ABSTRACT
BACKGROUND: Neurotoxic cancer treatments can cause chemotherapy-induced peripheral neuropathy and postural control deficits that cancer survivors report as a concern. Exercise-based sensorimotor training has emerged as a promising treatment for symptoms including balance deficits, however, more study is needed to optimize engagement and participation. We evaluated feasibility, satisfaction, and preliminary efficacy of a novel balance training program for cancer survivors: partnered, Adapted Argentine Tango dance (Tango). METHODS: Twenty-two individuals participated (nâ¯=â¯22). Tango classes (1â¯h) were offered twice/week. At baseline, midpoint (8 classes), and conclusion of the training (15 or 16 classes), we assessed postural control by measuring center-of-pressure (CoP) measures during quiet standing with eyes closed. We also documented attendance, barriers to attendance, and satisfaction (7 point scale; 1 high). At conclusion, we analyzed whether 1) attendance and satisfaction met feasibility criteria; 2) postural control improved among participants who were outside of normal range at baseline; and 3) co-enrolling with a companion increased attendance. FINDINGS: Feasibility criteria were met: more than half of participants attended more than half the classes offered with a mean satisfaction rate of 1.2 (SD 0.4). Those who enrolled with a companion (nâ¯=â¯9) attended more sessions than those who did not (nâ¯=â¯13) (Mann-Whitney U valueâ¯=â¯20; pâ¯=â¯0.012). Participants with demonstrated deficits (nâ¯=â¯9) improved in 3 CoP measures at midpoint (i.e., medial-lateral sway, ellipse area, medial-lateral velocity), retaining improvement in 2 CoP measures at endpoint (i.e., medial-lateral sway, ellipse area). INTERPRETATION: Partnered, Adapted Argentine Tango is feasible for cancer survivors and may improve postural control. Enrolling with a companion improved attendance.
Subject(s)
Cancer Survivors , Dance Therapy/methods , Neoplasms/physiopathology , Postural Balance , Adult , Aged , Feasibility Studies , Female , Humans , Male , Middle Aged , Neoplasms/rehabilitation , Peripheral Nervous System Diseases , Pilot Projects , Treatment OutcomeABSTRACT
Metastasis of solid tumors is associated with poor prognosis and bleak survival rates. Tumor-infiltrating myeloid cells (TIMs) are known to promote metastasis, but the mechanisms underlying their collaboration with tumor cells remain unknown. Here, we report an oncogenic role for microRNA (miR) in driving M2 reprogramming in TIMs, characterized by the acquisition of pro-tumor and pro-angiogenic properties. The expression of miR-21, miR-29a, miR-142-3p and miR-223 increased in myeloid cells during tumor progression in mouse models of breast cancer and melanoma metastasis. Further, we show that these miRs are regulated by the CSF1-ETS2 pathway in macrophages. A loss-of-function approach utilizing selective depletion of the miR-processing enzyme Dicer in mature myeloid cells blocks angiogenesis and metastatic tumor growth. Ectopic expression of miR-21 and miR-29a promotes angiogenesis and tumor cell proliferation through the downregulation of anti-angiogenic genes such as Col4a2, Spry1 and Timp3, whereas knockdown of the miRs impedes these processes. miR-21 and miR-29a are expressed in Csf1r+ myeloid cells associated with human metastatic breast cancer, and levels of these miRs in CD115+ non-classical monocytes correlates with metastatic tumor burden in patients. Taken together, our results suggest that miR-21 and miR-29a are essential for the pro-tumor functions of myeloid cells and the CSF1-ETS2 pathway upstream of the miRs serves as an attractive therapeutic target for the inhibition of M2 remodeling of macrophages during malignancy. In addition, miR-21 and miR-29a in circulating myeloid cells may potentially serve as biomarkers to measure therapeutic efficacy of targeted therapies for CSF1 signaling.
Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/pathology , Macrophages/metabolism , Melanoma, Experimental/genetics , MicroRNAs/genetics , Animals , Breast Neoplasms/blood supply , Breast Neoplasms/metabolism , Cell Line, Tumor , Cell Proliferation , Female , Humans , Macrophage Colony-Stimulating Factor/metabolism , Melanoma, Experimental/metabolism , Melanoma, Experimental/pathology , Melanoma, Experimental/secondary , Mice , Mice, Inbred C57BL , Neovascularization, Pathologic/genetics , Proto-Oncogene Protein c-ets-2/metabolism , Signal TransductionABSTRACT
Breast carcinogenesis is a multistep process involving both genetic and epigenetic changes. Epigenetics is defined as a reversible and heritable change in gene expression that is not accompanied by alteration in gene sequence. DNA methylation and histone modifications are the two major epigenetic changes that influence gene expression in cancer. The interaction between methylation and histone modification is intricately orchestrated by the formation of repressor complexes. Several genes involved in proliferation, antiapoptosis, invasion and metastasis have been shown to be methylated in various malignant and premalignant breast neoplasms. The histone deacetylase inhibitors (HDi) have emerged as an important class of drugs to be used synergistically with other systemic therapies in the treatment of breast cancer. Since epigenetic changes are potentially reversible processes, much effort has been directed toward understanding this mechanism with the goal of finding novel therapies as well as more refined diagnostic and prognostic tools in breast cancer.
