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Article ; Online: AKT inhibition sensitizes EVI1 expressing colon cancer cells to irinotecan therapy by regulating the Akt/mTOR axis.

Pradeepa / Suresh, Voddu / Senapati, Shantibhusan / Chakraborty, Soumen

2022 Volume 45, Issue 4, Page(s) 659–675

Abstract: Purpose: Ecotropic viral integration site 1 (EVI1) is an oncogenic transcription factor that has been attributed to chemotherapy resistance in different cancers. As yet, however, its role in colon cancer drug resistance is not completely understood. ... ...

Abstract	Purpose: Ecotropic viral integration site 1 (EVI1) is an oncogenic transcription factor that has been attributed to chemotherapy resistance in different cancers. As yet, however, its role in colon cancer drug resistance is not completely understood. Here, we set out to investigate the functional and therapeutic relevance of EVI1 in colon cancer drug resistance. Methods: The EVI1 gene was knocked down in colon cancer cells that were subsequently tested for susceptibility to irinotecan using in vitro assays and in vivo subcutaneous mouse colon cancer models. The effect of EVI1 knockdown on the AKT-mTOR signaling pathway was assessed using cell line models, immunohistochemistry and bioinformatics tools. The anti-proliferative activity of AKT inhibitor GSK690693 and its combination with irinotecan was tested in colon cancer cell line models (2D and 3D). Finally, the therapeutic efficacy of GSK690693 and its combination with irinotecan was evaluated in xenografted EVI1 expressing colon cancer mouse models. Results: We found that EVI1 knockdown decreased cancer stem cell-like properties and improved irinotecan responses in both cell line and subcutaneous mouse models. In addition, we found that EVI1 downregulation resulted in inhibition of AKT/mTOR signaling and RICTOR expression. Knocking down RICTOR expression increased the cytotoxic effects of irinotecan in EVI1 downregulated colon cancer cells. Co-treatment with irinotecan and ATP-competitive AKT inhibitor GSK690693 significantly reduced colon cancer cell survival and tumor progression rates. Conclusion: Inhibition of the AKT signaling cascade by GSK690693 may serve as an alternative to improve the irinotecan response in EVI1-expressing colon cancer cells.
MeSH term(s)	Animals ; Cell Line, Tumor ; Colonic Neoplasms/drug therapy ; Colonic Neoplasms/genetics ; Irinotecan/pharmacology ; Mice ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins c-akt/metabolism ; TOR Serine-Threonine Kinases ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	Protein Kinase Inhibitors ; Transcription Factors ; Irinotecan (7673326042) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2022-07-14
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2595109-9
ISSN	2211-3436 ; 1875-8606 ; 2211-3428
ISSN (online)	2211-3436
ISSN	1875-8606 ; 2211-3428
DOI	10.1007/s13402-022-00690-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Immunological and functional aspects of MAGEA3 cancer/testis antigen.

Das, Biswajit / Senapati, Shantibhusan

Advances in protein chemistry and structural biology

2020 Volume 125, Page(s) 121–147

Abstract: Identification of ectopic gene activation in cancer cells serves as a basis for both gene signature-guided tumor targeting and unearthing of oncogenic mechanisms to expand the understanding of tumor biology/oncogenic process. Proteins expressed only in ... ...

Abstract	Identification of ectopic gene activation in cancer cells serves as a basis for both gene signature-guided tumor targeting and unearthing of oncogenic mechanisms to expand the understanding of tumor biology/oncogenic process. Proteins expressed only in germ cells of testis and/or placenta (immunoprivileged organs) and in malignancies are called cancer testis antigens; they are antigenic because of the lack of antigen presentation by those specific cell types (germ cells), which limits the exposure of the proteins to the immune cells. Since the Cancer Testis Antigens (CTAs) are immunogenic and expressed in a wide variety of cancer types, CT antigens have become interesting target for immunotherapy against cancer. Among CT antigens MAGEA family is reported to have 12 members (MAGEA1 to MAGEA12). The current review highlights the studies on MAGEA3 which is a CT antigen and reported in almost all types of cancer. MAGEA3 is well tried for cancer immunotherapy. Recent advances on its functional and immunological aspect warranted much deliberation on effective therapeutic approach, thus making it a more interesting target for cancer therapy.
MeSH term(s)	Antigens, Neoplasm/immunology ; Female ; Gene Expression Regulation, Neoplastic/immunology ; Humans ; Immunotherapy ; Male ; Neoplasm Proteins/immunology ; Neoplasms/immunology ; Neoplasms/therapy
Chemical Substances	Antigens, Neoplasm ; MAGEA3 protein, human ; Neoplasm Proteins
Language	English
Publishing date	2020-10-01
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	1876-1631 ; 1876-1623
ISSN (online)	1876-1631
ISSN	1876-1623
DOI	10.1016/bs.apcsb.2020.08.001
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Article: Tissue Distribution of ACE2 Protein in Syrian Golden Hamster (

Suresh, Voddu / Parida, Deepti / Minz, Aliva P / Sethi, Manisha / Sahoo, Bhabani S / Senapati, Shantibhusan

Frontiers in pharmacology

2021 Volume 11, Page(s) 579330

Abstract: The Syrian golden hamster ( ...

Abstract	The Syrian golden hamster (
Language	English
Publishing date	2021-01-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2020.579330
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Article ; Online: Functional and mechanistic studies reveal MAGEA3 as a pro-survival factor in pancreatic cancer cells.

Das, Biswajit / Senapati, Shantibhusan

Journal of experimental & clinical cancer research : CR

2019 Volume 38, Issue 1, Page(s) 294

Abstract: Background: In the era of personalized therapy, functional annotation of less frequent genetic aberrations will be instrumental in adapting effective therapeutic in clinic. Overexpression of Melanoma associated antigen A3 (MAGEA3) is reported in certain ...

Abstract	Background: In the era of personalized therapy, functional annotation of less frequent genetic aberrations will be instrumental in adapting effective therapeutic in clinic. Overexpression of Melanoma associated antigen A3 (MAGEA3) is reported in certain pancreatic cancer (PCA) patients. The major objective of the current study was to investigate the functional role of MAGEA3 in pancreatic cancer cells (PCCs) growth and survival. Methods: Using overexpression (tet-on regulated system and constitutive expression system) and knockdown (by siRNA and shRNA) approach, we dissected the mechanistic role of MAGEA3 in pancreatic cancer pathogenesis. We generated MAGEA3 expressing stable PCA cell lines and mouse primary pancreatic epithelial cells. MAGEA3 was also depleted in certain MAGEA3 positive PCCs by siRNA or shRNA. The stable cells were subjected to in vitro assays like proliferation and survival assays under growth factor deprivation or in the presence of cytotoxic drugs. The MAGEA3 overexpressing or depleted stable PCCs were evaluated in vivo using xenograft model to check the role of MAGEA3 in tumor progression. We also dissected the mechanism behind the MAGEA3 role in tumor progression using western blot analysis and CCL2 neutralization. Results: MAGEA3 overexpression in PCA cells did not alter the cell proliferation but protected the cells during growth factor deprivation and also in the presence of cytotoxic drugs. However, depletion of MAGEA3 in MAGEA3 positive cells resulted in reduced cell proliferation and increased apoptosis upon growth factor deprivation and also in response to cytotoxic drugs. The in vivo xenograft study revealed that overexpression of MAGEA3 promoted tumor growth however depleting the same hindered the tumor progression. Mechanistically, our in vitro and in vivo study revealed that MAGEA3 has tumor-promoting role by reducing macro-autophagy and overexpressing pro-survival molecules like CCL2 and survivin. Conclusion: Our data proves tumor-promoting role of MAGEA3 and provides the rationale to target MAGEA3 and/or its functional mediators like CCL2 for PCA, which may have a better impact in PCA therapy.
MeSH term(s)	Animals ; Antigens, Neoplasm/metabolism ; Cell Line, Tumor ; Cell Proliferation ; Disease Models, Animal ; Humans ; Mice ; Neoplasm Proteins/metabolism ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; Survivin/metabolism
Chemical Substances	Antigens, Neoplasm ; MAGEA3 protein, human ; Neoplasm Proteins ; Survivin
Language	English
Publishing date	2019-07-08
Publishing country	England
Document type	Journal Article
ZDB-ID	803138-1
ISSN	1756-9966 ; 0392-9078
ISSN (online)	1756-9966
ISSN	0392-9078
DOI	10.1186/s13046-019-1272-2
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Article ; Online: Bioengineered probiotics to control SARS-CoV-2 infection

Shantibhusan Senapati / Jayalaxmi Dash / Manisha Sethi / Subhankar Chakraborty

Research Ideas and Outcomes, Vol 6, Iss , Pp 1-

2020 Volume 4

Abstract: The outbreak of 2019 novel corona virus disease (COVID-19) is now a global public health crisis and declared as a pandemic. Several recent studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds to human ... ...

Abstract	The outbreak of 2019 novel corona virus disease (COVID-19) is now a global public health crisis and declared as a pandemic. Several recent studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds to human angiotensin-converting enzyme 2 (ACE2). The information obtained from these structural and biochemical studies provides a strong rationale to target SARS-CoV-2 spike protein and ACE2 interaction for developing therapeutics against this viral infection. Here, we propose to discuss the scope of bioengineered probiotics expressing human ACE2 as a novel therapeutic to control the viral outbreak.
Keywords	SARS-CoV-2 ; ACE2 ; probiotics ; Science ; Q
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	Pensoft Publishers
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Bioengineered probiotics to control SARS-CoV-2 infection

Senapati, Shantibhusan / Dash, Jayalaxmi / Sethi, Manisha / Chakraborty, Subhankar

Research Ideas and Outcomes 6: e54802

2020

Abstract	The outbreak of 2019 novel corona virus disease (COVID-19) is now a global public health crisis and declared as a pandemic. Several recent studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds to human angiotensin-converting enzyme 2 (ACE2). The information obtained from these structural and biochemical studies provides a strong rationale to target SARS-CoV-2 spike protein and ACE2 interaction for developing therapeutics against this viral infection. Here, we propose to discuss the scope of bioengineered probiotics expressing human ACE2 as a novel therapeutic to control the viral outbreak.
Keywords	SARS-CoV-2 ; ACE2 ; probiotics ; covid19
Language	English
Publisher	Pensoft Publishers
Publishing country	bg
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Whole Genome Mining and Characterization of a New Probiotic Strain Levilactobacillus brevis ILSH3 from Handia: An Ethnic Fermented Beverage of Odisha, India.

Sethi, Manisha / Ok, Arjun / Dash, Jayalaxmi / Parida, Deepti / Kar, Salona / Mishra, Swayambara / Minz, Aliva P / Padhi, Anubhab / Das, Kirti Ranjan / Pradhan, Biswaranjan / Prakash, Tulika / Senapati, Shantibhusan

Probiotics and antimicrobial proteins

2024

Abstract: Isolation and characterization of probiotics from traditional fermented food have contributed many beneficial strains to the field of health and nutritional sciences. Handia, a traditional fermented alcoholic beverage popular in different parts of Odisha, ...

Abstract	Isolation and characterization of probiotics from traditional fermented food have contributed many beneficial strains to the field of health and nutritional sciences. Handia, a traditional fermented alcoholic beverage popular in different parts of Odisha, was our source of isolation. This study characterizes one such potential bacteria, Levilactobacillus brevis ILSH3 (H3) isolated from Handia. The investigation for the probiotic attributes as per ICMR-DBT guidelines qualified the checkpoint assays like acid and bile tolerance, bile salt hydrolase activity, antimicrobial properties, and pathogen exclusion ability. The whole genome sequence of H3 (2,460,966 bp in size with GC content of 45.62%) was subjected to comparative genome analysis for its taxonomic identification and validation of probiotic potential. Various genes pertaining to its probiotic potential were identified in the genome and it showed zero matches against any pathogenic families. Metabolite profiling of cell-free supernatant using liquid chromatography-mass spectrometry revealed the presence of essential amino acids, short-chain fatty acids, antimicrobial molecules, immunomodulatory molecules, and flavor/aroma-enhancing compounds. Immunomodulatory property investigation using Bioplex and qRT-PCR showed a reduction in the levels of pro-inflammatory cytokines in L. brevis ILSH3-treated Caco-2 cells. Collectively, the results demonstrate that this Handia-origin bacteria Levilactobacillus brevis ILSH3 possesses desirable attributes of a probiotic, which is now open for nutritional and health biologists to explore. This new probiotic strain may show promising results when utilized in healthcare or functional foods.
Language	English
Publishing date	2024-02-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2487792-X
ISSN	1867-1314 ; 1867-1306
ISSN (online)	1867-1314
ISSN	1867-1306
DOI	10.1007/s12602-024-10217-3
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Article ; Online: Zebrafish Larvae as a Model to Evaluate Potential Radiosensitizers or Protectors.

Mohapatra, Amlan P / Parida, Deepti / Mohapatra, Debasish / Nayak, Usharani / Swain, Rajeeb K / Senapati, Shantibhusan

Journal of visualized experiments : JoVE

2022 , Issue 186

Abstract: Zebrafish are extensively used in several kinds of research because they are one of the easily maintained vertebrate models and exhibit several features of a unique and convenient model system. As highly proliferative cells are more susceptible to ... ...

Abstract	Zebrafish are extensively used in several kinds of research because they are one of the easily maintained vertebrate models and exhibit several features of a unique and convenient model system. As highly proliferative cells are more susceptible to radiation-induced DNA damage, zebrafish embryos are a front-line in vivo model in radiation research. In addition, this model projects the effect of radiation and different drugs within a short time, along with major biological events and associated responses. Several cancer studies have used zebrafish, and this protocol is based on the use of radiation modifiers in the context of radiotherapy and cancer. This method can be readily used to validate the effects of different drugs on irradiated and control (non-irradiated) embryos, thus identifying drugs as radio sensitizing or protective drugs. Although this methodology is used in most drug screening experiments, the details of the experiment and the toxicity assessment with the background of X-ray radiation exposure are limited or only briefly addressed, making it difficult to perform. This protocol addresses this issue and discusses the procedure and toxicity evaluation with a detailed illustration. The procedure describes a simple approach for using zebrafish embryos for radiation studies and radiation-based drug screening with much reliability and reproducibility.
MeSH term(s)	Animals ; Drug Evaluation, Preclinical ; Larva/radiation effects ; Reproducibility of Results ; X-Rays ; Zebrafish/genetics
Language	English
Publishing date	2022-08-25
Publishing country	United States
Document type	Journal Article ; Video-Audio Media ; Research Support, Non-U.S. Gov't
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/64233
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Article: Bioengineered probiotics to control SARS-CoV-2 infection

Senapati, Shantibhusan / Dash, Jayalaxmi / Sethi, Manisha / Chakraborty, Subhankar

Research Ideas and Outcomes. 2020 May 29, v. 6

2020

Abstract	The outbreak of 2019 novel corona virus disease (COVID-19) is now a global public health crisis and declared as a pandemic. Several recent studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds to human angiotensin-converting enzyme 2 (ACE2). The information obtained from these structural and biochemical studies provides a strong rationale to target SARS-CoV-2 spike protein and ACE2 interaction for developing therapeutics against this viral infection. Here, we propose to discuss the scope of bioengineered probiotics expressing human ACE2 as a novel therapeutic to control the viral outbreak.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; humans ; pandemic ; peptidyl-dipeptidase A ; probiotics ; public health ; research ; therapeutics
Language	English
Dates of publication	2020-0529
Publishing place	Pensoft Publishers
Document type	Article
ZDB-ID	2833254-4
ISSN	2367-7163
ISSN	2367-7163
DOI	10.3897/rio.6.e54802
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Gemcitabine induces polarization of mouse peritoneal macrophages towards M1-like and confers antitumor property by inducing ROS production.

Minz, Aliva Prity / Das, Biswajit / Mohapatra, Debasish / Suresh, Voddu / Mishra, Swayambara / Senapati, Shantibhusan

Clinical & experimental metastasis

2022 Volume 39, Issue 5, Page(s) 783–800

Abstract: In patients with pancreatic cancer (PC), the peritoneal cavity is the second-most common site of metastasis after the liver. Peritoneal macrophages (PMs) have been demonstrated to play a significant role in the peritoneal metastases of different cancers. ...

Abstract	In patients with pancreatic cancer (PC), the peritoneal cavity is the second-most common site of metastasis after the liver. Peritoneal macrophages (PMs) have been demonstrated to play a significant role in the peritoneal metastases of different cancers. Gemcitabine (GEM) is known to affect PC-associated immune cells, including macrophages. However, its effect on PMs and its possible clinical implication is yet to be investigated. In this study, mouse-derived PMs were treated with GEM ex vivo to analyze the polarization status. Production of GEM-induced reactive oxygen species (ROS) and reactive nitrogen species was evaluated using DCFH-DA, DAF-FM, and Griess assay. Antitumor effects of PMs on UN-KC-6141and UN-KPC-961 murine PC cells were evaluated in presence and absence of GEM in vitro. Similarly, effect of GEM on human THP-1 macrophage polarization and its tumoricidal effect was studied in vitro. Furthermore, the effect of GEM-treated PMs on peritoneal metastasis of UN-KC-6141 cells was evaluated in a syngeneic mouse model of PC. GEM upregulated M1 phenotype-associated molecular markers (Tnf-α and Inos) in vitro in PMs obtained from naïve mouse. Moreover, IL-4-induced M2-like PMs reverted to M1-like after GEM treatment. Co-culture of UN-KC-6141 and UN-KPC-961 cancer cells with PMs in the presence of GEM increased apoptosis of these cells, whereas cell death was markedly reduced after N-acetyl-L-cysteine treatment. Corroborating these findings co-culture of GEM-treated human THP-1 macrophages also induced cell death in MIAPaCa-2 cancer cells. GEM-treated PMs injected intraperitoneally along with UN-KC-6141 cells into mice extended survival period, but did not stop disease progression and mortality. Together, GEM induced M1-like polarization of PMs from naive and/or M2-polarized PMs in a ROS-dependent manner. GEM-induced M1-like PMs prompted cytotoxicity in PC cells and delayed disease progression in vivo.
MeSH term(s)	Animals ; Deoxycytidine/analogs & derivatives ; Disease Progression ; Humans ; Macrophages ; Macrophages, Peritoneal/metabolism ; Mice ; Reactive Oxygen Species/metabolism
Chemical Substances	Reactive Oxygen Species ; Deoxycytidine (0W860991D6) ; gemcitabine (B76N6SBZ8R)
Language	English
Publishing date	2022-07-15
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604952-7
ISSN	1573-7276 ; 0262-0898
ISSN (online)	1573-7276
ISSN	0262-0898
DOI	10.1007/s10585-022-10178-3
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