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Article ; Online: Deciphering cellular plasticity in pancreatic cancer for effective treatments.

Uddin, Md Hafiz / Zhang, Dingqiang / Muqbil, Irfana / El-Rayes, Bassel F / Chen, Herbert / Philip, Philip A / Azmi, Asfar S

Cancer metastasis reviews

2024 Volume 43, Issue 1, Page(s) 393–408

Abstract: Cellular plasticity and therapy resistance are critical features of pancreatic cancer, a highly aggressive and fatal disease. The pancreas, a vital organ that produces digestive enzymes and hormones, is often affected by two main types of cancer: the pre- ...

Abstract	Cellular plasticity and therapy resistance are critical features of pancreatic cancer, a highly aggressive and fatal disease. The pancreas, a vital organ that produces digestive enzymes and hormones, is often affected by two main types of cancer: the pre-dominant ductal adenocarcinoma and the less common neuroendocrine tumors. These cancers are difficult to treat due to their complex biology characterized by cellular plasticity leading to therapy resistance. Cellular plasticity refers to the capability of cancer cells to change and adapt to different microenvironments within the body which includes acinar-ductal metaplasia, epithelial to mesenchymal/epigenetic/metabolic plasticity, as well as stemness. This plasticity allows heterogeneity of cancer cells, metastasis, and evasion of host's immune system and develops resistance to radiation, chemotherapy, and targeted therapy. To overcome this resistance, extensive research is ongoing exploring the intrinsic and extrinsic factors through cellular reprogramming, chemosensitization, targeting metabolic, key survival pathways, etc. In this review, we discussed the mechanisms of cellular plasticity involving cellular adaptation and tumor microenvironment and provided a comprehensive understanding of its role in therapy resistance and ways to overcome it.
MeSH term(s)	Humans ; Cell Plasticity ; Pancreatic Neoplasms/therapy ; Pancreatic Neoplasms/pathology ; Pancreas ; Cellular Reprogramming ; Carcinoma, Pancreatic Ductal/therapy ; Carcinoma, Pancreatic Ductal/pathology ; Tumor Microenvironment
Language	English
Publishing date	2024-01-09
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	604857-2
ISSN	1573-7233 ; 0167-7659
ISSN (online)	1573-7233
ISSN	0167-7659
DOI	10.1007/s10555-023-10164-5
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Article ; Online: Exportin 1 inhibition as antiviral therapy.

Uddin, Md Hafiz / Zonder, Jeffrey A / Azmi, Asfar S

Drug discovery today

2020 Volume 25, Issue 10, Page(s) 1775–1781

Abstract: Coronavirus 2019 (COVID-19; caused by Severe Acute Respiratory Syndrome Coronavirus 2; SARS-CoV-2) is a currently global health problem. Previous studies showed that blocking nucleocytoplasmic transport with exportin 1 (XPO1) inhibitors originally ... ...

Abstract	Coronavirus 2019 (COVID-19; caused by Severe Acute Respiratory Syndrome Coronavirus 2; SARS-CoV-2) is a currently global health problem. Previous studies showed that blocking nucleocytoplasmic transport with exportin 1 (XPO1) inhibitors originally developed as anticancer drugs can quarantine key viral accessory proteins and genomic materials in the nucleus of host cell and reduce virus replication and immunopathogenicity. These observations support the concept of the inhibition of nuclear export as an effective strategy against an array of viruses, including influenza A, B, and SARS-CoV. Clinical studies using the XPO1 inhibitor selinexor as a therapy for COVID-19 infection are in progress.
MeSH term(s)	Active Transport, Cell Nucleus ; Animals ; Antiviral Agents/therapeutic use ; COVID-19/immunology ; COVID-19/metabolism ; COVID-19/virology ; Cell Nucleus/drug effects ; Cell Nucleus/immunology ; Cell Nucleus/metabolism ; Cell Nucleus/virology ; Drug Design ; Host-Pathogen Interactions ; Humans ; Karyopherins/antagonists & inhibitors ; Karyopherins/metabolism ; Molecular Targeted Therapy ; Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors ; Receptors, Cytoplasmic and Nuclear/metabolism ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity ; COVID-19 Drug Treatment ; Exportin 1 Protein
Chemical Substances	Antiviral Agents ; Karyopherins ; Receptors, Cytoplasmic and Nuclear
Keywords	covid19
Language	English
Publishing date	2020-06-20
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1324988-5
ISSN	1878-5832 ; 1359-6446
ISSN (online)	1878-5832
ISSN	1359-6446
DOI	10.1016/j.drudis.2020.06.014
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Zs.A 4725: Show issues

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Article ; Online: Chi2-MI

Samrat Kumar Dey / Khandaker Mohammad Mohi Uddin / Hafiz Md. Hasan Babu / Md. Mahbubur Rahman / Arpita Howlader / K.M. Aslam Uddin

Intelligent Systems with Applications, Vol 16, Iss , Pp 200144- (2022)

A hybrid feature selection based machine learning approach in diagnosis of chronic kidney disease

2022

Abstract: Early detection and characterization are considered crucial in treating and controlling the chronic renal disease. Because of the rising number of patients, the high risk of progression to end-stage renal disease, and the poor prognosis of morbidity and ... ...

Abstract	Early detection and characterization are considered crucial in treating and controlling the chronic renal disease. Because of the rising number of patients, the high risk of progression to end-stage renal disease, and the poor prognosis of morbidity and mortality, chronic kidney disease (CKD) is a significant burden on the healthcare system. Detecting CKD in its early stages is critical for saving millions of lives. The uniqueness of this study lies in developing a diagnosis system to detect chronic kidney disease using different Machine Learning (ML) algorithms with the support of a hybrid feature selection approach. This study exploited the 400 clinical data of CKD patients based on the dataset supplied by the University of California Irvine (UCI) available at their Machine Learning repository. Different data preparation techniques like encoding categorical features, missing values imputation, removing outlier factors, handling data imbalance, scaling data at the same level, and selecting relevant features are adopted to prepare the dataset for the prediction model. A hybrid Chi-squared test (Chi2) and Mutual Information (MI) based feature selection approach is proposed to remove redundant features, and a Pearson correlation matrix is also computed to consider the top important features for the prediction. Lastly, the Extra tress classifier can diagnose CKD with 98% accuracy and a 2% true negative rate without data leakage out of 14 machine learning models. On the other hand, the Bagging classifier performed worst with only 60% accuracy.
Keywords	Machine learning ; CKD ; Classification ; Feature selection ; Healthcare informatics ; Cybernetics ; Q300-390 ; Electronic computers. Computer science ; QA75.5-76.95
Subject code	006
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Role of noncoding RNAs in pancreatic ductal adenocarcinoma associated cachexia.

Uddin, Md Hafiz / Mohammad, Ramzi M / Philip, Philip A / Azmi, Asfar S / Muqbil, Irfana

American journal of physiology. Cell physiology

2022 Volume 323, Issue 6, Page(s) C1624–C1632

Abstract: Cachexia is an acute syndrome that is very commonly observed in patients with cancer. Cachexia is the number one cause of death in patients with metastatic disease and is also the major factor for physical toxicity and financial burden. More importantly, ...

Abstract	Cachexia is an acute syndrome that is very commonly observed in patients with cancer. Cachexia is the number one cause of death in patients with metastatic disease and is also the major factor for physical toxicity and financial burden. More importantly, the majority of patients with advanced-stage pancreatic ductal adenocarcinoma (PDAC) cancer undergo cachexia. Pancreatic cancer causes deaths of ∼50,000 Americans and about 400,000 people worldwide every year. The high mortality rates in metastatic PDAC are due to systemic pathologies and cachexia, which quickens death in these patients. About 90% of all patients with PDAC undergo wasting of muscle causing mobility loss and leading to a number of additional pathological conditions. PDAC-associated cancer cachexia emanates from complex signaling cues involving both mechanical and biological signals. Tumor invasion is associated with the loss of pancreatic function-induced digestive disorders and malabsorption, which causes subsequent weight loss and eventually promotes cachexia. Besides, systemic inflammation of patients with PDAC could release chemical cues (e.g., cytokine-mediated Atrogin-1/MAFbx expression) that participate in muscle wasting. Our understanding of genes, proteins, and cytokines involved in promoting cancer cachexia has evolved considerably. However, the role of epigenetic factors, particularly the role of noncoding RNAs (ncRNAs) in regulating PDAC-associated cachexia is less studied. In this review article, the most updated knowledge on the various ncRNAs including microRNAs (miRs), long noncoding RNA (lncRNAs), piwi interacting RNAs (PiwiRNAs), small nucleolar RNA (snoRNAs), and circular RNAs (circRNA) and their roles in cancer cachexia are described.
MeSH term(s)	Humans ; Cachexia/genetics ; Carcinoma, Pancreatic Ductal/complications ; Carcinoma, Pancreatic Ductal/genetics ; Pancreatic Neoplasms/complications ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/metabolism ; RNA, Untranslated/genetics ; RNA, Long Noncoding/metabolism ; Adenocarcinoma/pathology ; Pancreatic Neoplasms
Chemical Substances	RNA, Untranslated ; RNA, Long Noncoding
Language	English
Publishing date	2022-10-24
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	392098-7
ISSN	1522-1563 ; 0363-6143
ISSN (online)	1522-1563
ISSN	0363-6143
DOI	10.1152/ajpcell.00424.2022
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Article ; Online: Feature fusion based VGGFusionNet model to detect COVID-19 patients utilizing computed tomography scan images.

Uddin, Khandaker Mohammad Mohi / Dey, Samrat Kumar / Babu, Hafiz Md Hasan / Mostafiz, Rafid / Uddin, Shahadat / Shoombuatong, Watshara / Moni, Mohammad Ali

Scientific reports

2022 Volume 12, Issue 1, Page(s) 21796

Abstract: COVID-19 is one of the most life-threatening and dangerous diseases caused by the novel Coronavirus, which has already afflicted a larger human community worldwide. This pandemic disease recovery is possible if detected in the early stage. We proposed an ...

Abstract	COVID-19 is one of the most life-threatening and dangerous diseases caused by the novel Coronavirus, which has already afflicted a larger human community worldwide. This pandemic disease recovery is possible if detected in the early stage. We proposed an automated deep learning approach from Computed Tomography (CT) scan images to detect COVID-19 positive patients by following a four-phase paradigm for COVID-19 detection: preprocess the CT scan images; remove noise from test image by using anisotropic diffusion techniques; make a different segment for the preprocessed images; and train and test COVID-19 detection using Convolutional Neural Network (CNN) models. This study employed well-known pre-trained models, including AlexNet, ResNet50, VGG16 and VGG19 to evaluate experiments. 80% of images are used to train the network in the detection process, while the remaining 20% are used to test it. The result of the experiment evaluation confirmed that the VGG19 pre-trained CNN model achieved better accuracy (98.06%). We used 4861 real-life COVID-19 CT images for experiment purposes, including 3068 positive and 1793 negative images. These images were acquired from a hospital in Sao Paulo, Brazil and two other different data sources. Our proposed method revealed very high accuracy and, therefore, can be used as an assistant to help professionals detect COVID-19 patients accurately.
MeSH term(s)	Humans ; COVID-19/diagnostic imaging ; Brazil ; Radionuclide Imaging ; Patients ; Tomography, X-Ray Computed
Language	English
Publishing date	2022-12-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-25539-x
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Article ; Online: Aberrant transcription factors in the cancers of the pancreas.

Uddin, Md Hafiz / Al-Hallak, Md Najeeb / Philip, Philip A / Chen, Herbert / El-Rayes, Bassel / Azmi, Asfar S

Seminars in cancer biology

2022 Volume 86, Issue Pt 2, Page(s) 28–45

Abstract: Transcription factors (TFs) are essential for proper activation of gene during the process of organogenesis, differentiation, lineage specificity. Reactivation or dysregulation of TFs regulatory networks could lead to deformation of organs, diseases ... ...

Abstract	Transcription factors (TFs) are essential for proper activation of gene during the process of organogenesis, differentiation, lineage specificity. Reactivation or dysregulation of TFs regulatory networks could lead to deformation of organs, diseases including various malignancies. Currently, understanding the mechanism of oncogenesis became a necessity for the development of targeted therapeutic strategy for different cancer types. It is evident that many TFs go awry in cancers of the pancreas such as pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine neoplasms (PanNENs). These mutated or dysregulated TFs abnormally controls various signaling pathways in PDAC and PanNENs including RTK, PI3K-PTEN-AKT-mTOR, JNK, TGF-β/SMAD, WNT/β-catenin, SHH, NOTCH and VEGF which in turn regulate different hallmarks of cancer. Aberrant regulation of such pathways have been linked to the initiation, progression, metastasis, and resistance in pancreatic cancer. As of today, a number of TFs has been identified as crucial regulators of pancreatic cancer and a handful of them shown to have potential as therapeutic targets in pre-clinical and clinical settings. In this review, we have summarized the current knowledge on the role and therapeutic usefulness of TFs in PDAC and PanNENs.
MeSH term(s)	Humans ; Carcinoma, Pancreatic Ductal/genetics ; Carcinoma, Pancreatic Ductal/pathology ; Gene Expression Regulation, Neoplastic ; Pancreas/metabolism ; Pancreas/pathology ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; Transcription Factors/genetics ; Pancreatic Neoplasms
Chemical Substances	Transcription Factors
Language	English
Publishing date	2022-09-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1033980-2
ISSN	1096-3650 ; 1044-579X
ISSN (online)	1096-3650
ISSN	1044-579X
DOI	10.1016/j.semcancer.2022.08.011
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Zs.A 2922: Show issues

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Article: Regulator of Chromosome Condensation (RCC1) a novel therapeutic target in pancreatic ductal adenocarcinoma drives tumor progression via the c-Myc-RCC1-Ran axis.

Bannoura, Sahar F / Aboukameel, Amro / Khan, Husain Yar / Uddin, Md Hafiz / Jang, Hyejeong / Beal, Eliza / Thangasamy, Amalraj / Kim, Seongho / Wagner, Kay Uwe / Mohammad, Ramzi / Al-Hallak, Mohammed Najeeb / Pasche, Boris C / Azmi, Asfar S

bioRxiv : the preprint server for biology

2023

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited therapeutic options. Here we for the first time evaluated the role of regulator of chromosome condensation 1 (RCC1) in PDAC subsistence and drug resistance. RCC1 ... ...

Abstract	Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited therapeutic options. Here we for the first time evaluated the role of regulator of chromosome condensation 1 (RCC1) in PDAC subsistence and drug resistance. RCC1 expression was found to be elevated in PDAC tissues in comparison with normal pancreatic tissues and was linked to poor prognosis. RCC1 silencing in a panel of PDAC cells by RNA interference and CRISPR-Cas9 resulted in reduced cellular proliferation in 2D and 3D cultures. RCC1 KD reduced migratory and clonogenic ability, enhanced apoptosis, and altered cell cycle distribution in human PDAC cells as well as cells isolated from the LSL-Kras
Language	English
Publishing date	2023-12-19
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.12.18.572102
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Article: Exportin 1 inhibition as antiviral therapy

Uddin, Md Hafiz / Zonder, Jeffrey A / Azmi, Asfar S

Drug discov. today

Abstract	Coronavirus 2019 (COVID-19; caused by Severe Acute Respiratory Syndrome Coronavirus 2; SARS-CoV-2) is a currently global health problem. Previous studies showed that blocking nucleocytoplasmic transport with exportin 1 (XPO1) inhibitors originally developed as anticancer drugs can quarantine key viral accessory proteins and genomic materials in the nucleus of host cell and reduce virus replication and immunopathogenicity. These observations support the concept of the inhibition of nuclear export as an effective strategy against an array of viruses, including influenza A, B, and SARS-CoV. Clinical studies using the XPO1 inhibitor selinexor as a therapy for COVID-19 infection are in progress.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #611872
Database	COVID19

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Article ; Online: Gastric Cancer Heterogeneity and Clinical Outcomes.

Sexton, Rachel E / Hallak, Mohammed Najeeb Al / Uddin, Md Hafiz / Diab, Maria / Azmi, Asfar S

Technology in cancer research & treatment

2020 Volume 19, Page(s) 1533033820935477

Abstract: Gastric adenocarcinoma is a highly aggressive disease with poor overall survival. The aggressive nature of this disease is in part due to the high intra and inter tumoral heterogeneity and also due to the late diagnosis at presentation. Once progression ... ...

Abstract	Gastric adenocarcinoma is a highly aggressive disease with poor overall survival. The aggressive nature of this disease is in part due to the high intra and inter tumoral heterogeneity and also due to the late diagnosis at presentation. Once progression occurs, treatment is more difficult due to the adaptation of tumors, which acquires resistance to commonly used chemotherapeutics. In this report, using publicly available data sets and pathway analysis, we highlight the vast heterogeneity of gastric cancer by investigating genes found to be significantly perturbed. We found several upregulated genes in the diffuse gastric cancer subtypes share similarity to gastric cancer as a whole which can be explained by the increase in this subtype of gastric cancer throughout the world. We report significant downregulation of genes that are underrepresented within the literature, such as
MeSH term(s)	Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Computational Biology/methods ; Databases, Genetic ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Genetic Heterogeneity ; Humans ; Male ; Neoplasm Grading ; Prognosis ; Sex Factors ; Stomach Neoplasms/etiology ; Stomach Neoplasms/metabolism ; Stomach Neoplasms/mortality ; Stomach Neoplasms/pathology ; Transcriptome
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2020-08-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2146365-7
ISSN	1533-0338 ; 1533-0346
ISSN (online)	1533-0338
ISSN	1533-0346
DOI	10.1177/1533033820935477
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Article ; Online: Glutathione improves rice tolerance to submergence: insights into its physiological and biochemical mechanisms.

Siddiqui, Md Nurealam / Mostofa, Mohammad Golam / Rahman, Md Mezanur / Tahjib-Ul-Arif, Md / Das, Ashim Kumar / Mohi-Ud-Din, Mohammed / Rohman, Md Motiar / Hafiz, Hafizur Rahman / Ansary, Md Mesbah Uddin / Tran, Lam-Son Phan

Journal of biotechnology

2020 Volume 325, Page(s) 109–118

Abstract: Complete submergence (Sub) imposes detrimental effects on growth and survival of crop plants, including rice. Here, we investigated the beneficial effects of reduced glutathione (GSH) in mitigating Sub-induced adverse effects in two high-yielding rice ... ...

Abstract	Complete submergence (Sub) imposes detrimental effects on growth and survival of crop plants, including rice. Here, we investigated the beneficial effects of reduced glutathione (GSH) in mitigating Sub-induced adverse effects in two high-yielding rice cultivars BRRI dhan29 and dhan52. Both cultivars experienced growth defects, severe yellowing, necrosis and chlorosis, when they were completely immersed in water for 14 days. The poor growth performance of these cultivars was linked to biomass reduction, decreased levels of photosynthetic pigments and proline, increased levels of H
MeSH term(s)	Antioxidants ; Catalase/metabolism ; Glutathione/metabolism ; Hydrogen Peroxide ; Oryza/metabolism ; Oxidative Stress ; Seedlings/metabolism ; Superoxide Dismutase/metabolism
Chemical Substances	Antioxidants ; Hydrogen Peroxide (BBX060AN9V) ; Catalase (EC 1.11.1.6) ; Superoxide Dismutase (EC 1.15.1.1) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2020-11-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	843647-2
ISSN	1873-4863 ; 0168-1656 ; 1389-0352
ISSN (online)	1873-4863
ISSN	0168-1656 ; 1389-0352
DOI	10.1016/j.jbiotec.2020.11.011
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