Chick Chorioallantoic Membrane (CAM) Assays as a Model of Patient-Derived Xenografts from Circulating Cancer Stem Cells (cCSCs) in Breast Cancer Patients.

Background: cCSCs are a small subset of circulating tumor cells with cancer stem cell features: resistance to cancer treatments and the capacity for generating metastases. PDX are an appreciated tool in oncology, providing biologically meaningful models of many cancer types, and potential platforms for the development of precision oncology approaches. Commonly, mouse models are used for the in vivo assessment of potential new therapeutic targets in cancers.

Influence of adjuvant radiotherapy on circulating epithelial tumor cells and circulating cancer stem cells in primary non-metastatic breast cancer.

Background: There is an unmet need to identify biomarkers that directly reflect response to adjuvant radiotherapy (RT). Circulating epithelial tumor cells (CETCs) represent the liquid component of solid tumors and are responsible for metastatic relapse. CETC subsets with cancer stem cell characteristics, circulating cancer stem cells (cCSCs), play a pivotal role in the metastatic cascade.

Influence of endocrine therapy on the ratio of androgen receptor (AR) to estrogen receptor (ER) positive circulating epithelial tumor cells (CETCs) in breast cancer.

Background: The androgen receptor (AR) is expressed in the majority of breast cancers and across the main breast cancer subtypes. Despite the high frequency of AR expression in breast cancer its appraisal remains controversial because its role is complex, dependent on the hormonal milieu. The aim of the current study was to investigate the frequency of AR and ER positive CETCs in breast cancer patients.

B7-H3 on circulating epithelial tumor cells correlates with the proliferation marker, Ki-67, and may be associated with the aggressiveness of tumors in breast cancer patients.

Circulating epithelial tumor cells (CETCs) in peripheral blood are a prerequisite for the development of metastases. B7-H3 is an important immune checkpoint member of the B7 family and inhibits T-cell mediated antitumor immunity. Its expression is associated with a negative prognosis and a poor clinical outcome.

Sensitive detection of PD-L1 expression on circulating epithelial tumor cells (CETCs) could be a potential biomarker to select patients for treatment with PD-1/PD-L1 inhibitors in early and metastatic solid tumors.

Background: The current cancer research strongly focuses on immune therapies, where the PD-1, with its ligands plays an important role. It is known that PD-L1 is frequently up-regulated in a number of different cancers and the relevance of this pathway has been extensively studied and therapeutic approaches targeting PD-1 and PD-L1 have been developed. We used a non-invasive, real-time biopsy for determining PD-L1 and PD-L2 expression in CETCs of solid cancer patients.

The number of tumorspheres cultured from peripheral blood is a predictor for presence of metastasis in patients with breast cancer.

Background: Tumor metastases are the major cause of cancer morbidity and mortality. A subpopulation of tumor cells with stem-like properties is assumed to be responsible for tumor invasion, metastasis, heterogeneity and therapeutic resistance. This population is termed cancer stem cells (CSCs).

Insulin-like growth factor receptor I (IGF-IR) and vascular endothelial growth factor receptor 2 (VEGFR-2) are expressed on the circulating epithelial tumor cells of breast cancer patients.

Background: Circulating epithelial tumor cell (CETC) analysis is a promising diagnostic field for estimating the risk for metastatic relapse and progression in patients with malignant disease. CETCs characterization can be used as a liquid biopsy for prognostic and predictive purposes in breast and other cancers. IGF-IR and VEGFR-2 play an important role in tumor growth and the progression of cancer disease.

Demasking of epithelial cell adhesion molecule (EpCAM) on circulating epithelial tumor cells by Tween®20 treatment in breast cancer patients.

Background: The epithelial cell adhesion molecule (EpCAM) embedded in the plasma membrane of circulating epithelial tumor cells (CETC) is used for detection and enrichment of circulating tumor cells in peripheral blood and as a target for anti-epithelial antibodies elicited during immune response in anti-tumor immunization. Although an efficient immune response against EpCAM can be generated, the clinical application of such approaches has not been successful so far and the detection of circulating epithelial cells is highly variable. One reason for these discrepancies may be that not all circulating tumor cells are equally accessible for the specific antibody.

Monitoring the response of circulating epithelial tumor cells to adjuvant chemotherapy in breast cancer allows detection of patients at risk of early relapse.

Purpose: To demonstrate that it is possible to monitor the response to adjuvant therapy by repeated analysis of circulating epithelial tumor cells (CETCs) and to detect patients early who are at risk of relapse.

Patients And Methods: In 91 nonmetastatic primary breast cancer patients, CETCs were quantified using laser scanning cytometry of anti-epithelial cell adhesion molecule-stained epithelial cells from whole unseparated blood before and during adjuvant chemotherapy.

Results: Numbers of CETCs were analyzed before therapy, before each new cycle, and at the end of chemotherapy.

An increase in cell number at completion of therapy may develop as an indicator of early relapse: quantification of circulating epithelial tumor cells (CETC) for monitoring of adjuvant therapy in breast cancer.

Purpose: Treatment efficiency of adjuvant therapy in breast cancer is only revealed after several years by statistical evaluation and gives no answer for the individual patient. We here present a method to analyze the response to adjuvant chemotherapy online in individual patients.

Methods/results: In 25 consecutive non-metastatic primary breast cancer patients adjuvant fluorouracil/epirubicin/cyclophosphamid (FEC) or EC followed by taxane (EC-T) or cyclophosphamid/methotrexate/fluorouracil (CMF) therapy were given.

Quantification of circulating tumour cells for the monitoring of adjuvant therapy in breast cancer: an increase in cell number at completion of therapy is a predictor of early relapse.

Treatment efficiency of adjuvant therapy in breast cancer is revealed after several years by statistical evaluation, but this gives no answer for the individual patient. Having shown that circulating epithelial tumour cells (CETC) respond to neoadjuvant therapy in exactly the same way as the tumour, we monitored adjuvant therapy in 25 non-metastatic breast cancer patients. Nineteen patients with a decline or no change in number of CETC showed no relapse whereas six patients with a more than ten-fold increase had five distant and one local relapse, indicating that the dynamic of CETC in the individual patient is predictive of outcome.

Evidence that human autoimmune thrombocytopenia mediated by both immunoglobulin isotypes IgM and IgG is an independent disease entity.

Autoimmune thrombocytopenic purpura (AITP) is a bleeding disorder caused by clonally restricted self-reactive antibodies with specificity for platelet glycoproteins. Anti-platelet autoantibodies in AITP mainly belong to the IgG class. The occurrence of anti-platelet autoantibodies of the IgM isotype has been reported, and AITP is partially mediated by antibodies of both isotypes, IgM and IgG.

Influence of isotypes of disease-associated autoantibodies on the expression of natural autoantibody repertoires in humans.

Current understanding of immune network interactions mediated by immunoglobulins focuses on the role of idiotypes expressed on antibody variable regions. Idiotype interactions account significantly for the functional integrity of natural self-reactive antibody repertoires, whereas immunoglobulin isotypes are not considered to direct natural autoimmunity. Autoimmune thrombocytopenic purpura (AITP), a bleeding disorder caused by clonally restricted platelet-specific autoantibodies of the IgM or IgG isotype, is an excellent model to investigate the impact of isotype differences of immunoglobulins on the selection of natural self-reactive antibody repertoires in humans.

Standardized quantification of circulating peripheral tumor cells from lung and breast cancer.

Detection and quantitation of circulating tumor cells from solid epithelial tumors could become a valuable tool for therapy monitoring if the procedure can be standardized. In the present work we assessed the influence of pre-analytical handling, storage and white blood cell isolation on analysis of a population of spiked tumor cell-line cells and intrinsically present epithelial cells in the peripheral blood of breast and lung cancer patients and the sensitivity of their detection. Sucrose density separation did not enrich epithelial cells, and even depleted them, leading to a gross underestimation of their numbers (3/13 positive, between 2.

Increase in number of circulating disseminated epithelial cells after surgery for non-small cell lung cancer monitored by MAINTRAC(R) is a predictor for relapse: A preliminary report.

BACKGROUND: Lung cancer still remains one of the most commonly occurring solid tumors and even in stage Ia, surgery fails in 30% of patients who develop distant metastases. It is hypothesized that these must have developed from occult circulating tumor cells present at the time of surgery, or before. The aim of the present study was to detect such cells in the peripheral blood and to monitor these cells following surgery.