Priyanka Banerjee - Academia.edu (original) (raw)

Papers by Priyanka Banerjee

Normalized cell viability MEC1 cells SUPPLEMENTARY FIGURES Supplementary Figure S1. Effect of tra... more Normalized cell viability MEC1 cells SUPPLEMENTARY FIGURES Supplementary Figure S1. Effect of trabectedin on CLL cells. (A) MEC1 cells were plated in 96-well plates alone (control), with increasing concentrations of trabectedin (0.001 µM, 0.01 µM, 0.1 µM, 1 µM, 10 µM) or with Vehicle (v1, v2 DMSO) and a luminescent assay was performed 24, 48 and 72 hours later to evaluate MEC1 cells' sensitivity to the drug. Cell viability of each sample has been normalized to its control. (B) Human primary CLL cells obtained from CLL patients (n=5, patients 1-5, Supplementary Table S1) were plated in 96-well plates alone (control), with increasing concentrations of trabectedin (0.001 µM, 0.01 µM, 0.1 µM, 1 µM or 10 µM) or with Vehicle (DMSO v1, v2) and subjected to a luminescent assay at 72 hours to assess the cells' sensitivity to the drug. Cell viability of each sample has been normalized to its control.

International Journal of Molecular Sciences

Cellular senescence—the irreversible cell cycle arrest driven by a variety of mechanisms and, mor... more Cellular senescence—the irreversible cell cycle arrest driven by a variety of mechanisms and, more specifically, the senescence-associated secretory phenotype (SASP)—is an important area of research in the context of different age-related diseases, such as cardiovascular disease and cancer. SASP factors play both beneficial and detrimental roles in age-related disease progression depending on the source of the SASPs, the target cells, and the microenvironment. The impact of senescence and the SASP on different cell types, the immune system, and the vascular system has been widely discussed. However, the impact of replicative or stress-induced senescence on lymphatic biology and pathological lymphangiogenesis remains underexplored. The lymphatic system plays a crucial role in the maintenance of body fluid homeostasis and immune surveillance. The perturbation of lymphatic function can hamper normal physiological function. Natural aging or stress-induced premature aging influences the ...

Cells, 2021

Cholangiocarcinoma (CCA), or cancer of bile duct epithelial cells, is a very aggressive malignanc... more Cholangiocarcinoma (CCA), or cancer of bile duct epithelial cells, is a very aggressive malignancy characterized by early lymphangiogenesis in the tumor microenvironment (TME) and lymph node (LN) metastasis which correlate with adverse patient outcome. However, the specific roles of lymphatic endothelial cells (LECs) that promote LN metastasis remains unexplored. Here we aimed to identify the dynamic molecular crosstalk between LECs and CCA cells that activate tumor-promoting pathways and enhances lymphangiogenic mechanisms. Our studies show that inflamed LECs produced high levels of chemokine CXCL5 that signals through its receptor CXCR2 on CCA cells. The CXCR2-CXCL5 signaling axis in turn activates EMT (epithelial-mesenchymal transition) inducing MMP (matrix metalloproteinase) genes such as GLI, PTCHD, and MMP2 in CCA cells that promote CCA migration and invasion. Further, rate of mitochondrial respiration and glycolysis of CCA cells was significantly upregulated by inflamed LECs ...

Journal of Clinical Microbiology, 2010

Hepatitis B virus (HBV) strains isolated from members of the primitive Paharia ethnic community o... more Hepatitis B virus (HBV) strains isolated from members of the primitive Paharia ethnic community of Eastern India were studied to gain insight into the genetic diversity and evolution of the virus. The Paharia tribe has remained quite separate from the rest of the Indians and differs culturally, genetically, and linguistically from the mainstream East Indian population, whose HBV strains were previously characterized. Full-length HBV DNA was PCR amplified, cloned, and sequenced. Phylogenetic relationships between the tribal sequences and reference sequences from the mainstream population were assessed, and divergence times of subgenotypes of HBV genotype D were estimated. HBV was found in 2% of the Paharias participating in the study. A predominance of hepatitis B e antigen-negative infection (73%) was observed among the Paharias, and the genome sequences of the HBV strains exhibited relative homogeneity, with a very low prevalence of mutations. The novel feature of Paharia HBV was t...

Clinical Microbiology and Infection, 2012

Hepatitis B e-antigen (HBeAg)-negative chronic HBV infection is highly prevalent in several parts... more Hepatitis B e-antigen (HBeAg)-negative chronic HBV infection is highly prevalent in several parts of the world, including India, with the clinical spectrum ranging from inactive carrier (IC) state to chronic 'e-negative' hepatitis B (CHB) and culminating in advanced liver disease such as cirrhosis (LC). The present study has for the first time investigated the natural diversity of HBV belonging to genotype D in treatment-naïve Indian patients representing the above phases of HBeAg-negative infection to identify candidate mutations associated with each disease state. Studies of full-length HBV/D sequences revealed that the progressive accumulation and persistence of mutations in basal core promoter, negative regulatory element, Pre-core region, the Band T-cell epitopes of X protein as well as deletions in the PreS region contribute significantly to disease progression from IC through CHB to LC. In addition, the development of CHB was associated with a significant increase in viral variants characterized by mutations in enhancer II, preS1 promoter, T-cell epitope of core and B-cell epitope region of PreS1. While few of the mutations were previously reported in the context of HBV genotypes B and C, others had not been documented before. Our results thus highlight a distinct pattern of mutation in HBV/D that may help in predicting clinical outcomes of HBeAg-negative infection and have implications for better clinical management of the patients.

Frontiers in Cardiovascular Medicine

Cancer survivors undergone treatment face an increased risk of developing atherosclerotic cardiov... more Cancer survivors undergone treatment face an increased risk of developing atherosclerotic cardiovascular disease (CVD), yet the underlying mechanisms remain elusive. Recent studies have revealed that chemotherapy can drive senescent cancer cells to acquire a proliferative phenotype known as senescence-associated stemness (SAS). These SAS cells exhibit enhanced growth and resistance to cancer treatment, thereby contributing to disease progression. Endothelial cell (EC) senescence has been implicated in atherosclerosis and cancer, including among cancer survivors. Treatment modalities for cancer can induce EC senescence, leading to the development of SAS phenotype and subsequent atherosclerosis in cancer survivors. Consequently, targeting senescent ECs displaying the SAS phenotype hold promise as a therapeutic approach for managing atherosclerotic CVD in this population. This review aims to provide a mechanistic understanding of SAS induction in ECs and its contribution to atheroscler...

Cancer Immunology Research, 2019

Chronic lymphocytic leukemia (CLL) is a B-cell neoplasia characterized by protumor immune dysregu... more Chronic lymphocytic leukemia (CLL) is a B-cell neoplasia characterized by protumor immune dysregulation involving nonmalignant cells of the microenvironment, including T lymphocytes and tumor-associated myeloid cells. Although therapeutic agents have improved treatment options for CLL, many patients still fail to respond. Some patients also show immunosuppression. We have investigated trabectedin, a marine-derived compound with cytotoxic activity on macrophages in solid tumors. Here, we demonstrate that trabectedin induces apoptosis of human primary leukemic cells and also selected myeloid and lymphoid immunosuppressive cells, mainly through the TRAIL/TNF pathway. Trabectedin modulates transcription and translation of IL6, CCL2, and IFNα in myeloid cells and FOXP3 in regulatory T cells. Human memory CD8+ T cells downregulate PD-1 and, along with monocytes, exert in vivo antitumor function. In xenograft and immunocompetent CLL mouse models, trabectedin has antileukemic effects and an...

Scientific Reports, 2017

The present study sought to evaluate the structure of HBV quasispecies in Lamivudine (LMV)-failed... more The present study sought to evaluate the structure of HBV quasispecies in Lamivudine (LMV)-failed chronic hepatitis B (CHB) patients and its impact in defining the subsequent virological responses to Tenofovir (TDF)-based rescue-therapy. By analyzing HBV clones encompassing reverse transcriptase (RT) and surface (S) region from LMV-failed and treatment-naïve CHB patients, we identified 5 classical and 12 novel substitutions in HBV/RT and 9 substitutions in immune-epitopes of HBV/S that were significantly associated with LMV failure. In silico analysis showed spatial proximity of some of the newly-identified, mutated RT residues to the RT catalytic centre while most S-substitutions caused alteration in epitope hydrophobicity. TDF administration resulted in virological response in 60% of LMV-failed patients at 24-week but non-response in 40% of patients even after 48-weeks. Significantly high frequencies of 6 S-substitutions and one novel RT-substitution, rtH124N with 6.5-fold-reduced susceptibility to TDF in vitro, were noted at baseline in TDF non-responders than responders. Follow-up studies depicted greater evolutionary drift of HBV quasispecies and significant decline in frequencies of 3 RT and 6 S-substitutions in responder-subgroup after 24-week TDF-therapy while most variants persisted in non-responders. Thus, we identified the HBV-RT/S variants that could potentially predict unfavorable response to LMV/TDF-therapy and impede immune-mediated viral clearance.

PLoS ONE, 2014

Background/Aims: HBV has been classified into ten genotypes (A-J) and multiple subgenotypes, some... more Background/Aims: HBV has been classified into ten genotypes (A-J) and multiple subgenotypes, some of which strongly influence disease outcome and their distribution also correlate with human migration. HBV infection is highly prevalent in India and its diverse population provides an excellent opportunity to study the distinctiveness of HBV, its evolution and disease biology in variegated ethnic groups. The NorthEast India, having international frontiers on three sides, is one of the most ethnically and linguistically diverse region of the country. Given the paucity of information on molecular epidemiology of HBV in this region, the study aimed to carry out an in-depth genetic characterization of HBV prevailing in NorthEast state of Tripura. Methods: From sera of chronically HBV infected patients biochemical/serological tests, HBV DNA quantification, PCRamplification, sequencing of PreS/S or full-length HBV genomes were done. HBV genotype/subgenotype determination and sequence variability were assessed by MEGA5-software. The evolutionary divergence times of different HBV subgenotypes were estimated by DNAMLK/PHYLIP program while jpHMM method was used to detect any recombination event in HBV genomes. Results: HBV genotypes D (89.5%), C (6.6%) and A (3.9%) were detected among chronic carriers. While all HBV/A and HBV/C isolates belonged to subgenotype-A1 and C1 respectively, five subgenotypes of HBV/D (D1-D5) were identified including the first detection of rare D4. These non-recombinant Indian D4 (IndD4) formed a distinct phylogenetic clade, had 2.7% nucleotide divergence and recent evolutionary radiation than other global D4. Ten unique amino acids and 9 novel nucleotide substitutions were identified as IndD4 signatures. All IndD4 carried T 120 and R 129 in ORF-S that may cause immune/vaccine/diagnostic escape and N 128 in ORF-P, implicated as compensatory Lamivudine resistance mutation. Conclusions: IndD4 has potential to undermine vaccination programs or anti-viral therapy and its introduction to NorthEast India is believed to be linked with the settlement of ancient Tibeto-Burman migrants from East-Asia.

F1000 - Post-publication peer review of the biomedical literature, 2017

Primary central nervous system lymphoma (PCNSL) harbors mutations that reinforce B cell receptor ... more Primary central nervous system lymphoma (PCNSL) harbors mutations that reinforce B cell receptor (BCR) signaling. Ibrutinib, a BTK inhibitor, targets BCR signaling and is particularly active in lymphomas with BCR and MYD88 mutations. We performed a proof of concept phase Ib study of ibrutinib monotherapy followed by ibrutinib plus chemotherapy (DA-TEDDi-R). In 18 PCNSL patients, 94% showed tumor reductions with ibrutinib alone, including patients having PCNSL with CD79B and/or MYD88 mutations, and 86% of evaluable patients achieved a

Scientific Reports, 2017

We characterized occult HBV (OHBV) from hepatitis B surface antigen (HBsAg)-negative chronic HCV ... more We characterized occult HBV (OHBV) from hepatitis B surface antigen (HBsAg)-negative chronic HCV carriers of Eastern India to explore the impact of genomic variability of HBV in causing undetectability of HBsAg and low viremia that define the occult phenomenon. Screening of sera samples revealed the presence of OHBV in 17.8% of HCV-infected patients. Determination of full-length OHBV sequences and comparison with that from HBsAg-positive carriers led to the detection of distinct substitutions/mutations in PreS2, S, P and X ORFs and in X-promoter and Enhancer-II of OHBV. These mutations were introduced in wild-type HBV and their effects were evaluated by transfection in Huh7 cells. In vitro assays demonstrated that S-substitutions resulted in antigenically modified HBsAg that escaped detection by immunoassays whereas those in ORF-P caused significant decline in viral replication. Impairment in Enhancer-II and X-promoter activities were noted due to occult-associated mutations that ge...

Journal of Hepatology, 2011

POSTERS respectively). An increased production of IFN-gamma was typical of both Vdelta1 and Vdelt... more POSTERS respectively). An increased production of IFN-gamma was typical of both Vdelta1 and Vdelta2 in non responders CHC. No differences were found in IL-17 and TGF-beta production. Conclusion: A selectively enriched and activated peripheral Vdelta1 population characterises HCV patients with advanced, more active and long-lasting infection; its enhanced IFN-gamma production may explain, possibly via the overxpression of IFN-gammainducible protein-10, non-response to antiviral therapy.

Journal of Clinical Microbiology, 2012

Leishmania donovani is considered the causative organism of visceral leishmaniasis (VL) and post-... more Leishmania donovani is considered the causative organism of visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL). Testing of 4/29 DNA samples from VL and PKDL patients as well as 2/7 field isolates showed an aberrant internal transcribed spacer 1 (ITS1) restriction fragment length polymorphism (RFLP) pattern, which upon sequencing strongly matched Leptomonas seymouri , thus confirming its presence in Indian leishmaniasis.

Normalized cell viability MEC1 cells SUPPLEMENTARY FIGURES Supplementary Figure S1. Effect of tra... more Normalized cell viability MEC1 cells SUPPLEMENTARY FIGURES Supplementary Figure S1. Effect of trabectedin on CLL cells. (A) MEC1 cells were plated in 96-well plates alone (control), with increasing concentrations of trabectedin (0.001 µM, 0.01 µM, 0.1 µM, 1 µM, 10 µM) or with Vehicle (v1, v2 DMSO) and a luminescent assay was performed 24, 48 and 72 hours later to evaluate MEC1 cells' sensitivity to the drug. Cell viability of each sample has been normalized to its control. (B) Human primary CLL cells obtained from CLL patients (n=5, patients 1-5, Supplementary Table S1) were plated in 96-well plates alone (control), with increasing concentrations of trabectedin (0.001 µM, 0.01 µM, 0.1 µM, 1 µM or 10 µM) or with Vehicle (DMSO v1, v2) and subjected to a luminescent assay at 72 hours to assess the cells' sensitivity to the drug. Cell viability of each sample has been normalized to its control.

International Journal of Molecular Sciences

Cellular senescence—the irreversible cell cycle arrest driven by a variety of mechanisms and, mor... more Cellular senescence—the irreversible cell cycle arrest driven by a variety of mechanisms and, more specifically, the senescence-associated secretory phenotype (SASP)—is an important area of research in the context of different age-related diseases, such as cardiovascular disease and cancer. SASP factors play both beneficial and detrimental roles in age-related disease progression depending on the source of the SASPs, the target cells, and the microenvironment. The impact of senescence and the SASP on different cell types, the immune system, and the vascular system has been widely discussed. However, the impact of replicative or stress-induced senescence on lymphatic biology and pathological lymphangiogenesis remains underexplored. The lymphatic system plays a crucial role in the maintenance of body fluid homeostasis and immune surveillance. The perturbation of lymphatic function can hamper normal physiological function. Natural aging or stress-induced premature aging influences the ...

Cells, 2021

Cholangiocarcinoma (CCA), or cancer of bile duct epithelial cells, is a very aggressive malignanc... more Cholangiocarcinoma (CCA), or cancer of bile duct epithelial cells, is a very aggressive malignancy characterized by early lymphangiogenesis in the tumor microenvironment (TME) and lymph node (LN) metastasis which correlate with adverse patient outcome. However, the specific roles of lymphatic endothelial cells (LECs) that promote LN metastasis remains unexplored. Here we aimed to identify the dynamic molecular crosstalk between LECs and CCA cells that activate tumor-promoting pathways and enhances lymphangiogenic mechanisms. Our studies show that inflamed LECs produced high levels of chemokine CXCL5 that signals through its receptor CXCR2 on CCA cells. The CXCR2-CXCL5 signaling axis in turn activates EMT (epithelial-mesenchymal transition) inducing MMP (matrix metalloproteinase) genes such as GLI, PTCHD, and MMP2 in CCA cells that promote CCA migration and invasion. Further, rate of mitochondrial respiration and glycolysis of CCA cells was significantly upregulated by inflamed LECs ...

Journal of Clinical Microbiology, 2010

Hepatitis B virus (HBV) strains isolated from members of the primitive Paharia ethnic community o... more Hepatitis B virus (HBV) strains isolated from members of the primitive Paharia ethnic community of Eastern India were studied to gain insight into the genetic diversity and evolution of the virus. The Paharia tribe has remained quite separate from the rest of the Indians and differs culturally, genetically, and linguistically from the mainstream East Indian population, whose HBV strains were previously characterized. Full-length HBV DNA was PCR amplified, cloned, and sequenced. Phylogenetic relationships between the tribal sequences and reference sequences from the mainstream population were assessed, and divergence times of subgenotypes of HBV genotype D were estimated. HBV was found in 2% of the Paharias participating in the study. A predominance of hepatitis B e antigen-negative infection (73%) was observed among the Paharias, and the genome sequences of the HBV strains exhibited relative homogeneity, with a very low prevalence of mutations. The novel feature of Paharia HBV was t...

Clinical Microbiology and Infection, 2012

Hepatitis B e-antigen (HBeAg)-negative chronic HBV infection is highly prevalent in several parts... more Hepatitis B e-antigen (HBeAg)-negative chronic HBV infection is highly prevalent in several parts of the world, including India, with the clinical spectrum ranging from inactive carrier (IC) state to chronic 'e-negative' hepatitis B (CHB) and culminating in advanced liver disease such as cirrhosis (LC). The present study has for the first time investigated the natural diversity of HBV belonging to genotype D in treatment-naïve Indian patients representing the above phases of HBeAg-negative infection to identify candidate mutations associated with each disease state. Studies of full-length HBV/D sequences revealed that the progressive accumulation and persistence of mutations in basal core promoter, negative regulatory element, Pre-core region, the Band T-cell epitopes of X protein as well as deletions in the PreS region contribute significantly to disease progression from IC through CHB to LC. In addition, the development of CHB was associated with a significant increase in viral variants characterized by mutations in enhancer II, preS1 promoter, T-cell epitope of core and B-cell epitope region of PreS1. While few of the mutations were previously reported in the context of HBV genotypes B and C, others had not been documented before. Our results thus highlight a distinct pattern of mutation in HBV/D that may help in predicting clinical outcomes of HBeAg-negative infection and have implications for better clinical management of the patients.

Frontiers in Cardiovascular Medicine

Cancer survivors undergone treatment face an increased risk of developing atherosclerotic cardiov... more Cancer survivors undergone treatment face an increased risk of developing atherosclerotic cardiovascular disease (CVD), yet the underlying mechanisms remain elusive. Recent studies have revealed that chemotherapy can drive senescent cancer cells to acquire a proliferative phenotype known as senescence-associated stemness (SAS). These SAS cells exhibit enhanced growth and resistance to cancer treatment, thereby contributing to disease progression. Endothelial cell (EC) senescence has been implicated in atherosclerosis and cancer, including among cancer survivors. Treatment modalities for cancer can induce EC senescence, leading to the development of SAS phenotype and subsequent atherosclerosis in cancer survivors. Consequently, targeting senescent ECs displaying the SAS phenotype hold promise as a therapeutic approach for managing atherosclerotic CVD in this population. This review aims to provide a mechanistic understanding of SAS induction in ECs and its contribution to atheroscler...

Cancer Immunology Research, 2019

Chronic lymphocytic leukemia (CLL) is a B-cell neoplasia characterized by protumor immune dysregu... more Chronic lymphocytic leukemia (CLL) is a B-cell neoplasia characterized by protumor immune dysregulation involving nonmalignant cells of the microenvironment, including T lymphocytes and tumor-associated myeloid cells. Although therapeutic agents have improved treatment options for CLL, many patients still fail to respond. Some patients also show immunosuppression. We have investigated trabectedin, a marine-derived compound with cytotoxic activity on macrophages in solid tumors. Here, we demonstrate that trabectedin induces apoptosis of human primary leukemic cells and also selected myeloid and lymphoid immunosuppressive cells, mainly through the TRAIL/TNF pathway. Trabectedin modulates transcription and translation of IL6, CCL2, and IFNα in myeloid cells and FOXP3 in regulatory T cells. Human memory CD8+ T cells downregulate PD-1 and, along with monocytes, exert in vivo antitumor function. In xenograft and immunocompetent CLL mouse models, trabectedin has antileukemic effects and an...

Scientific Reports, 2017

The present study sought to evaluate the structure of HBV quasispecies in Lamivudine (LMV)-failed... more The present study sought to evaluate the structure of HBV quasispecies in Lamivudine (LMV)-failed chronic hepatitis B (CHB) patients and its impact in defining the subsequent virological responses to Tenofovir (TDF)-based rescue-therapy. By analyzing HBV clones encompassing reverse transcriptase (RT) and surface (S) region from LMV-failed and treatment-naïve CHB patients, we identified 5 classical and 12 novel substitutions in HBV/RT and 9 substitutions in immune-epitopes of HBV/S that were significantly associated with LMV failure. In silico analysis showed spatial proximity of some of the newly-identified, mutated RT residues to the RT catalytic centre while most S-substitutions caused alteration in epitope hydrophobicity. TDF administration resulted in virological response in 60% of LMV-failed patients at 24-week but non-response in 40% of patients even after 48-weeks. Significantly high frequencies of 6 S-substitutions and one novel RT-substitution, rtH124N with 6.5-fold-reduced susceptibility to TDF in vitro, were noted at baseline in TDF non-responders than responders. Follow-up studies depicted greater evolutionary drift of HBV quasispecies and significant decline in frequencies of 3 RT and 6 S-substitutions in responder-subgroup after 24-week TDF-therapy while most variants persisted in non-responders. Thus, we identified the HBV-RT/S variants that could potentially predict unfavorable response to LMV/TDF-therapy and impede immune-mediated viral clearance.

PLoS ONE, 2014

Background/Aims: HBV has been classified into ten genotypes (A-J) and multiple subgenotypes, some... more Background/Aims: HBV has been classified into ten genotypes (A-J) and multiple subgenotypes, some of which strongly influence disease outcome and their distribution also correlate with human migration. HBV infection is highly prevalent in India and its diverse population provides an excellent opportunity to study the distinctiveness of HBV, its evolution and disease biology in variegated ethnic groups. The NorthEast India, having international frontiers on three sides, is one of the most ethnically and linguistically diverse region of the country. Given the paucity of information on molecular epidemiology of HBV in this region, the study aimed to carry out an in-depth genetic characterization of HBV prevailing in NorthEast state of Tripura. Methods: From sera of chronically HBV infected patients biochemical/serological tests, HBV DNA quantification, PCRamplification, sequencing of PreS/S or full-length HBV genomes were done. HBV genotype/subgenotype determination and sequence variability were assessed by MEGA5-software. The evolutionary divergence times of different HBV subgenotypes were estimated by DNAMLK/PHYLIP program while jpHMM method was used to detect any recombination event in HBV genomes. Results: HBV genotypes D (89.5%), C (6.6%) and A (3.9%) were detected among chronic carriers. While all HBV/A and HBV/C isolates belonged to subgenotype-A1 and C1 respectively, five subgenotypes of HBV/D (D1-D5) were identified including the first detection of rare D4. These non-recombinant Indian D4 (IndD4) formed a distinct phylogenetic clade, had 2.7% nucleotide divergence and recent evolutionary radiation than other global D4. Ten unique amino acids and 9 novel nucleotide substitutions were identified as IndD4 signatures. All IndD4 carried T 120 and R 129 in ORF-S that may cause immune/vaccine/diagnostic escape and N 128 in ORF-P, implicated as compensatory Lamivudine resistance mutation. Conclusions: IndD4 has potential to undermine vaccination programs or anti-viral therapy and its introduction to NorthEast India is believed to be linked with the settlement of ancient Tibeto-Burman migrants from East-Asia.

F1000 - Post-publication peer review of the biomedical literature, 2017

Primary central nervous system lymphoma (PCNSL) harbors mutations that reinforce B cell receptor ... more Primary central nervous system lymphoma (PCNSL) harbors mutations that reinforce B cell receptor (BCR) signaling. Ibrutinib, a BTK inhibitor, targets BCR signaling and is particularly active in lymphomas with BCR and MYD88 mutations. We performed a proof of concept phase Ib study of ibrutinib monotherapy followed by ibrutinib plus chemotherapy (DA-TEDDi-R). In 18 PCNSL patients, 94% showed tumor reductions with ibrutinib alone, including patients having PCNSL with CD79B and/or MYD88 mutations, and 86% of evaluable patients achieved a

Scientific Reports, 2017

We characterized occult HBV (OHBV) from hepatitis B surface antigen (HBsAg)-negative chronic HCV ... more We characterized occult HBV (OHBV) from hepatitis B surface antigen (HBsAg)-negative chronic HCV carriers of Eastern India to explore the impact of genomic variability of HBV in causing undetectability of HBsAg and low viremia that define the occult phenomenon. Screening of sera samples revealed the presence of OHBV in 17.8% of HCV-infected patients. Determination of full-length OHBV sequences and comparison with that from HBsAg-positive carriers led to the detection of distinct substitutions/mutations in PreS2, S, P and X ORFs and in X-promoter and Enhancer-II of OHBV. These mutations were introduced in wild-type HBV and their effects were evaluated by transfection in Huh7 cells. In vitro assays demonstrated that S-substitutions resulted in antigenically modified HBsAg that escaped detection by immunoassays whereas those in ORF-P caused significant decline in viral replication. Impairment in Enhancer-II and X-promoter activities were noted due to occult-associated mutations that ge...

Journal of Hepatology, 2011

POSTERS respectively). An increased production of IFN-gamma was typical of both Vdelta1 and Vdelt... more POSTERS respectively). An increased production of IFN-gamma was typical of both Vdelta1 and Vdelta2 in non responders CHC. No differences were found in IL-17 and TGF-beta production. Conclusion: A selectively enriched and activated peripheral Vdelta1 population characterises HCV patients with advanced, more active and long-lasting infection; its enhanced IFN-gamma production may explain, possibly via the overxpression of IFN-gammainducible protein-10, non-response to antiviral therapy.

Journal of Clinical Microbiology, 2012

Leishmania donovani is considered the causative organism of visceral leishmaniasis (VL) and post-... more Leishmania donovani is considered the causative organism of visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL). Testing of 4/29 DNA samples from VL and PKDL patients as well as 2/7 field isolates showed an aberrant internal transcribed spacer 1 (ITS1) restriction fragment length polymorphism (RFLP) pattern, which upon sequencing strongly matched Leptomonas seymouri , thus confirming its presence in Indian leishmaniasis.