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Article ; Online: Perioperative systemic therapy for bladder cancer.

Eulitt, Patrick J / Bjurlin, Marc A / Milowsky, Matthew I

2019 Volume 29, Issue 3, Page(s) 220–226

Abstract: Purpose of review: Recent advances in research related to biomarkers and immunotherapy has the potential to transform the landscape for the use of perioperative systemic therapy in patients with bladder cancer.: Recent findings: Predictive biomarkers ...

Abstract	Purpose of review: Recent advances in research related to biomarkers and immunotherapy has the potential to transform the landscape for the use of perioperative systemic therapy in patients with bladder cancer. Recent findings: Predictive biomarkers including DNA damage repair genes and gene expression profiling may soon lead to better selection of patients for neoadjuvant cisplatin-based chemotherapy. Success of immunotherapy for the treatment of metastatic bladder cancer has led to promising trials exploring immunotherapy in muscle-invasive disease. Summary: Current trials employing predictive biomarkers as well as those using immunotherapy have the potential to significantly improve the outcome of patients with muscle-invasive bladder cancer.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Antineoplastic Agents, Immunological/therapeutic use ; Biomarkers, Tumor/analysis ; Chemotherapy, Adjuvant ; Cisplatin/therapeutic use ; Cystectomy ; Humans ; Immunotherapy ; Neoadjuvant Therapy ; Neoplasm Invasiveness ; Perioperative Period ; Predictive Value of Tests ; Urinary Bladder Neoplasms/genetics ; Urinary Bladder Neoplasms/pathology ; Urinary Bladder Neoplasms/therapy
Chemical Substances	Antineoplastic Agents ; Antineoplastic Agents, Immunological ; Biomarkers, Tumor ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2019-03-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1091792-5
ISSN	1473-6586 ; 0963-0643
ISSN (online)	1473-6586
ISSN	0963-0643
DOI	10.1097/MOU.0000000000000600
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Article ; Online: Hemophagocytic lymphohistiocytosis in a patient with glioblastoma: a case report.

Kumar, Vaibhav / Eulitt, Patrick J / Bermudez, Ana / Khagi, Simon

CNS oncology

2019 Volume 8, Issue 4, Page(s) CNS45

Abstract: Adult onset hemophagocytic lymphohistiocytosis (HLH) is a rare condition, usually secondary to either a precipitating infective or hematologic malignancy. We present a case of Epstein-Barr virus associated HLH in a 55-year-old female receiving treatment ... ...

Abstract	Adult onset hemophagocytic lymphohistiocytosis (HLH) is a rare condition, usually secondary to either a precipitating infective or hematologic malignancy. We present a case of Epstein-Barr virus associated HLH in a 55-year-old female receiving treatment for a glioblastoma (GBM). It is possible that HLH is under recognized, as patients with GBM often have features of a nonspecific systemic inflammatory response syndrome, multiorgan failure and cognitive decline. A high index of suspicion and increased awareness can help improve timeliness of diagnosis. Therapeutically, Epstein-Barr virus associated HLH in patients with solid organ malignancy poses significant challenges. An individualized, multidisciplinary approach is essential when managing adult-onset HLH and providers will need to be mindful of the high mortality rate despite treatment.
MeSH term(s)	Brain Neoplasms/complications ; Brain Neoplasms/therapy ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/therapy ; Fatal Outcome ; Female ; Glioblastoma/complications ; Glioblastoma/therapy ; Humans ; Lymphohistiocytosis, Hemophagocytic/complications ; Lymphohistiocytosis, Hemophagocytic/therapy ; Middle Aged
Keywords	covid19
Language	English
Publishing date	2019-11-28
Publishing country	England
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2692808-5
ISSN	2045-0915 ; 2045-0907
ISSN (online)	2045-0915
ISSN	2045-0907
DOI	10.2217/cns-2019-0013
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Article ; Online: Philadelphia Chromosome-positive Acute Myeloid Leukemia With e1a3

Sheets, Julia W / Eulitt, Patrick / He, Rong / Olteanu, Horatiu / Coombs, Catherine C / Foster, Matthew C / Montgomery, Nathan D / Zeidner, Joshua F

HemaSphere

2020 Volume 4, Issue 6, Page(s) e484

Language	English
Publishing date	2020-10-14
Publishing country	United States
Document type	Case Reports
ISSN	2572-9241
ISSN (online)	2572-9241
DOI	10.1097/HS9.0000000000000484
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Article: Waldenström's macroglobulinemia masquerading as ovarian cancer with peritoneal carcinomatosis, ascites, and elevated CA-125.

Eulitt, Patrick / Fabian, Denise / Kelly, Crystal / Hemminger, Jessica / William, Basem M

Hematology/oncology and stem cell therapy

2017 Volume 12, Issue 1, Page(s) 54–59

Abstract: Waldenström's macroglobulinemia is a rare hematology malignancy which often presents with "B symptoms," anemia, and thrombocytopenia. A 46-year-old woman presented with 2 months of abdominal distension accompanied by an unintentional 20-lb weight loss. ... ...

Abstract	Waldenström's macroglobulinemia is a rare hematology malignancy which often presents with "B symptoms," anemia, and thrombocytopenia. A 46-year-old woman presented with 2 months of abdominal distension accompanied by an unintentional 20-lb weight loss. Her abdominal CT scan demonstrated diffuse carcinomatosis with bilateral ovarian lesions and screening labs revealed a markedly elevated CA-125, suggesting a diagnosis of ovarian cancer. Upon admission for workup, patient was found to have a significant protein gap, later attributed to a markedly elevated IgM. Omental and bone marrow biopsy confirmed the diagnosis of Waldenström's macroglobulinemia, with elevation in CA-125 thought to be secondary to peritoneal irritation. This patient has since been successfully treated with six cycles of bendamusine and rituximab with no evidence of disease on staging scans and normalization of both CA-125 and IgM. To our knowledge, this is the first documented case of Waldenström's macroglobulinemia presenting with symptoms classically associated with ovarian cancer and demonstrates the importance of maintaining a broad differential when evaluating patients with abdominal carcinomatosis.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Ascites/diagnosis ; Ascites/drug therapy ; Ascites/metabolism ; Ascites/pathology ; Bendamustine Hydrochloride/administration & dosage ; CA-125 Antigen/metabolism ; Female ; Humans ; Middle Aged ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Peritoneal Neoplasms/diagnosis ; Peritoneal Neoplasms/drug therapy ; Peritoneal Neoplasms/metabolism ; Peritoneal Neoplasms/pathology ; Rituximab/administration & dosage ; Waldenstrom Macroglobulinemia/diagnosis ; Waldenstrom Macroglobulinemia/drug therapy ; Waldenstrom Macroglobulinemia/metabolism ; Waldenstrom Macroglobulinemia/pathology
Chemical Substances	CA-125 Antigen ; Rituximab (4F4X42SYQ6) ; Bendamustine Hydrochloride (981Y8SX18M)
Language	English
Publishing date	2017-03-31
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	2651893-4
ISSN	1658-3876
ISSN	1658-3876
DOI	10.1016/j.hemonc.2017.02.004
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Article: Myeloid sarcoma manifesting as generalized lymphadenopathy in a patient with myelofibrosis.

Trennepohl, Christopher / Sorah, Jonathan / Eulitt, Patrick / Galeotti, Jonathan / Zeidner, Joshua F / Montgomery, Nathan D / Coombs, Catherine C

Clinical case reports

2019 Volume 7, Issue 11, Page(s) 2274–2276

Abstract: Immunophenotyping is critical to the diagnosis of MS, as it can be difficult to differentiate from other diagnoses including lymphoma using conventional light microscopy. ...

Abstract	Immunophenotyping is critical to the diagnosis of MS, as it can be difficult to differentiate from other diagnoses including lymphoma using conventional light microscopy.
Language	English
Publishing date	2019-10-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2740234-4
ISSN	2050-0904
ISSN	2050-0904
DOI	10.1002/ccr3.2473
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Article ; Online: Correction to: Fibroblast growth factor receptor 3 alterations and response to immune checkpoint inhibition in metastatic urothelial cancer: a real world experience.

Rose, Tracy L / Weir, William H / Mayhew, Gregory M / Shibata, Yoichiro / Eulitt, Patrick / Uronis, Joshua M / Zhou, Mi / Nielsen, Matthew / Smith, Angela B / Woods, Michael / Hayward, Michele C / Salazar, Ashley H / Milowsky, Matthew I / Wobker, Sara E / McGinty, Katrina / Millburn, Michael V / Eisner, Joel R / Kim, William Y

British journal of cancer

2022 Volume 126, Issue 8, Page(s) 1237

Language	English
Publishing date	2022-03-11
Publishing country	England
Document type	Published Erratum
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-022-01781-y
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Article ; Online: Screening elders in the emergency department at risk for mistreatment: a pilot study.

Eulitt, Patrick J / Tomberg, Ryan J / Cunningham, Tina D / Counselman, Francis L / Palmer, Robert M

Journal of elder abuse & neglect

2014 Volume 26, Issue 4, Page(s) 424–435

Abstract: Impaired functional status is associated with risk of elder mistreatment. Screening for functional impairment in elderly patients admitted to emergency departments could be performed to identify patients at risk for elder mistreatment who might benefit ... ...

Abstract	Impaired functional status is associated with risk of elder mistreatment. Screening for functional impairment in elderly patients admitted to emergency departments could be performed to identify patients at risk for elder mistreatment who might benefit from further evaluation. This study utilized a modified Identification of Seniors at Risk (ISAR) screening tool to identify the proportion of elderly at risk for mistreatment due to functional difficulties presenting to two emergency departments in southeastern Virginia, one urban, the other rural. Of a 180-patient cohort (90 per site), 82 screened positive (46%), ISAR > 2 (range 0-6), indicating nearly half of all patients enrolled are at risk for mistreatment. Patients presenting to the urban emergency departments were potentially more at risk than their rural counterparts (p < 0.01). Health care professionals, particularly in urban settings, should consider screening seniors with a simple tool to identify patients at risk of elder mistreatment.
MeSH term(s)	Aged ; Aged, 80 and over ; Cohort Studies ; Elder Abuse/diagnosis ; Elder Abuse/statistics & numerical data ; Emergency Service, Hospital/utilization ; Female ; Geriatric Assessment/methods ; Humans ; Male ; Middle Aged ; Patient Admission/statistics & numerical data ; Pilot Projects ; Risk Assessment/methods ; Rural Population/statistics & numerical data ; Urban Population/statistics & numerical data ; Virginia
Language	English
Publishing date	2014
Publishing country	England
Document type	Evaluation Studies ; Journal Article
ZDB-ID	1018101-5
ISSN	1540-4129 ; 0894-6566
ISSN (online)	1540-4129
ISSN	0894-6566
DOI	10.1080/08946566.2014.903549
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Zs.A 2820: Show issues

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Article ; Online: Fibroblast growth factor receptor 3 alterations and response to immune checkpoint inhibition in metastatic urothelial cancer: a real world experience.

British journal of cancer

2021 Volume 125, Issue 9, Page(s) 1251–1260

Abstract: Background: FGFR3-altered urothelial cancer (UC) correlates with a non-T cell-inflamed phenotype and has therefore been postulated to be less responsive to immune checkpoint blockade (ICB). Preclinical work suggests FGFR3 signalling may suppress ... ...

Abstract	Background: FGFR3-altered urothelial cancer (UC) correlates with a non-T cell-inflamed phenotype and has therefore been postulated to be less responsive to immune checkpoint blockade (ICB). Preclinical work suggests FGFR3 signalling may suppress pathways such as interferon signalling that alter immune microenvironment composition. However, correlative studies examining clinical trials have been conflicting as to whether FGFR altered tumours have equivalent response and survival to ICB in patients with metastatic UC. These findings have yet to be validated in real world data, therefore we evaluated clinical outcomes of patients with FGFR3-altered metastatic UC treated with ICB and investigate the underlying immunogenomic mechanisms of response and resistance. Methods: 103 patients with metastatic UC treated with ICB at a single academic medical center from 2014 to 2018 were identified. Clinical annotation for demographics and cancer outcomes, as well as somatic DNA and RNA sequencing, were performed. Objective response rate to ICB, progression-free survival, and overall survival was compared between patients with FGFR3-alterations and those without. RNA expression, including molecular subtyping and T cell receptor clonality, was also compared between FGFR3-altered and non-altered patients. Results: Our findings from this dataset confirm that FGFR3-altered (n = 17) and wild type (n = 86) bladder cancers are equally responsive to ICB (12 vs 19%, p = 0.73). Moreover, we demonstrate that despite being less inflamed, FGFR3-altered tumours have equivalent T cell receptor (TCR) diversity and that the balance of a CD8 T cell gene expression signature to immune suppressive features is an important determinant of ICB response. Conclusions: Our work in a real world dataset validates prior observations from clinical trials but also extends this prior work to demonstrate that FGFR3-altered and wild type tumours have equivalent TCR diversity and that the balance of effector T cell to immune suppression signals are an important determinant of ICB response.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; CD8-Positive T-Lymphocytes/metabolism ; Carcinoma, Transitional Cell/drug therapy ; Carcinoma, Transitional Cell/genetics ; Carcinoma, Transitional Cell/immunology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immune Checkpoint Inhibitors/administration & dosage ; Immune Checkpoint Inhibitors/pharmacology ; Male ; Middle Aged ; Receptor, Fibroblast Growth Factor, Type 3/genetics ; Receptors, Antigen, T-Cell/metabolism ; Retrospective Studies ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; Survival Analysis ; Treatment Outcome ; Urinary Bladder Neoplasms/drug therapy ; Urinary Bladder Neoplasms/genetics ; Urinary Bladder Neoplasms/immunology
Chemical Substances	Immune Checkpoint Inhibitors ; Receptors, Antigen, T-Cell ; FGFR3 protein, human (EC 2.7.10.1) ; Receptor, Fibroblast Growth Factor, Type 3 (EC 2.7.10.1)
Language	English
Publishing date	2021-07-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-021-01488-6
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Article ; Online: Pilot Study of [

Clinical genitourinary cancer

2020 Volume 18, Issue 5, Page(s) 378–386.e1

Abstract: Introduction: Computed tomography (CT) has limited diagnostic accuracy for staging of muscle-invasive bladder cancer (MIBC). [: Patients and methods: Twenty-one patients with MIBC with planned radical cystectomy were enrolled. Two teams of ... ...

Abstract	Introduction: Computed tomography (CT) has limited diagnostic accuracy for staging of muscle-invasive bladder cancer (MIBC). [ Patients and methods: Twenty-one patients with MIBC with planned radical cystectomy were enrolled. Two teams of radiologists reviewed FDG-PET/MRI scans to determine: (1) presence of primary bladder tumor; and (2) lymph node involvement and distant metastases. FDG-PET/MRI was compared with cystectomy pathology and computed tomography (CT). Results: Eighteen patients were included in the final analysis, most (72.2%) of whom received neoadjuvant chemotherapy. Final pathology revealed 10 (56%) patients with muscle invasion and only 3 (17%) patients with lymph node involvement. Clustered analysis of FDG-PET/MRI radiology team reads revealed a sensitivity of 0.80 and a specificity of 0.56 for detection of the primary tumor with a sensitivity of 0 and a specificity of 1.00 for detection of lymph node involvement when compared with cystectomy pathology. CT imaging demonstrated similar rates in evaluation of the primary tumor (sensitivity, 0.91; specificity, 0.43) and lymph node involvement (sensitivity, 0; specificity, 0.93) when compared with pathology. Conclusions: This pilot single-institution experience of FDG-PET/MRI for preoperative staging of MIBC performed similar to CT for the detection of the primary tumor; however, the determination of lymph node status was limited by few patients with true pathologic lymph node involvement. Further studies are needed to evaluate the potential role for FDG-PET/MRI in the staging of MIBC.
MeSH term(s)	Fluorodeoxyglucose F18 ; Humans ; Lymphatic Metastasis ; Magnetic Resonance Imaging ; Muscles/pathology ; Neoplasm Staging ; Pilot Projects ; Positron-Emission Tomography ; Radiopharmaceuticals ; Sensitivity and Specificity ; Urinary Bladder Neoplasms/diagnostic imaging ; Urinary Bladder Neoplasms/pathology
Chemical Substances	Radiopharmaceuticals ; Fluorodeoxyglucose F18 (0Z5B2CJX4D)
Language	English
Publishing date	2020-03-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2225121-2
ISSN	1938-0682 ; 1558-7673
ISSN (online)	1938-0682
ISSN	1558-7673
DOI	10.1016/j.clgc.2020.02.008
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Article ; Online: Poly(ADP-ribose) polymerase 1 modulates the lethality of CHK1 inhibitors in carcinoma cells.

Mitchell, Clint / Park, Margaret / Eulitt, Patrick / Yang, Chen / Yacoub, Adly / Dent, Paul

Molecular pharmacology

2010 Volume 78, Issue 5, Page(s) 909–917

Abstract: Prior studies have demonstrated that inhibition of CHK1 can promote the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and phosphorylation of histone H2AX and that inhibition of poly(ADP-ribose) polymerase 1 (PARP1) can affect ... ...

Abstract	Prior studies have demonstrated that inhibition of CHK1 can promote the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and phosphorylation of histone H2AX and that inhibition of poly(ADP-ribose) polymerase 1 (PARP1) can affect growth factor-induced ERK1/2 activation. The present studies were initiated to determine whether CHK1 inhibitors interacted with PARP1 inhibition to facilitate apoptosis. Transient expression of dominant-negative CHK1 raised basal ERK1/2 activity and prevented CHK1 inhibitors from activating ERK1/2. CHK1 inhibitors modestly increased the levels of PARP1 ADP ribosylation and molecular or small-molecule inhibition of PARP1 blocked CHK1 inhibitor-stimulated histone H2AX phosphorylation and activation of ERK1/2. Stimulated histone H2AX phosphorylation was ataxia telangiectasia-mutated protein-dependent. Multiple CHK1 inhibitors interacted in a greater than additive fashion with multiple PARP1 inhibitors to cause transformed cell-killing in short-term viability assays and synergistically killed tumor cells in colony-formation assays. Overexpression of BCL-xL or loss of BAX/BAK function, but not the function of BID, suppressed CHK1 inhibitor + PARP1 inhibitor lethality. Inhibition of BCL-2 family protein function enhanced CHK1 inhibitor + PARP1 inhibitor lethality and restored drug-induced cell-killing in cells overexpressing BCL-xL. Thus, PARP1 plays an important role in regulating the ability of CHK1 inhibitors to activate ERK1/2 and the DNA damage response. An inability of PARP1 to modulate this response results in transformed cell death mediated through the intrinsic apoptosis pathway.
MeSH term(s)	Cell Death/drug effects ; Cell Line, Tumor ; Checkpoint Kinase 1 ; Drug Synergism ; Enzyme Activation ; Histones/metabolism ; Humans ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Phosphorylation ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerase Inhibitors ; Poly(ADP-ribose) Polymerases/physiology ; Protein Kinase Inhibitors/pharmacology ; Protein Kinases/metabolism ; Signal Transduction/drug effects ; Staurosporine/analogs & derivatives ; Staurosporine/pharmacology ; Thiophenes/pharmacology ; Urea/analogs & derivatives ; Urea/pharmacology
Chemical Substances	3-(carbamoylamino)-5-(3-fluorophenyl)-N-(3-piperidyl)thiophene-2-carboxamide ; H2AX protein, human ; Histones ; Poly(ADP-ribose) Polymerase Inhibitors ; Protein Kinase Inhibitors ; Thiophenes ; 7-hydroxystaurosporine (7BU5H4V94A) ; Urea (8W8T17847W) ; PARP1 protein, human (EC 2.4.2.30) ; Poly (ADP-Ribose) Polymerase-1 (EC 2.4.2.30) ; Poly(ADP-ribose) Polymerases (EC 2.4.2.30) ; Protein Kinases (EC 2.7.-) ; CHEK1 protein, human (EC 2.7.11.1) ; Checkpoint Kinase 1 (EC 2.7.11.1) ; Mitogen-Activated Protein Kinase 1 (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 3 (EC 2.7.11.24) ; Staurosporine (H88EPA0A3N)
Language	English
Publishing date	2010-08-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	124034-1
ISSN	1521-0111 ; 0026-895X
ISSN (online)	1521-0111
ISSN	0026-895X
DOI	10.1124/mol.110.067199
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