4.3 Article

Characterization and use of HapT1-derived homologous tumors as a preclinical model to evaluate therapeutic efficacy of drugs against pancreatic tumor desmoplasia

Journal

ONCOTARGET
Volume 7, Issue 27, Pages 41825-41842

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.9729

Keywords

pancreatic cancer; desmoplasia; HapT1; pancreatic stellate cells; hamster homologous orthotopic model

Funding

  1. Institute of Life Sciences (ILS)
  2. Department of Biotechnology (DBT), Government of India

Ask authors/readers for more resources

Desmoplasia in human pancreatic cancer (PC) promotes cancer progression and hinders effective drug delivery. The objectives of this study were to characterize a homologous orthotopic model of PC in Syrian golden hamster and investigate the effect of anti-fibrotic (pirfenidone), antioxidant (N-acetyl cysteine, NAC) and anti-addiction (disulfiram, DSF) drugs on desmoplasia and tumor growth in this model. The HapT1 PC cells when implanted orthotopically into hamsters formed tumors with morphological, cellular and molecular similarities to human PC. Protein profiling of activated hamster pancreatic stellate cells (ha-PSCs) revealed expression of proteins involved in fibrosis, cancer cells growth and metastasis. Pirfenidone, suppressed growth of HapT1 cells and the desmoplastic response in vivo; these effects were enhanced by co-administration of NAC. Disulfiram alone or in combination with copper (Cu) was toxic to HapT1 cells and PSCs in vitro; but co-administration of DSF and Cu accelerated growth of HapT1 cells in vivo. Moreover, DSF had no effect on tumor-associated desmoplasia. Overall, this study identifies HapT1-derived orthotopic tumors as a useful model to study desmoplasia and tumor-directed therapeutics in PC. Pirfenidone in combination with NAC could be a novel combination therapy for PC and warrants investigation in human subjects.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.3
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Oncology

Gemcitabine induces polarization of mouse peritoneal macrophages towards M1-like and confers antitumor property by inducing ROS production

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

Summary: In patients with pancreatic cancer, the peritoneal cavity is a common site of metastasis. Peritoneal macrophages play a significant role in peritoneal metastases of different cancers. This study investigates the effect of Gemcitabine (GEM), a chemotherapy drug, on the polarization of macrophages and its potential clinical implications in pancreatic cancer. The results show that GEM induces a M1-like polarization of macrophages, resulting in cytotoxicity towards pancreatic cancer cells and delayed disease progression in a mouse model.

CLINICAL & EXPERIMENTAL METASTASIS (2022)

Article Pharmacology & Pharmacy

Therapeutic role of N-acetyl cysteine (NAC) for the treatment and/or management of SARS-CoV-2-induced lung damage in hamster model

Voddu Suresh, Padmanava Behera, Deepti Parida, Amlan Priyadarshee Mohapatra, Suraja Kumar Das, Sneha Kumari, Kiran Avula, Amruta Mohapatra, Gulam Hussain Syed, Shantibhusan Senapati

Summary: Oxidative stress caused by ROS is the main mediator of SARS-CoV-2-induced pathology. NAC, with its antioxidant, anti-inflammatory, mucolytic, and antiviral properties, may have beneficial effects in COVID-19 patients. This study shows that high doses of NAC can suppress severe lung damage caused by SARS-CoV-2, but fail to restrict viral load. However, high doses of NAC with and without remdesivir significantly suppress the expression of pro-inflammatory genes in lung tissues.

EUROPEAN JOURNAL OF PHARMACOLOGY (2023)

Article Biotechnology & Applied Microbiology

Fructose-induced topographical changes in fructophilic, pseudofructophilic and non-fructophilic lactic acid bacterial strains with genomic comparison

Pradip Behare, Syed Azmal Ali, Vinay S. N. Mishra, Laura G. Gomez-Mascaraque, Olivia McAuliffe

Summary: In this study, the viability and morphology of different bacterial strains were examined under high fructose concentrations. It was found that fructophilic lactic acid bacteria had reduced viability, while a non-fructophilic strain was significantly affected. Electron microscopy revealed that fructophilic strains remained intact but expanded, while the non-fructophilic strain ruptured and formed cell debris. Genomic analysis showed that fructophilic strains had fewer genes related to fructose metabolism and transport.

WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY (2023)

Article Biotechnology & Applied Microbiology

Postbiotics Implication in the Microbiota-Host Intestinal Epithelial Cells Mutualism

Harpreet Kaur, Gurjeet Kaur, Syed Azmal Ali

Summary: To maintain host health and create a conducive environment for the gut microbiota, the host and gut microbiota interact with each other. These interactions primarily occur between commensal bacteria and intestinal epithelial cells (IECs), serving as the primary defense mechanism to preserve intestinal homeostasis. The use of post-biotics, such as p40, positively influences IECs by acting as transactivators of the EGF receptor (EGFR), inducing protective responses and alleviating colitis. Moreover, post-biotics play a role in reprogramming IECs during the neonatal period for sustained protection against colitis in adulthood through regulation of TGF-beta release and expansion of regulatory T cells (Tregs).

PROBIOTICS AND ANTIMICROBIAL PROTEINS (2023)

Article Chemistry, Medicinal

Probiotic-prebiotic therapeutic potential: A new horizon of microbial biotherapy to reduce female reproductive complications

Kavita Rani, Gurjeet Kaur, Syed Azmal Ali

Summary: Probiotics and prebiotics have emerged as a novel method for treating health issues, including reproductive disorders and infertility. They regulate gut microbiota and restore the control and synthesis of reproductive hormones. This review provides evidence that the use of probiotics and prebiotics could offer a new approach to alleviate female reproductive complications.

PHARMANUTRITION (2023)

Review Medicine, Research & Experimental

IL-33's role in the gut immune system: A comprehensive review of its crosstalk and regulation

Harpreet Kaur, Gurjeet Kaur, Syed Azmal Ali

Summary: The intestinal tract is the largest immune organ, playing important roles in nutrient absorption and immune responses. IL-33 is a cytokine that regulates inflammatory disorders and can induce various immune responses. IL-33 activates different cell types to produce cytokines and is also involved in the initiation of type 2 immunity. However, the mechanisms by which IL-33 promotes type 2 immunity in the gastrointestinal tract are not fully understood. IL-33 also plays a role in regulatory immune responses. This review provides a comprehensive summary of IL-33's role in the gut immune system and its potential applications in the treatment of gut inflammatory disorders.

LIFE SCIENCES (2023)

Review Biotechnology & Applied Microbiology

Molecular complexity of mammary glands development: a review of lactogenic differentiation in epithelial cells

Manoj Kumar Jena, Farheen Badrealam Khan, Syed Azmal Ali, Abdullah Abdullah, Amarish Kumar Sharma, Vikas Yadav, Sudhakar Kancharla, Prachetha Kolli, Gowtham Mandadapu, Anjan Kumar Sahoo, Prasana Kumar Rath, Jalal Taneera, Sudarshan Kumar, Ashok Kumar Mohanty, Khang Wen Goh, Long Chiau Ming, Chrismawan Ardianto

Summary: The mammary gland undergoes physiological processes such as cellular proliferation, differentiation, and apoptosis during the pregnancy-lactation-involution cycle. Understanding the molecular changes during the lactogenic differentiation of mammary epithelial cells (MECs) is crucial. Various molecular mediators including hormones, growth factors, cytokines, miRNAs, and regulatory proteins govern this process. Studying the molecular transitions from pregnancy to lactation will aid in further research, such as manipulating genes responsible for milk synthesis and secretion, and identifying protein signatures of lactation.

ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY (2023)

Review Biology

Integrating Omics Technologies for a Comprehensive Understanding of the Microbiome and Its Impact on Cattle Production

Harpreet Kaur, Gurjeet Kaur, Taruna Gupta, Deepti Mittal, Syed Azmal Ali

Summary: This article highlights the importance of ruminant production in global agriculture and discusses the challenges related to population growth and environmental concerns. Recent research has revealed a connection between the composition of the rumen microbiome and economically advantageous traits in cattle, driving the need for innovative strategies to improve feed efficiency and reduce environmental impact. The article also emphasizes the role of the rumen microbiome in plant fiber digestion and its influence on ruminant production and health.

BIOLOGY-BASEL (2023)

Article Biochemistry & Molecular Biology

Probiotic and prebiotic supplementation ameliorates chronic restraint stress-induced male reproductive dysfunction

Mohd Akram, Syed Azmal Ali, Gautam Kaul

Summary: This study aimed to investigate the effects of probiotics on stress-induced male reproductive deficits. The results showed that Lactobacillus rhamnosus NCDC-610 and Lactobacillus fermentum NCDC-400 can improve sperm deficits caused by stress and improve intestinal health. In addition, probiotics can also alleviate oxidative stress and activate the hypothalamic-pituitary-adrenal axis caused by stress. Therefore, L. rhamnosus NCDC-610 and L. fermentum NCDC-400 are safe and effective probiotics for mitigating stress-induced male reproductive deficits.

FOOD & FUNCTION (2023)

Article Food Science & Technology

Physicochemical and rheological characterizations of a novel exopolysaccharide EPSKar1 and its iron complex EPSKar1-Fe: Towards potential iron-fortification applications

Manorama Kumari, Rolly Kumari, Basavaprabhu Haranahalli Nataraj, Prashant Ashok Shelke, Syed Azmal Ali, Ravinder Nagpal, Pradip Behare

Summary: Iron is essential for human health, and iron fortification is a promising solution for combating iron-deficiency anemia. This study investigates the physical and chemical properties of a new exopolysaccharide called EPSKar1 and its iron complex EPSKar1-Fe (II). The findings demonstrate that EPSKar1 is a high molecular-weight heteropolysaccharide with strong emulsifying and water-holding capacities. EPSKar1 forms stable complexes with iron and exhibits beneficial rheological properties for food applications. Overall, EPSKar1-Fe (II) complex shows great potential as a novel iron fortifier.

CURRENT RESEARCH IN FOOD SCIENCE (2023)

Review Biochemistry & Molecular Biology

Probiotics and postbiotics play a role in maintaining dermal health

Swasti Rawal, Syed Azmal Ali

Summary: Probiotics and postbiotics are effective alternatives to antibiotics for treating persistent skin infections. They promote the growth of beneficial bacteria and inhibit harmful bacteria, prevent colonization of harmful bacteria on the skin, and produce antimicrobial substances. Traditional antibiotic treatments have adverse effects and antibiotic-resistant pathogens can form biofilms. Probiotics and postbiotics stimulate the immune system, enhance skin barrier components, and modulate inflammation for maintaining healthy skin. This review summarizes the therapeutic potential of probiotics and postbiotics for persistent skin infections and their impact on dermal health.

FOOD & FUNCTION (2023)

Review Oncology

Multifaceted Pharmacological Potentials of Curcumin, Genistein, and Tanshinone IIA through Proteomic Approaches: An In-Depth Review

Farheen Badrealam Khan, Parul Singh, Yahya F. Jamous, Syed Azmal Ali, Abdullah, Shahab Uddin, Qamar Zia, Manoj Kumar Jena, Mohsina Khan, Mohammad Owais, Chih Yang Huang, Venkatesh Chanukuppa, Chrismawan Ardianto, Long Chiau Ming, Waqas Alam, Haroon Khan, Mohammad Akli Ayoub

Summary: This article reviews the use of proteomics to study the molecular details of phytochemicals such as curcumin, genistein, and tanshinone IIA. These phytochemicals have various pharmacological properties that are extensively studied to understand their mechanisms of action. Proteomics technology has proved to be a reliable approach to unravel the molecular intricacies of phytochemicals.

CANCERS (2023)

Article Food Science & Technology

Safety evaluation of indigenous probiotic Limosilactobacillus fermentum NCDC 400 using whole genome sequences and in vitro approaches

Basavaprabhu Haranahalli Nataraj, Manorama Kumari, Ravinder Nagpal, Syed Azmal Ali, Pradip V. Behare

Summary: This study evaluated the safety of an indigenous probiotic strain, Limosilactobacillus fermentum NCDC 400, using both in silico and in vitro approaches. The results show that NCDC 400 does not possess potential antibiotic-resistance or virulence genes, lacks harmful metabolites or enzymes, and does not exhibit harmful phenotypes. In addition, it is sensitive to human serum and antibiotics and shows no cytotoxicity to Caco-2 cells.

FOOD BIOSCIENCE (2023)

Article Chemistry, Multidisciplinary

Proteomics analysis of MSN, MWCNT and ZnO nanoparticle-induced alteration in prepubertal rat ovary

Karmveer Yadav, Syed Azmal Ali, Noyonika Kaul, Ashok Kumar Mohanty, Gautam Kaul

Summary: The study found that nanoparticles have a negative impact on the ovarian function of female rats, leading to reduced body weight, smaller ovaries, decreased follicle count, and follicular cyst development. The distribution of nanoparticles in the body directly affects ovarian function and alters the expression of critical proteins.

ENVIRONMENTAL SCIENCE-NANO (2022)

Review Immunology

Interactions between the gut microbiota-derived functional factors and intestinal epithelial cells - implication in the microbiota-host mutualism

Harpreet Kaur, Syed Azmal Ali, Fang Yan

Summary: The mutual interactions between the gut microbiota and the host are crucial for maintaining human health and creating a favorable environment for the gut microbial community. Intestinal epithelial cells (IECs) act as the first responders to the gut microbiota in order to maintain intestinal balance. Recent studies suggest that components derived from commensal bacteria play a functional role in protecting intestinal integrity and reducing susceptibility to intestinal inflammation. Additionally, IECs have been found to communicate with the gut commensal bacteria, shaping the composition and function of the microbial community. This review highlights the beneficial effects of functional factors secreted by commensal bacteria on IECs, focusing on soluble proteins, metabolites, and surface layer components, as well as the impact of IECs on the commensal microbial profile. This knowledge provides a proof-of-concept model for understanding the mechanisms underlying the microbiota-host mutualism.

FRONTIERS IN IMMUNOLOGY (2022)

No Data Available