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Yi AQ, Xie GH. Pancreatic neuroendocrine neoplasms coexisting with biliary intraductal papillary mucinous neoplasm: A case report and review of literature. World J Gastrointest Oncol 2025; 17:100497. [DOI: 10.4251/wjgo.v17.i4.100497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 12/06/2024] [Accepted: 02/25/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND Pancreatic neuroendocrine neoplasms (pNENs) are rare, heterogeneous tumors accounting for 1%-2% of pancreatic tumors, with significant malignant potential. Intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) is a rare precancerous lesion in the bile duct system, with potential for malignancy. The combination of pNENs and IPMN-B is exceptionally rare and often leads to misdiagnosis. This study aims to report a rare case of pNENs combined with IPMN-B treated at Yanbian University Hospital to improve understanding and management of this unusual tumor combination.
CASE SUMMARY We retrospectively analyzed a case from Yanbian University Hospital. We reviewed clinical records, imaging findings, endoscopic retrograde cholangiopancreatography, surgical exploration, and histopathological examination. The patient was diagnosed with pNENs and IPMN-B. Surgical treatment was performed, with follow-up showing effective management and no significant recurrence.
CONCLUSION This case represents the first report of pNENs combined with IPMN-B. It highlights the need for thorough diagnostic evaluation to prevent misdiagnosis and improve treatment strategies.
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Affiliation(s)
- An-Qi Yi
- Department of Hepatobiliary Surgery, Yanbian University Affiliated Hospital, Yanji 133099, Jilin Province, China
| | - Guang-Hua Xie
- Department of Hepatobiliary Surgery, Yanbian University Affiliated Hospital, Yanji 133099, Jilin Province, China
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2
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Wang Y, Song J, Zheng S, Wang S. Advancements in understanding the molecular mechanisms and clinical implications of Von Hippel-Lindau syndrome: A comprehensive review. Transl Oncol 2025; 51:102193. [PMID: 39571489 PMCID: PMC11617254 DOI: 10.1016/j.tranon.2024.102193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Revised: 05/06/2024] [Accepted: 10/30/2024] [Indexed: 12/08/2024] Open
Abstract
Von Hippel-Lindau Syndrome (VHL) is a rare genetic disorder characterized by tumors in multiple organs, including the kidneys, pancreas, and central nervous system. This comprehensive review discusses the genetic basis and clinical manifestations of VHL, as well as recent advancements in understanding the molecular mechanisms that lead to tumor formation. The authors highlight the role of hypoxia-inducible factors and the ubiquitin-proteasome system in VHL-associated cancer development .The review also discusses the potential clinical implications of these findings, such as the development of targeted therapies for VHL-associated cancers. However, the authors note the challenges associated with developing effective treatments for this complex disease, including limited patient availability for clinical trials due to its rarity .Overall, this review provides valuable insights into our current understanding of VHL and offers important avenues for future research aimed at improving the diagnosis, treatment, and management of VHL patients. By illuminating the molecular underpinnings of VHL-associated cancers, this work may ultimately help to develop more effective treatments and improve outcomes for patients with this challenging disease.
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Affiliation(s)
- Yaochun Wang
- Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, PR China
| | - Jingzhuo Song
- Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, PR China
| | - Shuxing Zheng
- Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, PR China
| | - Shuhong Wang
- Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, PR China.
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Liang SY, Zhang TY, Chen ZC, Du W, Chen YC. Functional-Group-Directed Regiodivergent (3 + 2) Annulations of Electronically Distinct 1,3-Dienes and 2-Formyl Arylboronic Acids. Org Lett 2024; 26:1483-1488. [PMID: 38345825 DOI: 10.1021/acs.orglett.4c00160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2024]
Abstract
Presented herein is a palladium-catalyzed asymmetric (3 + 2) annulation reaction between 1,3-dienes and 2-formylarylboronic acids, proceeding in a cascade vinylogous addition and Suzuki coupling process. Both electron-neutral and electron-deficient 1,3-dienes are compatible under similar catalytic conditions, and distinct regioselectivity is observed via functional-group control of 1,3-diene substrates. A collection of 1-indanols with dense functionalities is constructed stereoselectively.
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Affiliation(s)
- Shu-Yuan Liang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Tian-Ying Zhang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Zhi-Chao Chen
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Wei Du
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Ying-Chun Chen
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
- Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu 610041, China
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Badve SS, Gökmen-Polar Y. Targeting the Tumor-Tumor Microenvironment Crosstalk. Expert Opin Ther Targets 2023; 27:447-457. [PMID: 37395003 DOI: 10.1080/14728222.2023.2230362] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Accepted: 06/23/2023] [Indexed: 07/04/2023]
Abstract
INTRODUCTION Cancer development and progression is a complex process influenced by co-evolution of the cancer cells and their microenvironment. However, traditional anti-cancer therapy is mostly targeted toward cancer cells. To improve the efficacy of cancer drugs, the complex interactions between the tumor (T) and the tumor microenvironment (TME) should be considered while developing therapeutics. AREAS COVERED The present review article will discuss the components of T-TME as well as the potential to co-target these two distinct elements. We document that these approaches have resulted in success in preventing tumor progression and metastasis, albeit in animal models in some cases. Lastly, it is important to consider the tissue context and tumor type as these could significantly modify the role of these molecules/pathways and hence the overall likelihood of response. Furthermore, we discuss the potential strategies to target the components of tumor microenvironment in anti-cancer therapy. PubMed and ClinicalTrials.gov was searched through May 2023. EXPERT OPINION The tumor-tumor microenvironment cross talk and heterogeneity are major mechanisms conferring resistance to standard of care. Better understanding of the tissue specific T-TME interactions and dual targeting has the promise of improving cancer control and clinical outcomes.
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Affiliation(s)
- Sunil S Badve
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA
| | - Yesim Gökmen-Polar
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA
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Cao G, Chang Y, Yang G, Jiang Y, Han K. A novel risk score model based on four angiogenesis long non-coding RNAs for prognosis evaluation of pancreatic adenocarcinoma. Aging (Albany NY) 2022; 14:9090-9102. [PMID: 36384673 PMCID: PMC9740371 DOI: 10.18632/aging.204387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 11/07/2022] [Indexed: 11/17/2022]
Abstract
BACKGROUND Long non-coding RNAs (lncRNAs) have been reported to play significant roles in tumour angiogenesis which prominently facilitates pancreatic adenocarcinoma (PAAD) progression. METHODS The clinical PAAD data were obtained from TCGA database and clinical specimens of 122 PAAD patients. The Molecular Signatures Database v4.0 was used to identify angiogenesis-related long non-coding RNAs (ARLNRs). Survival-related ARLNRs (sARLNRs) were further validated by univariate and multivariate COX regression analyses. The expressions of CASC8, AC015660.1, Z97832.2 and PAN3-AS1 in PAAD cell lines and tissues were examined by qPCR. The correlations between sARLNRs (CASC8 and AC015660.1) and clinicopathological characteristics of the 122 PAAD patients were analyzed by the chi-square test and Fisher's exact probability method. RESULTS 590 lncRNAs were identified as ARLNRs, of which four sARLNRs were further used to establish an angiogenesis-related risk score model (ARRS), by which patients in the low-risk group have better survival probabilities than those in the high-risk group. The expression levels of CASC8 and AC015660.1 were significantly higher in PAAD cell lines and tumor tissues especially in patients with advanced grades and T-stages, while Z97832.2 and PAN3-AS1 were inverse. In addition, the higher expression of CASC8 and AC015660.1 prominently associated with the larger tumour size, and the more advanced grade and T-stage. However, the relevance between the sARLNRs (CASC8 and AC015660.1) expression and lymph node metastasis status was not significant. CONCLUSIONS In the study, we illuminate the clinical significance, angiogenesis relevance and prognosis-predictive value of four sARLNRs for PAAD. The results build a bridge between sARLNRs and tumour vascularization, and also establish a reliable and accurate risk scoring model for PAAD antiangiogenic strategy.
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Affiliation(s)
- Guangbiao Cao
- Department of Hepatobiliary Surgery, Songshan General Hospital, Chongqing, China
| | - Yihang Chang
- Department of Hepatobiliary Surgery, Songshan General Hospital, Chongqing, China
| | - Guang Yang
- Department of Hepatobiliary Surgery, Songshan General Hospital, Chongqing, China
| | - Yong Jiang
- Department of Hepatobiliary Surgery, Songshan General Hospital, Chongqing, China
| | - Keqiang Han
- Department of Hepatobiliary Surgery, Songshan General Hospital, Chongqing, China
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Locatelli F, Minutolo R, De Nicola L, Del Vecchio L. Evolving Strategies in the Treatment of Anaemia in Chronic Kidney Disease: The HIF-Prolyl Hydroxylase Inhibitors. Drugs 2022; 82:1565-1589. [PMID: 36350500 PMCID: PMC9645314 DOI: 10.1007/s40265-022-01783-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/11/2022] [Indexed: 11/11/2022]
Abstract
Chronic kidney disease (CKD) affects approximately 10% of the worldwide population; anaemia is a frequent complication. Inadequate erythropoietin production and absolute or functional iron deficiency are the major causes. Accordingly, the current treatment is based on iron and erythropoiesis stimulating agents (ESAs). Available therapy has dramatically improved the management of anaemia and the quality of life. However, safety concerns were raised over ESA use, especially when aiming to reach near-to-normal haemoglobin levels with high doses. Moreover, many patients show hypo-responsiveness to ESA. Hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) inhibitors (HIF-PHIs) were developed for the oral treatment of anaemia in CKD to overcome these concerns. They simulate the body's exposure to moderate hypoxia, stimulating the production of endogenous erythropoietin. Some molecules are already approved for clinical use in some countries. Data from clinical trials showed non-inferiority in anaemia correction compared to ESA or superiority for placebo. Hypoxia-inducible factor-prolyl hydroxylase domain inhibitors may also have additional advantages in inflamed patients, improving iron utilisation and mobilisation and decreasing LDL-cholesterol. Overall, non-inferiority was also shown in major cardiovascular events, except for one molecule in the non-dialysis population. This was an unexpected finding, considering the lower erythropoietin levels reached using these drugs due to their peculiar mechanism of action. More data and longer follow-ups are necessary to better clarifying safety issues and further investigate the variety of pathways activated by HIF, which could have either positive or negative effects and could differentiate HIF-PHIs from ESAs.
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Affiliation(s)
- Francesco Locatelli
- Past Director of the Department of Nephrology and Dialysis, Alessandro Manzoni Hospital, via Fratelli Cairoli 60, 23900, Lecco, Italy.
| | - Roberto Minutolo
- Nephrology and Dialysis Unit, Department of Advanced Medical and Surgical Sciences, University L. Vanvitelli, Naples, Italy
| | - Luca De Nicola
- Nephrology and Dialysis Unit, Department of Advanced Medical and Surgical Sciences, University L. Vanvitelli, Naples, Italy
| | - Lucia Del Vecchio
- Department of Nephrology and Dialysis, Sant' Anna Hospital, ASST Lariana, Como, Italy
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Locatelli F, Del Vecchio L. Hypoxia-Inducible Factor-Prolyl Hydroxyl Domain Inhibitors: From Theoretical Superiority to Clinical Noninferiority Compared with Current ESAs? J Am Soc Nephrol 2022; 33:1966-1979. [PMID: 36041790 PMCID: PMC9678041 DOI: 10.1681/asn.2022040413] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Anemia is a common complication of chronic kidney disease; it is mainly treated with erythropoiesis-stimulating agents (ESAs) and iron. Experimental studies extensively investigated the mechanisms involved in the body's response to hypoxia and led to the discovery of the hypoxia-inducible factor (HIF) pathway and the enzymes regulating its function. HIF-prolyl-hydroxyl domain (PHD) inhibitors are a new class of oral drugs developed to treat anemia in chronic kidney disease. By inhibiting the function of PHD enzymes, they mimic the exposure to moderate hypoxia and stimulate the production of endogenous erythropoietin and very likely increase iron availability. Some data also suggest that their efficacy and, consequently, dose needs are less influenced by inflammation than ESAs. Overall, data from phases 2 and 3 clinical development showed efficacy in anemia correction and maintenance for all of the class molecules compared with placebo (superiority) or erythropoiesis-stimulating agents (noninferiority). Three molecules, roxadustat, vadadustat, and daprodustat, underwent extensive clinical investigation to assess their safety on hard cardiovascular end points, mortality, and special interest events (including cancer and thrombosis). Aside from vadadustat in the nondialysis population, at the prespecified primary analyses, all three molecules met the noninferiority margin for the risk of major cardiovascular events compared with erythropoiesis-stimulating agents or placebo. The reason for this discrepancy is difficult to explain. Other safety signals came from secondary analyses of some of the other randomized clinical trials, including a higher incidence of thrombosis. A more extensive clinical experience with post-marketing data on hard safety issues is needed to define better when and how to use HIF-PHD inhibitors compared with already available ESAs.
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Affiliation(s)
- Francesco Locatelli
- Department of Nephrology and Dialysis, Alessandro Manzoni Hospital (past Director) ASST Lecco, Lecco, Italy
| | - Lucia Del Vecchio
- Department of Nephrology and Dialysis, Sant’Anna Hospital, ASST Lariana, Como, Italy
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Bai R, Li Y, Jian L, Yang Y, Zhao L, Wei M. The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies. Mol Cancer 2022; 21:177. [PMID: 36071472 PMCID: PMC9454207 DOI: 10.1186/s12943-022-01645-2] [Citation(s) in RCA: 125] [Impact Index Per Article: 41.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Accepted: 08/25/2022] [Indexed: 02/08/2023] Open
Abstract
Given that hypoxia is a persistent physiological feature of many different solid tumors and a key driver for cancer malignancy, it is thought to be a major target in cancer treatment recently. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME), which have a large impact on tumor development and immunotherapy. TAMs massively accumulate within hypoxic tumor regions. TAMs and hypoxia represent a deadly combination because hypoxia has been suggested to induce a pro-tumorigenic macrophage phenotype. Hypoxia not only directly affects macrophage polarization, but it also has an indirect effect by altering the communication between tumor cells and macrophages. For example, hypoxia can influence the expression of chemokines and exosomes, both of which have profound impacts on the recipient cells. Recently, it has been demonstrated that the intricate interaction between cancer cells and TAMs in the hypoxic TME is relevant to poor prognosis and increased tumor malignancy. However, there are no comprehensive literature reviews on the molecular mechanisms underlying the hypoxia-mediated communication between tumor cells and TAMs. Therefore, this review has the aim to collect all recently available data on this topic and provide insights for developing novel therapeutic strategies for reducing the effects of hypoxia.
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Affiliation(s)
- Ruixue Bai
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, People's Republic of China.,Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, China Medical University, Shenyang, 110122, People's Republic of China.,Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China
| | - Yunong Li
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, People's Republic of China.,Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, China Medical University, Shenyang, 110122, People's Republic of China
| | - Lingyan Jian
- Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China
| | - Yuehui Yang
- Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China
| | - Lin Zhao
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, People's Republic of China. .,Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, China Medical University, Shenyang, 110122, People's Republic of China.
| | - Minjie Wei
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, People's Republic of China. .,Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, China Medical University, Shenyang, 110122, People's Republic of China. .,Shenyang Kangwei Medical Laboratory Analysis Co. LTD, Shenyang, 110000, People's Republic of China.
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Hypoxia as a Modulator of Inflammation and Immune Response in Cancer. Cancers (Basel) 2022; 14:cancers14092291. [PMID: 35565420 PMCID: PMC9099524 DOI: 10.3390/cancers14092291] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 04/25/2022] [Accepted: 04/25/2022] [Indexed: 02/01/2023] Open
Abstract
A clear association between hypoxia and cancer has heretofore been established; however, it has not been completely developed. In this sense, the understanding of the tumoral microenvironment is critical to dissect the complexity of cancer, including the reduction in oxygen distribution inside the tumoral mass, defined as tumoral hypoxia. Moreover, hypoxia not only influences the tumoral cells but also the surrounding cells, including those related to the inflammatory processes. In this review, we analyze the participation of HIF, NF-κB, and STAT signaling pathways as the main components that interconnect hypoxia and immune response and how they modulate tumoral growth. In addition, we closely examine the participation of the immune cells and how they are affected by hypoxia, the effects of the progression of cancer, and some innovative applications that take advantage of this knowledge, to suggest potential therapies. Therefore, we contribute to the understanding of the complexity of cancer to propose innovative therapeutic strategies in the future.
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