Understanding the dynamic changes in gene expression during Acute Respiratory Distress Syndrome (... more Understanding the dynamic changes in gene expression during Acute Respiratory Distress Syndrome (ARDS) progression in post-acute infection patients is crucial for unraveling the underlying mechanisms. Study investigates the longitudinal changes in gene/transcript expression patterns in hospital-admitted severe COVID-19 patients with ARDS post-acute SARS-CoV-2 infection. Blood samples were collected at three time points and patients were stratified into severe and mild ARDS, based on their oxygenation saturation (SpO2/FiO2) kinetics over 7 d. Decline in transcript diversity was observed over time, particularly in patients with higher severity, indicating dysregulated transcriptional landscape. Comparing gene/transcript-level analyses highlighted a rather limited overlap. With disease progression, a transition towards an inflammatory state was evident. Strong association was found between antibody response and disease severity, characterized by decreased antibody response and activate...
Abstract The exponential increase in diabetes prevalence in certain parts of the world has been l... more Abstract The exponential increase in diabetes prevalence in certain parts of the world has been linked to increased adiposity, especially visceral fat and associated increased insulin resistance (IR). This review highlights the role of lipid-induced IR, the associated small molecules and peptides, and their relation with immunometabolic dysfunction, diabetes pathogenesis, nonalcoholic fatty liver disease (NAFLD), and atherosclerotic cardiovascular disease. Increased circulating free fatty acids have been directly linked to increased IR and lesser glucose disposition. Lean NAFLD is strongly linked to IR and diabetes. Fetuin-A, a hepatokine, is a key regulator of lipid-induced IR. Cytokines, such as tumor necrosis factor alpha, interleukins, and the soluble receptor antagonists have a complex interplay in lipid-induced IR. As of today there are limited pharmacologic options to reverse lipid-induced IR. Pioglitazone and glitazars (saroglitazar) provide promising data on reducing hepatic adiposity and improving IR and glucose disposal. Many novel compounds such as dimethyl peroxyvanadate are being evaluated to reverse lipid-induced IR.
AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 216 Introduction: Tumor infiltrating lymph... more AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 216 Introduction: Tumor infiltrating lymphocytes (TILs) have been documented in different types of tumors both in humans and mouse models. Many studies have found TILs to be favorable prognostic factors in patients with different tumors. Tumor cells may evade immune surveillance by different immunoregulatory strategies. Osteosarcoma, comprising 45% of all bone sarcomas, is a common solid tumor in adolescents and children. In the present study we determined the extent of TIL-infiltration in the tumor stroma in both primary osteosarcomas and metastatic osteosarcomas in lung using archival sections of metastatic lung osteosarcoma and a tissue microarray (TMA) generated from primary tumors. Methods: We performed immunohistochemical analysis of archival FFPE sections from patient-derived pulmonary metastatic osteosarcoma nodules (N=15) and a TMA of primary osteosarcomas (N=27) to assess the infiltration of CD8+ T cells and their activational status based on Granzyme-B positivity. We also assessed infiltration of FoxP3+ regulatory T cells (T-regs) in tumor stroma in the same specimens. The data obtained from immunohistochemical analysis were correlated with the clinical outcomes and histological grades for individual patients. Results: 12 of 15 specimens (80%) of metastatic lung osteosarcoma showed infiltration by CD8+ T cells in the tumor stroma; while in only one sample (8.3%) did these cells express Granzyme-B. CD8+ T cells present in adjacent lung tissue expressed Granzyme-B, indicating functional responsiveness and serving as an internal positive control for each sample. In a tissue microarray of primary jaw osteosarcomas only 2 of 27 specimens (7.4%) showed intratumor CD8+ T cell infiltration; none were positive for Granzyme B. Of the 11 metastatic specimens showing inactivation of infiltrating CTLs, only 3 (27%) showed infiltrating FoxP3+ T-regs in tumor stroma. Thus concomitant infiltration of T-regs did not account for the CTL inactivation in all specimens. Discussion: Our data show that osteosarcoma evades immune response by specifically anergizing TILs by T-reg dependent and independent mechanisms. There have been multiple clinical trials attempting eradication of osteosarcomas by activating anti-tumor immune response, e.g. GM-CSF inhalation therapy and use of muramyl tripeptide-phosphatidylethanolamine (MTP-PE) for lung metastases of osteosarcoma. We envisage that these treatments may work by circumventing immunoregulatory strategies taken up by tumor cells. Elucidation of these mechanisms might thus prove to be extremely important in designing rational immunotherapeutic strategies.
Introduction A major concern amidst the ongoing coronavirus pandemic has been the longer term per... more Introduction A major concern amidst the ongoing coronavirus pandemic has been the longer term persistence of morbidities in individuals recovering from COVID-19 disease, called long COVID. We aimed at documenting the prevalence and key associations of post-COVID symptoms (PCS) in India in telephonic survey among recovered patients in a single hospital in eastern India as well as a parallel web-survey covering a wider population of the country. Methods Self-reported PCS, ranging up to one year since the original COVID-19 diagnosis, were documented in a telephonic survey of subjects (analyzed N=986), treated for acute COVID-19 in Infectious Diseases and Beleghata General Hospital, Kolkata, between April 1, 2020 and April 13, 2021. In parallel, we ran a web-based survey (analyzed N=580), to evaluate concordance. Results Shortness of breath, fatigue and insomnia were identified to be the most commonly reported PCS in both the surveys, with higher prevalence in females. In the telephonic...
Understanding the dynamic changes in gene expression during Acute Respiratory Distress Syndrome (... more Understanding the dynamic changes in gene expression during Acute Respiratory Distress Syndrome (ARDS) progression in post-acute infection patients is crucial for unraveling the underlying mechanisms. Study investigates the longitudinal changes in gene/transcript expression patterns in hospital-admitted severe COVID-19 patients with ARDS post-acute SARS-CoV-2 infection. Blood samples were collected at three time points and patients were stratified into severe and mild ARDS, based on their oxygenation saturation (SpO2/FiO2) kinetics over 7 d. Decline in transcript diversity was observed over time, particularly in patients with higher severity, indicating dysregulated transcriptional landscape. Comparing gene/transcript-level analyses highlighted a rather limited overlap. With disease progression, a transition towards an inflammatory state was evident. Strong association was found between antibody response and disease severity, characterized by decreased antibody response and activate...
Abstract The exponential increase in diabetes prevalence in certain parts of the world has been l... more Abstract The exponential increase in diabetes prevalence in certain parts of the world has been linked to increased adiposity, especially visceral fat and associated increased insulin resistance (IR). This review highlights the role of lipid-induced IR, the associated small molecules and peptides, and their relation with immunometabolic dysfunction, diabetes pathogenesis, nonalcoholic fatty liver disease (NAFLD), and atherosclerotic cardiovascular disease. Increased circulating free fatty acids have been directly linked to increased IR and lesser glucose disposition. Lean NAFLD is strongly linked to IR and diabetes. Fetuin-A, a hepatokine, is a key regulator of lipid-induced IR. Cytokines, such as tumor necrosis factor alpha, interleukins, and the soluble receptor antagonists have a complex interplay in lipid-induced IR. As of today there are limited pharmacologic options to reverse lipid-induced IR. Pioglitazone and glitazars (saroglitazar) provide promising data on reducing hepatic adiposity and improving IR and glucose disposal. Many novel compounds such as dimethyl peroxyvanadate are being evaluated to reverse lipid-induced IR.
AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 216 Introduction: Tumor infiltrating lymph... more AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 216 Introduction: Tumor infiltrating lymphocytes (TILs) have been documented in different types of tumors both in humans and mouse models. Many studies have found TILs to be favorable prognostic factors in patients with different tumors. Tumor cells may evade immune surveillance by different immunoregulatory strategies. Osteosarcoma, comprising 45% of all bone sarcomas, is a common solid tumor in adolescents and children. In the present study we determined the extent of TIL-infiltration in the tumor stroma in both primary osteosarcomas and metastatic osteosarcomas in lung using archival sections of metastatic lung osteosarcoma and a tissue microarray (TMA) generated from primary tumors. Methods: We performed immunohistochemical analysis of archival FFPE sections from patient-derived pulmonary metastatic osteosarcoma nodules (N=15) and a TMA of primary osteosarcomas (N=27) to assess the infiltration of CD8+ T cells and their activational status based on Granzyme-B positivity. We also assessed infiltration of FoxP3+ regulatory T cells (T-regs) in tumor stroma in the same specimens. The data obtained from immunohistochemical analysis were correlated with the clinical outcomes and histological grades for individual patients. Results: 12 of 15 specimens (80%) of metastatic lung osteosarcoma showed infiltration by CD8+ T cells in the tumor stroma; while in only one sample (8.3%) did these cells express Granzyme-B. CD8+ T cells present in adjacent lung tissue expressed Granzyme-B, indicating functional responsiveness and serving as an internal positive control for each sample. In a tissue microarray of primary jaw osteosarcomas only 2 of 27 specimens (7.4%) showed intratumor CD8+ T cell infiltration; none were positive for Granzyme B. Of the 11 metastatic specimens showing inactivation of infiltrating CTLs, only 3 (27%) showed infiltrating FoxP3+ T-regs in tumor stroma. Thus concomitant infiltration of T-regs did not account for the CTL inactivation in all specimens. Discussion: Our data show that osteosarcoma evades immune response by specifically anergizing TILs by T-reg dependent and independent mechanisms. There have been multiple clinical trials attempting eradication of osteosarcomas by activating anti-tumor immune response, e.g. GM-CSF inhalation therapy and use of muramyl tripeptide-phosphatidylethanolamine (MTP-PE) for lung metastases of osteosarcoma. We envisage that these treatments may work by circumventing immunoregulatory strategies taken up by tumor cells. Elucidation of these mechanisms might thus prove to be extremely important in designing rational immunotherapeutic strategies.
Introduction A major concern amidst the ongoing coronavirus pandemic has been the longer term per... more Introduction A major concern amidst the ongoing coronavirus pandemic has been the longer term persistence of morbidities in individuals recovering from COVID-19 disease, called long COVID. We aimed at documenting the prevalence and key associations of post-COVID symptoms (PCS) in India in telephonic survey among recovered patients in a single hospital in eastern India as well as a parallel web-survey covering a wider population of the country. Methods Self-reported PCS, ranging up to one year since the original COVID-19 diagnosis, were documented in a telephonic survey of subjects (analyzed N=986), treated for acute COVID-19 in Infectious Diseases and Beleghata General Hospital, Kolkata, between April 1, 2020 and April 13, 2021. In parallel, we ran a web-based survey (analyzed N=580), to evaluate concordance. Results Shortness of breath, fatigue and insomnia were identified to be the most commonly reported PCS in both the surveys, with higher prevalence in females. In the telephonic...
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Papers by Dipyaman Ganguly