Review
Immunology
Sunghark Kwon
Summary: JAKs are important enzymes in the JAK-STAT signaling pathway, and dysfunctional JAKs can lead to severe immune system-related diseases. Various JAK inhibitors have been developed to block abnormal JAK-STAT signaling, but drug selectivity and resistance to these inhibitors remain challenges. This review discusses the role and structure of JAKs, as well as strategies for disrupting JAK dimerization to develop novel inhibitors.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sarah M. M. AL-Qabbaa, Samaher I. I. Qaboli, Tahani K. K. Alshammari, Maha A. A. Alamin, Haya M. M. Alrajeh, Lama A. A. Almuthnabi, Rana R. R. Alotaibi, Asma S. S. Alonazi, Anfal F. F. Bin Dayel, Nawal M. M. Alrasheed, Nouf M. M. Alrasheed
Summary: This study examined the therapeutic effects of sitagliptin, a dipeptidyl peptidase inhibitor, on diabetic nephropathy (DN). The results showed that sitagliptin can reduce inflammation and improve DN by inhibiting PTP1B and modulating the JAK/STAT signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Atsunori Kaneshige, Longchuan Bai, Mi Wang, Donna McEachern, Jennifer L. Meagher, Renqi Xu, Paul D. Kirchhoff, Bo Wen, Duxin Sun, Jeanne A. Stuckey, Shaomeng Wang
Summary: We discovered a potent and selective STAT5 degrader with strong antitumor activity in vivo. Using PROTAC technology, we transformed small-molecule ligands into selective STAT5 degraders, with AK-2292 as the best compound. AK-2292 effectively induced degradation of STAT5 proteins in AML cell lines and showed strong antitumor activity in mice.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Ge Jin, Lintao Wang, Jun Ma
Summary: Cardiac hypertrophy is a compensatory response to chronic pressure overload, and excessive angiotensin II plays a significant role in inducing cardiac hypertrophy. Previous studies have shown that STAT5, a member of the STATs family, is closely linked to non-tumor diseases, but its specific role in hypertrophy progression remains unclear. In this study, STAT5-IN-1, a STAT5 inhibitor, was administered to mice and H9c2s cells were used as cell models to investigate the effects of STAT5-IN-1 on cardiac hypertrophy induced by angiotensin II. The findings demonstrated that STAT5 inhibitor substantially decreased cardiac hypertrophy by reducing inflammation.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Review
Dermatology
Stephanie Chapman, Michael Kwa, Linda Stein Gold, Henry W. Lim
Summary: The JAK-STAT pathway is important in inflammatory dermatoses, and JAK inhibitors have shown efficacy in treating various dermatologic conditions.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Jingjing Wang, Zixuan Huang, Li Ji, Cheng Chen, Quan Wan, Yu Xin, Zhening Pu, Koukou Li, Jiantong Jiao, Ying Yin, Yaling Hu, Lingli Gong, Rui Zhang, Xusheng Yang, Xiangming Fang, Mei Wang, Bo Zhang, Junfei Shao, Jian Zou
Summary: The study identified SH2 domain-containing adapter protein F (SHF) as a tumor suppressor in glioblastoma Multiforme (GBM), which negatively regulates STAT3 activity. Additionally, peptide C16 derived from SHF shows remarkable growth inhibition in GBM cells.
Review
Cell Biology
Lena Puigdevall, Camille Michiels, Clara Stewardson, Laure Dumoutier
Summary: A subset of cytokines triggers the JAK-STAT pathway to exert various functions such as inflammation and immune responses. There are alternative modes of STAT activation, including association between the tyrosine-free region of cytokine receptors and STATs, and direct interaction between JAK and STAT proteins. These noncanonical mechanisms by cytokine receptors suggest their importance and are discussed in this review.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Atsunori Kaneshige, Longchuan Bai, Mi Wang, Donna McEachern, Jennifer L. Meagher, Renqi Xu, Yu Wang, Wei Jiang, Hoda Metwally, Paul D. Kirchhoff, Lijie Zhao, Hui Jiang, Meilin Wang, Bo Wen, Duxin Sun, Jeanne A. Stuckey, Shaomeng Wang
Summary: AK-2292 is a potent and selective small-molecule degrader of both STAT5A and STAT5B isoforms. It selectively inhibits STAT5 activity and induces degradation of STAT5A/B proteins without affecting other STAT proteins and numerous non-STAT proteins. AK-2292 effectively induces STAT5 depletion in both normal tissues and CML xenograft tissues, leading to tumor regression in CML xenograft mouse models. It is not only a powerful research tool to study STAT5 biology and therapeutic potential, but also a promising lead compound for STAT5-targeted therapy development.
NATURE CHEMICAL BIOLOGY
(2023)
Review
Dermatology
Stephanie Chapman, Linda Stein Gold, Henry W. Lim
Summary: The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is important in the development of inflammatory skin conditions, and JAK inhibitors have shown efficacy in treating various dermatologic diseases. This review focuses on JAK inhibitors being investigated for the treatment of alopecia areata, vitiligo, sarcoidosis, necrobiosis lipoidica, granuloma annulare, and systemic lupus erythematosus, with a discussion on safety and the implications of JAK inhibitors during the COVID-19 pandemic.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2022)
Article
Infectious Diseases
Zhao-Ming Chen, Xiao-Yun Yang, Zheng-Tu Li, Wei-Jie Guan, Ye Qiu, Shao-Qiang Li, Yang-Qing Zhan, Zi-Ying Lei, Jing Liu, Jian-Quan Zhang, Zhong-Fang Wang, Feng Ye
Summary: The presence of anti-IFN-gamma autoantibodies inhibits immune responses of CD4(+) Th1 and CD8(+) T cells, and increases the release of IL-10.
INFECTION AND DRUG RESISTANCE
(2022)
Article
Medicine, Research & Experimental
Jiameng Lu, Xiaoqing Ji, Lixia Wang, Fei Sun, Chuanjun Huang, Haiying Peng, Yunxiu Jiang, Zihan Guo, Xinyi Liu, Yanbo Ji, Degan Lu
Summary: This study found that prophylactic administration of IL-27 can improve asthma by restoring the STAT1 and STAT3 pathways, alleviating the Th2 inflammatory environment in the lungs.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2022)
Article
Obstetrics & Gynecology
Sachiko Matsuzaki, Jean-Luc Pouly, Michel Canis
Summary: Persistent activation of signal transducer and activator of transcription 3 (STAT3) via interleukin-6 (IL-6) trans-signaling is involved in fibrosis of endometriosis.
HUMAN REPRODUCTION
(2022)
Article
Chemistry, Medicinal
Peng He, Ying Miao, Yue Sun, Aiwu Bian, Wangrui Jin, Jiangnan Ye, Huang Chen, Jia He, Yangrui Peng, Haijun Gu, Mingyao Liu, Zhengfang Yi, Yihua Chen
Summary: This study describes the design, synthesis, and structure-activity relationship studies of triaromatic heterocyclic derivatives as potent dual phosphorylation STAT3 inhibitors. The best compound 3h (HP590) was discovered with high inhibitory activity against p-Tyr(705) and p-Ser(727), resulting in the growth inhibition of gastric cancer both in vitro and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Yuhan Su, Tianyu Tao, Xiuxing Liu, Wenru Su
Summary: This review summarizes the diverse roles of the JAK-STAT signaling pathway in ocular homeostasis and non-infectious uveitis (NIU) pathology, and discusses the safety and efficacy of JAK inhibitors for treating NIU and potential approaches for treatment optimization.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Plant Sciences
Xing Zhang, Jie Su, Jiacheng Lin, Lujiong Liu, Jiamin Wu, Wenli Yuan, Yibao Zhang, Qi Chen, Zi jian Su, Guihua Xu, Meng Sun, Yile Zhang, Xuan Chen, Wei Zhang
Summary: The Chinese herbal prescription Fu-Zheng-Tong-Luo (FZTL) formula is used to treat idiopathic pulmonary fibrosis (IPF). This study found that FZTL can alleviate IPF injury and inhibit lung fibroblast activation by regulating the JAK2/STAT3 signaling pathway, making it a potential complementary therapy for IPF.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Oncology
Hyo-Joon Yang, Su Youn Nam, Byung-Hoon Min, Ji Yong Ahn, Jae-Young Jang, Jung Kim, Jie-Hyun Kim, Wan-Sik Lee, Bong Eun Lee, Moon Kyung Joo, Jae Myung Park, Woon Geon Shin, Hang Lak Lee, Tae-Geun Gweon, Moo In Park, Jeongmin Choi, Chung Hyun Tae, Young-Il Kim, Il Ju Choi
Summary: This study found that for undifferentiated-type early gastric cancer patients with tumor size > 2 cm as the only non-curative factor undergoing endoscopic resection, the risk of lymph node or distant metastasis was as low as 1%, and there was no significant difference in overall survival rates between the observation group and the surgery group.
Article
Oncology
Ji Yong Ahn, Young- Kim, Woon Geon Shin, Hyo-Joon Yang, Su Youn Nam, Byung-Hoon Min, Jae-Young Jang, Joo Hyun Lim, Jie-Hyun Kim, Wan Sik Lee, Bong Eun Lee, Moon Kyung Joo, Jae Myung Park, Hang Lak Lee, Tae- Geun Gweon, Moo In Park, Jeongmin Choi, Chung Hyun Tae, Young-Woo Kim, Boram Park, I. I. Ju Choi
Summary: Comparing outcomes of ESD and surgery for UD EGC within expanded indication, the study found that ESD shows comparable results to surgery, but appropriate patient selection is necessary due to the risk of lymph node metastasis.
Article
Gastroenterology & Hepatology
Gwang Ha Kim, Hang Lak Lee, Moon Kyung Joo, Hong Jun Park, Sung Woo Jung, Ok-Jae Lee, Hyungkil Kim, Hoon Jai Chun, Soo Teik Lee, Ji Won Kim, Han Ho Jeon, Il-Kwun Chung, Hyun-Soo Kim, Dong Ho Lee, Kyoung-Oh Kim, Yun Jeong Lim, Seun-Ja Park, Soo-Jeong Cho, Byung-Wook Kim, Kwang Hyun Ko, Seong Woo Jeon, Jae Gyu Kim, In-Kyung Sung, Tae Nyeun Kim, Jae Kyu Sung, Jong-Jae Park
Summary: The new formulation AD-203 of rebamipide 150 mg twice daily was found to be non-inferior to the standard treatment of rebamipide 100 mg thrice daily in treating erosive gastritis. Both formulations showed similar efficacy in improving erosion and other symptoms.
Article
Gastroenterology & Hepatology
Hyo-Joon Yang, Wan-Sik Lee, Bong Eun Lee, Ji Yong Ahn, Jae-Young Jang, Joo Hyun Lim, Su Youn Nam, Jie-Hyun Kim, Byung-Hoon Min, Moon Kyung Joo, Jae Myung Park, Woon Geon Shin, Hang Lak Lee, Tae-Geun Gweon, Moo In Park, Jeongmin Choi, Chung Hyun Tae, Young-Il Kim, Il Ju Choi
Summary: The study examined the long-term outcomes of undifferentiated-type early gastric cancer with positive horizontal margins after endoscopic resection and found favorable results and a very low risk of lymph node metastasis. Nonsurgical management may be a viable alternative for older patients or those with chronic illnesses.
Article
Surgery
Jie-Hyun Kim, Young- Kim, Ji Yong Ahn, Woon Geon Shin, Hyo-Joon Yang, Su Youn Nam, Byung-Hoon Min, Jae-Young Jang, Joo Hyun Lim, Wan Sik Lee, Bong Eun Lee, Moon Kyung Joo, Jae Myung Park, Hang Lak Lee, Tae-Geun Gweon, Moo In Park, Jeongmin Choi, Chung Hyun Tae, Young-Woo Kim, Boram Park, I. I. Ju Choi
Summary: The study compared the long-term outcomes of ESD followed by additional surgery and initial surgery in UD EGC patients. The surgery group had significantly longer OS than the ESD + OP group, especially in PDA patients. However, the ESD-only group had a shorter RFS compared to the ESD + OP and surgery groups. The ESD + OP group showed comparable RFS to the surgery group.
SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES
(2022)
Article
Surgery
Hyo-Joon Yang, Moon Kyung Joo, Jae Myung Park, Ji Yong Ahn, Jae-Young Jang, Joo Hyun Lim, Su Youn Nam, Jie-Hyun Kim, Byung-Hoon Min, Wan-Sik Lee, Bong Eun Lee, Woon Geon Shin, Hang Lak Lee, Tae-Geun Gweon, Moo In Park, Jeongmin Choi, Chung Hyun Tae, Young-Il Kim, Keun Won Ryu, Il Ju Choi
Summary: The study developed a six-score prediction model to help predict the likelihood of curative ESD for undifferentiated-type EGC, based on factors such as tumor size and location. This model showed good performance in both the development and validation cohorts, providing valuable information for treatment decision-making.
SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES
(2022)
Article
Genetics & Heredity
Namjoo Kim, Jeong-An Gim, Beom Jae Lee, Byung il Choi, Seung Bin Park, Hee Sook Yoon, Sang Hee Kang, Seung Han Kim, Moon Kyung Joo, Jong-Jae Park, Chungyeul Kim, Han-Kyeom Kim
Summary: By comparing gene expression profiles using RNA sequencing in high-risk adenoma, advanced colorectal cancer patients, and normal controls, differential expression of mRNAs like CD44 and ANXA3 were identified in high-risk adenoma, indicating their potential as markers for high-risk colorectal adenomas.
FUNCTIONAL & INTEGRATIVE GENOMICS
(2021)
Article
Health Care Sciences & Services
Moon Kyung Joo, Ji Won Yoo, Zahra Mojtahedi, Pearl Kim, Jinwook Hwang, Ja Seol Koo, Hee-Taik Kang, Jay J. Shen
Summary: This study analyzed the hospitalization and palliative care consultation trends of gastric cancer patients in the US from 2009 to 2018. It found a decrease in hospitalizations, but an increase in the utilization of palliative care and procedures. The study suggests that palliative care consultation can help reduce medical resource utilization and hospital costs for patients with gastric cancer.
BMC HEALTH SERVICES RESEARCH
(2022)
Article
Multidisciplinary Sciences
Namjoo Kim, Jeong-An Gim, Beom Jae Lee, Byung Il Choi, Hee Sook Yoon, Seung Han Kim, Moon Kyung Joo, Jong-Jae Park, Chungyeul Kim
Summary: Various biomarkers related to colorectal cancer (CRC) have been identified using omics-based approaches. In this study, the gut microbiome and host gene expression were analyzed to identify potential biomarkers for the initiation and progression of CRC. The results revealed specific bacterial species and genes that are associated with CRC, suggesting their potential as diagnostic markers and therapeutic targets.
SCIENTIFIC REPORTS
(2022)
Article
Medicine, General & Internal
Won Shik Kim, Hayeon Kim, Moon Kyung Joo, Byung Il Choi, Ah Young Yoo, Jong-Jae Park, Beom Jae Lee, Seung Han Kim, Hoon Jai Chun
Summary: This study investigated the differential expression of CLDN-4 in early gastric cancer (EGC) and found a significant association between high CLDN-4 expression and intestinal-type EGC, open-type atrophic change, and the presence of synchronous tumors. These findings suggest that CLDN-4 may serve as an auxiliary tool for screening synchronous tumors in patients with EGC.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Seong Min Kim, Jong-Jae Park, Moon Kyung Joo, Beom Jae Lee, Hoon Jai Chun, Sang Woo Lee
Summary: This study evaluated the effectiveness and long-term outcomes of endoscopic submucosal dissection (ESD) for gastric neoplasms involving the pyloric channel (GNPC) and introduced a novel technique for the resection of GNPC. The retrograde resection method may offer a simpler procedure, but risk factors need to be considered.
Article
Oncology
Seung Han Kim, Moon Kyung Joo, Ah-Young Yoo, Seong Min Kim, Won Shik Kim, Beom Jae Lee, Jong Jae Park, Hoon Jai Chun, Sang Woo Lee
Summary: This study compared the long-term efficacy and safety of endoscopic submucosal dissection (ESD) in patients with gastric cancer (GC), with and without liver cirrhosis (LC). The results demonstrated that ESD was an effective and safe treatment method for early GC in patients with LC, although further studies are needed to assess recurrence.
Review
Gastroenterology & Hepatology
Chung Hyun Tae, Ju Yup Lee, Moon Kyung Joo, Chan Hyuk Park, Eun Jeong Gong, Cheol Min Shin, Hyun Lim, Hyuk Soon Choi, Miyoung Choi, Sang Hoon Kim, Chul-Hyun Lim, Jeong-Sik Byeon, Ki-Nam Shim, Geun Am Song, Moon Sung Lee, Jong-Jae Park, Oh Young Lee
Summary: With an aging population, the use of nasogastric tubes for enteral nutrition in patients with swallowing difficulties is increasing. However, long-term use of nasogastric tubes leads to complications and reduced quality of life. Percutaneous endoscopic gastrostomy (PEG) is an alternative method that involves the percutaneous placement of a tube into the stomach for long-term enteral nutrition. This paper presents the first Korean clinical guideline for PEG, providing evidence-based recommendations for indications, timing, methods, and management of PEG.
CLINICAL ENDOSCOPY
(2023)
Review
Gastroenterology & Hepatology
Chung Hyun Tae, Ju Yup Lee, Moon Kyung Joo, Chan Hyuk Park, Eun Jeong Gong, Cheol Min Shin, Hyun Lim, Hyuk Soon Choi, Miyoung Choi, Sang Hoon Kim, Chul-Hyun Lim, Jeong-Sik Byeon, Ki-Nam Shim, Geun Am Song, Moon Sung Lee, Jong-Jae Park, Oh Young Lee
Summary: With the increasing number of patients experiencing difficulty in swallowing due to medical conditions as a result of an aging population, percutaneous endoscopic gastrostomy (PEG) is being explored as an alternative to nasogastric tubes for long-term enteral nutrition. This paper presents the first clinical guideline for PEG in Korea, developed jointly by the Korean College of Helicobacter and Upper Gastrointestinal Research and led by the Korean Society of Gastrointestinal Endoscopy.
KOREAN JOURNAL OF GASTROENTEROLOGY
(2023)
Article
Gastroenterology & Hepatology
Ah Young Yoo, Beom Jae Lee, Won Shik Kim, Seong Min Kim, Seung Han Kim, Moon Kyung Joo, Hyo Jung Kim, Jong-Jae Park
Summary: This study investigated the clinicopathological features of small bowel malignant tumors diagnosed by VCE and DBE, revealing different clinical characteristics among small bowel malignancies and highlighting the importance of further research in this area.
CLINICAL ENDOSCOPY
(2021)