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pediatric acute myeloid leukemia patients with i(17)(q10)mimicking acute promyelocytic leukemia:Two case reports

World Journal of Clinical Cases 2022年第16期10卷 5446-5455页

作者： Hong-Xia Yan Wei-Hua Zhang Jin-Quan Wen Yan-He Liu Bao-Juan Zhang A-Duo Ji Department of Healthcare Rainbow Hospital of XianyangXianyang 721000Shaanxi ProvinceChina Department of pediatric Intensive Care Unit Rainbow Hospital of XianyangXianyang 721000Shaanxi ProvinceChina Department of pediatric Hematology/oncology Rainbow Hospital of XianyangXianyang 721000Shaanxi ProvinceChina Department of pediatric Hemato-logy/oncology Rainbow Hospital of XianyangXianyang 721000Shaanxi ProvinceChina

BACKGROUND Chromosome i(17)(q10)abnormality is mainly associated with chronic myeloid leukemia(CML),myelodysplastic syndrome/myeloproliferative tumors(MDS/MPD),and acute myeloid leukemia(AML).The role of i(17)(q10)in AML is still unknown,the differences between AML and acute promyelocytic leukemia(APL)-like AML with i(17)(q10)need more *** study aimed to investigate the clinical characteristics and laboratory evidence of 2 AML cases with i(17)(q10),similar to APL *** SUMMARY Both pediatric patients were males;case 1 had newly diagnosed AML,and case 2 showed relapsed tumor after 1 year of drug *** marrow cell morphology,chromosome karyotype analysis,Fully-instrumented submersible housing test,immunological assays,molecular biological methods,and blood tumor panoramic gene test were ***-trans retinoic acid(ATRA)combined with arsenic acid(As2O3)were used in the first course of *** marrow was dominated by abnormal promyelocytic *** test revealed i(17)(q10)*** phenotype mainly included positive expressions of CD9,CD13,CD33,and *** 1 suffered intracranial hemorrhage after re-chemotherapy and died on *** case 2,on D145 and D265,bone marrow promyelocytic granulocytes accounted for 2%.Flow cytometric residual lesion detection showed no abnormal immunophenotype *** copy number of WT1 gene in two cases were 1087 and 1010,respectively,and the expression rates were 55.29% and 59.5%,*** ATRA,As2O3,and chemotherapy may be ineffective in treating APL-like AML with i(17)(q10)but without t(15;17)and PML-RARA fusion gene.

关键词： Chromosome i(17)(q10) Gene mutations Acute promyelocytic leukemia Acute myeloid leukemia Case report

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Microbiota in colorectal cancer related to liver metastasis

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Chinese Journal of Cancer Research 2024年第1期36卷 17-24页

作者： Peijun Wei Weiming Han Zitong Zhang Xue Tian Chen Yang Qiaoxuan Wang Weihao Xie Ying Liu Yuanhong Gao Hui Chang Department of Radiation oncology State Key Laboratory of Oncology in South ChinaGuangzhou 510060China Guangdong Provincial Clinical Research Center for Cancer Guangzhou 510060China Sun Yat-sen University Cancer Center Guangzhou 510060China Department of pediatric oncology State Key Laboratory of Oncology in South ChinaGuangzhou 510060China

The prevalence of colorectal cancer(CRC) is increasing annually and metastasis is the principal cause of death in patients with CRC, with the liver being the most frequently affected site. Many studies have shown a strong interplay between the gut flora, particularly Fusobacterium nucleatum(F. nucleatum), Escherichia coli, and Bacteroides fragilis, and the development of gut tumors. Some strains can induce gut inflammation and produce toxins that directly harm gut epithelial cells, ultimately accelerating the onset and progression of CRC. However,little clinical evidence exists on the specific interplay between the gut microflora and colorectal cancer liver metastasis(CRLM). Some research showed the existence of viable F. nucleatum in distant metastasis of ***, gut microbiota products, such as lipopolysaccharides, sodium butyrate, and protein cathepsin K, were also found to affect the development of CRC. This article summarizes the mechanism and research status of the interplay between gut microflora and CRLM, discusses the importance of gut microflora in the treatment of CRLM, and proposes a new approach to understanding the mechanism of CRLM and potential treatments for the microbiome. It is anticipated that the gut microbiota will be a formidable therapeutic and prophylactic tool for treating and preventing CRLM.

关键词： Gut microbiota liver metastasis colorectal cancer

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Deciphering the role of hedgehog signaling in pancreatic cancer

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The Journal of Biomedical Research 2016年第5期30卷 353-360页

作者： Dongsheng Gu Kelly E Schlotman Jingwu Xie Wells Center for pediatric Research Division of Hematology and OncologyDepartment of PediatricsIndiana University Simon Cancer CenterIndiana University

Pancreatic cancer, mostly pancreatic ductal adenocarcinoma （PDAC）, is a leading cause of cancer-related death in the US, with a dismal median survival of 6 months. Thus, there is an urgent unmet need to identify ways to diagnose and to treat this deadly cancer. Although a number of genetic changes have been identified in pancreatic cancer, their mechanisms of action in tumor development, progression and metastasis are not completely understood. Hedgehog signaling, which plays a major role in embryonic development and stem cell regulation, is known to be activated in pancreatic cancer; however, specific inhibitors targeting the smoothened molecule failed to improve the condition of pancreatic cancer patients in clinical trials. Furthermore, results regarding the role of Hh signaling in pancreatic cancer are controversial with some reporting tumor promoting activities whereas others tumor suppressive actions. In this review, we will summarize what we know about hedgehog signaling in pancreatic cancer, and try to explain the contradicting roles of hedgehog signaling as well as the reason（s） behind the failed clinical trials. In addition to the canonical hedgehog signaling, we will also discuss several non-canonical hedgehog signaling mechanisms.

关键词： hedgehog pancreatic cancer Glil non-canonical signaling cancer metastasis

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Development of a novel multi-functional integrated bioconjugate effectively targeting K-Ras mutant pancreatic cancer

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Journal of Pharmaceutical Analysis 2022年第2期12卷 232-242页

作者： Yang-Yang Wang Liang Li Xiu-Jun Liu Qing-Fang Miao Yi Li Meng-Ran Zhang Yong-Su Zhen Department of pediatric oncology Tianjin Medical University Cancer Institute and HospitalTianjin300060China NHC Key Laboratory of Biotechnology of Antibiotics Department of OncologyInstitute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100050China

Folate receptor(FR)overexpression occurs in a variety of cancers,including pancreatic *** addition,enhanced macropinocytosis exists in K-Ras mutant pancreatic ***,the occurrence of intensive desmoplasia causes a hypoxic microenvironment in pancreatic *** this study,a novel FR-directed,macropinocytosis-enhanced,and highly cytotoxic bioconjugate folate(F)-human serum albumin(HSA)-apoprotein of lidamycin(LDP)-active enediyne(AE)derived from lidamycin was designed and prepared.F-HSA-LDP-AE consisted of four moieties:F,HSA,LDP,and AE.F-HSA-LDP presented high binding efficiency with the FR and pancreatic cancer *** uptake in wild-type cells was more extensive than in K-Ras mutant-type *** in vivo optical imaging,F-HSA-LDP displayed prominent tumor-specific biodistribution in pancreatic cancer xenograft-bearing mice,showing clear and lasting tumor localization for 360 *** the MTT assay,F-HSA-LDP-AE demonstrated potent cytotoxicity in three types of pancreatic cancer cell *** also induced apoptosis and caused G2/M cell cycle arrest.F-HSALDP-AE markedly suppressed the tumor growth of AsPc-1 pancreatic cancer xenografts in athymic *** well-tolerated doses of 0.5 and 1 mg/kg,(i.v.,twice),the inhibition rates were 91.2%and 94.8%,respectively(P<0.01).The results of this study indicate that the F-HSA-LDP multi-functional bioconjugate might be effective for treating K-Ras mutant pancreatic cancer.

关键词： Pancreatic cancer Folate receptor Multi-functional Macropinocytosis-enhanced Bioconjugate K-Ras PEGylation

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Safety and efficacy of intravitreal anti vascular endothelial growth factor for severe posterior retinopathy of prematurity with flat fibrovascular proliferation

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World Journal of Clinical pediatrics 2023年第4期12卷 220-229页

作者： Puja Maitra Subramaniam Prema Venkatapathy Narendran Parag K Shah pediatric Retina and Ocular oncology Aravind Eye Hospital and Postgraduate Institute of OphthalmologyCoimbatore 641014Tamil NaduIndia

BACKGROUND Intravitreal anti-vascular endothelial growth factor(IVA)injection is known to cause contraction of fibrovascular proliferation(FVP),when present in severe retinopathy of prematurity(ROP).AIM To assess the structural outcomes of IVA injection in the treatment of severe posterior ROP with significant *** It was a retrospective study in which 36 eyes of 18 preterm babies who developed>4 clock hours of FVP in zone I or posterior zone II,were treated with either intravitreal 0.625 mg bevacizumab or intravitreal 0.2 mg of *** structural outcome included resolution of plus disease and FVP without the development of tractional retinal *** outcome measure included either full retinal maturation at follow-up or development of recurrent disease requiring additional *** outcomes included progression to retinal *** The mean gestational age of the 18 preterm babies was 30 wk(range 27-36),and mean birth weight was 1319 g(range 650-1980 g).Mean post-menstrual age(PMA)at the time of primary treatment was 35.5 wk(range 31-41 wk).All eyes showed regression of plus disease and FVP.5 eyes of 3 babies showed reactivation of disease and were treated with repeat IVA(n=2 eyes)or peripheral laser photocoagulation(n=3 eyes)respectively.16 out of 36(44%)reached retinal vascular maturation at final follow up at 5 *** There was good resolution of severe posterior ROP with FVP with IVA,with retinal maturity of 44%at 5 year follow-up and a reactivation rate of 13.8%.When the IVA injection is given prior to 37 wk PMA,while disease is in phase 2,it is less likely to cause contracture of pre-existing FVP.

关键词： Retinopathy of prematurity Anti-vascular endothelial growth factor injection Contraction Crunch phenomenon

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Haploidentical hematopoietic stem cell transplantation for pediatric patients with chronic active Epstein-Barr virus infection:a retrospective analysis of a single center

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World Journal of pediatrics 2021年第6期17卷 626-636页

作者： Yan-Hui Luo Jun Yang Ang Wei© Guang-Hua Zhu Bin Wang Rui Zhang Chen-Guang Jia Yan Yan Kai Wang Sidan Li Xuan Zhou Mao-Quan Qin Tian-You Wang Beijing Key Laboratory of pediatric Hematology oncology National Key Discipline of Pediatrics(Capital Medical University)Key Laboratory of Major Diseases in ChildrenMinistry of EducationHematology Oncology CenterDepartment of Hematology and OncologyBeijing Children's HospitalCapital Medical UniversityNational Center for Children’s HealthNanlishi Road No.56Beijing 100045China

Background This study aimed to evaluate the feasibility and clinical effect of haploidentical hematopoietic stem cell transplantation(haplo-HSCT)for the treatment of pediatric patients with chronic active Epstein-Barr virus infection(CAEBV).Methods Children with CAEBV who did not have matched donors and underwent haplo-HSCT in Beijing Children's Hospital,Capital Medical University,from October 2016 to June 2020 were analyzed *** relating to the clinical manifestations,engraftment,and prognosis of the children were extracted from medical *** Twenty-five patients,including 16 males and 9 females,with an onset age of 5.0±2.6 years and a transplantation age of 6.9±2.9 years,were enrolled irnhis *** mean time from diagnosis to transplantation was 3.8(2.0-40.2)*** mean observation time was 19.0±12.0 *** patients received the reduced intensity conditioning regimen,and the remaining patients all received the modified myeloablative conditioning *** the end of the follow-up,23 patients were characterized by disease-free survival(DFS),22 were characterized by event-free survival(EFS).and two *** of the patients died of thrombotic microangiopathy(TMA),and another died of graft versus host disease(GVHD);this patient discontinued the treatment for economic *** 3-year overall survival(OS)rate was estimated to be 92.0%±5.4%,and the 3-year EFS rate was estimated to be 87.4%±6.8%.All active patients survived after HSCT *** GVHD degrees 1-3 were observed in ten patients(40.0%),and degree IV was observed in six(24.0%),who were all cured except for one *** GVHD was observed in nine(36.0%),and most of these cases were *** incidence of TMA and veno-occlusive disease(VOD)was 28.0%and 4.0%.Conclusions Haploidentical hematopoietic stem cell transplantation is safe and effective in the treatment of pediatric CAEBV and can be used as an alternative therapy without matched donors or emergency tr

关键词： Chronic active Epstein-Barr virus infection Haploidentical hematopoietic stem cell transplantation Prognosis Graft versus host diseases Thrombotic microangiopathy

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Germinal-center type B-cell classification and clinical characteristics of Chinese pediatric diffuse large B-cell lymphoma:a report of 76 cases

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Chinese Journal of Cancer 2013年第10期32卷 561-566页

作者： Yan Chen Xiao-Fei Sun Zi-Jun Zhen Juan Wang Jia Zhu Su-Ying Lu Fei-Fei Sun Fei Zhang Peng-Fei Li Rui-Qing Cai State Key Laboratory of oncology in South China Department of pediatric oncology Sun Yat-sen University Cancer Center

pediatric diffuse large B-cell lymphoma(DLBCL)is a highly aggressive disease with unique clinical *** study analyzed the germinal-center type B-cell(GCB)classification and clinical characteristics of Chinese pediatric DLBCL.A total of 76 patients with DLBCL newly diagnosed in Sun Yatsen University Cancer Center between February 2000 and May 2011,with an age younger than 18 years,were included in the *** male/female ratio was 3.47:*** median age was 12 years(range,2 to 18 years),and 47(61.8%)patients were at least 10 years *** the 76 patients,48(63.2%)had stage III/IV disease,9(11.8%)had bone marrow involvement,1(1.3%)had central nervous system(CNS)involvement,and 5(6.6%)had bone *** GCB classification was assessed in 45 patients:26(57.8%)were classified as GCB subtype,and 19(42.2%)were classified as non-GCB *** modified B-NHL-BFM-90/95 regimen was administered to 50 patients,and the 4-year event-free survival(EFS)rate was 85.8%.Among these 50 patients,31 were assessed for the GCB classification:17(54.8%)were classified as GCB subtype,with a 4-year EFS rate of 88.2%;14(45.2%)were classified as non-GCB subtype,with a 4-year EFS rate of 92.9%.Our data indicate that bone marrow involvement and stage III/IV disease are common in Chinese pediatric DLBCL patients,whereas the percentage of patients with the GCB subtype is similar to that of patients with the non-GCB *** modified B-NHL-BFM-90/95protocol is an active and effective treatment protocol for Chinese pediatric patients with DLBCL.

关键词： B细胞淋巴瘤临床特征弥漫性中国分类小儿生发中枢神经系统

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Cardiovascular dysfunction and vitamin D status in childhood acute lymphoblastic leukemia survivors

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World Journal of pediatrics 2019年第5期15卷 465-470页

作者： Paola Muggeo Vito Michele Rosario Muggeo Paola Giordano Maurizio Delvecchio Maria Altomare Chiara Novielli Marco Matteo Ciccone Gabriele D'Amato Maria Felicia Faienza Nicola Santoro Department of pediatric oncology and Hematology University Hospital of PoliclinicoPiazza G.Cesare 1170124 BariItaly Department of Economical Business and Statistical SciencesUniversity of PalermoPalermoItaly Department of Biomedicine and Human oncology Pediatric SectionUniversity"A.Moro"BariItaly pediatric and Neonatology Unit Mother and Children Health Care Department"Madonna delle Grazie"HospitalASL MateraMateraItaly Cardiovascular Diseases Section Department of Emergency and Organ TransplantationUniversity"A.Moro"BariItaly Neonatal Intensive Care Unit Di Venere HospitalBariItaly

Background Vitamin D(25-OHD)has a role in bone health after treatment for cancer.25-OHD deficiency has been associated with risk factors for cardiovascular disease,but no data focusing on this topic in childhood cancer survivors have been *** investigated the 25-OHD status in children treated for acute lymphoblastic leukemia(ALL),and evaluated its influence on vascular *** 25-OHD levels were evaluated in 52 ALL survivors and 40 matched healthy *** were grouped according to 25-OHD level(<20 ng/m or≥20 ng/ml).Auxological parameters,biochemical and hemostatic markers of endothelial function(AD,HMW-AD,ET-1,vWFAg,TAT,D-dimers,Fbg,and hs-CRP),ultrasound markers of vascular endothelial function(flow-mediated dilatation,FMD,common carotid intima-media thickness,C-IMT,and antero-posterior diameter of infra-renal abdominal aorta,APAO)were evaluated in the *** Cases showed higher prevalence of 25-OHD deficiency than controls(p=0.002).In univariate analysis via mean comparisons,25-OHD deficient(<20 ng/ml)patients showed higher C-IMT values compared to the 25-OHD non-deficient(≥20 ng/ml)group(P=0.023).Significant differences were also found for ET-1(P=0.035)and AD-HMW(P=0.015).In the multiple regression models controlling for some confounders,25-OHD still was associated with C-IMT(P=0.0163),ET-1(P=0.0077),and AD-HMW(P=0.0008).Conclusions Childhood ALL survivors show higher prevalence of 25-OHD deficiency as compared to *** 25-OHD levels appear to be linked to indicators of endothelial and vascular *** monitoring of 25-OHD balance may help to prevent cardiovascular diseases in childhood ALL survivors,characterized by high cardiovascular risk.

关键词： Acute lymphoblastic leukemia Cardiovascular disease C-IMT Vascular ultrasound studies Vitamin D

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Safety of in vitro amplified HLA-haploidentical donor immune cell infusions for childhood malignancies

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Chinese Journal of Cancer 2013年第12期32卷 661-666页

作者： Fei Zhang Xiao-Fei Sun Yong-Qiang Li Zi-Jun Zhen Hai-Xia Zheng Jia Zhu Qi-Jing Wang Su-Ying Lu Jia He Juan Wang Ke Pan Rui-Qing Cai Yan Chen De-Sheng Weng Fei-Fei Sun Jian-Chuan Xia State Key Laboratory of oncology in South China Department of pediatric oncology Department of Biotherapy Sun Yat-sen University Cancer Center

In vitro amplified human leukocyte antigen(HLA)-haploidentical donor immune cell infusion(HDICI)is not commonly used in ***,our study sought to evaluate its safety for treating childhood *** September 2011 and September 2012,12 patients with childhood malignancies underwent HDICI in Sun Yat-sen University Cancer *** median patient age was 5.1 years(range,1.7-8.4 years).Of the 12 patients,9 had high-risk neuroblastoma(NB)[7 showed complete response(CR),1 showed partial response(PR),and 1 had progressive disease(PD)after multi-modal therapies],and 3 had Epstein-Barr virus(EBV)-positive lymphoproliferative disease(EBV-LPD).The 12 patients underwent a total of 92 HDICIs at a mean dose of 1.6×108immune cells/kg body weight:71 infusions with natural killer(NK)cells,8 with cytokine-induced killer(CIK)cells,and 13 with cascade primed immune cells(CAPRIs);83 infusions with immune cells from the mothers,whereas 9 with cells from the *** cases(21.7%)of fever,including 6 cases(6.5%)accompanied with chills and 1(1.1%)with febrile convulsion,occurred during infusions and were alleviated after symptomatic *** cases(5.4%)of mild emotion changes were *** other adverse events occurred during and after the completion of *** acute nor chronic graft versus host disease(GVHD)was observed following *** a median of 5.0 months(range,1.0-11.5 months)of follow-up,the 2 NB patients with PR and PD developed PD during *** the other 7 NB patients in CR,2 relapsed in the sixth month of HDICIs,and 5 maintained CR with disease-free survival(DFS)ranging from 4.5 to 11.5 months(median,7.2months).One EBV-LPD patient achieved PR,whereas 2 had stable disease(SD).Our results show that HDICI is a safe immunotherapy for childhood malignancies,thus warranting further studies.

关键词：免疫细胞恶性肿瘤体外扩增安全性 HLA 儿童人类白细胞抗原移植物抗宿主病

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Recurrent lymphoma presenting as painless, chronic intussusception: A case report

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World Journal of Clinical Cases 2020年第2期8卷 306-312页

作者： Parker Giroux Anderson Collier Michael Nowicki Department of pediatrics University of Mississippi Medical CenterJacksonMS 39216United States Division of pediatric Hematology and oncology University of Mississippi Medical CenterJacksonMS 39216United States Division of pediatric Gastroenterology University of Mississippi Medical CenterJacksonMS 39216United States

BACKGROUND The clinical presentation of acute lymphoblastic lymphoma is highly *** prognosis is good, recurrence of disease can occur. Gastrointestinal relapse, including intussusception, is well-described but the absence of abdominal pain in this setting is *** SUMMARY We report a 13-year-old male with B-cell precursor acute lymphoblastic leukemia in remission presenting with anemia and weight loss. Examination was significant for absence of abdominal pain, but a stool sample was positive for occult blood. Pan-endoscopy was performed with colonoscopy revealing a mass filling the colonic lumen. Biopsy of the mass confirmed recurrence of recurrent Bcell lymphoma. Computed tomography scan revealed ileocolic intussusception resulting from the tumor. This case is unusual in that the patient had no abdominal pain despite the presence of *** While intestinal involvement with lymphoma has been well described in the literature, presentation as painless intussusception has not been reported. This case report highlights the wide spectrum of clinical manifestations of recurrent Bcell lymphoma involving the gastrointestinal tract, in particular the near absence of symptoms despite the finding of intussusception.

关键词： B-cell acute lymphoblastic leukemia Tumor relapse Intussusception Case report Anemia

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