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Article ; Online: Preclinical Repurposing of Sitagliptin as a Drug Candidate for Colorectal Cancer by Targeting

Shih, Jing-Wen / Wu, Alexander T H / Mokgautsi, Ntlotlang / Wei, Po-Li / Huang, Yan-Jiun

International journal of molecular sciences

2024 Volume 25, Issue 1

Abstract: Despite significant advances in treatment modalities, colorectal cancer (CRC) remains a poorly understood and highly lethal malignancy worldwide. Cancer stem cells (CSCs) and the tumor microenvironment (TME) have been shown to play critical roles in ... ...

Abstract	Despite significant advances in treatment modalities, colorectal cancer (CRC) remains a poorly understood and highly lethal malignancy worldwide. Cancer stem cells (CSCs) and the tumor microenvironment (TME) have been shown to play critical roles in initiating and promoting CRC progression, metastasis, and treatment resistance. Therefore, a better understanding of the underlying mechanisms contributing to the generation and maintenance of CSCs is crucial to developing CSC-specific therapeutics and improving the current standard of care for CRC patients. To this end, we used a bioinformatics approach to identify increased
MeSH term(s)	Humans ; Sitagliptin Phosphate/pharmacology ; Sitagliptin Phosphate/therapeutic use ; Dipeptidyl Peptidase 4 ; Drug Repositioning ; Molecular Docking Simulation ; beta Catenin ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Tumor Microenvironment ; SOXC Transcription Factors/genetics ; CD24 Antigen
Chemical Substances	Sitagliptin Phosphate (TS63EW8X6F) ; Dipeptidyl Peptidase 4 (EC 3.4.14.5) ; beta Catenin ; SOX4 protein, human ; SOXC Transcription Factors ; CD24 protein, human ; CD24 Antigen ; CTNNB1 protein, human
Language	English
Publishing date	2024-01-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25010609
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Laryngeal Mask Airway as an Appropriate Option in Pediatric Laparoscopic Inguinal Hernia Repair: A Systematic Review and Meta-Analysis.

Yang, Cheng-Jui / Cheng, Po-Lung / Huang, Yan-Jiun / Huang, Fu-Huan

Journal of pediatric surgery

2023 Volume 59, Issue 4, Page(s) 660–666

Abstract: Objective: To elucidate the safety and effectiveness of laryngeal mask airway (LMA) use in pediatric patients undergoing laparoscopic inguinal hernia repair.: Methods: Studies were searched on the PubMed, EMBASE, and Cochrane Library databases. Only ... ...

Abstract	Objective: To elucidate the safety and effectiveness of laryngeal mask airway (LMA) use in pediatric patients undergoing laparoscopic inguinal hernia repair. Methods: Studies were searched on the PubMed, EMBASE, and Cochrane Library databases. Only randomized controlled trials (RCTs) were included. Primary outcomes were major perioperative respiratory adverse events (PRAEs), namely laryngospasm, bronchospasm, desaturation, and aspiration. Secondary outcomes were minor PRAEs, anesthesia time, and recovery time. A meta-analysis was performed to calculate risk ratios (RR), weighted mean difference (WMD), and 95 % confidence intervals (CI) by using random effects models. Results: In total, 5 RCTs comprising 402 patients were included. Regarding major PRAEs, laryngospasm (RR: 0.43, 95 % CI: 0.12 to 1.47; p = 0.18), bronchospasm, and aspiration all demonstrated no difference between the laryngeal and endotracheal groups. Desaturation exhibited a trend, but this trend was not sufficiently supported with statistical evidence (p = 0.09). For minor PRAEs, fewer patients experienced incidence of cough after laryngeal mask use (RR: 0.27, 95 % CI: 0.11 to 0.67; p = 0.005). Other PRAE, namely hoarseness (p = 0.06), sore throat (RR: 1.88, 95 % CI: 0.76 to 4.66; p = 0.18), and stridor, did not differ between the 2 groups. Additionally, both anesthesia time (WMD: -6.88 min, 95 % CI: -11.88 to -1.89; p < 0.00001) and recovery time (WMD: -4.85 min, 95 % CI: -6.51 to -3.19; p < 0.00001) were shortened in the LMA group. Conclusion: LMA used in pediatric laparoscopic inguinal hernia repair demonstrated no greater safety risks than endotracheal tube intubation did. Thus, anesthesiologists may shift from conventional endotracheal tube use to LMA use. Moreover, anesthesia and recovery times were shortened in the LMA group, which resulted in more efficient use of the operating room. Because of these benefits, LMA could be an appropriate option for pediatric patients undergoing laparoscopic inguinal hernia repair. Level of evidence: Treatment Study, LEVEL III.
MeSH term(s)	Child ; Humans ; Laryngeal Masks/adverse effects ; Laryngismus/epidemiology ; Laryngismus/etiology ; Bronchial Spasm/complications ; Hernia, Inguinal/complications ; Intubation, Intratracheal/adverse effects ; Respiration Disorders/etiology ; Laparoscopy/adverse effects
Language	English
Publishing date	2023-12-08
Publishing country	United States
Document type	Meta-Analysis ; Systematic Review ; Journal Article
ZDB-ID	80165-3
ISSN	1531-5037 ; 0022-3468
ISSN (online)	1531-5037
ISSN	0022-3468
DOI	10.1016/j.jpedsurg.2023.11.024
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Article ; Online: Preclinical Repurposing of Sitagliptin as a Drug Candidate for Colorectal Cancer by Targeting CD24 / CTNNB1 / SOX4 -Centered Signaling Hub

Jing-Wen Shih / Alexander T. H. Wu / Ntlotlang Mokgautsi / Po-Li Wei / Yan-Jiun Huang

International Journal of Molecular Sciences, Vol 25, Iss 1, p

2024 Volume 609

Abstract	Despite significant advances in treatment modalities, colorectal cancer (CRC) remains a poorly understood and highly lethal malignancy worldwide. Cancer stem cells (CSCs) and the tumor microenvironment (TME) have been shown to play critical roles in initiating and promoting CRC progression, metastasis, and treatment resistance. Therefore, a better understanding of the underlying mechanisms contributing to the generation and maintenance of CSCs is crucial to developing CSC-specific therapeutics and improving the current standard of care for CRC patients. To this end, we used a bioinformatics approach to identify increased CD24 / SOX4 expression in CRC samples associated with poor prognosis. We also discovered a novel population of tumor-infiltrating CD24 + cancer-associated fibroblasts (CAFs), suggesting that the CD24 / SOX4 -centered signaling hub could be a potential therapeutic target. Pathway networking analysis revealed a connection between the CD24 / SOX4 -centered signaling, β-catenin , and DPP4 . Emerging evidence indicates that DPP4 plays a role in CRC initiation and progression, implicating its involvement in generating CSCs. Based on these bioinformatics data, we investigated whether sitagliptin, a DPP4 inhibitor and diabetic drug, could be repurposed to inhibit colon CSCs. Using a molecular docking approach, we demonstrated that sitagliptin targeted CD24 / SOX4 -centered signaling molecules with high affinity. In vitro experimental data showed that sitagliptin treatment suppressed CRC tumorigenic properties and worked in synergy with 5FU and this study thus provided preclinical evidence to support the alternative use of sitagliptin for treating CRC.
Keywords	colorectal cancer (CRC) ; cancer stem cells (CSCs) ; cancer-associated fibroblasts (CAFs) ; sitagliptin ; CSC inhibitor ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	004
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparison of robotic reduced-port and laparoscopic approaches for left-sided colorectal cancer surgery.

Wei, Po-Li / Huang, Yan-Jiun / Wang, Weu / Huang, Yu-Min

Asian journal of surgery

2022 Volume 46, Issue 2, Page(s) 698–704

Abstract: Background/objective: The reduced-port approach can overcome the limitations of single-incision laparoscopic surgery while maintaining its advantages. Here, we compared the effects of robotic reduced-port surgery and conventional laparoscopic approaches ...

Abstract	Background/objective: The reduced-port approach can overcome the limitations of single-incision laparoscopic surgery while maintaining its advantages. Here, we compared the effects of robotic reduced-port surgery and conventional laparoscopic approaches for left-sided colorectal cancer. Methods: Between January 2015 and December 2016, the clinicopathological characteristics and treatment outcomes of 17 patients undergoing robotic reduced-port surgery and 49 patients undergoing laparoscopic surgery for left-sided colorectal cancer were compared. Results: The two groups were comparable in almost all outcome measures except for the distal resection margin, which was significantly longer in the laparoscopic group (P < 0.001). The between-group differences in reoperation, incisional hernia development, and overall and progression-free survival were nonsignificant; however, the total hospital cost was significantly higher in the robotic group than in the laparoscopic group (US$13779.6 ± US$3114.8 vs. US$8556.3 ± US$2056.7, P < 0.001). Conclusion: Robotic reduced-port surgery for left-sided colorectal cancer is safe and effective but more expensive with no additional benefit compared with the conventional laparoscopic approach. This observation warrants further evaluation.
MeSH term(s)	Humans ; Robotic Surgical Procedures/adverse effects ; Length of Stay ; Digestive System Surgical Procedures ; Laparoscopy/adverse effects ; Colorectal Neoplasms/surgery ; Retrospective Studies
Language	English
Publishing date	2022-06-29
Publishing country	China
Document type	Journal Article
ZDB-ID	1068461-x
ISSN	0219-3108 ; 1015-9584
ISSN (online)	0219-3108
ISSN	1015-9584
DOI	10.1016/j.asjsur.2022.06.079
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Article ; Online: Author Correction: Comparison of clinical outcomes between laparoscopic and open surgery for left-sided colon cancer: a nationwide population-based study.

Huang, Yu-Min / Lee, Yuan-Wen / Huang, Yan-Jiun / Wei, Po-Li

Scientific reports

2021 Volume 11, Issue 1, Page(s) 9084

Language	English
Publishing date	2021-04-21
Publishing country	England
Document type	Published Erratum
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-88762-y
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Article ; Online: Corrigendum to "Early versus delayed surgery after short-course radiotherapy for rectal cancer: A network meta-analysis of randomized controlled trials" [Asian J Surg S1015-9584 (19) (2019) 30824-3].

Huang, Yan-Jiun / Tai, Chi / Kang, Yi-No / Wei, Po-Li

Asian journal of surgery

2021 Volume 44, Issue 2, Page(s) 526

Language	English
Publishing date	2021-01-19
Publishing country	China
Document type	Published Erratum
ZDB-ID	1068461-x
ISSN	0219-3108 ; 1015-9584
ISSN (online)	0219-3108
ISSN	1015-9584
DOI	10.1016/j.asjsur.2020.12.008
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Article ; Online: Multiomics Study of a Novel Naturally Derived Small Molecule, NSC772864, as a Potential Inhibitor of Proto-Oncogenes Regulating Cell Cycle Progression in Colorectal Cancer

Ntlotlang Mokgautsi / Yu-Cheng Kuo / Chien-Hsin Chen / Yan-Jiun Huang / Alexander T. H. Wu / Hsu-Shan Huang

Cells, Vol 12, Iss 340, p

2023 Volume 340

Abstract: Colorectal cancer (CRC) is one of the most prevalent malignant tumors, and it contributes to high numbers of deaths globally. Although advances in understanding CRC molecular mechanisms have shed significant light on its pathogenicity, current treatment ... ...

Abstract	Colorectal cancer (CRC) is one of the most prevalent malignant tumors, and it contributes to high numbers of deaths globally. Although advances in understanding CRC molecular mechanisms have shed significant light on its pathogenicity, current treatment options, including combined chemotherapy and molecular-targeted agents, are still limited due to resistance, with almost 25% of patients developing distant metastasis. Therefore, identifying novel biomarkers for early diagnosis is crucial, as they will also influence strategies for new targeted therapies. The proto-oncogene, c-Met , a tyrosine kinase that promotes cell proliferation, motility, and invasion; c-MYC , a transcription factor associated with the modulation of the cell cycle, proliferation, apoptosis; and cyclin D1 ( CCND1 ), an essential regulatory protein in the cell cycle, all play crucial roles in cancer progression. In the present study, we explored computational simulations through bioinformatics analysis and identified the overexpression of c-Met/GSK3β/MYC/CCND1 oncogenic signatures that were associated with cancer progression, drug resistance, metastasis, and poor clinical outcomes in CRC. We further demonstrated the anticancer activities of our newly synthesized quinoline-derived compound, NSC772864, against panels of the National Cancer Institute’s human CRC cell lines. The compound exhibited cytotoxic activities against various CRC cell lines. Using target prediction tools, we found that c-Met/GSK3β/MYC/CCND1 were target genes for the NSC772864 compound. Subsequently, we performed in silico molecular docking to investigate protein–ligand interactions and discovered that NSC772864 exhibited higher binding affinities with these oncogenes compared to FDA-approved drugs. These findings strongly suggest that NSC772864 is a novel and potential antiCRC agent.
Keywords	colorectal cancer ; drug resistance ; protein–ligand interaction ; molecular docking simulation ; small molecule ; Biology (General) ; QH301-705.5
Subject code	500
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Preclinical Evaluation of a Novel Small Molecule LCC-21 to Suppress Colorectal Cancer Malignancy by Inhibiting Angiogenic and Metastatic Signatures.

Mokgautsi, Ntlotlang / Kuo, Yu-Cheng / Huang, Yan-Jiun / Chen, Chien-Hsin / Mukhopadhyay, Debabrata / Wu, Alexander T H / Huang, Hsu-Shan

Cells

2023 Volume 12, Issue 2

Abstract: Colorectal cancer (CRC) is one of the most common cancers, and it frequently metastasizes to the liver and lymph nodes. Despite major advances in treatment modalities, CRC remains a poorly characterized biological malignancy, with high reported cases of ... ...

Abstract	Colorectal cancer (CRC) is one of the most common cancers, and it frequently metastasizes to the liver and lymph nodes. Despite major advances in treatment modalities, CRC remains a poorly characterized biological malignancy, with high reported cases of deaths globally. Moreover, cancer stem cells (CSCs) and their microenvironment have been widely shown to promote colon cancer development, progression, and metastasis. Therefore, an understanding of the underlying mechanisms that contribute to the maintenance of CSCs and their markers in CRC is crucial in efforts to treat cancer metastasis and develop specific therapeutic targets for augmenting current standard treatments. Herein, we applied computational simulations using bioinformatics to identify potential theranostic markers for CRC. We identified the overexpression of vascular endothelial growth factor-α (
MeSH term(s)	Humans ; Cell Line, Tumor ; Colorectal Neoplasms/pathology ; Vascular Endothelial Growth Factor A/metabolism ; Molecular Docking Simulation ; Tumor Microenvironment
Chemical Substances	Vascular Endothelial Growth Factor A
Language	English
Publishing date	2023-01-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12020266
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Article ; Online: Multiomics Study of a Novel Naturally Derived Small Molecule, NSC772864, as a Potential Inhibitor of Proto-Oncogenes Regulating Cell Cycle Progression in Colorectal Cancer.

Mokgautsi, Ntlotlang / Kuo, Yu-Cheng / Chen, Chien-Hsin / Huang, Yan-Jiun / Wu, Alexander T H / Huang, Hsu-Shan

Cells

2023 Volume 12, Issue 2

Abstract	Colorectal cancer (CRC) is one of the most prevalent malignant tumors, and it contributes to high numbers of deaths globally. Although advances in understanding CRC molecular mechanisms have shed significant light on its pathogenicity, current treatment options, including combined chemotherapy and molecular-targeted agents, are still limited due to resistance, with almost 25% of patients developing distant metastasis. Therefore, identifying novel biomarkers for early diagnosis is crucial, as they will also influence strategies for new targeted therapies. The proto-oncogene,
MeSH term(s)	Humans ; Glycogen Synthase Kinase 3 beta/genetics ; Multiomics ; Molecular Docking Simulation ; Cell Line, Tumor ; Cell Cycle/genetics ; Proto-Oncogenes ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism
Chemical Substances	Glycogen Synthase Kinase 3 beta (EC 2.7.11.1)
Language	English
Publishing date	2023-01-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12020340
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Article ; Online: Author Correction

Yu-Min Huang / Yuan-Wen Lee / Yan-Jiun Huang / Po-Li Wei

Scientific Reports, Vol 11, Iss 1, Pp 1-

Comparison of clinical outcomes between laparoscopic and open surgery for left-sided colon cancer: a nationwide population-based study

2021 Volume 1

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

Abstract	An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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