Significance of apoptotic and non‐apoptotic disseminated tumor cells in the bone marrow of patients with clinically localized prostate cancer

Todenhöfer, Tilman; Hennenlotter, Jörg; Faber, Frank; Wallwiener, D.; Schilling, David; Kühs, Ursula; Aufderklamm, Stefan; Bier, Simone; Mischinger, Johannes; Gakis, Georgios; Fehm, Tanja; Stenzl, Arnulf; Schwentner, Christian

doi:10.1002/pros.22947

Cited by 17 publications

(12 citation statements)

References 35 publications

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“…[4] [5] [32] [33] There are no FDA-approved assays to detect DTCs, which make it difficult to standardize detection of PCa DTCs as the field attempts to determine the significance of disseminated cells at the time of primary therapy. [34] CTC systems are being adapted to isolate and detect DTCs in the BM. [24] Another technique used for the detection of DTCs is the reverse transcriptase polymerase chain reaction (RT-PCR) to detect PSA.…”

Section: Detection Of Circulating and Disseminated Tumor Cellsmentioning

confidence: 99%

Disseminated tumor cells and dormancy in prostate cancer metastasis

Toom

Verdone²,

Pienta

2016

Current Opinion in Biotechnology

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It has been reported that disseminated tumor cells (DTCs) can be found in the majority of prostate cancer (PCa) patients, even at the time of primary treatment with no clinical evidence of metastatic disease. This suggests that these cells escaped the primary tumor early in the disease and exist in a dormant state in distant organs until they develop in some patients as overt metastases. Understanding the mechanisms by which cancer cells exit the primary tumor, survive the circulation, settle in a distant organ, and exist in a quiescent state is critical to understanding tumorigenesis, developing new prognostic assays, and designing new therapeutic modalities to prevent and treat clinical metastases.

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Section: Detection Of Circulating and Disseminated Tumor Cellsmentioning

confidence: 99%

Disseminated tumor cells and dormancy in prostate cancer metastasis

Toom

Verdone²,

Pienta

2016

Current Opinion in Biotechnology

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“…Although various techniques such as TUNEL has been described, we used M30 to evaluate apoptotic index which was more simple and easy to perform (12). M30 is much more sensitive and specific for epithelial cells whereas TUNEL identifies all apoptotic cells in addition to epithelial lineage (19). Also M30 positivity comes out at an early stage of apoptosis and remains positive till to the necrosis of the tumor cells (15,18).…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Study of Cyclooxygenase-2 Expression in Prostate Carcinoma: It’s Relation with Apoptosis and Angiogenesis

Bağır¹,

Acikalin²,

İzol³

et al. 2016

uob

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SummaryObjective: Prostate carcinoma (PC) is one of the most commonly diagnosed cancer types with significant rates of mortality and morbidity. The etiology of PC is not clear. Cytokine and mediators at the inflammatory pathway plays role at the various steps of the relation between chronic inflammation and cancer. The objective of this study is to determine if there is relationship between cyclooxygenase-2 (COX) apoptosis and angiogenesis in patients with PC. Materials and Methods: Sample of 49 cases who were at pathologic stage pT2 and underwent radical prostatectomy, were selected retrospectively between 2005-2010, from the archives of Pathology Department of Çukurova University Faculty of Medicine. Histologic slides of each case were reviewed for the diagnostic reassessment and graded by the Gleason scoring system. COX-2, vascular endothelial growth factor (VEGF), monoclonal antibody (M30) and bcl-2 were immunohistochemically applied to the cases and they were evaluated. Results: The mean age of the patients were 63.8. Twenty-one cases had their Gleason score ≤6 and 28 had their Gleason score ≥7. COX-2 expression was detected in 81.6% of cases. While COX-2 expression was significantly correlated with bcl-2 expression, there was no correlation between VEGF and COX-2 expression. Gleason score was negatively correlated with M30. It was detected that as COX-2 expression increased mean survival time significantly decreased. Conclusion: This study makes us think that in the PC carcinogenesis COX-2 inhibits apoptosis rather than promoting angiogenesis. These results may offer new insights for the treatment strategies, also they may be useful for the prediction of clinical outcomes.

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“…Our recent study reported detection of DTC in the bone marrow of PCa patients who have no evidence of disease (NED) for up to 18 years after surgery [6]. Controversies persist in whether the detection of PCa DTC pre- or post-surgery correlate with clinical parameters or outcomes, partly due to the lack of standardized methodologies to detect DTC [7,8]. In the past, detection and analysis of DTC has been limited by technology.…”

Section: Detection Of Dtcmentioning

confidence: 99%

“…This approach relied on the successful identification of DTC using epithelial markers including cytokeratin (CK) or epithelial cell adhesion molecule (EpCAM). A recent study by Todenhöfer et al summarized DTC studies that assessed the percentage of positive DTC detected in PCa patients pre- or post-surgery [8]. The rates of detection ranged from 13–45% using pan-CK staining [1,9,11,13,17–22] and 72–90% using EpCAM staining [2,10].…”

Section: Detection Of Dtcmentioning

confidence: 99%

The biology and clinical implications of prostate cancer dormancy and metastasis

et al. 2015

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Disseminated tumor cells (DTC) are detected early in the disease process in prostate cancer (PCa) patients and can persist after radical prostatectomy. DTC can remain dormant in patients with no evidence of disease for a prolonged period of time only to recur 10 or more years later. Recent advances in single cell genomics and transcriptomics have provided much needed insight into DTC biology and cancer dormancy in patients. With the development of new in vitro and preclinical models, researchers recapitulate the clinical events in patients and therefore allow further elucidation of the molecular mechanisms underlying cancer dormancy and escape. In this review we explore novel ideas on the detection, heterogeneous transcriptomic profiles, molecular and cellular mechanisms of dormancy, and potential mechanisms underlying dormancy escape by DTC. As such there is hope that identifying and targeting novel dormancy-associated pathways in patients with residual disease will have significant clinical implications for the treatment of PCa patients in the future.

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Significance of apoptotic and non‐apoptotic disseminated tumor cells in the bone marrow of patients with clinically localized prostate cancer

Cited by 17 publications

References 35 publications

Disseminated tumor cells and dormancy in prostate cancer metastasis

Disseminated tumor cells and dormancy in prostate cancer metastasis

Immunohistochemical Study of Cyclooxygenase-2 Expression in Prostate Carcinoma: It’s Relation with Apoptosis and Angiogenesis

The biology and clinical implications of prostate cancer dormancy and metastasis

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