This study aims to evaluate the therapeutic potential of Ivermectin, an FDA-approved antiparasitic drug commonly used for laboratory animals, for its anti-cancer efficacy. Specifically, the investigation will focus on its effects in a 4NQO-induced tongue tumor model of oral squamous cell carcinoma (OSCC) in C57BL/6 mice. The study will assess Ivermectin’s anti-tumor activity both as a monotherapy and in combination with Celecoxib, Erlotinib, and Methotrexate, clinically approved drugs routinely used in the metronomic chemotherapy of head and neck cancers. The goal is to determine the therapeutic benefits and underlying molecular mechanisms of Ivermectin-based interventions, potentially revealing novel combinatorial treatment strategies for OSCC
This study aims to evaluate the therapeutic potential of Ivermectin, an FDA-approved antiparasitic drug commonly used for laboratory animals, for its anti-cancer efficacy. Specifically, the investigation will focus on its effects in a 4NQO-induced tongue tumor model of oral squamous cell carcinoma (OSCC) in C57BL/6 mice. The study will assess Ivermectin’s anti-tumor activity both as a monotherapy and in combination with Celecoxib, Erlotinib, and Methotrexate, clinically approved drugs routinely used in the metronomic chemotherapy of head and neck cancers.
This study focuses on the development and characterization of a modified 4NQO-induced tongue tumour model of oral squamous cell carcinoma (OSCC) in C57BL/6 mice. Unlike the conventional continuous 4NQO exposure for 16 weeks followed by a no-treatment phase, this protocol employs a thrice-weekly dosing schedule for 28 weeks. The strategic modification was designed to reduce 4NQO-associated toxicity and mortality while creating a therapeutic window for administering chemopreventive agents in an ad libitum setting. A dose optimization experiment comparing 50 ppm and 100 ppm concentrations of 4NQO revealed that 50 ppm yielded more consistent and reproducible tumour development, establishing it as the preferred dose for subsequent studies. To comprehensively understand disease progression, a sequential carcinogenesis study is being conducted, with animals being sacrificed at defined intervals to document the histopathological and molecular changes throughout the progression from premalignant lesions to invasive malignancies. With this refined and reproducible model in place, the current phase of research also explores the chemopreventive potential of polymeric black tea polyphenols (thearubigins), aiming to assess their efficacy and underlying mechanisms within a more physiologically relevant and experimentally controlled OSCC model.
This study focuses on the development and characterization of a modified 4NQO-induced tongue tumour model of oral squamous cell carcinoma (OSCC) in C57BL/6 mice. Unlike the conventional continuous 4NQO exposure for 16 weeks followed by a no-treatment phase, this protocol employs a thrice-weekly dosing schedule for 28 weeks. The strategic modification was designed to reduce 4NQO-associated toxicity and mortality while creating a therapeutic window for administering chemopreventive agents in an ad libitum setting.
Head and neck squamous cell carcinomas (HNSCCs) is a complex and heterogeneous disease regulated at multiple levels and associated with high mortality and morbidity. HNSCCs are related to environmental risk factors, especially excessive tobacco and alcohol consumption. Oral squamous cell carcinomas (OSCCs) are the prevalent forms of HNSCC, representing approximately 90% of all tumors in this region. The high mortality associated with OSCC is related mainly to the locoregional advancement of the disease. Although significant improvements have been made in achieving local control of the disease and increasing the survival rate of patients with primary malignant oral tumors via surgical intervention, physicians face yet another challenge—that of preserving oral functions, such as articulation, mastication, and deglutition, and retaining visual aesthetics for improving HNSCC patients' quality of life. Effective treatment for advanced HNSCC (T3 and T4), but non-resectable tumors involves the use of multidisciplinary therapies, such as multiple chemotherapies (CTs) and radiotherapy (RT). However, most patients present in an advanced stage, wherein tumor resection is rendered questionable because of the positive resection margins. The prognosis of such unresectable stage IVA or IVB tumors treated with a non-surgical approach is poor, with median survival ranging from 2 to 12 months. for these locally advanced borderline operable cases, where the role of neoadjuvant chemotherapy (NACT) has been postulated as an alternative to the current existing therapeutic modalities. Although NACT provides a promising scenario for managing this patient subgroup, it should be known that response rates to this modality vary from 35-40%. Although NACT has been evaluated over the last decade, the chemoresistance phenomenon and its molecular mechanisms are yet to be studied comprehensively. There exists a need to identify biomarkers that will help us in better therapeutic stratification of these patients. There has been no study focusing specifically on the markers to predict response in oral cavity cancers, which is the aim of the present study.
Head and neck squamous cell carcinomas (HNSCCs) is a complex and heterogeneous disease regulated at multiple levels and associated with high mortality and morbidity. HNSCCs are related to environmental risk factors, especially excessive tobacco and alcohol consumption. Oral squamous cell carcinomas (OSCCs) are the prevalent forms of HNSCC, representing approximately 90% of all tumors in this region. The high mortality associated with OSCC is related mainly to the locoregional advancement of the disease.
Hydrogen has three naturally occurring isotopes, the stable forms; the Protium (1H), and Deuterium (2H), while the unstable radioactive form is Tritium (3H). Of the stable isotopes of hydrogen, Deuterium (D) and protium (H) have different chemical and physical properties. The ratio of Deuterium to hydrogen (D/H) in natural water is approximately 1:6600, and the natural fraction of Deuterium is approximately 0.0139–0.0151%. When the deuterium concentration is lower than 0.015% (150 ppm), the fraction is called ‘light water’ or deuterium-depleted water (DDW). D-concentration in living organisms is 12mmol/L. Recent research reported the anticancer potential of DDW in which the deuterium volume fraction in normal water (~150 parts per million) is reduced by 65%. Studies have demonstrated that incorporating low deuterium concentrations into conventional cancer therapy can significantly hinder the growth rate of various tumor cells and block metastasis and recurrence both in vitro and in vivo. The apoptosis-triggering was also studied both in vitro and in vivo. Deuterium depletion also influences proto-oncogenes such as c-Myc, H-Ras, and tumour suppressor genes like p53, thus significantly reducing growth when the carcinogen-exposed animals were given DDW to drink in a preclinical setting. However, the major missing understanding in the field is how DDW is effective as an anticancer agent. Hence, we propose to conduct a systemically planned experimental study to understand the molecular mechanisms underlying the anticancer potential of deuterium-depleted water.
Hydrogen has three naturally occurring isotopes, the stable forms; the Protium (1H), and Deuterium (2H), while the unstable radioactive form is Tritium (3H). Of the stable isotopes of hydrogen, Deuterium (D) and protium (H) have different chemical and physical properties. The ratio of Deuterium to hydrogen (D/H) in natural water is approximately 1:6600, and the natural fraction of Deuterium is approximately 0.0139–0.0151%. When the deuterium concentration is lower than 0.015% (150 ppm), the fraction is called ‘light water’ or deuterium-depleted water (DDW).
- Reference No.:GEM/2025/B/6340123Date & Time of Tender Opening :Date & Time of Tender Submission :Type :GEMName of Equipments :
Desktop Computer with 8GB RAM with 21.5'' Display
Desktop Computer with 8GB RAM with 21.5'' Display