Papers by Mohammad Raghibul Hasan
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in late 2019, causes ... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in late 2019, causes COVID-19, a disease that has been spreading rapidly worldwide. In human lung epithelial cells and monocytes, RLF-100 (aviptadil) has been found to inhibit the RNA replication machinery of SARS-CoV-2, which includes several non-structural proteins (nsp) that play essential roles in synthesizing and replicating viral RNA. This virus is unique in requiring nsp10 and nsp16 for methyltransferase (MTase) activity. This enzyme is essential for RNA stability, protein translation, and viral ability to escape the host's immune recognition. Therefore, we aimed to use bioinformatics tools to analyze aviptadil's inhibitory effect on the SARS-CoV-2 nsp10/nsp16 complex. We present a comprehensive, in silico-generated picture showing how aviptadil may interact with the nsp complex. Specifically, our model predicts how the initial binding of aviptadil to nsp10 and nsp16 may occur. This knowledge ...
Scientific Reports
Lung cancer is the leading cause of mortality from cancer worldwide. Lung adenocarcinoma (LUAD) i... more Lung cancer is the leading cause of mortality from cancer worldwide. Lung adenocarcinoma (LUAD) is a type of non-small cell lung cancer (NSCLC) with highest prevalence. Kinesins a class of motor proteins are shown to be involved in carcinogenesis. We conducted expression, stage plot and survival analyses on kinesin superfamily (KIF) and scrutinized the key prognostic kinesins. Genomic alterations of these kinesins were studied thereafter via cBioPortal. A protein–protein interaction network (PPIN) of selected kinesins and 50 closest altering genes was constructed followed by gene ontology (GO) term and pathway enrichment analyses. Multivariate survival analysis based on CpG methylation of selected kinesins was performed. Lastly, we conducted tumor immune infiltration analysis. Our results found KIF11/15/18B/20A/2C/4A/C1 to be significantly upregulated and correlated with poor survival in LUAD patients. These genes also showed to be highly associated with cell cycle. Out of our seven...
Journal of Biomolecular Structure and Dynamics
Parasites & Vectors
Malaria is a vector-borne parasitic disease caused by the apicomplexan protozoan parasite Plasmod... more Malaria is a vector-borne parasitic disease caused by the apicomplexan protozoan parasite Plasmodium. Malaria is a significant health problem and the leading cause of socioeconomic losses in developing countries. WHO approved several antimalarials in the last 2 decades, but the growing resistance against the available drugs has worsened the scenario. Drug resistance and diversity among Plasmodium strains hinder the path of eradicating malaria leading to the use of new technologies and strategies to develop effective vaccines and drugs. A timely and accurate diagnosis is crucial for any disease, including malaria. The available diagnostic methods for malaria include microscopy, RDT, PCR, and non-invasive diagnosis. Recently, there have been several developments in detecting malaria, with improvements leading to achieving an accurate, quick, cost-effective, and non-invasive diagnostic tool for malaria. Several vaccine candidates with new methods and antigens are under investigation an...
Biomedicines
Breast cancer has been acknowledged as one of the most notorious cancers, responsible for million... more Breast cancer has been acknowledged as one of the most notorious cancers, responsible for millions of deaths around the globe. Understanding the various factors, genetic mutations, comprehensive pathways, etc., that are involved in the development of breast cancer and how these affect the development of the disease is very important for improving and revitalizing the treatment of this global health issue. The forkhead-box gene family, comprising 19 subfamilies, is known to have a significant impact on the growth and progression of this cancer. The article looks into the various forkhead genes and how they play a role in different types of cancer. It also covers their impact on cancer drug resistance, interaction with microRNAs, explores their potential as targets for drug therapies, and their association with stem cells.
Molecules
In most cases, cancer develops due to abnormal cell growth and subsequent tumour formation. Due t... more In most cases, cancer develops due to abnormal cell growth and subsequent tumour formation. Due to significant constraints with current treatments, natural compounds are being explored as potential alternatives. There are now around 30 natural compounds under clinical trials for the treatment of cancer. Tulsi, or Holy Basil, of the genus Ocimum, is one of the most widely available and cost-effective medicinal plants. In India, the tulsi plant has deep religious and medicinal significance. Tulsi essential oil contains a valuable source of bioactive compounds, such as camphor, eucalyptol, eugenol, alpha-bisabolene, beta-bisabolene, and beta-caryophyllene. These compounds are proposed to be responsible for the antimicrobial properties of the leaf extracts. The anticancer effects of tulsi (Ocimum sanctum L.) have earned it the title of “queen of herbs” and “Elixir of Life” in Ayurvedic treatment. Tulsi leaves, which have high concentrations of eugenol, have been shown to have anticancer...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in late 2019, causes ... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in late 2019, causes COVID-19, a disease that has been spreading rapidly worldwide. In human lung epithelial cells and monocytes, RLF-100 (aviptadil) has been found to inhibit the RNA replication machinery of SARS-CoV-2, which includes several non-structural proteins (nsp) that play essential roles in synthesizing and replicating viral RNA. This virus is unique in requiring nsp10 and nsp16 for methyltransferase (MTase) activity. This enzyme is essential for RNA stability, protein translation, and viral ability to escape the host's immune recognition. Therefore, we aimed to use bioinformatics tools to analyze aviptadil's inhibitory effect on the SARS-CoV-2 nsp10/nsp16 complex. We present a comprehensive, in silico-generated picture showing how aviptadil may interact with the nsp complex. Specifically, our model predicts how the initial binding of aviptadil to nsp10 and nsp16 may occur. This knowledge ...
Cancer Investigation, 2011
Proteins do not operate as individual units, and components of intracellular canonical pathways o... more Proteins do not operate as individual units, and components of intracellular canonical pathways often cross talk in tumor genesis. We hypothesized that G-protein-coupled receptor 56 (GPR56), transglutaminase (TG2), and nuclear factor-κB (NF-κB) may collaborate in interconnected pathways and contribute to the aggressive behavior of esophageal squamous cell carcinoma (ESCC). Immunohistochemical analysis of GPR56, TG2, and NF-κB was carried out using ESCC tissue microarrays. Immunostaining of all the three proteins revealed a significant increase in their expression in ESCCs as compared with normal epithelia and correlated with their concomitant expression. A significant correlation between GPR56, TG2, and NF-κB was observed that correlated with nodal metastasis and tumor invasion in ESCCs.
Indian Journal of Clinical Biochemistry
To explore the potentials of allicin (an organosulfur compound) from garlic, a natural anti-oxida... more To explore the potentials of allicin (an organosulfur compound) from garlic, a natural anti-oxidant, in inducing apoptosis in monocytes from patients of cervical cancer. The effect of allicin on the cell viability of cervical cancer monocytes was determined by MTT assay. Induction of programmed cell death was ascertained by PARP-cleavage and Caspase-3 assay. To assess whether allicin affects the viability of cervical cancer monocytes, these were treated with varying concentrations of allicin (0-1 μg/ml), and the cell viability was determined by MTT assay. We showed allicin to inhibit cell proliferation in a dose-dependent manner, where ~only 21% viable cells were observed after 24 hrs of co-culturing with 1 μg/ml of allicin. The IC50 for allicin was found to be in the range of 300-350 ng/ml. We also observed allicin-induced PARP-cleavage and activation of caspase-3. Thus, our results indicate that allicin from garlic induces apoptosis in cervical cancer monocytes.
Cancer immunotherapy has become a powerful clinical strategy as well as an established pillar for... more Cancer immunotherapy has become a powerful clinical strategy as well as an established pillar for the treatment of cancers to improving the prognosis of many cancer patients with a broad variety of solid tumors as well as blood cancers. The primary goals of immunotherapy are (a) to increase anti-tumor response, (b) decrease the immune suppression, and (c) to enhance the immunogenicity of tumors. This chapter aims to discuss the mechanism and different types of immunotherapies used for different cancers. It will also focus on recombinant products including immunostimulants, immunotoxins, antibodies, fusion proteins, engineered cytotoxic T cells, engineered immunocytokines, vaccines, checkpoint inhibitors, CAR T-cell therapy, and nanomedicine. Although immunotherapy has a rare side effect, it is not fully understood. The development of new strategies has been on the clinical trial to enhance the benefit of cancer patients to meet with challenges of limited efficacy and/or toxicity.
Handbook of Research on Advancements in Cancer Therapeutics
In this chapter, the authors first review nano-devices that are mixtures of biologic molecules an... more In this chapter, the authors first review nano-devices that are mixtures of biologic molecules and synthetic polymers like nano-shells and nano-particles for the most encouraging applications for different cancer therapies. Nano-sized medications additionally spill especially into tumor tissue through penetrable tumor vessels and are then held in the tumor bed because of diminished lymphatic drainage. This procedure is known as the enhanced penetrability and retention (EPR) impact. Nonetheless, while the EPR impact is generally held to improve conveyance of nano-medications to tumors, it in certainty offers not exactly a 2-overlay increment in nano-drug conveyance contrasted with basic ordinary organs, bringing about medication concentration that is not adequate for restoring most malignant growths. In this chapter, the authors likewise review different obstructions for nano-sized medication conveyance and to make the conveyance of nano-sized medications to tumors progressively succ...
Handbook of Research on Advancements in Cancer Therapeutics
Cancer immunotherapy has become a powerful clinical strategy as well as an established pillar for... more Cancer immunotherapy has become a powerful clinical strategy as well as an established pillar for the treatment of cancers to improving the prognosis of many cancer patients with a broad variety of solid tumors as well as blood cancers. The primary goals of immunotherapy are (a) to increase anti-tumor response, (b) decrease the immune suppression, and (c) to enhance the immunogenicity of tumors. This chapter aims to discuss the mechanism and different types of immunotherapies used for different cancers. It will also focus on recombinant products including immunostimulants, immunotoxins, antibodies, fusion proteins, engineered cytotoxic T cells, engineered immunocytokines, vaccines, checkpoint inhibitors, CAR T-cell therapy, and nanomedicine. Although immunotherapy has a rare side effect, it is not fully understood. The development of new strategies has been on the clinical trial to enhance the benefit of cancer patients to meet with challenges of limited efficacy and/or toxicity.
Oncotarget, 2014
Biomarkers to predict the risk of disease recurrence in Esophageal squamous cell carcinoma (ESCC)... more Biomarkers to predict the risk of disease recurrence in Esophageal squamous cell carcinoma (ESCC) patients are urgently needed to improve treatment. We developed proteins expression-based risk model to predict recurrence free survival for ESCC patients. Alterations in Wnt pathway components expression and subcellular localization were analyzed by immunohistochemistry in 80 ESCCs, 61 esophageal dysplastic and 47 normal tissues; correlated with clinicopathological parameters and clinical outcome over 86 months by survival analysis. Significant prognostic factors were identified by multivariable Cox regression analysis. Biomarker signature score based on cytoplasmic β-catenin, nuclear c-Myc, nuclear DVL and membrane α-catenin was associated with recurrence free survival [Hazard ratio = 1.11 (95% CI = 1.05, 1.17), p < 0.001, C-index = 0.68] and added significant prognostic value over clinical parameters (p < 0.001). The inclusion of Slug further improved prognostic utility (p < 0.001, C-index = 0.71). Biomarker Signature Scoreslug improved risk classification abilities for clinical outcomes at 3 years, accurately predicting recurrence in 79% patients in 1 year and 97% in 3 years in high risk group; 73% patients within low risk group did not have recurrence in 1 year, with AUC of 0.76. Our comprehensive risk model predictive for recurrence allowed us to determine the robustness of our biomarker panel in stratification of ESCC patients at high or low risk of disease recurrence; high risk patients are stratified for more rigorous personalized treatment while the low risk patients may be spared from harmful side effects of toxic therapy.
Oncotarget, 2014
Biomarkers to predict the risk of disease recurrence in Esophageal squamous cell carcinoma (ESCC)... more Biomarkers to predict the risk of disease recurrence in Esophageal squamous cell carcinoma (ESCC) patients are urgently needed to improve treatment. We developed proteins expression-based risk model to predict recurrence free survival for ESCC patients. Alterations in Wnt pathway components expression and subcellular localization were analyzed by immunohistochemistry in 80 ESCCs, 61 esophageal dysplastic and 47 normal tissues; correlated with clinicopathological parameters and clinical outcome over 86 months by survival analysis. Significant prognostic factors were identified by multivariable Cox regression analysis. Biomarker signature score based on cytoplasmic β-catenin, nuclear c-Myc, nuclear DVL and membrane α-catenin was associated with recurrence free survival [Hazard ratio = 1.11 (95% CI = 1.05, 1.17), p < 0.001, C-index = 0.68] and added significant prognostic value over clinical parameters (p < 0.001). The inclusion of Slug further improved prognostic utility (p < 0.001, C-index = 0.71). Biomarker Signature Scoreslug improved risk classification abilities for clinical outcomes at 3 years, accurately predicting recurrence in 79% patients in 1 year and 97% in 3 years in high risk group; 73% patients within low risk group did not have recurrence in 1 year, with AUC of 0.76. Our comprehensive risk model predictive for recurrence allowed us to determine the robustness of our biomarker panel in stratification of ESCC patients at high or low risk of disease recurrence; high risk patients are stratified for more rigorous personalized treatment while the low risk patients may be spared from harmful side effects of toxic therapy.
PLoS ONE, 2013
Background: Slug, a regulator of epithelial mesenchymal transition, was identified to be differen... more Background: Slug, a regulator of epithelial mesenchymal transition, was identified to be differentially expressed in esophageal squamous cell carcinoma (ESCC) using cDNA microarrays by our laboratory. This study aimed to determine the clinical significance of Slug overexpression in ESCC and determine its correlation with clinicopathological parameters and disease prognosis for ESCC patients.
PloS one, 2010
We previously demonstrated that nuclear and cytoplasmic accumulation of the intracellular domain ... more We previously demonstrated that nuclear and cytoplasmic accumulation of the intracellular domain (Ep-ICD) of epithelial cell adhesion molecule (EpCAM) accompanied by a reciprocal reduction of its extracellular domain (EpEx), occurs in aggressive thyroid cancers. This study was designed to determine whether similar accumulation of Ep-ICD is a common event in other epithelial cancers. Ten epithelial cancers were immunohistochemically analyzed using Ep-ICD and EpEx domain-specific antibodies. The subcellular localization of EpEx and Ep-ICD in the human colon adenocarcinoma cell line CX-1 was observed using immunofluorescence. Nuclear and cytoplasmic Ep-ICD expression was increased in cancers of the breast (31 of 38 tissues, 82%), prostate (40 of 49 tissues, 82%), head and neck (37 of 57 tissues, 65%) and esophagus (17 of 46 tissues, 37%) compared to their corresponding normal tissues that showed membrane localization of the protein. Importantly, Ep-ICD was not detected in the nuclei of...
World Journal of Gastroenterology, 2012
To determine the functional significance of TC21 in esophageal squamous cell carcinoma (ESCC).
International Journal of Cancer, 2010
Expression of sperm protein 17 (Sp17) mRNA has been reported in various malignancies. In an earli... more Expression of sperm protein 17 (Sp17) mRNA has been reported in various malignancies. In an earlier study, we reported the upregulation of Sp17 transcripts in primary esophageal squamous cell carcinomas (ESCCs) using differential display and detected Sp17 transcripts in 86% of ESCCs by RT-PCR, whereas no transcripts were detected in the paired normal esophageal tissues. Herein we hypothesized that Sp17 might be used as a marker for detecting the response of anticancer therapies in ESCCs. Our results indicated that Sp17 protein levels in esophageal squamous cancer cell lines decreased in response to treatment with (i) the HSP90 activity inhibitor geldanamycin, (ii) the tyrosine kinase inhibitor erlotinib and (iii) cisplatin (chemotherapeutic agent commonly used in management of ESCC). In contrast, the Sp17 levels did not decrease in response to radiation therapy and treatment with the chemotherapeutic agent, gemcitabine. Further investigations showed that cisplatin induced decrease in Sp17 levels was due to transcriptional inhibition and cisplatin-resistant cell lines did not show this decrease in Sp17 levels in response to cisplatin treatment. In addition, we also carried our mass spectophotometric analysis to identify the binding partners of Sp17 to characterize its possible involvement in esophageal tumorigenesis and chemoresistance.
Cellular Oncology, 2011
Background Expression of oncostatin M receptor beta (OSMRβ) has been reported in human cancers, h... more Background Expression of oncostatin M receptor beta (OSMRβ) has been reported in human cancers, however its role in esophageal squamous cell carcinoma (ESCC) remains unknown. Using differential display, earlier we reported the identification of an alternatively spliced variant of OSMRβ in ESCC. Here in we characterized this novel variant encoding a soluble form of this receptor (sOSMRβ) and determined its clinical significance and correlation with the expression of oncostatin (OSM) and leukemia inhibitory factor receptor beta (LIFR β) in ESCC. Materials and Methods In silico analysis was carried out to characterize the differentially expressed transcript of OSMRβ and its expression was determined in ESCCs and matched normal esophageal tissues using semiquantitative RT-PCR. The expressions of both truncated and full length OSMRβ proteins were analyzed in ESCC tissues and patients' sera using western blotting and immunoprecipita-Tasneem Kausar and Rinu Sharma have equal contribution.
BMC Cancer, 2014
Mitogen-activated protein kinase kinase kinase3 (MAP3K3/MEKK3) was identified to be differentiall... more Mitogen-activated protein kinase kinase kinase3 (MAP3K3/MEKK3) was identified to be differentially expressed in esophageal squamous cell carcinoma (ESCC) using cDNA microarrays by our laboratory. Here in we determined the clinical significance of MEKK3 in ESCC. Immunohistochemical analysis of MEKK3 expression was carried out in archived tissue sections from 93 ESCCs, 47 histologically normal and 61 dysplastic esophageal tissues and correlated with clinicopathological parameters and disease prognosis over up to 7.5 years for ESCC patients. MEKK3 expression was significantly increased in esophageal dysplasia and ESCC in comparison with normal mucosa (ptrend < 0.001). Kaplan Meier survival analysis showed significantly reduced median disease free survival median DFS = 10 months in patients with MEKK3 positive ESCCs compared to patients with no immunopositivity (median DFS = 19 months, p = 0.04). ESCC patients with MEKK3 positive and lymph node positive tumors had median DFS = 9 months, as compared to median DFS = 21 months in patients who did not show the alterations (p = 0.01). In multivariate Cox regression analysis, combination of MEKK3 overexpression and node positivity [p = 0.015, hazard ratio (HR) = 2.082, 95% CI = 1.154 - 3.756] emerged as important predictor of reduced disease free survival and poor prognosticator for ESCC patients. Alterations in MEKK3 expression occur in early stages of development of ESCC and are sustained during disease progression; MEKK3 in combination with lymph node positivity has the potential to serve as adverse prognosticator in ESCC.
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Papers by Mohammad Raghibul Hasan