involved at multiple steps, i.e., initiation, promotion, and progression of cancer. Amongst environmental chemopreventive compounds, diet/beverage-derived components are under evaluation, because of their long history of exposure to humans, high tolerability, low toxicity, and reported biological activities. This compilation briefly covers and compares the available evidence on chemopreventive efficacy and probable mechanism of chemoprevention by selected dietary phytochemicals (capsaicin, curcumin, diallyl sulphide, genistein, green/black tea polyphenols, indoles, lycopene, phenethyl isocyanate, resveratrol, retinoids and tocopherols) in experimental systems and clinical trials. All the dietary phytochemicals covered in this review have demonstrated chemopreventive efficacy against spontaneous or carcinogen-ind...
Toxicol Appl Pharmacol, 2008
Arzneimittel-Forschung
Effect of isoniazid on nucleic acid biosynthesis was studied in Swiss mice. It was observed that ... more Effect of isoniazid on nucleic acid biosynthesis was studied in Swiss mice. It was observed that i.p. injection of isoniazid stimulated activities of nuclease. Isoniazid also inhibits RNA biosynthesis in lung and liver tissue of 3-weeks old mice but has no inhibitory effect on the same in 6 weeks old mice. It inhibits DNA biosynthesis in lung tissue of 3- and 6-week old mice. With the decrease in nucleic acid biosynthesis and increased activities of nucleases the nucleotide pool is increased. I.p. injection of ammonium chloride produces inhibition of nucleic acid biosynthesis to a similar extent. Administration of amino acids L-arginine or L-Na-glutamate or of vitamins pyridoxine or folic acid along with isoniazid prevents the inhibitory effect of isoniazid on nucleic acid biosynthesis.
Indian journal of physiology and pharmacology
Preliminary studies on the in vivo and in vitro interactions of ltC-metronidazole with macromolec... more Preliminary studies on the in vivo and in vitro interactions of ltC-metronidazole with macromolecules showed that the agent or its metabolite(s) can interac(with nucleic acids and proteins in vivo. In vitro studies suggest that in absence of DNA synthesis trace amount of metronidazole does bind to DNA/protein and addition of metabolic activation system (from mouse liver) generates more reactive species from metronidazole.
Journal of Biomedical Optics, 2015
The lung is one of the most common sites of metastases, with approximately 50% of patients with e... more The lung is one of the most common sites of metastases, with approximately 50% of patients with extrathoracic cancer exhibiting pulmonary metastases. Correct identification of the metastatic status of a lung lesion is vital to therapeutic planning and better prognosis. However, currently available diagnostic techniques, such as conventional radiography and low dose computed tomography (LDCT), may fail to identify metastatic lesions. Alternative techniques such as Raman spectroscopy (RS) are hence being extensively explored for correct diagnosis of metastasis. The current ex vivo study aims to evaluate the ability of a fiber optic-based Raman system to distinguish breast cancer metastasis in lung from primary breast and lung tumor in animal models. In this study, spectra were acquired from normal breast, primary breast tumor, normal lung, primary lung tumor, and breast cancer metastasis in lung tissues and analyzed using principal component analysis and principal component-linear discriminant analysis. Breast cancer metastasis in lung could be classified with 71% classification efficiency. Approximately 6% breast metastasis spectra were misclassified with breast tumor, probably due to the presence of breast cancer cells in metastasized lungs. Test prediction results show 64% correct prediction of breast metastasis, while 13% breast metastasis spectra were wrongly predicted as breast tumor, suggesting the possible influence of breast cancer cells. Thus, findings of this study, the first of such explorations, demonstrate the potential of RS in classifying breast metastasis in lungs from primary lung and primary breast tumor. Prospective evaluation on a larger cohort with better multivariate analysis, combined with LDCT and recently developed real-time in vivo probes, RS can play a significant role in nonsurgical screening of lesions, which can lead to individualized therapeutic regimes and improved prognoses.
Journal of cancer research and therapeutics
Technology in cancer research & treatment, Oct 13, 2015
Oral cancers suffer from poor 5-year survival rates, owing to late detection of the disease. Curr... more Oral cancers suffer from poor 5-year survival rates, owing to late detection of the disease. Current diagnostic/screening tools need to be upgraded in view of disadvantages like invasiveness, tedious sample preparation, long output times, and interobserver variances. Raman spectroscopy has been shown to identify many disease conditions, including oral cancers, from healthy conditions. Further studies in exploring sequential changes in oral carcinogenesis are warranted. In this Raman spectroscopy study, sequential progression in experimental oral carcinogenesis in Hamster buccal pouch model was investigated using 3 approaches-ex vivo, in vivo sequential, and in vivo follow-up. In all these studies, spectral changes show lipid dominance in early stages while later stages and tumors showed increased protein to lipid ratio and nucleic acids. On similar lines, early weeks of 7,12-dimethylbenz(a)anthracene-treated and control groups showed higher overlap and low classification. The classi...
Journal of Raman Spectroscopy, 2015
ABSTRACT Breast cancer is the most common cancer amongst women worldwide. Early detection of this... more ABSTRACT Breast cancer is the most common cancer amongst women worldwide. Early detection of this cancer results in better prognosis. Owing to the disadvantages of currently available screening tools for early detection of this cancer, rapid and sensitive alternatives such as optical spectroscopic techniques are being extensively explored. Detection of premalignant lesions using these techniques has been reported. However, premalignant lesions are risk indicators and may not be true predictors of tumor development. Therefore, the current study aims at correlation between spectral changes and tumor appearance. In this context, transcutaneous in vivo spectra were acquired from same carcinogen-induced rats immediately before carcinogen treatment, 3, 8–10, and 12–14 weeks after carcinogen treatment and from frank tumors. These were analyzed using multivariate statistical tools principal component analysis and principal component linear discriminant analysis. Further, a complex test data set consisting of spectra from rats of varying ages, tumor appearance times, and tumor induction protocols was used to test the feasibility of correctly identifying controls and pretumors using Raman spectroscopy. Results suggest feasibility of distinguishing pretumor spectra from controls. Taking into consideration the heterogeneity of afflicted breast, rat-wise analysis was performed wherein a rat was declared ‘will develop tumor’, even if one spectrum was found abnormal. Using this criterion, in vivo Raman spectroscopy could predict tumor appearance with 82% sensitivity and 95% specificity. Prospectively, combined with emerging technologies like deep Raman spectroscopy and fiber-probe-based whole sample imaging, Raman spectroscopy may prove as an invaluable adjunct to currently available breast cancer screening tools. Copyright
Indian journal of experimental biology, 1981