Prognostic impact of isolated tumor cells in breast cancer axillary nodes: single tumor cell(s) versus tumor cell cluster(s) and microanatomic location

2011 ◽  
Vol 131 (2) ◽  
pp. 645-651 ◽  
Author(s):  
Johanna H. Vestjens ◽  
Maaike de Boer ◽  
Paul J. van Diest ◽  
Carolien H. van Deurzen ◽  
Jos A. van Dijck ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Cluster ◽  
Prognostic Impact ◽  
Isolated Tumor Cells ◽  
Axillary Nodes ◽  
Single Tumor Cell ◽  
Single Tumor

The IMiDs® Immunomodulatory Drugs Revlimid® (Lenalidomide) and CC-4047 Induce Growth Arrest and Apoptosis in NHL Tumor Cells In Vitro.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2388-2388 ◽  
Author(s):  
Laura G. Corral ◽  
Dan Zhu ◽  
Yuedi Wang ◽  
Bernd Stein
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Growth Arrest ◽  
Additive Effect ◽  
Immunomodulatory Drugs ◽  
Raji Cells ◽  
Pre Treatment ◽  
Single Tumor Cell ◽  
Single Tumor

Abstract IMiDs® immunomodulatory drugs are thalidomide analogues that have been developed for improved anti-cancer and anti-inflammatory properties and decreased side effects. Many IMiDs® immunomodulatory drugs have been shown to have activities in hematologic cancers and solid malignancies, as well as having profound effects on the bone marrow microenvironment. Specifically in NHL, it was shown that addition of Revlimid® or CC-4047 to Rituxan enhances anti-tumor activity in a SCID mouse lymphoma model. Here we tested the direct effects of Revlimid® and CC-4047 on NHL tumor cells by treating Raji cells with each drug alone or with each drug in combination with anti-CD20 antibodies B1 and Rituxan. CC-4047 alone caused up to 40% inhibition of proliferation at 10 μM in Raji cells, which corresponded to G1 arrest. In combination with B1, CC-4047 showed a small additive effect at 10 μM while Revlimid® effects were minimal up to 10 μM. In combination with Rituxan, CC-4047 showed a slight additive effect at 10 μM and Revlimid® at 50 μM. We have also developed a co-culture assay of PBMC and NHL tumor cells as an in vitro model of tumor-host immune system interaction, to further explore the anti-tumor potential of the drugs in NHL. This assay is non-radioactive and flow cytometry based. In this co-culture system using Raji and PBMC, we have shown that pre-treatment of PBMC with Revlimid® or CC-4047 can enhance the PBMC activity in inducing Raji cell apoptosis in a dose dependent manner. In addition, our data indicate that pre-treatment of Raji cells with Rituxan can further enhance the apoptosis induced by PBMC pre-treated with Revlimid® or CC-4047. Since minimal additive effect between each drug and Rituxan was observed in the Raji single tumor cell model, these studies suggest that the co-culture system is a more appropriate cellular model to assess the anti-tumor activities of certain IMiDs® immunomodulatory drugs. This system can reveal the effects of certain IMiD® immunomodulatory drugs not observable with single tumor cell proliferation models. In summary, our data clearly demonstrate that Revlimid® and CC-4047 directly induce NHL tumor cell growth arrest and effectively enhance tumor cell apoptosis induced by PBMC. These results support clinical evaluation of Revlimid® and certain IMiDs® immunomodulatory drugs in relapsed B-cell NHL in combination with Rituxan.

scholarly journals Clusters, Assemblies and Aggregates of Tumor Cells in the Blood of Breast Cancer Patients; Composition, Mode of Action, Detection and Impact on Metastasis and Survival

2021 ◽  
Vol 1 (1) ◽  
pp. 55-68
Author(s):  
Urszula Smietanka ◽  
Małgorzata Szostakowska-Rodzos ◽  
Sylwia Tabor ◽  
Anna Fabisiewicz ◽  
Ewa A. Grzybowska
Keyword(s):  
Breast Cancer ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Diagnostic Tool ◽  
Therapeutic Target ◽  
Mode Of Action ◽  
Breast Cancer Patients ◽  
Single Ctcs ◽  
Methods Of Isolation

Circulating tumor cells (CTCs) are gaining momentum as a diagnostic tool and therapeutic target. CTC clusters are more metastatic, but harder to study and characterize, because they are rare and the methods of isolation are mostly focused on single CTCs. This review highlights the recent advances to our understanding of tumor cell clusters with the emphasis on their composition, origin, biology, methods of detection, and impact on metastasis and survival. New approaches to therapy, based on cluster characteristics are also described.

scholarly journals Single-cell evaluation reveals shifts in the tumor-immune niches that shape and maintain aggressive lesions in the breast

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Vidya C. Sinha ◽  
Amanda L. Rinkenbaugh ◽  
Mingchu Xu ◽  
Xinhui Zhou ◽  
Xiaomei Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Mouse Model ◽  
Transition State ◽  
Tumor Cell ◽  
Single Cell ◽  
Tumor Cells ◽  
Breast Lesions ◽  
Aggressive Tumor ◽  
Insight Into

AbstractThere is an unmet clinical need for stratification of breast lesions as indolent or aggressive to tailor treatment. Here, single-cell transcriptomics and multiparametric imaging applied to a mouse model of breast cancer reveals that the aggressive tumor niche is characterized by an expanded basal-like population, specialization of tumor subpopulations, and mixed-lineage tumor cells potentially serving as a transition state between luminal and basal phenotypes. Despite vast tumor cell-intrinsic differences, aggressive and indolent tumor cells are functionally indistinguishable once isolated from their local niche, suggesting a role for non-tumor collaborators in determining aggressiveness. Aggressive lesions harbor fewer total but more suppressed-like T cells, and elevated tumor-promoting neutrophils and IL-17 signaling, disruption of which increase tumor latency and reduce the number of aggressive lesions. Our study provides insight into tumor-immune features distinguishing indolent from aggressive lesions, identifies heterogeneous populations comprising these lesions, and supports a role for IL-17 signaling in aggressive progression.

scholarly journals Biochemical and Anti-Triple Negative Metastatic Breast Tumor Cell Properties of Psammaplins

Marine Drugs ◽  
2018 ◽  
Vol 16 (11) ◽  
pp. 442 ◽  
Author(s):  
Yu-Dong Zhou ◽  
Jun Li ◽  
Lin Du ◽  
Fakhri Mahdi ◽  
Thuy Le ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Breast Tumor ◽  
Triple Negative ◽  
Hdac Inhibitors ◽  
Metastatic Breast ◽  
Dependent Manner ◽  
Breast Tumor Cells ◽  
Metastatic Breast Tumor

Breast tumors reprogram their cellular metabolism, nutrient uptake, and utilization-associated biochemical processes. These processes become further transformed as genetically predisposed metastatic breast tumor cells colonize specific organs. Breast tumor cells often metastasize to the brain, bone, lung and liver. Massagué and colleagues isolated organotropic subclones and established organ-specific gene signatures associated with lung-, bone-, and brain-specific metastatic triple-negative breast cancer (TNBC) MDA-MB-231 cells. Using these genetically characterized metastatic subclones specific to lung (LM4175), bone (BoM1833), and brain (BrM-2a), we evaluated marine natural products for the ability to differentially suppress metastatic breast cancer cells in a target organ-dependent manner. Psammaplin-based histone deacetylase (HDAC) inhibitors were found to differentially inhibit HDAC activity, induce activation of hypoxia-inducible factor-1 (HIF-1), and disrupt organotropic metastatic TNBC subclone growth. Further, psammaplins distinctly suppressed the outgrowth of BoM1833 tumor spheroids in 3D-culture systems. Similar results were observed with the prototypical HDAC inhibitor trichostatin A (TSA). These organotropic tumor cell-based studies suggest the potential application of HDAC inhibitors that may yield new directions for anti-metastatic breast tumor research and drug discovery.

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