Influence of stromal-epithelial interactions on breast cancer in vitro and in vivo.

Stromal cell-secreted chemokines including CCL2 have been implicated in the primary tumor microenvironment, as mediators of tumor cell migration, proliferation, and angiogenesis. Expression of CCL2 and its principal receptor CCR2 was analyzed by RQ-PCR in primary tumor cells and breast cancer cell lines. Breast cancer cell lines (MDA-MB-231, T47D) were co-cultured directly on a monolayer of primary breast tumor and normal stromal cells, retrieved using EpCAM+ magnetic beads, and changes in expression of CCL2, CCR2, MMP11, ELK1, VIL2, and Ki67 detected by RQ-PCR. Epithelial cell migration and proliferation in response to stromal cell-secreted factors was also analyzed. In vivo, tumor xenografts were formed by co-injecting T47D cells with primary tumor stromal cells. Following establishment, tumors were harvested and digested, epithelial cells retrieved and analyzed by RQ-PCR. Whole tumor tissue was also analyzed by immunohistochemistry for CD31 and the VIL2 encoded protein Ezrin. Tumor stromal cells expressed significantly higher levels of CCL2 than normal cells, with no CCR2 expression detected. Primary epithelial cells and breast cancer cell lines expressed elevated CCL2, with relative expression of CCR2 found to be higher than the ligand. Interaction of breast cancer epithelial cells with primary tumor, but not normal stromal cells, stimulated increased expression of CCL2 (8-fold), ELK1 (6-fold), VIL2 (6-fold), and MMP11 (17-fold). Factors secreted by stromal cells, including CCL2, stimulated a significant increase in epithelial cell migration, with no effect on cell proliferation in vitro observed. In vivo, the presence of stromal cells resulted in tumors of increased volume, mediated at least in part through neoangiogenesis demonstrated by immunohistochemistry (CD31). Admixed tumor xenografts exhibited increased expression of Ki67, MMP11, VIL2, and ELK1. Elevated Ezrin protein was also detected, with increased cytoplasmic localization. The results presented highlight mechanisms through which breast cancer epithelial cells can harness stromal cell biology to support tumor progression.

Use of infrared thermography for the assessment of free flap perforators in autologous breast reconstruction: A systematic review.

Perforator-based flaps have in recent years become the mainstay of autologous breast reconstruction practice. Imaging modalities ranging from Doppler ultrasound to CT angiography demonstrate varying utility in the preoperative identification and localisation of perforators. Despite these available radiological investigations, finding and quantitatively assessing perforators remain a time-consuming and tedious process that is often complicated by a number of factors including variable anatomy prior surgery and body habitus. Thermographic imaging shows promise as a novel modality for preoperative localisation of perforator vessels. This review summarises the currently available evidence for its application in perforator mapping for abdominal-based autologous breast reconstruction. We discuss the development of the technology over the years, its current use, its advantages and how it may impact on reconstructive breast surgery.

Circulating Melanoma-Derived Extracellular Vesicles: Impact on Melanoma Diagnosis, Progression Monitoring, and Treatment Response.

Malignant melanoma, one of the most aggressive human malignancies, is responsible for 80% of skin cancer deaths. Whilst early detection of disease progression or metastasis can improve patient survival, this remains a challenge due to the lack of reliable biomarkers. Importantly, these clinical challenges are not unique to humans, as melanoma affects many other species, including companion animals, such as the dog and horse. Extracellular vesicles (EVs) are tiny nanoparticles involved in cell-to-cell communication. Several protein and genomic EV markers have been described in the literature, as well as a wide variety of methods for isolating EVs from body fluids. As such, they may be valuable biomarkers in cancer and may address some clinical challenges in the management melanoma. This review aimed to explore the translational applications of EVs as biomarkers in melanoma, as well as their role in the clinical setting in humans and animals. A summary of melanoma-specific protein and genomic EV markers is presented, followed by a discussion of the role EVs in monitoring disease progression and treatment response. Finally, herein, we reviewed the advantages and disadvantages of methods utilised to isolate EVs from bodily fluids in melanoma patients (human and animals) and describe some of the challenges that will need to be addressed before EVs can be introduced in the clinical setting.

Systemic chemokine levels in breast cancer patients and their relationship with circulating menstrual hormones.

INTRODUCTION: The chemokines Stromal Cell-Derived Factor-1alpha (SDF-1alpha/CXCL12) and Monocyte Chemotactic Protein-1 (MCP-1/CCL2) have been implicated in breast cancer progression. We recently reported elevated systemic MCP-1 in breast cancer patients. This study investigated circulating levels of SDF-1alpha in breast cancer patients, and addressed potential hormonal regulation of these two potent chemokines. METHODS: SDF-1alpha levels were determined by ELISA in 114 breast cancer patients and 85 controls, and correlated with clinical data. Blood samples were collected from 36 healthy premenopausal volunteers weekly for four weeks to measure Luteinising Hormone (LH), Follicular Stimulating Hormone (FSH), Oestradiol and Progesterone using a Bayer ADVIA Centaur Immunoassay system, in parallel with SDF-1alpha and MCP-1. CXCL12 expression was determined using RQ-PCR in primary tumour stromal cells (n = 16) harvested at surgery. RESULTS: Plasma SDF-1alpha was significantly higher in breast cancer patients than age-matched controls and had a significant correlation with tumour grade and epithelial subtype. Investigation of menstrual variations of these chemokines revealed lower SDF-1alpha levels in the mid-luteal phase of the menstrual cycle and a significant positive correlation with circulating Oestradiol. MCP-1 levels showed no correlation with menstrual hormones. There was a trend towards increased CXCL12 expression in tumour compared to normal stromal cells. CONCLUSIONS: The elevated level of SDF-1alpha detected in breast cancer patients, and it's correlation with prognostic indicators, highlights the importance of this chemokine in disease progression. Elucidation of factors influencing chemokine secretion supports clarification of their role in tumourigenesis.

Vascularized Thoracodorsal to Suprascapular Nerve Transfer, a Novel Technique to Restore Shoulder Function in Partial Brachial Plexopathy.

We describe the clinical outcome of a novel nerve transfer to restore active shoulder motion in upper brachial plexus injury. The thoracodorsal nerve (TDN) was successfully used as a vascularized donor nerve to neurotize to the suprascapular nerve (SSN) in a patient with limited donor nerve availability. At 4 years follow-up, he had regained useful external rotation of the injured limb, with no significant donor site morbidity. Shoulder abduction return was less impressive, however, and reasons for this are discussed. We provide a comprehensive review of the literature on this topic and a subsequent discussion on the details of this novel technique. This is the first reported case of TDN to SSN transfer, and also the first reported case of a vascularized TDN transfer in the English language literature. We advocate direct thoracodorsal to SSN transfer as a valid surgical option for the restoration of shoulder function in patients with partial brachial plexus avulsion, when conventional nerve donors are unavailable.