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Personalized chemotherapy in clear cell adenocarcinoma of the urethra:A case report

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World Journal of Clinical Oncology 2020年第4期11卷 243-249页

作者： Lisa B E Shields Arash Rezazadeh Kalebasty norton Neuroscience institute Norton HealthcareLouisvilleKY 40202United States norton cancer institute Norton HealthcareLouisvilleKY 40202United States

BACKGROUND Clear cell adenocarcinoma of the urethra is a rare type of aggressive cancer with a poor prognosis.Clear cell carcinoma of the urethra represents less than 0.02%of all malignancies in women.Adenocarcinomas account for 10%of female urethral carcinomas,of which 40%are the clear cell variant.Determining the presence or absence of certain mutations through genetic testing may predict whether a patient with cancer may benefit from a particular chemotherapy regimen.CASE SUMMARY A 40-year-old woman presented with a 3-year history of slow urinary flow and a 3-mo history of urinary urgency and frequency as well as gross hematuria.An abdominal and pelvic computed tomography scan demonstrated enlarged lymph nodes in the abdomen and pelvis.A biopsy of a left inguinal lymph node microscopically confirmed a metastatic adenocarcinoma of the urethra.Specialized genetic testing determined personalized chemotherapy.She was treated successfully with a non-platinum-based chemotherapy consisting of paclitaxel and bevacizumab.Following 3 cycles of paclitaxel and bevacizumab,she attained significant clinical improvement,and response by FDG-Positron emission tomography(PET)imaging showed a definite improvement in size and metabolic activity.She achieved complete response after 6 cycles of therapy by PET scan.The patient concluded 11 cycles of paclitaxel and bevacizumab,and a subsequent PET scan confirmed progression of metastatic disease.The patient was then treated with two cycles of doxorubicin after which a PET scan revealed a mixed response to the treatment.CONCLUSION We report the first case of a patient with metastatic clear cell adenocarcinoma of the urethra who underwent personalized chemotherapy after testing for cancer gene alterations.Our unique case represents the safe and effective use of nonplatinum-based chemotherapy in clear cell adenocarcinoma of the urethra.

关键词： Oncology Clear cell adenocarcinoma Urethra Chemotherapy Personalized Genetic testing Case report

Concurrent renal cell carcinoma and hematologic malignancies: Nine case reports

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World Journal of Clinical Oncology 2020年第8期11卷 644-654页

作者： Lisa BE Shields Arash Rezazadeh Kalebasty norton Neuroscience institute Norton HealthcareLouisvilleKY 40202United States norton cancer institute Norton HealthcareLouisvilleKY 40202United States

BACKGROUND The presence of renal cell carcinoma(RCC)and hematologic malignancies(HM)in the same patient is rarely observed.Three primary findings have been described in these patients,including male gender and lymphoid malignancy predominance,and the HM are usually diagnosed before or simultaneously with the RCC.There is a lack of evidence about clinical outcomes in this setting.We report the common characteristics of 9 patients diagnosed with concurrent RCC and HM and their clinical course and response to treatment.CASE SUMMARY Four(44%)patients were diagnosed with RCC prior to the HM,the diagnosis was simultaneous in 4(44%)patients,and 1(11%)patient was diagnosed with the HM prior to the RCC.No patients were treated with cytotoxic chemotherapy or radiation between the diagnosis of RCC and HM.Several unique features were seen in our case series,such as 3 simultaneous cancers in 1(11%)patient,a splenectomy leading to remission of diffuse large B cell lymphoma without the use of chemotherapy in 1(11%)patient,chemotherapy and rituximab for lymphoma resulting in a complete response in primary RCC in 1(11%)patient,and immunotherapy providing an excellent response for primary renal leiomyosarcoma in 1(11%)patient.CONCLUSION These findings highlight the potential role of immune system dysregulation in patients with the diagnosis of RCC and HM whereby the first malignancy predisposes to the second through an immunomodulatory effect.HM have the potential of being confused with lymph node metastasis from kidney cancer.Lymph node biopsy may be necessary at the time of initial diagnosis or in cases of mixed response to therapy.Long-term medical surveillance is warranted when a patient is diagnosed with RCC or HM.Clinicians should be aware of the higher prevalence of male gender and lymphoid malignancy with concurrent RCC and HM and that either of these conditions may be diagnosed first or they may be diagnosed simultaneously.

关键词： Oncology Renal cell cancer Hematologic malignancy Lymphoma Immune system Immunotherapy Case report

Metastatic clear cell renal cell carcinoma in isolated retroperitoneal lymph node without evidence of primary tumor in kidneys: A case report

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World Journal of Clinical Oncology 2020年第2期11卷 103-109页

作者： Lisa BE Shields Arash Rezazadeh Kalebasty norton Neuroscience institute Norton HealthcareLouisvilleKY 40202United States norton cancer institute Norton HealthcareLouisvilleKY 40202United States

BACKGROUND Retroperitoneal lymph node dissection(RPLND)plays a diagnostic,therapeutic,and prognostic role in myriad urologic malignancies,including testicular carcinoma,renal cell carcinoma(RCC),and upper urinary tract urothelial carcinoma.RCC represents 2%of all cancers with approximately 25%of patients presenting with advanced disease.Clear cell RCC(CCRCC)is the most common RCC,accounting for 75%-80%of all RCC.CASE SUMMARY A 71-year-old man presented with a history of benign prostatic hypertrophy.He was asymptomatic without any hematuria,pain,or other urinary symptoms.A computed tomography(CT)scan of the abdomen and pelvis showed a 1.8 cm left retroperitoneal lymph node.There was no evidence of renal pathology.A core biopsy was performed of the left para-aortic lymph node.Although the primary tumor site was unknown,the morphological and immunohistochemical features were most consistent with CCRCC.A RPLND was performed which revealed a single mass 5.5 cm in greatest dimension with extensive necrosis.The retroperitoneal lymph node was most compatible with CCRCC.A nephrectomy was not conducted as a renal mass had not been detected on any prior imaging studies.The patient did not receive any type of adjuvant therapy.The patient underwent surveillance with serial CT scans with contrast of the chest,abdomen,and pelvis for the next 5 years,all of which demonstrated no recurrent or metastatic disease and no evidence of retroperitoneal adenopathy.CONCLUSION Our unique case emphasizes the therapeutic role of metastasectomy in metastatic CCRCC even in the absence of primary tumor in the kidneys.

关键词： Oncology Renal cell carcinoma Clear cell carcinoma Lymph node dissection Retroperitoneal Metastasis Nephrectomy without primary site Case report

Surgical decompression in acute spinal cord injury： A review of clinical evidence, animal model studies, and potential future directions of investigation

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Frontiers in Biology 2014年第2期9卷 127-136页

作者： Yiping LI Chandler L. WALKER Yi Ping ZHANG Christopher B. SHIELDS Xiao-Ming XU Spinal Cord and Brain Injury Research Group Stark Neurosciences Research Institute Department of Neurological Surgery and Goodmanand Campbell Brain and Spine Indiana University School of Medicine Indianapolis IN 46202 USA norton Neuroscience institute Norton Healthcare Louisville KY 40202 USA

The goal for treatment in acute spinal cord injury （SCI） is to reduce the extent of secondary damage and facilitate neurologic regeneration and functional recovery. Although multiple studies have investigated potential new therapies for the treatment of acute SCI, outcomes and management protocols aimed at ameliorating neurologic injury in patients remain ineffective. More recent clinical and basic science research have shown surgical interventions to be a potentially valuable modality for treatment; however, the role and timing of surgical decompression, in addition to the optimal surgical intervention, remain one of the most controversial topics pertaining to surgical treatment of acute SCI. As an increasing number of potential treatment modalities emerge, animal models are pivotal for investigating its clinical application and translation into human trials. This review critically appraises the available literature for both clinical and basic science studies to highlight the extent of investigation that has occurred, specific therapies considered, and potential areas for future research.

关键词： acute spinal cord injury surgical decompression durotomy animal models

Dynamic glial response and crosstalk in demyelination-remyelination and neurodegeneration processes

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Neural Regeneration Research 2021年第7期16卷 1359-1368页

作者： Tianci Chu Lisa B.E.Shields Wenxin Zeng Yi Ping Zhang Yuanyi Wang Gregory N.Barnes Christopher B.Shields Jun Cai Pediatric Research institute Department of PediatricsUniversity of Louisville School of MedicineLouisvilleKYUSA norton Neuroscience institute Norton HealthcareLouisvilleKYUSA Department of Spine Surgery The First Hospital of Jilin UniversityChangchunJilin ProvinceChina Department of Neurology University of Louisville School of MedicineLouisvilleKYUSA Department of Pharmacology and Toxicology University of LouisvilleLouisvilleKYUSA Department of Neurological Surgery University of Louisville School of MedicineLouisvilleKYUSA

Multiple sclerosis is an autoimmune disease in which the immune system attacks the myelin sheath in the central nervous system.It is characterized by blood-brain barrier dysfunction throughout the course of multiple sclerosis, followed by the entry of immune cells and activation of local microglia and astrocytes.Glial cells(microglia, astrocytes, and oligodendrocyte lineage cells) are known as the important mediators of neuroinflammation, all of which play major roles in the pathogenesis of multiple sclerosis.Network communications between glial cells affect the activities of oligodendrocyte lineage cells and influence the demyelination-remyelination process.A finely balanced glial response may create a favorable lesion environment for efficient remyelination and neuroregeneration.This review focuses on glial response and neurodegeneration based on the findings from multiple sclerosis and major rodent demyelination models.In particular, glial interaction and molecular crosstalk are discussed to provide insights into the potential cell-and molecule-specific therapeutic targets to improve remyelination and neuroregeneration.

关键词： astrocyte crosstalk demyelination glial response microglia/macrophage multiple sclerosis neurodegeneration neuroinflammation oligodendrocyte lineage cells remyelination

Thromboembolic events in metastatic testicular cancer treated with cisplatin-based chemotherapy

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World Journal of Clinical Oncology 2021年第3期12卷 183-194页

作者： Lisa B E Shields Michael W Daniels Nataliya Mar Arash Rezazadeh Kalebasty norton Neuroscience institute Norton HealthcareLouisvilleKY 40202United States Department of Bioinformatics and Biostatistics University of LouisvilleLouisvilleKY 40292United States Division of Hematology/Oncology Department of MedicineUCI Medical CenterOrangeCA 92868United States

BACKGROUND Testicular germ cell tumor(TGCT)is the most curable solid tumor and most common cancer among men 18-39 years.While cisplatin-based chemotherapy has significantly lengthened the survival of patients with TGCT,it is associated with a high rate of thromboembolic events(TEE).AIM To summarize our single-center experience highlighting patients who were diagnosed with TGCT and received platinum-based chemotherapy,with special attention to those patients who suffered a TEE.METHODS A retrospective analysis of the medical records and imaging studies of 68 consecutive individuals who were diagnosed with TGCT and received platinumbased chemotherapy at our Institution in a metropolitan community between January 1,2014 and December 31,2019.RESULTS A total of 19(28%)patients experienced a TEE following orchiectomy which occurred during chemotherapy in 13(68%)of these patients.Patients with a higher pathologic stage(stage III)were significantly(P=0.023)more likely to experience a TEE compared to patients who had a lower stage.Additionally,patients who were treated with 3 cycles of bleomycine,etoposide,and cisplatin and 1 cycle of etoposide and cisplatin or 4 cycles of etoposide and cisplatin were significantly 5(P=0.02)times more likely to experience a TEE compared to patients who were treated with only 3 cycles of bleomycine,etoposide,and cisplatin.CONCLUSION Due to numerous factors that predispose to a TEE such as large retroperitoneal disease,higher clinical stage,greater number of chemotherapy cycle,central venous catheter,cigarette smoking,and possible cannabis use,high-risk ambulatory patients with TGCT treated with cisplatin-based chemotherapy may benefit from prophylactic anticoagulation.Randomized studies to evaluate the safety and efficacy of prophylactic anticoagulants are warranted in this young patient population generally devoid of medical co-morbidities.

关键词： Oncology Testicular cancer Thromboembolic Cisplatin Pulmonary embolism Thromboprophylaxis

Parallel evolution of fish bi-modal breathing and expansion of olfactory receptor(OR)genes:toward a universal ORs nomenclature

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遗传学报:英文版 2023年第8期50卷 600-610页

作者： Liliana Silva Tito Mendes Luana Ramos Guojie Zhang Agostinho Antunes CIIMAR/CIMAR Interdisciplinary Centre of Marine and Environmental ResearchUniversity of PortoTerminal de Cruzeiros do Porto de LeixõesAv.General Norton de Matoss/n4450-208PortoPortugal Department of Biology Faculty of SciencesUniversity of PortoRua do Campo Alegre4169-007PortoPortugal Villum Centre for Biodiversity Genomics Section for Ecology and EvolutionDepartment of BiologyUniversity of CopenhagenDK-2100 CopenhagenDenmark BGI-Shenzhen Beishan Industrial ZoneShenzhenGuangdong 518083China State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China

Olfactory receptors(ORs)play a key role in the prime sensorial perception,being highly relevant for intra/interspecific interactions.ORs are a subgroup of G-protein coupled receptors that exhibit highly complex subgenomes in vertebrates.However,OR repertoires remain poorly studied in fish lineages,precluding finely retracing their origin,evolution,and diversification,especially in the most basal groups.Here,we conduct an exhaustive gene screening upon 43 high-quality fish genomes exhibiting varied gene repertoires(2e583 genes).While the early vertebrates performed gas exchange through gills,we hypothesize that the emergence of new breathing structures(swim bladder and paired lungs)in early osteichthyans may be associated with expansions in the ORs gene families sensitive to airborne molecules.Additionally,we verify that the OR repertoire of moderns actinopterygians has not increased as expected following a whole genome duplication,likely due to regulatory mechanisms compensating the gene load excess.Finally,we identify 25 distinct OR families,allowing us to propose an updated universal nomenclature for the fish ORs.

关键词： Fish OR repertoires Updated ORs nomenclature ORs expansion Bi-modal breathing WGD and ORs diversification

Airway pressure release ventilation forin-vivodonor lung management and lung transplant outcomes

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中华胸部外科电子杂志 2022年第2期9卷 65-74页

作者： Sreeja Biswas Roy Deepika Razia Ashwini Arjuna Paul Kang Michael T.Olson Ross M.Bremner Michael A.Smith Rajat Walia norton Thoracic institute St.Joseph’s Hospital and Medical CenterCenter for Thoracic Disease and TransplantationPhoenixAZUSA Creighton University School of Medicine-Phoenix Regional Campus PhoenixAZUSA University of Arizona College of Public Health PhoenixAZUSA University of Arizona College of Medicine-Phoenix Campus PhoenixAZUSA

Background:Airway pressure release ventilation(APRV)can be used for cadaveric donor lung recruitment.APRV elevates PaO_(2)in donor lungs;however,reported outcomes in recipients with APRVmanaged donor lungs are limited.Methods:We retrospectively reviewed patients who underwent lung transplantation(LTx)from 2012 to 2013 and divided them into two groups based on mode of ventilation used during donor management and organ extraction(A:non-APRV;B:APRV).Kaplan-Meier method and multivariate Cox regression were used for analysis.Results:We found 126 LTx recipients(LTxRs);9 were excluded for use of portable ventilation perfusion systems.Of the remaining 117 patients,81(69%)were in Group A;36(31%)were in Group B.Preoperative LTxR characteristics(age,sex,lung allocation score,endstage lung disease type)were comparable between groups.Donors for Group B were older(P=0.03)and had higher body mass index(BMI)(P<0.001),higher incidence of death from chest trauma(P=0.008),longer ventilation duration after brain death(P<0.001),and higher pre-explant PaO_(2)/FiO_(2)ratios(P<0.001).Post-LTx duration of mechanical ventilation,hospital stay,and median survival were similar in both groups.Risk of death was comparable between the two groups at the end of follow-up(HR=1.42;95%CI:0.57-3.56;P=0.45).Conclusions:APRV is a safe and effective pre-LTx donor lung management strategy.Short-and long-term survival outcomes were comparable in LTx recipients,irrespective of donor ventilation mode.APRV may help recruit lungs from older donors with higher BMI who die from chest trauma and have anticipated longer ventilation duration.

关键词： Lung transplantation donor lungs airway pressure release ventilation(APRV) outcomes

Low-dose radiation and Alzheimer's disease:Neuronal effects and a potential modality for therapy?

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中华放射医学与防护杂志 2019年第8期39卷 581-589页

作者： Feng Li Liu Qiang Wang Bing Cai Lu Qianfoshan Hospital of Shandong Province Jinan 250014 China institute of Radiation Medicine Chinese Academy of Medical Science & Peking Union Medical College Tianjin 300192 China National institute of Radiological Sciences National Institutes for Quantum and Radiological Science and Technology Chiba 263-8555 Japan Departments of Radiation Oncology and Pharmacology and Toxicology University of Louisville School of Medicine Louisville KY 40202 USA Feng Li is working on Department of Pediatrics University of Louisville School of Medicine Norton Healthcare Pediatric Research Institute Louisville KY 40202 USA

Exposure to low-dose radiation(LDR,mostly less than 100 mGy)may reduce the vulnerability of exposed tissues to subsequent high-dose radiation(HDR)-induced damage,a phenomenon known as adaptive responses,which occurs via mechanisms including anti-inflammation and anti-oxidation.Alzheimer′s disease(AD)is a type of dementia that causes problems with memory,thinking,and behavior.Using the available literature,this review will examine whether there is any effect of LDR on AD.The available evidence shows that although LDR can alter the expression of some genes related to AD such as Apbb1,Lrp1,and Il1α,these alterations do not cause AD-like syndromes in animals,suggesting that LDR may also simultaneously upregulate several protective mechanisms that prevent the eventual development of AD.Furthermore,LDR seems capable of improving the symptoms of AD,as evidenced by the experience of an 81-year-old female AD patient.This patient was diagnosed with AD more than 10 years ago and gradually progressed to advanced AD in 2015,despite routine treatment.The patient then received about 12 computed tomography scans(about 40 mGy each)up until Nov.2017,which significantly improved her quality of life and reduced several AD symptoms.The improvement in this patient′s medical condition led to a few recent clinical trials investigating the effects of LDR on AD.To date,there is no efficient therapy available for AD,thus whether exposure to LDR at 100 mGy can provide a preventive or therapeutic effect for AD is an important issue.If LDR is a potential treatment for AD,as suggested by this reported case,this non-invasive approach would also bear the merit that it would be unlikely to cause a significant radiation health risk,as the LDR could be delivered locally to the head without any impact on other organs.

关键词： Low-dose radiation Alzheimer's disease Adaptive response Hormesis Neuronal stimulation