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Article ; Online: Peripheral androgen blockade in men with castrate-sensitive biochemical recurrent prostate cancer.

Reyes, Diane K / Pienta, Kenneth J

Medical oncology (Northwood, London, England)

2021 Volume 38, Issue 7, Page(s) 80

Abstract: The aim of the study was to evaluate the feasibility of utilizing peripheral androgen blockade in men with biochemical recurrent castrate-sensitive prostate cancer. A registration study to track outcomes of men with biochemical recurrent castrate- ... ...

Abstract	The aim of the study was to evaluate the feasibility of utilizing peripheral androgen blockade in men with biochemical recurrent castrate-sensitive prostate cancer. A registration study to track outcomes of men with biochemical recurrent castrate-sensitive prostate cancer treated with peripheral androgen blockade utilizing concomitant administration of finasteride and bicalutamide. Men were on intermittent peripheral blockade for a median 20.2 months, continuous peripheral blockade for a median 6.8 months, intermittent triple dose peripheral androgen blockade for a median 10.7 months, and continuous triple dose peripheral androgen blockade for 4.4 months before failing therapy. Six men (21%) had additional therapies during treatment that included metastasis-directed therapy (5/37, 14%), systemic Lu-177 (2/37, 5%), and salvage RT (1/37, 3%). The median time to progression, which includes time from initiation through all therapies to the initiation of ADT, was 37.6 months (IQR 20-74.7). From the start of PAB, median time to castrate resistance was 49.8 months (IQR 40.9-NR). After starting ADT, median time to castrate resistance was 8.8 months (IQR 4.6-17.7). Our data support the exploration of PAB as a treatment option in carefully selected patients who present with biochemical recurrence after failure of definitive local therapy for prostate cancer.
MeSH term(s)	Aged ; Androgen Antagonists/administration & dosage ; Androgens/metabolism ; Anilides/administration & dosage ; Antineoplastic Agents, Hormonal/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Finasteride/administration & dosage ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/diagnosis ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/metabolism ; Nitriles/administration & dosage ; Prostatic Neoplasms, Castration-Resistant/diagnosis ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/metabolism ; Tosyl Compounds/administration & dosage
Chemical Substances	Androgen Antagonists ; Androgens ; Anilides ; Antineoplastic Agents, Hormonal ; Nitriles ; Tosyl Compounds ; Finasteride (57GNO57U7G) ; bicalutamide (A0Z3NAU9DP)
Language	English
Publishing date	2021-06-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	1201189-7
ISSN	1559-131X ; 0736-0118 ; 1357-0560
ISSN (online)	1559-131X
ISSN	0736-0118 ; 1357-0560
DOI	10.1007/s12032-021-01506-w
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Article ; Online: Dormant cancer cells: programmed quiescence, senescence, or both?

Truskowski, Kevin / Amend, Sarah R / Pienta, Kenneth J

Cancer metastasis reviews

2023 Volume 42, Issue 1, Page(s) 37–47

Abstract: Metastasis is the overwhelming driver of cancer mortality, accounting for the majority of cancer deaths. Many patients present with metastatic relapse years after eradication of the primary lesion. Disseminated cancer cells can undergo a durable ... ...

Abstract	Metastasis is the overwhelming driver of cancer mortality, accounting for the majority of cancer deaths. Many patients present with metastatic relapse years after eradication of the primary lesion. Disseminated cancer cells can undergo a durable proliferative arrest and lie dormant in secondary tissues before reentering the cell cycle to seed these lethal relapses. This process of cancer cell dormancy remains poorly understood, largely due to difficulties in studying these dormant cells. In the face of these challenges, the application of knowledge from the cellular senescence and quiescence fields may help to guide future thinking on the study of dormant cancer cells. Both senescence and quiescence are common programs of proliferative arrest that are integral to tissue development and homeostasis. Despite phenotypic differences, these two states also share common characteristics, and both likely play a role in cancer dormancy and delayed metastatic relapse. Understanding the cell biology behind these states, their overlaps and unique characteristics is critical to our future understanding of dormant cancer cells, as these cells likely employ some of the same molecular programs to promote survival and dissemination. In this review, we highlight the biology underlying these non-proliferative states, relate this knowledge to what we currently know about dormant cancer cells, and discuss implications for future work toward targeting these elusive metastatic seeds.
MeSH term(s)	Humans ; Neoplasms/pathology ; Cell Cycle ; Recurrence
Language	English
Publishing date	2023-01-04
Publishing country	Netherlands
Document type	Journal Article ; Review ; 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	604857-2
ISSN	1573-7233 ; 0167-7659
ISSN (online)	1573-7233
ISSN	0167-7659
DOI	10.1007/s10555-022-10073-z
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Article ; Online: Disrupting prostate cancer research: Challenge accepted; report from the 2023 Coffey-Holden Prostate Cancer Academy Meeting.

Miyahira, Andrea K / Kamran, Sophia C / Jamaspishvili, Tamara / Marshall, Catherine H / Maxwell, Kara N / Parolia, Abhijit / Zorko, Nicholas A / Pienta, Kenneth J / Soule, Howard R

The Prostate

2024

Abstract: Introduction: The 2023 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, themed "Disrupting Prostate Cancer Research: Challenge Accepted," was convened at the University of California, Los Angeles, Luskin Conference Center, in Los Angeles, CA, from ...

Abstract	Introduction: The 2023 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, themed "Disrupting Prostate Cancer Research: Challenge Accepted," was convened at the University of California, Los Angeles, Luskin Conference Center, in Los Angeles, CA, from June 22 to 25, 2023. Methods: The 2023 marked the 10th Annual CHPCA Meeting, a discussion-oriented scientific think-tank conference convened annually by the Prostate Cancer Foundation, which centers on innovative and emerging research topics deemed pivotal for advancing critical unmet needs in prostate cancer research and clinical care. The 2023 CHPCA Meeting was attended by 81 academic investigators and included 40 talks across 8 sessions. Results: The central topic areas covered at the meeting included: targeting transcription factor neo-enhancesomes in cancer, AR as a pro-differentiation and oncogenic transcription factor, why few are cured with androgen deprivation therapy and how to change dogma to cure metastatic prostate cancer without castration, reducing prostate cancer morbidity and mortality with genetics, opportunities for radiation to enhance therapeutic benefit in oligometastatic prostate cancer, novel immunotherapeutic approaches, and the new era of artificial intelligence-driven precision medicine. Discussion: This article provides an overview of the scientific presentations delivered at the 2023 CHPCA Meeting, such that this knowledge can help in facilitating the advancement of prostate cancer research worldwide.
Language	English
Publishing date	2024-04-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	604707-5
ISSN	1097-0045 ; 0270-4137
ISSN (online)	1097-0045
ISSN	0270-4137
DOI	10.1002/pros.24721
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Article ; Online: Late HeartMate 3 Thrombosis.

Pienta, Michael J / Knott, Kevin / Bitar, Abbas / Haft, Jonathan W

ASAIO journal (American Society for Artificial Internal Organs : 1992)

2021 Volume 68, Issue 5, Page(s) e87–e89

Abstract: There are few reports of HeartMate 3 pump thrombosis, with existing reports relating to outflow occlusion or early perioperative thrombosis. We present a case of late pump thrombosis requiring pump exchange. ...

Abstract	There are few reports of HeartMate 3 pump thrombosis, with existing reports relating to outflow occlusion or early perioperative thrombosis. We present a case of late pump thrombosis requiring pump exchange.
MeSH term(s)	Heart Failure/etiology ; Heart Failure/surgery ; Heart-Assist Devices/adverse effects ; Humans ; Retrospective Studies ; Thrombosis/etiology
Language	English
Publishing date	2021-05-22
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	759982-1
ISSN	1538-943X ; 0162-1432 ; 1058-2916
ISSN (online)	1538-943X
ISSN	0162-1432 ; 1058-2916
DOI	10.1097/MAT.0000000000001479
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Article ; Online: Cancer recurrence and lethality are enabled by enhanced survival and reversible cell cycle arrest of polyaneuploid cells.

Pienta, K J / Hammarlund, E U / Brown, J S / Amend, S R / Axelrod, R M

Proceedings of the National Academy of Sciences of the United States of America

2021 Volume 118, Issue 7

Abstract: We present a unifying theory to explain cancer recurrence, therapeutic resistance, and lethality. The basis of this theory is the formation of simultaneously polyploid and aneuploid cancer cells, polyaneuploid cancer cells (PACCs), that avoid the toxic ... ...

Abstract	We present a unifying theory to explain cancer recurrence, therapeutic resistance, and lethality. The basis of this theory is the formation of simultaneously polyploid and aneuploid cancer cells, polyaneuploid cancer cells (PACCs), that avoid the toxic effects of systemic therapy by entering a state of cell cycle arrest. The theory is independent of which of the classically associated oncogenic mutations have already occurred. PACCs have been generally disregarded as senescent or dying cells. Our theory states that therapeutic resistance is driven by PACC formation that is enabled by accessing a polyploid program that allows an aneuploid cancer cell to double its genomic content, followed by entry into a nondividing cell state to protect DNA integrity and ensure cell survival. Upon removal of stress, e.g., chemotherapy, PACCs undergo depolyploidization and generate resistant progeny that make up the bulk of cancer cells within a tumor.
MeSH term(s)	Aneuploidy ; Animals ; Cell Cycle Checkpoints ; Cell Survival ; Evolution, Molecular ; Humans ; Neoplasms/genetics ; Neoplasms/pathology ; Polyploidy
Language	English
Publishing date	2021-01-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2020838118
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Article ; Online: CT-based assessment of body composition following neoadjuvant chemohormonal therapy in patients with castration-naïve oligometastatic prostate cancer.

Sheikhbahaei, Sara / Reyes, Diane K / Rowe, Steven P / Pienta, Kenneth J

The Prostate

2020 Volume 81, Issue 2, Page(s) 127–134

Abstract: Background: The purpose of this study is to assess the body composition changes in men with recently diagnosed oligometastatic prostate cancer following neoadjuvant chemohormonal therapy. Further, we evaluated whether CT-based body composition ... ...

Abstract	Background: The purpose of this study is to assess the body composition changes in men with recently diagnosed oligometastatic prostate cancer following neoadjuvant chemohormonal therapy. Further, we evaluated whether CT-based body composition parameters are associated with biochemical recurrence or imaging progression. Material and methods: Recently diagnosed castration-naïve oligometastatic prostate cancer patients who received neoadjuvant docetaxel chemotherapy and androgen deprivation treatment (ADT) before prostatectomy and consolidation of local and oligometastatic disease (total eradication therapy), as part of a phase-II prospective clinical trial were included. Body composition parameters including cross-sectional areas of the psoas muscle, total, visceral, and subcutaneous adipose tissue were measured on serial CT scans obtained before and following completion of neoadjuvant treatment. Results: A total of 22 prostate cancer patients were included (median age 58 years, median Gleason score 8). The median time intervals between commencement of neoadjuvant chemohormonal therapy and first and second follow-up CTs were 3 and 12 months, respectively. Compared to the baseline scan, there were significant declines in psoas muscle cross-sectional areas with estimated percentage declines of -13.9% (IQR: 7.6%-16.5%, p < .001) and -13.2% (IQR: 6%-11.2%, p < .001) on first and second follow-up CTs. There were significant increases in subcutaneous adipose tissue following neoadjuvant chemohormonal therapy with percentage increases of +8.9% (IQR: 5.1%-21.5%, p = .002) and +18.9% (IQR: 6.1%-33.8%, p < .001), respectively. The median follow-up was 34.5 months. The estimated 2-year prostate-specific antigen progression-free and radiologic progression-free survival were 95.5%. No significant association between baseline or percentage change in body composition parameters and disease progression were identified. Conclusions: Our findings showed a significant reduction in muscle mass and an increase in subcutaneous adiposity in men treated with neoadjuvant docetaxel and ADT, more pronounced on the first follow-up scan after completion of neoadjuvant treatment. Body composition parameters were not found to be significant predictors of disease progression in our cohort.
MeSH term(s)	Aged ; Androgen Antagonists/therapeutic use ; Antineoplastic Agents/therapeutic use ; Body Composition ; Disease Progression ; Docetaxel/therapeutic use ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy/methods ; Neoplasm Metastasis/pathology ; Neoplasm Metastasis/physiopathology ; Neoplasm Metastasis/therapy ; Prospective Studies ; Prostatectomy ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/pathology ; Prostatic Neoplasms, Castration-Resistant/physiopathology ; Psoas Muscles/diagnostic imaging ; Subcutaneous Fat/diagnostic imaging ; Tomography, X-Ray Computed
Chemical Substances	Androgen Antagonists ; Antineoplastic Agents ; Docetaxel (15H5577CQD)
Language	English
Publishing date	2020-12-01
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article
ZDB-ID	604707-5
ISSN	1097-0045 ; 0270-4137
ISSN (online)	1097-0045
ISSN	0270-4137
DOI	10.1002/pros.24088
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Article: Novel urinary tract obstruction marker discovery by multi-marker profiling of urinary extracellular vesicles derived from a rat UTO model.

Haney, Nora M / Kim, Chi-Ju / Kuczler, Morgan D / Lee, Cheng-Fan / Lombardo, Kara / Bivalacqua, Trinity J / Pienta, Kenneth J / Amend, Sarah R

American journal of clinical and experimental urology

2023 Volume 11, Issue 2, Page(s) 136–145

Abstract: Introduction: Congenital urinary obstruction is a common cause of end-stage renal disease in the pediatric population. However, non-invasive diagnostics to predict which patients will benefit from early intervention are lacking.: Methods: Using a rat ...

Abstract	Introduction: Congenital urinary obstruction is a common cause of end-stage renal disease in the pediatric population. However, non-invasive diagnostics to predict which patients will benefit from early intervention are lacking. Methods: Using a rat model of upper and lower urinary tract partial obstruction and the Nanostring nCounter Fibrosis V2 Panel, we evaluated the mRNA cargo of urinary small extracellular vesicles (sEVs) and mRNA expression patterns of kidney and bladder tissues from rats with lower tract urinary obstruction and upper tract urinary obstruction. Results: While mRNA hierarchical clustering of urinary sEVs was unable to differentiate upper compared to lower tract urinary obstruction, clustering was able to detect overall disease state (UUTO or LUTO) versus healthy controls. Further, urinary sEVs carried genes unique to each treatment group (UUTO: 59 genes, LUTO: 17 genes), while only one gene was uniquely carried in the control group. Notable genes of interest found in urinary sEVs were VCAM-1 and NOS1 for UUTO, Egfr for LUTO, and Pck1 for healthy controls. Conclusion: This study provides support that differential gene expression of urinary sEV mRNA has potential to act as biomarkers in the diagnosis and prognosis of UTO. Urinary sEVs demonstrated higher numbers of unique genes representative of injury to the kidney than that of injury to the bladder. Importantly, there were genes unique to UUTO sEVs, indicating the extent and reversibility of renal damage can be independent of the function, damage, and architecture of the bladder.
Language	English
Publishing date	2023-04-15
Publishing country	United States
Document type	Journal Article
ISSN	2330-1910
ISSN	2330-1910
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Article ; Online: Deep-learning-based image segmentation for image-based computational hemodynamic analysis of abdominal aortic aneurysms: a comparison study.

Lyu, Zonghan / King, Kristin / Rezaeitaleshmahalleh, Mostafa / Pienta, Drew / Mu, Nan / Zhao, Chen / Zhou, Weihua / Jiang, Jingfeng

Biomedical physics & engineering express

2023 Volume 9, Issue 6

Abstract: Computational hemodynamics is increasingly being used to quantify hemodynamic characteristics in and around abdominal aortic aneurysms (AAA) in a patient-specific fashion. However, the time-consuming manual annotation hinders the clinical translation of ... ...

Abstract	Computational hemodynamics is increasingly being used to quantify hemodynamic characteristics in and around abdominal aortic aneurysms (AAA) in a patient-specific fashion. However, the time-consuming manual annotation hinders the clinical translation of computational hemodynamic analysis. Thus, we investigate the feasibility of using deep-learning-based image segmentation methods to reduce the time required for manual segmentation. Two of the latest deep-learning-based image segmentation methods, ARU-Net and CACU-Net, were used to test the feasibility of automated computer model creation for computational hemodynamic analysis. Morphological features and hemodynamic metrics of 30 computed tomography angiography (CTA) scans were compared between pre-dictions and manual models. The DICE score for both networks was 0.916, and the correlation value was above 0.95, indicating their ability to generate models comparable to human segmentation. The Bland-Altman analysis shows a good agreement between deep learning and manual segmentation results. Compared with manual (computational hemodynamics) model recreation, the time for automated computer model generation was significantly reduced (from ∼2 h to ∼10 min). Automated image segmentation can significantly reduce time expenses on the recreation of patient-specific AAA models. Moreover, our study showed that both CACU-Net and ARU-Net could accomplish AAA segmentation, and CACU-Net outperformed ARU-Net in terms of accuracy and time-saving.
MeSH term(s)	Humans ; Deep Learning ; Image Processing, Computer-Assisted ; Aortic Aneurysm, Abdominal/diagnostic imaging ; Tomography, X-Ray Computed ; Hemodynamics
Language	English
Publishing date	2023-09-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2057-1976
ISSN (online)	2057-1976
DOI	10.1088/2057-1976/acf3ed
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Article ; Online: Nuclear morphology predicts cell survival to cisplatin chemotherapy.

Kim, Chi-Ju / Gonye, Anna Lk / Truskowski, Kevin / Lee, Cheng-Fan / Cho, Yoon-Kyoung / Austin, Robert H / Pienta, Kenneth J / Amend, Sarah R

Neoplasia (New York, N.Y.)

2023 Volume 42, Page(s) 100906

Abstract: The emergence of chemotherapy resistance drives cancer lethality in cancer patients, with treatment initially reducing overall tumor burden followed by resistant recurrent disease. While molecular mechanisms underlying resistance phenotypes have been ... ...

Abstract	The emergence of chemotherapy resistance drives cancer lethality in cancer patients, with treatment initially reducing overall tumor burden followed by resistant recurrent disease. While molecular mechanisms underlying resistance phenotypes have been explored, less is known about the cell biological characteristics of cancer cells that survive to eventually seed the recurrence. To identify the unique phenotypic characteristics associated with survival upon chemotherapy exposure, we characterized nuclear morphology and function as prostate cancer cells recovered following cisplatin treatment. Cells that survived in the days and weeks after treatment and resisted therapy-induced cell death showed increasing cell size and nuclear size, enabled by continuous endocycling resulting in repeated whole genome doubling. We further found that cells that survive after therapy release were predominantly mononucleated and likely employ more efficient DNA damage repair. Finally, we show that surviving cancer cells exhibit a distinct nucleolar phenotype and increased rRNA levels. These data support a paradigm where soon after therapy release, the treated population mostly contains cells with a high level of widespread and catastrophic DNA damage that leads to apoptosis, while the minority of cells that have successful DDR are more likely to access a pro-survival state. These findings are consistent with accession of the polyaneuploid cancer cell (PACC) state, a recently described mechanism of therapy resistance and tumor recurrence. Our findings demonstrate the fate of cancer cells following cisplatin treatment and define key cell phenotypic characteristics of the PACC state. This work is essential for understanding and, ultimately, targeting cancer resistance and recurrence.
MeSH term(s)	Humans ; Male ; Cisplatin/pharmacology ; Cell Survival/genetics ; Neoplasm Recurrence, Local ; DNA Repair ; DNA Damage ; Apoptosis/genetics ; Drug Resistance, Neoplasm/genetics ; Cell Line, Tumor
Chemical Substances	Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2023-05-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	1483840-0
ISSN	1476-5586 ; 1522-8002
ISSN (online)	1476-5586
ISSN	1522-8002
DOI	10.1016/j.neo.2023.100906
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Article ; Online: The biology and treatment of oligometastatic cancer.

Reyes, Diane K / Pienta, Kenneth J

Oncotarget

2015 Volume 6, Issue 11, Page(s) 8491–8524

Abstract: Clinical reports of limited and treatable cancer metastases, a disease state that exists in a transitional zone between localized and widespread systemic disease, were noted on occasion historically and are now termed oligometastasis. The ramification of ...

Abstract	Clinical reports of limited and treatable cancer metastases, a disease state that exists in a transitional zone between localized and widespread systemic disease, were noted on occasion historically and are now termed oligometastasis. The ramification of a diagnosis of oligometastasis is a change in treatment paradigm, i.e. if the primary cancer site (if still present) is controlled, or resected, and the metastatic sites are ablated (surgically or with radiation), a prolonged disease-free interval, and perhaps even cure, may be achieved. Contemporary molecular diagnostics are edging closer to being able to determine where an individual metastatic deposit is within the continuum of malignancy. Preclinical models are on the outset of laying the groundwork for understanding the oligometastatic state. Meanwhile, in the clinic, patients are increasingly being designated as having oligometastatic disease and being treated owing to improved diagnostic imaging, novel treatment options with the potential to provide either direct or bridging therapy, and progressively broad definitions of oligometastasis.
MeSH term(s)	Animals ; Bayes Theorem ; Carcinoma/secondary ; Carcinoma/therapy ; Clinical Trials as Topic ; Cryosurgery ; Evidence-Based Medicine ; Humans ; Lymph Node Excision ; Lymphatic Irradiation ; Lymphatic Metastasis ; Melanoma/secondary ; Melanoma/therapy ; Mice ; MicroRNAs/genetics ; Models, Biological ; Neoplasm Metastasis/diagnosis ; Neoplasm Metastasis/genetics ; Neoplasm Metastasis/physiopathology ; Neoplasm Metastasis/therapy ; Organ Specificity ; RNA, Neoplasm/genetics ; Radiosurgery ; Sarcoma/secondary ; Sarcoma/therapy ; Tumor Burden ; Tumor Escape ; Tumor Microenvironment
Chemical Substances	MicroRNAs ; RNA, Neoplasm
Language	English
Publishing date	2015-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.3455
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