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Gene expression profiling as a prognostic tool in multiple myeloma

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Cancer Drug Resistance 2021年第4期4卷 1008-1018页

作者： Harmony Black Siobhan Glavey department of haematology Beaumont HospitalDublin D09 V2N0Ireland department of Pathology Royal College of Surgeons in IrelandDublin D02 YN77Ireland

Multiple myeloma(MM)is an aggressive plasma cell malignancy with high degrees of variability in outcome,some patients experience long remissions,whilst others survive less than two years from *** refractoriness and relapse remain challenges in MM management,and there is a need for improved prognostication and targeted therapies to improve overall survival(OS).The past decade has seen a surge in gene expression profiling(GEP)studies which have elucidated the molecular landscape of MM and led to the identification of novel gene signatures that predict OS and outperform current clinical *** this review,we discuss the limitations of current prognostic tools and the emerging role of GEP in diagnostics and in the development of personalised medicine approaches to combat drug resistance.

关键词： Multiple myeloma gene expression profiling prognostication risk stratification risk-adapted therapies SKY92 drug resistance

Prevalence of Asymptomatic Bacteriuria in HIV Infected Patients in a Tertiary Hospital in Lagos, Nigeria

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World Journal of AIDS 2013年第2期3卷 105-110页

作者： Akinsegun Akinbami Ibidun Bode-Shojobi Sarah Ajibola Olajumoke Oshinaike Adewumi Adediran Olaitan Ojelabi Kamal Ismail Bodunrin Osikomaiya department of haematology and Blood Transfusion College of Medicine Lagos State University Ikeja Nigeria department of haematology and Blood Transfusion Faculty of Clinical Sciences College of Medicine University of La- gos Lagos Nigeria department of haematology and Blood Transfusion Lagos State University Teaching Hospital Ikeja Nigeria department of haematology and Blood Transfusion Lagos University Teaching Hospital Idiaraba Nigeria department of Medical Microbiology Lagos University Teaching Hospital Idiaraba Nigeria department of Medicine College of Medicine Lagos State University Ikeja Nigeria

Background: People living with Human Immunodeficiency Virus (HIV) are more predisposed to urinary tract infections due to suppression of their immunity by the virus. Asymptomatic bacteriuria is associated with an increased risk of symptomatic urinary tract infection and the latter being an important contributor to development of chronic renal failure, hypertension and toxaemia of pregnancy. The aim of this study was to determine the prevalence of asymptomatic bacteriuria in HIV-infected patients and proffer a recommendation on the need or otherwise to screen. Methods: This was a cross sectional study of treatment-naive HIV-infected patients attending the HIV clinics of Lagos State University Teaching Hospital (LASUTH), Ikeja. A single voided aseptically collected mid-stream urine (MSU) was obtained from each patient and all samples processed immediately, were sent for urinalysis and culture. Isolates were considered significant if there were ≥105 colony forming unit/mL (CFU/mL) with 2 or less isolates, doubtful significance if 5 CFU/mL. Significant isolates were selected for identification. Data were analyzed using SPSS version 16.0 (Statistical Package for Social Sciences, Inc., Chicago, Ill). Results: A total of 156 consenting participants were recruited into the study. The mean age was 36.45 ± 8.65 years. There were 60 of 156 (38.4%) males and 96 of 156 (61.56%) females. Only 33 of 156 (21.2%) had significant bacteriuria, out of the 33 participants, 19 (57.8%) were asymptomatic, while 14 of 33 (42.4%) had significant growth but were symptomatic or on antibiotics. E. coli was isolated in 9 of 19 (47.3%), followed by Staph aureus 4 of 19 (21.05%). Conclusion: More than half of participants who had significant growth had asymptomatic bacteriuria, while one-fifth of all patients had significant growth. Considering this statistics, screening for or treatment of asymptomatic bacteriuria may be recommended in all HIV-infected patients.

关键词： Prevalence Screening Asymptomatic Bacteriuria HIV-Infected Patients

Immune checkpoint inhibitors in breast cancer: development, mechanisms of resistance and potential management strategies

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Cancer Drug Resistance 2023年第4期6卷 768-787页

作者： Rachel SJ Wong Rebecca JM Ong Joline SJ Lim department of haematology-Oncology National University Cancer InstituteNational University HospitalSingapore 119228Singapore Yong Loo Lin School of Medicine National University of SingaporeSingapore 119228Singapore

The use of immune checkpoint inhibitors(iCls)has increased exponentially in the past decade,although its progress specifically for breast cancer has been *** first *** and Drug Administration approval for ICl in breast cancer came in 2019,eight years after the first-ever approval of an *** present,current indications for ICls are relevant only to a subset of patients with triple-negative breast cancer,or those displaying high microsatellite instability or deficiency in the mismatch repair protein *** an increasing understanding of the limitations of using ICls,which stem from breast cancer being innately poorly immunogenic,as well as the presence of various intrinsic and acquired resistance pathways,ongoing trials are evaluating different combination therapies to overcome these *** this review,we aim to describe the development timeline of ICls and resistance mechanisms limiting their utility,and summarise the available approaches and ongoing trials relevant to overcoming each resistance mechanism.

关键词： Immunotherapy immune checkpoint inhibitors resistance mechanisms breast cancer

Modern diagnostic approaches to cholangiocarcinoma

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Hepatobiliary & Pancreatic Diseases International 2012年第4期11卷 349-359页

作者： Larisa E Vasilieva Stefanos I Papadhimitriou Spyros P Dourakis Second department of Internal Medicine University of Athens Medical SchoolHippokration General Hospital114 Vas Sofias AvenueAthens 11527Greece Molecular Cytogenetics Unit Haematology Laboratory"G.Genimatas" Regional General HospitalAthensGreece

BACKGROUND:Cholangiocarcinoma is a very aggressive tumor with poor ***,early diagnosis and surgical resection are of paramount *** diagnosis is difficult because access to the tumor is not *** is possible only for intrahepatic cholangiocarcinoma,which accounts for 10% of *** brush cytology from endoscopic retrograde cholangiopancreatography(ERCP) has a high specificity of 100% but unfortunately a low sensitivity of 30%.In this review we briefly describe new diagnostic techniques applicable to ERCP brush cytology specimens and targeting the genetic background of the disease,in particular fluorescence in situ hybridization(FISH) and digital image analysis(DIA).DATE SOURCES:The PubMed database up to 2011 was used for the retrieval of relevant *** search terms FISH,fluorescence in situ hybridization,DIA,digital image analysis and cholangiocarcinoma were *** original and review articles were ***:FISH identifies cells with chromosomal abnormalities,mainly numerical aberrations,using a mixture of fluorescencelabeled *** offers a higher sensitivity than routine cytology,retaining a high level of *** DIA criterion for malignancy is demonstration of *** technique increases the sensitivity to 40%,but the specificity remains *** data from application to other tumors suggest that combination of FISH and DIA may be of further ***:The new techniques offer a significantly enhanced diagnostic efficacy in the evaluation of ERCP brush *** from contributing to a more timely diagnosis,their wider application to cholangiocarcinoma may also facilitate the genetic study of the disease and add to our understanding of oncogenesis at the molecular level,with the prospect of identifying targets for novel therapeutic interventions.

关键词： cholangiocarcinoma fluorescence in situ hybridization digital image analysis

Acute leukemic iridocylitis in an adult with acute lymphoblastic leukemia as an initial presentation of relapse

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Chinese Medical Journal 2013年第18期126卷 3596-3596页

作者： TIAN Yuan LIU Hui CHANG Nai-bai LI Jiang-tao department of haematology Beijing Hospital Public Health Administry Beijing 100730 China

To the editor： A 25-year-old male had been well until October 2009, when he developed abdominal pain, diarrhea, and *** results of the hematological examination were as follows. White blood ceils were 108.76× 10^9/L. The bone marrow was hypercellular with 32.5% lymophoblasts and 55.5% infantile lymphocytes which were cytochemically positive for PAS. Flow cytometric analysis revealed that the blasts were positive for CD7, CD2, CD3, CD8,

关键词： HYPOPYON

GLYR1 could regulate transcription of PER3 and affect the growth and regulate bortezomib sensitivity of multiple myeloma cells

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GLYR1 could regulate transcription of PER3 and affect the gr...

Gastrointestinal bleeding as initial presentation of extramedullary plasma cell neoplasms: A case report and review of the literature

浙江省免疫学会第十三次学术大会

作者： Xiao Yan Kaihong Xu BinbinLai Lieguang Chen Qunfang Ge Lixia Sheng Guifang Ouyang department of haematology The First Affiliated Hospital of Ningbo University

Background:Period circadian regulator 3(PER3) functions as a tumor suppressor in various ***,the roles of PER3 in multiple myeloma(MM) have not been ***:This study aimed to investigate the effects of PER3 on MM cell growth and bortezomib *** and methods:RT-qPCR was applied for determining mRNA expression and western blot for detecting protein *** binding sites of glyoxylate reductase 1 homolog(GLYR1) on the promoter of PER3 was analyzed by UCSC and confirmed by luciferase and Chromatin immunoprecipitation(ChIP) *** behaviors were determined by CCK-8,colony formation,TUNEL,as well as transwell ***:The expression of PER3 in choroid plexus,placenta,appendix,bone marrows and thymus,especially in bone marrows,was relatively ***,we further analyzed PER3 expression in various ***3 expression was reduced in *** we analyzed PER3 expression in MM *** found that PER3 expression,generally,was low in MM ***,bioinformatics analysis indicated that low expression of PER3 in MM patients showed significantly poor 5-year overall survival(OS) rates and event-free survival(EFS) rates compared with MM patients with highly expressed *** of PER3 suppressed the proliferative,migrative,and invasive ability of MM cells,and also increased the sensitivity of MM cells to ***,results of bioinformatic analysis suggested that GLYR1 was able to regulate the transcription of PER3,meanwhile,overexpressed GLYR1 significantly increased the mRNA expression of ***,PER3 was markedly enriched by the treatment of ***,co-transfection with PER-WT and GLYR1 overexpression plasmids markedly increased luciferase activity,while PER-MT had no significant effects on luciferase *** results suggested that GLYR1 can regulate the transcription of ***,overexpressed GLYR1 significantly decreased the viability,migration,and in

关键词： multiple myeloma period circadian regulator 3 glyoxylate reductase 1 homolog apoptosis

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World Journal of Gastrointestinal Endoscopy 2019年第4期11卷 308-321页

作者： Evangelia Iosif Clare Rees Salome Beeslaar Awad Shamali Roberto Lauro Charis Kyriakides department of Gastrointestinal Surgery Frimley Park Hospital department of haematology Frimley Park Hospital department of Histopathology Frimley Park Hospital

BACKGROUND Plasma-cell neoplasms rarely involve the gastrointestinal tract and manifest as gastrointestinal bleeding. Plasmablastic myeloma is an aggressive plasma cell neoplasm associated with poor outcomes. A small number of cases with gastrointestinal involvement is reported in the literature and therefore high index of suspicion is essential for avoiding delays in diagnosis and *** SUMMARY Our aim is to present our experience of a 70-year-old patient with a secondary presentation of plasmablastic myeloma manifesting as unstable upper gastrointestinal bleeding and to review the literature with the view to consolidate and discuss information about diagnosis and management of this rare entity. In addition to our case, a literature search(Pub Med database) of case reports of extramedullary plasma cell neoplasms manifesting as upper gastrointestinal bleeding was performed. Twenty-seven cases of extramedullary plasmacytoma(EMP) involving the stomach and small bowel presenting with upper gastrointestinal bleeding were retrieved. The majority of patients were males(67%). The average age on diagnosis was 62.7 years. The most common site of presentation was the stomach(41%), followed by the duodenum(15%). The most common presenting complaint was melena(44%). In the majority of cases, the EMPs were a secondary manifestation(63%) at the background of multiple myeloma(26%), plasmablastic myeloma(7%) or high-grade plasma cell myeloma(4%). Oesophagogastroscopy was the main diagnostic modality and chemotherapy the preferred treatment option for secondary *** Despite their rare presentation, upper gastrointestinal EMPs should be considered in the differential diagnosis of patients with gastrointestinal bleeding especially in the presence of systemic haematological malignancy.

关键词： Gastrointestinal bleeding Extramedullary plasma cell neoplasm Plasmablastic myeloma Multiple myeloma Extramedullary plasmacytoma Case report

Levels of Immunoglobulin Classes Are Not Associated with Severity of HIV Infection in Nigerian Patients

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World Journal of AIDS 2012年第3期2卷 232-236页

作者： Oluwaseun O. Akinpelu Yetunde A. Aken'Ova O. Ganiyu Arinola department of haematology College of Health Sciences Ladoke Akintola University of Technology Ogbomoso Nigeria department of haematology College of Medicine University of Ibadan Ibadan Nigeria department of Immunology College of Medicine University of Ibadan Ibadan Nigeria

The serum concentrations of immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), total protein and albumin were measured in 35 Human Immunodeficiency Virus—positive, HAART (highly active antiretroviral therapy) na?ve subjects attending the PEPFAR (President's Emergency Plan for AIDS relief) clinic, University College Hospital, Ibadan and in 30 apparently healthy control subjects to assess the relationship between serum protein, immunoglobulin concentrations and laboratory indices of HIV disease (CD4 cell counts and viral load). Serum IgG (1008.6 ± 530.7 mg/dl), IgA (170.4 ± 69 mg/dl) and total protein (9.9 ± 1.7 g/dl) levels were higher among HIV positive subjects compared with mean values in healthy subjects (549.8 ± 193.8 mg/dl, 106.8 ± 26.4 mg/dl and 7.8 ± 0.5 g/dl respectively). The median serum IgM concentration (131mg/dl) was significantly higher in HIV positive subjects compared with 35 mg/dl in healthy controls (p 200 cells/μL. There was also no statistically significant correlation observed between viral load and serum immunoglobulin levels.

关键词： HIV Immunoglobulins

Chronic lymphocytic leukemia in China

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Chinese Medical Journal 2022年第8期135卷 883-886页

作者： Robert Peter Gale haematology Research Centre Department of Immunology and InflammationImperial College LondonLondon SW72AZUK.

Chronic lymphocytic leukemia(CLL)is 10-to 20-fold less common in Han Chinese in China compared with persons of predominately European descent translating to inci-dences of 0.2 to 0.6 per 10E+5 population/year vs.4.6 per 10E+5 population/year.[1-3] Reason(s)for this markedly lower incidence and therefore prevalence in China is unknown but is shared with the other Asian nationalities ***,Koreans,and others,.+-61 Studies of large cohorts of Chinese with CLL are relatively rare and there are no population-based studies in the mainland of *** seeming differences between CLL in Chinese and persons of predominately European descent are reported such as younger age at diagnosis,different background genotypes,increased frequency of IGHV mutation,different stereotype use and different mutation topographies.7 However,in general,most cases of CLL in Han Chinese are like CLL in persons of predominately European descent.

关键词： lymphocytic markedly diagnosis