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Article ; Online: Too Much or Just Enough of a Good Thing: Vascular Endothelial Growth Factor Inhibition in Renal Cell Carcinoma?

Harshman, Lauren C

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2017 Volume 35, Issue 16, Page(s) 1755–1757

MeSH term(s)	Carcinoma, Renal Cell ; Humans ; Kidney Neoplasms ; Neoplasms, Second Primary ; Sunitinib ; Vascular Endothelial Growth Factor A
Chemical Substances	Vascular Endothelial Growth Factor A ; Sunitinib (V99T50803M)
Language	English
Publishing date	2017-03-13
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.2016.71.8007
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Zs.A 1847: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 650: Show issues

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Article ; Online: Mind the gap: What is driving the survival disparity between the sexes in bladder cancer?

Harshman, Lauren C

Cancer

2016 Volume 122, Issue 13, Page(s) 1966–1970

MeSH term(s)	African Americans ; Humans ; Sexual Behavior ; Urinary Bladder Neoplasms
Language	English
Publishing date	2016--01
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.30027
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Uh III Zs.146: Show issues

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Article ; Online: Adjuvant Therapy Options in Renal Cell Carcinoma: Where Do We Stand?

Martinez Chanza, Nieves / Tripathi, Abhishek / Harshman, Lauren C

Current treatment options in oncology

2019 Volume 20, Issue 5, Page(s) 44

Abstract: Opinion statement: Adjuvant therapy for non-metastatic renal cell carcinoma (RCC) remains controversial. Of the four reported randomized controlled trials evaluating adjuvant vascular endothelial growth factor (VEGF) inhibition, only one met its primary ...

Abstract	Opinion statement: Adjuvant therapy for non-metastatic renal cell carcinoma (RCC) remains controversial. Of the four reported randomized controlled trials evaluating adjuvant vascular endothelial growth factor (VEGF) inhibition, only one met its primary endpoint. The S-TRAC study demonstrated a statistically significant improvement in disease-free survival (DFS) of greater than 1 year with adjuvant sunitinib compared to placebo in patients with high-risk localized RCC and earned it FDA approval. However, the larger ASSURE study which reported first did not find a difference in DFS or overall survival between 1 year of adjuvant sunitinib or sorafenib compared to placebo. Given the discordant results of the two sunitinib studies, two other negative studies of adjuvant targeted therapy with pazopanib and axitinib, the lack of definite overall survival benefit in any study, and the high incidence of treatment-related adverse events with sunitinib, we do not recommend the routine use of adjuvant sunitinib. The decision to offer adjuvant sunitinib should be considered on an individual basis after an informed discussion of the potential toxicities and the risk/benefit ratio. Despite numerous efforts and recently published works, there is a paucity of prognostic and predictive molecular biomarkers in RCC. Further investigation is needed to discover new tools that can enhance the identification of patients who are most likely to benefit from adjuvant treatment beyond pathologic stage. Immune checkpoint inhibitors have great potential to significantly improve outcomes in high-risk localized RCC. Building on their established efficacy in the metastatic setting, several ongoing clinical trials are evaluating their value as single agents or in combination in the neoadjuvant and adjuvant settings. At this time, we recommend participation in clinical trials as the preferred therapeutic option for patients with high-risk, non-metastatic RCC planned for nephrectomy.
MeSH term(s)	Carcinoma, Renal Cell/diagnosis ; Carcinoma, Renal Cell/etiology ; Carcinoma, Renal Cell/therapy ; Chemotherapy, Adjuvant ; Clinical Trials as Topic ; Combined Modality Therapy ; Disease Management ; Humans ; Kidney Neoplasms/diagnosis ; Kidney Neoplasms/etiology ; Kidney Neoplasms/therapy ; Neoadjuvant Therapy ; Neoplasm Staging
Language	English
Publishing date	2019-05-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2057351-0
ISSN	1534-6277 ; 1527-2729
ISSN (online)	1534-6277
ISSN	1527-2729
DOI	10.1007/s11864-019-0639-0
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Zs.A 5523: Show issues

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Article ; Online: Global and Regional White Matter Fractional Anisotropy in Children with Chronic Kidney Disease.

van der Plas, Ellen / Solomon, Matthew A / Hopkins, Lauren / Koscik, Timothy / Schultz, Jordan / Brophy, Patrick D / Nopoulos, Peggy C / Harshman, Lyndsay A

The Journal of pediatrics

2021 Volume 242, Page(s) 166–173.e3

Abstract: Objective: To investigate the associations between neurocognition and white matter integrity in children with chronic kidney disease (CKD).: Study design: This cross-sectional study included 17 boys (age 6-16 years) with a diagnosis of mild to ... ...

Abstract	Objective: To investigate the associations between neurocognition and white matter integrity in children with chronic kidney disease (CKD). Study design: This cross-sectional study included 17 boys (age 6-16 years) with a diagnosis of mild to moderate (stages 1-3, nondialysis/nontransplant) CKD because of congenital anomalies of the kidney and urinary tract and 20 typically developing community controls. Participants underwent 3T neuroimaging and diffusion-weighted magnetic resonance imaging to assess white matter fractional anisotropy. Multivariable linear regression models were used to evaluate the impact of each group (controls vs CKD) on white matter fractional anisotropy, adjusting for age. Associations between white matter fractional anisotropy and neurocognitive abilities within the CKD group were also evaluated using regression models that were adjusted for age. The false discovery rate was used to account for multiple comparisons; wherein false discovery values <0.10 were considered significant. Results: Global white matter fractional anisotropy was reduced in patients with CKD relative to controls (standardized estimate = -0.38, 95% CI -0.69:-0.07), driven by reductions within the body of the corpus callosum (standardized estimate = -0.44, 95% CI -0.75:-0.13), cerebral peduncle (SE = -0.37, 95% CI -0.67:-0.07), cingulum (hippocampus) (standardized estimate = -0.45, 95% CI -0.75:-0.14), and posterior limb of the internal capsule (standardized estimate = -0.46, 95% CI -0.76:-0.15). Medical variables and neurocognitive abilities were not significantly associated with white matter fractional anisotropy. Conclusions: White matter development is vulnerable in children with CKD because of congenital causes, even prior to the need for dialysis or transplantation.
MeSH term(s)	Adolescent ; Anisotropy ; Brain/diagnostic imaging ; Child ; Cross-Sectional Studies ; Diffusion Magnetic Resonance Imaging ; Diffusion Tensor Imaging ; Female ; Humans ; Male ; Renal Insufficiency, Chronic ; White Matter/diagnostic imaging
Language	English
Publishing date	2021-11-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3102-1
ISSN	1097-6833 ; 0022-3476
ISSN (online)	1097-6833
ISSN	0022-3476
DOI	10.1016/j.jpeds.2021.11.006
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Article ; Online: Associations between neurofilament light-chain protein, brain structure, and chronic kidney disease.

van der Plas, Ellen / Lullmann, Olivia / Hopkins, Lauren / Schultz, Jordan L / Nopoulos, Peggy C / Harshman, Lyndsay A

Pediatric research

2021 Volume 91, Issue 7, Page(s) 1735–1740

Abstract: Background: Neurofilament light-chain (NfL) protein is a blood-based marker of neuroaxonal injury. We sought to (1) compare plasma NfL levels in children with chronic kidney disease (CKD) and healthy peers, (2) characterize the relationship between NfL ... ...

Abstract	Background: Neurofilament light-chain (NfL) protein is a blood-based marker of neuroaxonal injury. We sought to (1) compare plasma NfL levels in children with chronic kidney disease (CKD) and healthy peers, (2) characterize the relationship between NfL level and kidney function, and (3) evaluate NfL as a predictor of abnormal brain structure in CKD. Methods: Sixteen children with CKD due to congenital kidney anomalies and 23 typically developing peers were included. Plasma NfL was quantified using single-molecule array immunoassay. Participants underwent structural magnetic resonance imaging. Multiple linear regression models were used to evaluate the association between plasma NfL levels, kidney function, and brain structure. Results: An age × group interaction was identified whereby NfL levels increased with age in the CKD group only (estimate = 0.65; confidence interval (CI) = 0.08-1.22; p = 0.026). Decreased kidney function was associated with higher NfL levels (estimate = -0.10; CI = -0.16 to -0.04; p = 0.003). Lower cerebellar gray matter volume predicted increased plasma NfL levels (estimate = -0.00024; CI = -0.00039 to 0.00009; p = 0.004) within the CKD group. Conclusions: Children with CKD show accelerated age-related increases in NfL levels. NfL level is associated with lower kidney function and abnormal brain structure in CKD. Impact: NfL is a component of the neuronal cytoskeleton providing structural axonal support. Elevated NfL has been described in relation to gray and white matter brain volume loss. We have previously described the abnormal cerebellar gray matter in CKD. We explored the relationship between NfL, CKD, and brain volume. There is an accelerated, age-related increase in NfL level in CKD. Within the CKD sample, NfL level is associated with abnormal kidney function and brain structure. Decreased kidney function may be linked to abnormal neuronal integrity in pediatric CKD.
MeSH term(s)	Biomarkers ; Brain/diagnostic imaging ; Brain/pathology ; Child ; Gray Matter ; Humans ; Intermediate Filaments ; Neurofilament Proteins ; Renal Insufficiency, Chronic
Chemical Substances	Biomarkers ; Neurofilament Proteins
Language	English
Publishing date	2021-07-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	4411-8
ISSN	1530-0447 ; 0031-3998
ISSN (online)	1530-0447
ISSN	0031-3998
DOI	10.1038/s41390-021-01649-6
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Zs.A 564: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 373: Show issues

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Article ; Online: Targeting the hepatocyte growth factor/c-Met signaling pathway in renal cell carcinoma.

Harshman, Lauren C / Choueiri, Toni K

Cancer journal (Sudbury, Mass.)

2013 Volume 19, Issue 4, Page(s) 316–323

Abstract: The product of a proto-oncogene, the c-Met protein is a transmembrane receptor tyrosine kinase ... invasion, proliferation, and angiogenesis. Dysregulation of c-Met and hepatocyte growth factor have been ... between loss of von Hippel-Lindau and up-regulation of c-Met. As in other cancers, high expression of c ...

Abstract	The product of a proto-oncogene, the c-Met protein is a transmembrane receptor tyrosine kinase. Its only known ligand, hepatocyte growth factor/scatter factor, regulates cell growth, motility, migration, invasion, proliferation, and angiogenesis. Dysregulation of c-Met and hepatocyte growth factor have been observed in both clear cell and non-clear cell renal cell carcinomas (RCCs), although only papillary RCCs harbor activating mutations in the MET gene. In clear cell RCC, there is evidence of a direct link between loss of von Hippel-Lindau and up-regulation of c-Met. As in other cancers, high expression of c-Met correlates with worse outcomes in RCC. In vitro and in vivo preclinical RCC models demonstrate cancer control with small molecule and antibodies against c-Met. Given these findings, the c-Met pathway is a logical therapeutic target in RCC, and several agents are in clinical testing with early signs of efficacy.
MeSH term(s)	Carcinoma, Renal Cell/drug therapy ; Carcinoma, Renal Cell/genetics ; Carcinoma, Renal Cell/pathology ; Hepatocyte Growth Factor/genetics ; Hepatocyte Growth Factor/metabolism ; Hepatocyte Growth Factor/therapeutic use ; Humans ; Kidney Neoplasms/drug therapy ; Kidney Neoplasms/genetics ; Kidney Neoplasms/pathology ; Molecular Targeted Therapy ; Mutation ; Proto-Oncogene Proteins c-met/genetics ; Proto-Oncogene Proteins c-met/metabolism ; Proto-Oncogene Proteins c-met/therapeutic use ; Signal Transduction
Chemical Substances	Hepatocyte Growth Factor (67256-21-7) ; Proto-Oncogene Proteins c-met (EC 2.7.10.1)
Language	English
Publishing date	2013-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2018400-1
ISSN	1540-336X ; 1528-9117 ; 1081-4442
ISSN (online)	1540-336X
ISSN	1528-9117 ; 1081-4442
DOI	10.1097/PPO.0b013e31829e3c9a
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Zs.A 4470: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 163: Show issues

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Article ; Online: Abiraterone acetate: targeting persistent androgen dependence in castration-resistant prostate cancer.

Harshman, Lauren C / Taplin, Mary-Ellen

Advances in therapy

2013 Volume 30, Issue 8, Page(s) 727–747

Abstract: Abiraterone acetate is the first second-line hormonal agent proven to improve survival in metastatic castration-resistant prostate cancer. It selectively inhibits cytochrome P450 17 (CYP17) α-hydroxylase and cytochrome17,20 (C17,20)-lyase, which are ... ...

Abstract	Abiraterone acetate is the first second-line hormonal agent proven to improve survival in metastatic castration-resistant prostate cancer. It selectively inhibits cytochrome P450 17 (CYP17) α-hydroxylase and cytochrome17,20 (C17,20)-lyase, which are enzymes critical for androgen synthesis. Abiraterone acetate was initially approved in the United States in 2011 after demonstrating a 4-month survival benefit in docetaxel-refractory metastatic prostate cancer. The FDA recently expanded its indication for use in the pre-chemotherapy setting after it elicited significant delays in disease progression and a strong trend for increased overall survival in phase III studies. Ongoing investigations of abiraterone are evaluating its efficacy in earlier disease states, exploring its synergy in combination with other therapeutic agents, and assessing the necessity for administration of concurrent steroids and gonadal suppression. The identification and development of predictive biomarkers will optimize the incorporation of abiraterone into the management of advanced prostate cancer.
MeSH term(s)	Abiraterone Acetate ; Androstadienes/therapeutic use ; Antineoplastic Agents, Hormonal/therapeutic use ; Disease-Free Survival ; Humans ; Male ; Neoplasm Metastasis/drug therapy ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/pathology ; Steroid 17-alpha-Hydroxylase/antagonists & inhibitors ; Treatment Outcome
Chemical Substances	Androstadienes ; Antineoplastic Agents, Hormonal ; Steroid 17-alpha-Hydroxylase (EC 1.14.14.19) ; Abiraterone Acetate (EM5OCB9YJ6)
Language	English
Publishing date	2013-08-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	632651-1
ISSN	1865-8652 ; 0741-238X
ISSN (online)	1865-8652
ISSN	0741-238X
DOI	10.1007/s12325-013-0050-3
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Article ; Online: Second-line therapies in metastatic urothelial carcinoma.

Narayanan, Sujata / Harshman, Lauren C / Srinivas, Sandy

Hematology/oncology clinics of North America

2015 Volume 29, Issue 2, Page(s) 341–59, x

Abstract: Patients with relapsed or refractory urothelial carcinoma (UC) face a poor prognosis and a dearth of available treatment options that improve their survival. End-organ function and performance status play a vital role in the choice of second-line ... ...

Abstract	Patients with relapsed or refractory urothelial carcinoma (UC) face a poor prognosis and a dearth of available treatment options that improve their survival. End-organ function and performance status play a vital role in the choice of second-line therapies. Evidence supporting the use of cytotoxic chemotherapy, as single agents or in combination, arises from small phase 2 studies with modest responses. With the evolution of genomic testing in UC, several pathways amenable to available targeted therapies have emerged. Encouraging patient participation in clinical trials is critical to improve patient outcomes and to advance the current modest treatment armamentarium.
MeSH term(s)	Carcinoma/pathology ; Carcinoma/therapy ; Clinical Trials as Topic ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Salvage Therapy/methods ; Treatment Outcome ; Urologic Neoplasms/mortality ; Urologic Neoplasms/pathology ; Urologic Neoplasms/therapy
Language	English
Publishing date	2015-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	93115-9
ISSN	1558-1977 ; 0889-8588
ISSN (online)	1558-1977
ISSN	0889-8588
DOI	10.1016/j.hoc.2014.10.007
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Se 1077: Show issues

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Article ; Online: Differential comorbidity profiles in avoidant/restrictive food intake disorder and anorexia nervosa: Does age play a role?

Kambanis, P Evelyna / Harshman, Stephanie G / Kuhnle, Megan C / Kahn, Danielle L / Dreier, Melissa J / Hauser, Kristine / Slattery, Meghan / Becker, Kendra R / Breithaupt, Lauren / Misra, Madhusmita / Micali, Nadia / Lawson, Elizabeth A / Eddy, Kamryn T / Thomas, Jennifer J

The International journal of eating disorders

2022 Volume 55, Issue 10, Page(s) 1397–1403

Abstract: Objective: Research comparing psychiatric comorbidities between individuals with avoidant/restrictive food intake disorder (ARFID) and anorexia nervosa (AN) is limited. ARFID often develops in childhood, whereas AN typically develops in adolescence or ... ...

Abstract	Objective: Research comparing psychiatric comorbidities between individuals with avoidant/restrictive food intake disorder (ARFID) and anorexia nervosa (AN) is limited. ARFID often develops in childhood, whereas AN typically develops in adolescence or young adulthood. Understanding how age may impact differential psychological comorbidity profiles is important to inform etiological conceptualization, differential diagnosis, and treatment planning. We aimed to compare the lifetime frequency of psychiatric comorbidities and suicidality between females with ARFID (n = 51) and AN (n = 40), investigating the role of age as a covariate. Method: We used structured interviews to assess the comparative frequency of psychiatric comorbidities/suicidality. Results: When age was omitted from analyses, females with ARFID had a lower frequency of depressive disorders and suicidality compared to AN. Adjusting for age, only suicidality differed between groups. Discussion: This is the first study to compare comorbidities in a similar number of individuals with ARFID and AN, and a structured clinical interview to confer ARFID and comorbidities, covarying for age, and the first to compare suicidality. Although suicidality is at least three times less common in ARFID than AN, observed differences in other psychiatric comorbidities may reflect ARFID's relatively younger age of presentation compared to AN. Public significance: Our results highlight that, with the exception of suicidality, which was three times less common in ARFID than AN irrespective of age, observed differences in psychiatric comorbidities in clinical practice may reflect ARFID's younger age at clinical presentation compared to AN.
MeSH term(s)	Adolescent ; Adult ; Anorexia Nervosa/diagnosis ; Anorexia Nervosa/epidemiology ; Anorexia Nervosa/psychology ; Avoidant Restrictive Food Intake Disorder ; Comorbidity ; Eating ; Feeding and Eating Disorders ; Female ; Humans ; Retrospective Studies ; Young Adult
Language	English
Publishing date	2022-07-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	603170-5
ISSN	1098-108X ; 0276-3478
ISSN (online)	1098-108X
ISSN	0276-3478
DOI	10.1002/eat.23777
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Zs.A 1749: Show issues

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Article ; Online: Randomized Phase II Study Evaluating the Addition of Pembrolizumab to Radium-223 in Metastatic Castration-resistant Prostate Cancer.

Choudhury, Atish D / Kwak, Lucia / Cheung, Alexander / Allaire, Kathryn M / Marquez, Jaqueline / Yang, David D / Tripathi, Abhishek / Kilar, Jacqueline M / Flynn, Meredith / Maynard, Brianna / Reichel, Rebecca / Pace, Amanda F / Chen, Brandon K / Van Allen, Eliezer M / Kilbridge, Kerry / Wei, Xiao X / McGregor, Bradley A / Pomerantz, Mark M / Bhatt, Rupal S /

Sweeney, Christopher J / Bubley, Glenn J / Jacene, Heather A / Taplin, Mary-Ellen / Huang, Franklin W / Harshman, Lauren C / Fong, Lawrence

Cancer immunology research

2024 , Page(s) OF1–OF15

Abstract: The checkpoint immunotherapeutic pembrolizumab induces responses in a small minority of patients with metastatic castration-resistant prostate cancer (mCRPC). Radium-223 (R223) may increase immunogenicity of bone metastases and increase pembrolizumab (P) ...

Abstract	The checkpoint immunotherapeutic pembrolizumab induces responses in a small minority of patients with metastatic castration-resistant prostate cancer (mCRPC). Radium-223 (R223) may increase immunogenicity of bone metastases and increase pembrolizumab (P) activity. In a randomized phase II study, we assessed the effect of R223+P compared with R223 on tumor immune infiltration, safety, and clinical outcomes in patients with mCRPC. The primary endpoint was differences in CD4+ and CD8+ T-cell infiltrate in 8-week versus baseline bone metastasis biopsies; secondary endpoints were safety, radiographic progression-free survival (rPFS), and overall survival (OS). Of the 42 treated patients (29 R223+P, 13 R223), 18 R223+P and 8 R223 patients had evaluable paired tumor biopsies. Median fold-change of CD4+ T cells was -0.7 (range: -9.3 to 4.7) with R223+P and 0.1 (-11.1 to 3.7) with R223 (P = 0.66); for CD8+ T cells, median fold-change was -0.6 (-7.4 to 5.3) with R223+P and -1.3 (-3.1 to 4.8) with R223 (P = 0.66). Median rPFS and OS was 6.1 (95% confidence interval: 2.7-11.0) and 16.9 months [12.7-not reached (NR)], respectively, with R223+P and 5.7 (2.6-NR) and 16.0 (9.0-NR), respectively, with R223. Although R223+P was well tolerated with no unexpected toxicity, the combination did not improve efficacy. High-dimensional flow cytometry demonstrated minimal immune modulation with R223, whereas R223+P induced CTLA-4 expression on circulating CD4+ T cells. Clinical responders possessed lower circulating frequencies of Ki67+ T and myeloid cells at baseline and higher circulating frequencies of TIM-3+ T and myeloid cells by week 9. Although R223+P did not induce T-cell infiltration into the tumor microenvironment, exhaustion of induced peripheral T-cell immune responses may dampen the combination's clinical activity.
Language	English
Publishing date	2024-03-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2732489-8
ISSN	2326-6074 ; 2326-6066
ISSN (online)	2326-6074
ISSN	2326-6066
DOI	10.1158/2326-6066.CIR-22-0306
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