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Molecular pathogenesis and therapeutic strategies of human osteosarcoma

The Journal of Biomedical Research 2016年第1期30卷 5-18页

作者： Sahitya K Denduluri Zhongliang Wang Zhengjian Yan Jing Wang Qiang Wei maryam K mohammed Rex C Haydon Hue H Luu Tong-Chuan He The University of Chicago Pritzker School of Medicine and Molecular Oncology LaboratoryDepartment of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical UniversityChongqing 400016China

Osteosarcoma（OS）is a devastating illness with rapid rates of dissemination and a poor overall prognosis,despite aggressive standard-of-care surgical techniques and combination chemotherapy *** the molecular mechanisms involved in disease pathogenesis and progression may offer insight into new therapeutic *** in mesenchymal stem cell differentiation,abnormal expression of oncogenes and tumor suppressors,and dysregulation within various important signaling pathways have all been implicated in development of various disease *** such,a variety of basic science and translational studies have shown promise in identifying novel markers and modulators of these disease-specific *** out of these and similar investigations,a variety of emerging therapies are now undergoing various phases of OS clinical *** broadly include angiogenesis inhibitors,drugs that act on the bone microenvironment,receptor tyrosine kinase inhibitors,immune system modulators,and other radio-or chemo-sensitizing *** new forms of drug delivery are being developed simultaneously,the possibility of targeting tumors locally while minimizing systemic toxicityis is seemingly more achievable now than *** this review,we not only summarize our current understanding of OS disease processes,but also shed light on the multitude of potential therapeutic strategies the scientific community can use to make long-term improvements in patient prognosis.

关键词： osteosarcoma soft tissue tumors bone tumors cancer therapy osteogenic tumors osteogenic differentiation

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Stem cells, growth factors and scaffolds in craniofacial regenerative medicine

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Genes & Diseases 2016年第1期3卷 56-71页

作者： Viktor Tollemar Zach J.Collier maryam K.mohammed Michael J.Lee Guillermo A.Ameer Russell R.Reid The University of Chicago Pritzker School of Medicine ChicagoIL 60637USA Department of Orthopedic Surgery and Rehabilitation Medicine The University of Chicago Medical CenterChicagoIL 60637USA Laboratory of Craniofacial Biology and Development Section of Plastic and Reconstructive SurgeryDepartment of SurgeryThe University of Chicago MedicineChicagoIL 60637USA Department of Surgery Feinberg School of MedicineChicagoIL 60611USA Biomedical Engineering Department Northwestern UniversityEvanstonIL 60208USA

Current reconstructive approaches to large craniofacial skeletal defects are often complicated and ***-sized defects are unable to heal via natural regenerative processes and require surgical intervention,traditionally involving autologous bone(mainly in the form of nonvascularized grafts)or *** bone grafts remain the gold standard of care in spite of the associated risk of donor site *** engineering approaches represent a promising alternative that would serve to facilitate bone regeneration even in large craniofacial skeletal *** strategy has been tested in a myriad of iterations by utilizing a variety of osteoconductive scaffold materials,osteoblastic stem cells,as well as osteoinductive growth factors and small *** of the major challenges facing tissue engineers is creating a scaffold fulfilling the properties necessary for controlled bone *** properties include osteoconduction,osteoinduction,biocompatibility,biodegradability,vascularization,and progenitor cell *** review will provide an overview of how optimization of the aforementioned scaffold parameters facilitates bone regenerative capabilities as well as a discussion of common osteoconductive scaffold materials.

关键词： Bone regeneration Craniofacial defects Osteogenesis Regenerative medicine Scaffolds Tissue engineering

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Insulin-like growth factor(IGF)signaling in tumorigenesis and the development of cancer drug resistance

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Genes & Diseases 2015年第1期2卷 13-25页

作者： Sahitya K.Denduluri Olumuyiwa Idowu Zhongliang Wang Zhan Liao Zhengjian Yan maryam K.mohammed Jixing Ye Qiang Wei Jing Wang Lianggong Zhao Hue H.Luu The University of Chicago Pritzker School of Medicine ChicagoIL 60637USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation Medicine5841 South Maryland AvenueMC 3079ChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine The Affiliated Hospitals of Chongqing Medical UniversityChongqing 400016China Department of Orthopaedic Surgery Xiang-Ya Hospital of Central South UniversityChangsha 410008China School of Bioengineering Chongqing UniversityChongqingChina Department of Orthopaedic Surgery the Second Affiliated Hospital of Lanzhou UniversityLanzhouGansu 730000China

One of the greatest obstacles to current cancer treatment efforts is the development of drug resistance by *** recent advances in diagnostic practices and surgical interventions,many neoplasms demonstrate poor response to adjuvant or neoadjuvant radiation and *** a result,the prognosis for many patients afflicted with these aggressive cancers remains *** insulin-like growth factor(IGF)signaling axis has been shown to play critical role in the development and progression of various *** basic science and translational studies have shown that IGF pathway modulators can have promising effects when used to treat various *** also exists a substantial body of recent evidence implicating IGF signaling dysregulation in the dwindling response of tumors to current standard-of-care *** better understanding both the IGF-dependent and-independent mechanisms by which pathway members can influence drug sensitivity,we can eventually aim to use modulators of IGF signaling to augment the effects of current *** review summarizes and synthesizes numerous recent investigations looking at the role of the IGF pathway in drug *** offer a brief overview of IGF signaling and its general role in neoplasia,and then delve into detail about the many types of human cancer that have been shown to have IGF pathway involvement in resistance and/or sensitization to ***,our hope is that such a compilation of evidence will compel investigators to carry out much needed studies looking at combination treatment with IGF signaling modulators to overcome current therapy resistance.

关键词： Cancer Insulin-like growth factor Resistance Therapy Tumorigenesis

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Opening the LOX to bone metastasis: The role of secreted lysyl oxidase in skeletal recurrence of breast cancers

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Genes & Diseases 2015年第4期2卷 288-290页

作者： maryam K.mohammed Connie Shao Hue H.Luu Rex C.Haydon The University of Chicago Pritzker School of Medicine and Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA

Breast cancer is the second-most prevalent cancer in the United States,with 234,190 new cases projected to be diagnosed in *** initial diagnosis is commonly made early in its disease course due to the use of routine screening mammography.1 Combined with advances in adjuvant chemotherapy,this has led to promising overall outcomes,including a 5-year survival rate of 89.4%and a 10%e12%rate of locoregional recurrence at 20 years for stage I/II disease.1-3 By comparison,prognosis remains poor for patients with metastatic disease at diagnosis or for those who present after initial cure of disease with distant recurrence.4 Among cases of distant recurrence,skeletal recurrence occurs frequently and can be accompanied by hypercalcemia,pain,and functional compromise often requiring a protracted course of palliative therapy.

关键词： diagnosis metastasis chemotherapy

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Multifaceted signaling regulators of chondrogenesis:Implications in cartilage regeneration and tissue engineering

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Genes & Diseases 2015年第4期2卷 307-327页

作者： Jordan D.Green Viktor Tollemar Mark Dougherty Zhengjian Yan Liangjun Yin Jixing Ye Zachary Collier maryam K.mohammed Rex C.Haydon Hue H.Luu Richard Kang Michael J.Lee Sherwin H.Ho Tong-Chuan He Lewis L.Shi Aravind Athiviraham The University of Chicago Pritzker School of Medicine ChicagoIL 60637USA Department of Orthopaedic Surgery and Rehabilitation Medicine The University of Chicago Medical CenterChicagoIL 60637USA Department of Orthopaedic Surgery The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China School of Bioengineering Chongqing UniversityChongqingChina

Defects of articular cartilage present a unique clinical challenge due to its poor self-healing capacity and avascular *** surgical treatment options do not ensure consistent regeneration of hyaline cartilage in favor of fibrous ***,we review the current understanding of the most important biological regulators of chondrogenesis and their interactions,to provide insight into potential applications for cartilage tissue *** include various signaling pathways,including fibroblast growth factors(FGFs),transforming growth factor b(TGF-b)/bone morphogenic proteins(BMPs),Wnt/b-catenin,Hedgehog,Notch,hypoxia,and angiogenic signaling *** and epigenetic regulation of chondrogenesis will also be *** in our understanding of these signaling pathways have led to promising advances in cartilage regeneration and tissue engineering.

关键词： BMPs Cartilage Cell signaling Chondrogenesis FGF Regenerative medicine

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Current interventional options for palliative care for patients with advanced-stage cholangiocarcinoma

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World Journal of Clinical Oncology 2024年第3期15卷 381-390页

作者： maryam Makki Malak Bentaleb mohammed Abdulrahman Amal Abdulla Suhool Salem Al Harthi Marcelo AF Ribeiro Jr Department of Surgery Division of TraumaCritical Care and Acute Care SurgerySheikh Shakhbout Medical CityAbu Dhabi 11001United Arab Emirates Department of Surgery College of Medicine and Health SciencesKhalifa UniversityAbu Dhabi 11001United Arab Emirates Department of Surgery Division of Hepato-Pancreato-Biliary(HPB)SurgerySheikh Shakhbout Medical CityAbu Dhabi 91888United Arab Emirates

Primary biliary tract tumors are malignancies that originate in the liver,bile ducts,or *** tumors often present with jaundice of unknown etiology,leading to delayed diagnosis and advanced ***,several palliative treatment options are available for primary biliary tract *** include percutaneous transhepatic biliary drainage(PTBD),biliary stenting,and surgical interventions such as biliary *** therapy is also commonly used for the palliative treatment of primary biliary tract *** involves the administration of chemotherapy drugs,such as gemcitabine and cisplatin,which have shown promising results in improving overall survival in patients with advanced biliary tract *** is another palliative treatment option for patients with unresectable or inoperable malignant biliary *** stenting can also be used as a palliative treatment option to alleviate symptoms in patients with unresectable or inoperable malignant biliary *** interventions,such as biliary diversion,have traditionally been used as palliative options for primary biliary tract ***,biliary diversion only provides temporary relief and does not remove the *** biliary tract tumors often present in advanced stages,making palliative treatment the primary option for improving the quality of life of patients.

关键词： Cholangiocarcinoma Palliative care Endoscopic treatment Surgery Complications Interventional radiology

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Wnt and BMP signaling crosstalk in regulating dental stem cells:Implications in dental tissue engineering

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Genes & Diseases 2016年第4期3卷 263-276页

作者： Fugui Zhang Jinlin Song Hongmei Zhang Enyi Huang Dongzhe Song Viktor Tollemar Jing Wang Jinhua Wang maryam mohammed Qiang Wei Jiaming Fan Junyi Liao Yulong Zou Feng Liu Xue Hu Xiangyang Qu Liqun Chen Xinyi Yu Hue H.Luu Michael J.Lee Tong-Chuan He Ping Ji Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences and the Affiliated Hospital of Stomatology of Chongqing Medical UniversityChongqing 401147China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Conservative Dentistry and Endodontics West China School of StomatologySichuan UniversityChengdu 610041China Ministry of Education Key Laboratory of Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical UniversityChongqing 400016China

Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP *** injuries and/or loss of tooth or periodontal tissues may significantly impact aesthetic appearance,essential oral functions and the quality of *** dentistry holds great promise in treating oral/dental *** past decade has witnessed a rapid expansion of our understanding of the biological features of dental stem cells,along with the signaling mechanisms governing stem cell self-renewal and *** this review,we first summarize the biological characteristics of seven types of dental stem cells,including dental pulp stem cells,stem cells from apical papilla,stem cells from human exfoliated deciduous teeth,dental follicle precursor cells,periodontal ligament stem cells,alveolar bone-derived mesenchymal stem cells(MSCs),and MSCs from *** then focus on how these stem cells are regulated by bone morphogenetic protein(BMP)and/or Wnt signaling by examining the interplays between these ***,we analyze the current status of dental tissue engineering strategies that utilize oral/dental stem cells by harnessing the interplays between BMP and Wnt *** also highlight the challenges that must be addressed before the dental stem cells may reach any clinical ***,we can expect to witness significant progresses to be made in regenerative dentistry in the coming decade.

关键词： BMP signaling Dental stem cells Oral stem cells Regenerative dentistry Signal transduction Tissue engineering Wnt signaling

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Insider information:Testing cancer drug sensitivity for personalized therapy

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Genes & Diseases 2015年第3期2卷 219-221页

作者： Jing Wang Qiang Wei Jixing Ye Sahitya K.Denduluri Xin Wang maryam K.mohammed Hue H.Luu Rex C.Haydon Tong-Chuan He Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA

Cancer death is usually caused by incurable drug-resistant and metastatic *** tremendous progress has been made in anticancer drug development during the past two decades,cancer medicine still faces unprecedented challenges associated with choosing effective treatments for individual *** recent reports have offered encouraging approaches towards potentially personalized cancer drug selection.

关键词： Cancer Chemotherapy Drug discovery Drug resistance Drug screening Personalized medicine

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Unraveling the Impact of Direct-Acting Antivirals on Hepatitis-Linked Cirrhosis: A Comprehensive Analysis of Fibrosis, Child Score, and Disease Progression

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Open Journal of Gastroenterology 2024年第6期14卷 203-212页

作者： Hajar Cherkaoui maryam Elkhayari Maria Lahlali Asmae Lamine Nada Lahmidani Amine Mekkaoui Mounia Elyousfi Dafr Allah Benajah mohammed El Abkari Adil Ibrahimi Hakima Abid Department of Hepato-Gastroenterology Hassan II University Hospital Fez Morocco Faculty of Medicine and Pharmacy of Fez USMBA Fez Morocco

The treatment of hepatitis C has undergone a significant boom since the advent of direct acting antivirals (DAA). Indeed, the interferon-ribavirin combination that has been used to treat hepatitis C has a virological response in only 45% of cases with significant side effects. The advent of direct-acting antivirals has changed the prognosis of cirrhotic patients with hepatitis C. DAAs have ensured a sustained viral response in the majority of patients. Our work aims to see the evolution of hepatitis C patients at the cirrhosis stage under DAA. We conducted a retrospective study over 15 years (January 2009, January 2024) including all patients with post-viral cirrhosis C, whom we divided into two groups: group A, cirrhotic patients who received ribavirin and interferon, and group B, patients on DAA. From January 2009 to January 2024, we conducted a study of 182 patients with viral hepatitis C, including 102 cirrhotic patients. The mean age was 55 years. 66% of patients were initially treated with the ribavirin interferon combination, while 34% received direct-acting antivirals (DAAs). Since the introduction of DAAs, the most commonly used regimens have been sofosbuvir/daclatasvir with or without ribavirin and sofosbuvir/ledipasvir with or without ribavirin. Group A achieved sustained virological response (SVR) in 60% of cases, with notable side effects. In Group B, SVR was 98.18%, with improved tolerability and fewer side effects than previous treatments. Fifteen patients developed hepatocellular carcinoma (HCC), with a significantly lower mortality rate in those treated with DAAs compared with pegylated dual therapy (p: 0.001).

关键词： Post-Viral Cirrhosis C Pegylated Interferon Direct Acting Antivirals Sustained Viral Response Child Score Fibrosis

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Transition to resistance:An unexpected role of the EMT in cancer chemoresistance

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Genes & Diseases 2016年第1期3卷 3-6页

作者： Jing Wang Qiang Wei Xin Wang Shengli Tang Hao Liu Fugui Zhang maryam K.mohammed Jiayi Huang Dan Guo Minpeng Lu Feng Liu Jianxiang Liu Chao Ma Xue Hu Rex C.Haydon Tong-Chuan He Hue H.Luu Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical UniversityChongqing 400016China Department of Surgery West China Hospital of Sichuan UniversityChengdu 610041China Department of General Surgery the Affiliated Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Orthopaedic Surgery Union Hospital of Tongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430022China Department of Neurosurgery the Affiliated Zhongnan Hospital of Wuhan UniversityWuhan 430071China

Two recent studies provide intriguing evidence that challenges the role of the epithelialemesenchymal transition(EMT)as a critical mediator of cancer metastasis,while revealing an unexpected role in cancer drug resistance.1,2 While these findings may not settle the EMT’s role in metastasis,these studies suggest that targeting the EMT may inhibit both cancer metastasis and chemoresistance.

关键词： Breast cancer Cancer metastasis Chemoresistance Drug resistance EMT Pancreatic cancer Targeted therapies

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