Detection of Occult Lymph Node Metastases in Locally Advanced Node-Negative Prostate Cancer

Pagliarulo, Vincenzo; Hawes, Debra; Brands, F.; Groshen, Susan; Cai, Jie; Stein, John P.; Lieskovsky, Gary; Skinner, Donald G.; Côté, Richard J.

doi:10.1200/jco.2005.05.4767

Cited by 111 publications

(73 citation statements)

References 35 publications

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“…Thus, prostate cancer appears to adhere to the model of parallel metastatic spread (1). In support of this model, 13.3% of patients with pT3 prostate carcinoma treated by radical prostatectomy and bilateral LN dissection, and classified as node negative, harbored instead occult LN metastases, which were an independent predictor of recurrence and death in a multivariable analysis (39).…”

Section: Discussionmentioning

confidence: 84%

Tenascin-C Protects Cancer Stem–like Cells from Immune Surveillance by Arresting T-cell Activation

et al. 2015

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Precociously disseminated cancer cells may seed quiescent sites of future metastasis if they can protect themselves from immune surveillance. However, there is little knowledge about how such sites might be achieved. Here, we present evidence that prostate cancer stem-like cells (CSC) can be found in histopathologically negative prostate draining lymph nodes (PDLN) in mice harboring oncogene-driven prostate intraepithelial neoplasia (mPIN). PDLN-derived CSCs were phenotypically and functionally identical to CSC obtained from mPIN lesions, but distinct from CSCs obtained from frank prostate tumors. CSC derived from either PDLN or mPIN used the extracellular matrix protein Tenascin-C (TNC) to inhibit T-cell receptor-dependent T-cell activation, proliferation, and cytokine production. Mechanistically, TNC interacted with a5b1 integrin on the cell surface of T cells, inhibiting reorganization of the actin-based cytoskeleton therein required for proper T-cell activation. CSC from both PDLN and mPIN lesions also expressed CXCR4 and migrated in response to its ligand CXCL12, which was overexpressed in PDLN upon mPIN development. CXCR4 was critical for the development of PDLN-derived CSC, as in vivo administration of CXCR4 inhibitors prevented establishment in PDLN of an immunosuppressive microenvironment. Taken together, our work establishes a pivotal role for TNC in tuning the local immune response to establish equilibrium between disseminated nodal CSC and the immune system. Cancer Res; 75(10); 2095-108. Ó2015 AACR.

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Section: Discussionmentioning

confidence: 84%

Tenascin-C Protects Cancer Stem–like Cells from Immune Surveillance by Arresting T-cell Activation

et al. 2015

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“…Data indicates that lymph node metastasis is a critical benchmark in cancer disease and is often the earliest sign of tumor progression. 31,32 Once the protocol has been adapted for such an application, as mentioned above, even the lower cut off levels might be used for selection of patients with low tumor burden.…”

Section: Discussionmentioning

confidence: 99%

High Quality Assessment of DNA Methylation in Archival Tissues from Colorectal Cancer Patients Using Quantitative High-Resolution Melting Analysis

Balić

Pichler

Strutz

et al. 2009

The Journal of Molecular Diagnostics

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High-resolution melting (HRM) analysis is a novel tool for analysis of promoter methylation. The aim of the present study was to establish and validate HRM analysis for detection of promoter methylation on archival formalin-fixed paraffin-embedded tissues from colorectal cancer patients. We first evaluated HRM assays for O 6 -methylguanine-DNA methyltransferase (MGMT) and adenomatous polyposis coli (APC) promoter methylation on a methylated DNA dilution matrix and DNA extracted from eight fresh or formalin-fixed paraffin-embedded human cancer cell lines. Then we used these assays for the analysis of MGMT and APC promoter methylation in a subset of archival formalin-fixed paraffin-embedded colorectal tumor specimens. All samples with promoter methylation of MGMT or APC and randomly selected samples without promoter methylation were analyzed twice. All results generated by HRM were validated with MGMT and APC MethyLight assays. APC and MGMT promoter methylation data were consistent and reproducible throughout the dilutions and all three replicates in the methylated DNA dilution matrix and between two experiments in clinical samples. There was high concordance between HRM and MethyLight results. HRM for APC promoter methylation revealed consistent results between fresh and formalin-fixed paraffin-embedded human cancer cell line DNA. The methylation status in archival tumor specimens from patients with colorectal cancer can therefore be determined with high quality by HRM. The ability to analyze archival tissues greatly facilitates further research and its clinical implementation.

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“…Lymph node metastasis is a significant indicator for low survival and poor prognosis and is predictive of a higher risk for distant metastases (25,26), which are responsible for most HNC deaths (27). Thus, accurate detection of lymph nodes metastasis close to the primary tumor is fundamental for appropriate treatment, especially for individuals diagnosed with oral cavity or oropharyngeal squamous cell carcinoma (28).…”

Section: Discussionmentioning

confidence: 99%

Multimodal Image-Guided Surgical and Photodynamic Interventions in Head and Neck Cancer: From Primary Tumor to Metastatic Drainage

Muhanna

Cui

Chan

et al. 2016

Clinical Cancer Research

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Purpose: The low survival rate of head and neck cancer (HNC) patients is attributable to late disease diagnosis and high recurrence rate. Current HNC staging has inadequate accuracy and low sensitivity for effective diagnosis and treatment management. The multimodal porphyrin lipoprotein-mimicking nanoparticle (PLP), intrinsically capable of positron emission tomography (PET), fluorescence imaging, and photodynamic therapy (PDT), shows great potential to enhance the accuracy of HNC staging and potentially HNC management.Experimental Design: Using a clinically relevant VX-2 buccal carcinoma rabbit model that is able to consistently develop metastasis to regional lymph nodes after tumor induction, we investigated the abilities of PLP for HNC diagnosis and management.Results: PLPs facilitated accurate detection of primary tumor and metastatic nodes (their PET image signal to surrounding muscle ratios were 10.0 and 7.3, respectively), and provided visualization of the lymphatic drainage from tumor to regional lymph nodes by both preoperative PET and intraoperative fluorescence imaging, allowing the identification of unknown primaries and recurrent tumors. PLP-PDT significantly enhanced cell apoptosis in mouse tumors (73.2% of PLP-PDT group vs 7.1% of PLP alone group) and demonstrated complete eradication of primary tumors and obstruction of tumor metastasis in HNC rabbit model without toxicity in normal tissues or damage to adjacent critical structures.Conclusions: PLPs provide a multimodal imaging and therapy platform that could enhance HNC diagnosis by integrating PET/ computed tomography and fluorescence imaging, and improve HNC therapeutic efficacy and specificity by tailoring treatment via fluorescence-guided surgery and PDT.

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Detection of Occult Lymph Node Metastases in Locally Advanced Node-Negative Prostate Cancer

Abstract: The detection of occult lymph node metastases in patients with pT3N0 prostate cancer identifies those with significantly increased risk of prostate cancer recurrence and death.

Cited by 111 publications

References 35 publications

Tenascin-C Protects Cancer Stem–like Cells from Immune Surveillance by Arresting T-cell Activation

Tenascin-C Protects Cancer Stem–like Cells from Immune Surveillance by Arresting T-cell Activation

High Quality Assessment of DNA Methylation in Archival Tissues from Colorectal Cancer Patients Using Quantitative High-Resolution Melting Analysis

Multimodal Image-Guided Surgical and Photodynamic Interventions in Head and Neck Cancer: From Primary Tumor to Metastatic Drainage

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