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Case Report: Pazopanib Treatment Response in a Patient with Metastatic Pleomorphic Dermal Sarcoma (Atypical Fibroxanthoma) with Circulating Tumor Cell-Derived Colonies as a Predictive Marker

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Journal of Cancer Therapy 2016年第11期7卷 785-793页

作者： Wolfram E. Samlowski Joseph Wojcik Suzanne Samlowski Douglas Fife Todd Murry Comprehensive Cancer Centers of Nevada Las Vegas USA truecells LLC Las Vegas USA Surgical Dermatology and Laser Center Las Vegas USA LMC Pathology Las Vegas USA

Atypical fibroxanthomas (AFX) are rare skin tumors. These generally are superficial tumors, usually 376 colonies. The patient could not tolerate additional chemotherapy. She was therefore treated with the oral targeted agent pazopanib. The patient developed a dramatic biopsy-confirmed complete response. After 11 months of pazopanib treatment, a repeat CTC-derived culture sample grew only 8 colonies/10 ml blood. The complete response to pazopanib is still ongoing at over 41 months. To our knowledge, this is the first demonstration of clinical complete response of a PDS tumor following targeted therapy. An additional novel feature was the demonstration that CTC-derived colonies could be grown from the blood of a PDS patient. The number of colonies appeared to correlate with the clinical treatment response and seemed to fu

关键词： Atypical Fibroxanthoma Pleomorphic Dermal Sarcoma Vascular Endothelial Growth Factor Receptor Targeted Therapy Circulating Tumor Cells Circulating Tumor Cell-Derived Cultures

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Growth of Circulating Tumor Cell-Derived Colonies from Peripheral Blood of Melanoma Patients: Preliminary Characterization of Colony Composition

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Health 2014年第12期6卷 1467-1481页

作者： Wolfram E. Samlowski John R. McGregor Suzanne T. Samlowski Shweta Tharkar Shirley Shen Joel S. Bentz Department of Oncology Comprehensive Cancer Centers of Nevada Las Vegas USA Genomics Core Facility University of Nevada Las Vegas Las Vegas USA LMC Pathology Las Vegas USA truecells llc Las Vegas USA

Circulating tumor cells (CTC) are rarely detected in the blood of cancer patients, even though they are a direct harbinger of eventual patient demise. We developed an innovative CTC culture technology to allow more sensitive isolation, expansion, and characterization of viable colonies from patient blood. In this assay, the entire leukocyte fraction from 10 ml of anticoagulated patient blood is placed into culture medium without any pre-selection. After 16 days in culture, CTC derived colonies are counted. As a proof-of-principle, blood samples from 58 Stage IIa-IV melanoma patients were tested. Ninety percent of these samples grew colonies. The colony numbers ranged from 0 - 308 (mean 63 ± 9.5 SEM). Ten normal volunteers had virtually no growth (mean 0.5 ± 1.4 colonies). Colonies were harvested using a micropipette for characterization. Tumor-cell containing spheroids were embedded in paraffin, sectioned, and stained with melanoma-specific mAb for histologic characterization. MITF proved to be the most consistent immunostain that identified melanoma cells in these colonies. A host-cell component in colonies was also identified using CD68 and CD43 mAb staining. Following enzymatic dissociation of colonies, a variety of immunostains were tested. Papanicolau staining proved most useful for identifying the abnormal nuclei of tumor cells. Flow cytometry could readily distinguish host and tumor cell populations based on DNA content and forward/side scatter in dissociated colonies. The stem cell marker ALDH1A1 associated with the aneuploid population, but CD45 was expressed on both diploid and aneuploid cells. The ability to repeatedly isolate CTC derived colonies from cancer patient blood samples opens the door to a novel type of long-term clinical monitoring. This novel CTC culture technology may prove useful to perform molecular characterization, assessment of treatment response, and testing of drug sensitivity and resistance in patients during treatment.

关键词： Circulating Tumor Cells CTC Colonies CTC Cultures Melanoma Flow Cytometry CTC Derived Colonies

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Circulating Tumor Cell Cultures as a Predictive Marker during Salvage Therapy of Refractory Merkel Cell Carcinoma with Chemotherapy and Electron Beam Radiation

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Journal of Cancer Therapy 2013年第7期4卷 1162-1166页

作者： Sreekanth Donepudi Susan A. Reisinger John R. McGregor Shweta Tharkar Suzanne Samlowski Daniel Ostler Shirley Shen Wolfram E. Samlowski 21st Century Radiation Oncology Las Vegas USA Comprehensive Cancer Centers of Nevada Las Vegas USA Genomics Core Facility of UNLV Las Vegas USA LMC Pathology Las Vegas USA truecells LLC Las Vegas USA

Metastatic Merkel Cell carcinoma (MCC) is a highly unusual and aggressive skin cancer that presents as a small, pink to violet skin lesion and metastasizes early in its growth. Metastatic MCC is generally treated with small cell lung cancer chemotherapy regimens, because the tumor consists of neuroendocrine cells, but patients generally do not have durable responses. The pathogenesis of MCC has recently been attributed to the Merkel Cell polyoma virus. This virus activates the cellular retinoblastoma oncoprotein and cell cycle machinery, triggering continual cellular proliferation. A 77-year-old man developed extensive MCC metastases, involving more than one fourth of his scalp and numerous cervical lymph nodes. Following failure of initial chemotherapy and radiation, effective palliation was achieved by using a sequence of electron-beam radiotherapy, low dose gemcitabine, and etoposide, resulting in significant periods of tumor regression and prolonged survival. A novel circulating tumor cell (CTC) culture assay was performed on four separate clinic visits during the treatment period. Tumor colonies were cultured from the patient’s peripheral blood and CTC colony counts were correlated with clinical treatment response. Not only did the patient respond to palliative cell cycle directed chemotherapy and electron beam radiation, but we demonstrated that CTC can be cultured from peripheral blood of MCC patients and serve as a predictive marker to monitor treatment response.

关键词： Merkel Cell Carcinoma Chemotherapy Radiotherapy Circulating Tumor Cells CTC Culture

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