28 research outputs found
Recommended from our members
Bilateral pseudoangiomatous stromal hyperplasia tumors in axillary male gynecomastia: report of a case
Pseudoangiomatous stromal hyperplasia (PASH) is a rare benign proliferation of breast stromal cells with a complex pattern of interanastomosing spaces lined by myofibroblasts. The exact etiology is still unknown, but a proliferative response of myofibroblasts to hormonal stimuli has been postulated. PASH is a relatively common incidental finding in breast tissue removed for other reasons and rarely manifests as a localized mass. Fewer than 150 cases of tumoral PASH have been reported since it was first described in 1986. Although PASH tends to grow over time, most lesions are cured by surgical excision and the prognosis is excellent. We report an unusual case of bilateral axillary tumoral PASH in a 44-year-old man. Awareness of this disease is important when considering the differential diagnosis of axillary masses. To our knowledge, only one other case of unilateral axillary tumoral PASH in a male patient has been described in English and this is the first case of PASH occurring in male bilateral axillary gynecomastia
Abstract 1636: Altering the function of cancer-associated fibroblasts via activation of Notch signaling to inhibit tumor growth
Abstract
Objectives. Cancer-associated fibroblasts (CAF) play critical roles in determining tumor growth, invasion, metastasis, drug response and tumor angiogenesis. We have previously demonstrated that activation of the Notch1 pathway confers normal human dermal fibroblasts a suppressive phenotype to melanoma growth. Here, we further investigated whether manipulation of Notch signaling in melanoma-associated fibroblasts (MAF) alter their regulatory phenotype by which affects melanoma growth.
Methods. MAF were isolated from human metastatic melanoma and characterized. Notch pathway activity in MAF versus normal human dermal fibroblasts was examined using Notch pathway RT2-PCRArray and immunoblotting. Enforced activation of Notch pathway was achieved by transducing MAF with lentiviral vector encoding active form of Notch1 (NIC). The effect of active Notch1-engineered MAF on melanoma growth was tested by in vitro co-culture and in vivo co-xenografting animal model.
Results. Isolated MAF are α-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP) positive. MAF exhibited a relatively lower Notch activity compared to normal human dermal fibroblasts. Enforced activation of Notch1 pathway suppressed cellular activities of MAF. Active Notch1-engineered MAF significantly inhibited melanoma cell growth in vitro and retarded xenografted human melanoma cell growth on mouse skin.
Conclusions. Notch pathway activity is lower in MAF. Constitutive activation of Notch pathway confers MAF to a suppressive phenotype in regulating melanoma growth. Our study demonstrated that Notch signaling functions as a critical molecular switch in determining the regulatory role of tumor stromal fibroblasts and provided a novel approach to target tumor microenvironment through modulating stromal fibroblasts by manipulation of Notch signaling.
Citation Format: Hongwei Shao, Mecker G. Moller, Omaida C. Velazquez, Zhao-Jun Liu. Altering the function of cancer-associated fibroblasts via activation of Notch signaling to inhibit tumor growth. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1636. doi:10.1158/1538-7445.AM2013-1636</jats:p
Abstract 5010: Activation of the notch signaling pathway confers a tumor-suppressive phenotype on melanoma-associated fibroblasts
Abstract
Objectives. The tumor microenvironment (TME) is an emerging therapeutic target for cancer treatment. Cancer-associated fibroblasts (CAF) play a crucial role in cancer progression. We aim to target TME by altering intracellular signaling which determines the biological function of CAF. We have recently showed that the Notch signaling pathway likely functions as a molecular switch in controlling the tumor regulatory role of CAF in animal models and experimentally created “CAF”. Here, we investigated the status of Notch signaling in human melanoma-associated fibroblasts (MAF) versus their normal counterparts and tested whether manipulation of the Notch pathway activity in MAF alter their tumor-regulating function.
Methods. We examined levels of Hes1, a canonical Notch target, in MAF of human malignant melanoma at different stages (I-IV) and fibroblasts in either adjacent or non-adjacent normal skin tissues using tissue microarray. MAF were isolated from human metastatic melanoma tissues. Notch pathway RT2-PCRArray and immunoblot were used to assess Notch pathway activity in MAF versus normal human dermal fibroblasts. Activation of Notch signaling pathway in MAF was achieved by lentiviral vector encoding active form of Notch1 (NIC). The effect of Notch1-engineered MAF on melanoma growth was tested by in vitro co-cultures and in a mouse co-xenograft model (n=6/group). Tumor angiogenesis was analyzed by immunochemistry.
Results. MAF expressed decreased levels of Hes1 compared with adjacent skin fibroblasts. Isolated MAF also exhibited lower Notch activity than normal human dermal fibroblasts. Notch1-engineered MAF significantly inhibited melanoma cell growth in vitro (p&lt;0.01) and suppressed melanoma growth and tumor angiogenesis in mice (p&lt;0.05).
Conclusions. Notch pathway activity is down-regulated in MAF. Increase of Notch pathway activity confers MAF with inhibition to melanoma growth and tumor angiogenesis. Our study demonstrates that Notch signaling is a critical molecular switch in determining the tumor regulatory role of MAF and provides potential targets for cancer therapeutic interventions on the TME.
Citation Format: Hongwei Shao, Mecker G. Moller, Long Cai, Leiming Zhang, Zhao-Jun Liu. Activation of the notch signaling pathway confers a tumor-suppressive phenotype on melanoma-associated fibroblasts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5010. doi:10.1158/1538-7445.AM2017-5010</jats:p
Recommended from our members
Factors Affecting Family Planning and Fertility Preservation Decisions among US General Surgery Residents: A Nationwide Survey
Recommended from our members
Coverage of Fertility Preservation and Treatment among US General Surgery Residents: The First Nationwide Survey
Recommended from our members
Evaluation of Simplified Lymphatic Microsurgical Preventing Healing Approach (SLYMPHA) for the prevention of breast cancer-related lymphedema after axillary lymph node dissection using bioimpedance spectroscopy
Lymphedema is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 20%. Simplified Lymphatic Microsurgical Preventing Healing Approach (SLYMPHA) is a safe and relatively simple method, which decreases incidence of lymphedema dramatically. Our initial study showed an 88% decrease in clinical lymphedema rate. In the initial study, we used arm circumference measurement for the diagnosis of lymphedema and median follow up was 15 months. The aim of this study was to confirm these results after a long-term follow up period and by using bioimpedance spectroscopy (L-Dex) technology in detecting lymphedema.
All patients, undergoing ALND with or without SLYMPHA between January 2014 and November 2020 were included in the study. Patients with no postoperative L-Dex measurements were excluded. A L-Dex score outside the normal range (±10 L-Dex unit) or ≥10 L-Dex unit increase above patient's baseline was considered as lymphedema. The incidence of lymphedema was compared between patients with and without SLYMPHA.
194 patients were included in the study. 57% of cohort underwent SLYMPHA. Mean follow-up time was 47 ± 37 months. Patients, who underwent SLYMPHA, had a significantly lower rate of lymphedema (16% vs 32%; p = 0.01; OR 0.4 [0.2-0.8]).
SLYMPHA is a safe and relatively simple method, which continued its efficacy after a long-term follow up period. It should be considered as an adjunct procedure to ALND for all patients during initial surgery
Recommended from our members
Surgical and Oncologic Outcomes With Intraoperative Radiation Therapy for Early Breast Cancer
Background For selected patients with early-stage breast cancer (BC), intraoperative radiation therapy (IORT) has emerged as a convenient alternative to standard whole breast irradiation (WBI). We report a single institution experience with IORT in terms of oncologic outcomes, toxicities, and cosmesis. Methods Clinicopathological and perioperative outcomes of patients who underwent IORT for early-stage BC at a public hospital from 2017 to 2020 were retrospectively retrieved. Toxicity was categorized to acute or chronic based on 6 months post-IORT cutoff. Results 85 patients underwent IORT and had complete data, aged 49‐85 years (mean 62). Intraoperative radiation therapy added 23 minutes on average to the total operative time. Final stage was 0, I, and II in 40%, 58.9%, and 1.1% of patients, respectively. Mean tumor size was 0.8 cm (range .1-2.1), with ductal histology comprising 94% of cases. Surgical margins were positive in 2 patients, and adjuvant WBI was required in 5 patients. After a median follow‐up of 17 months (range 3-41), none of the patients had local recurrence and no mortality was recorded. Early wound complications included wound dehiscence (n = 1), seroma/hematoma (n = 15), and re-operation with loss of nipple-areola complex (n = 1). Chronic skin toxicities were reported in 10 (12%) patients and good or excellent cosmetic outcome was reported in 93% of patients. Conclusions Utilizing IORT among low-risk early BC patients may be a safe and more convenient alternative to traditional WBI, with low toxicity rate, acceptable cosmetic results, and good oncologic outcomes at 17 months. Longer follow-up and further prospective controlled studies are needed to confirm these findings
Recommended from our members
Axillary Response to Neoadjuvant Therapy in Node-Positive, Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Patients: Predictors and Oncologic Outcomes
Background One potential benefit of neoadjuvant therapy (NAT) in node-positive, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) patients is axillary downstaging to avoid axillary dissection. Objective The aim of this study was to evaluate axillary response to NAT with chemotherapy (NCT) or endocrine therapy (NET) and identify potential predictors of response. Methods A prospectively collected database was queried for node-positive, ER+, HER2- breast cancer patients treated with NAT and surgery from January 2011 to September 2020. Axillary response was categorized into pathologic complete response (pCR) versus no pCR, and was correlated to demographic and clinicopathologic parameters in a logistic regression model. Results A cohort of 176 eligible patients was identified and 178 breast cancers were included in the study. The overall axillary pCR rate was 12.3% (22/178). NCT and NET achieved response rates of 13.9% (19/137) and 7.3% (3/41), respectively (p = 0.232). A significantly higher axillary pCR rate was identified in patients with clinical stage II at diagnosis (12/60, 20%) compared with stage III (10/118, 8.4%; p = 0.03). NET patients with ypN0 were younger and were treated for a longer period of time (>6 months). Completion axillary dissection was omitted in the majority (73.7%) of NCT patients achieving axillary pCR. Conclusions For patients with node-positive, ER+, HER2- breast cancer, a lower burden of disease at the time of diagnosis (stage II) is associated with a significantly higher axillary pCR, enabling those patients to be spared axillary dissection. Further studies are necessary to define the role of genomic profiling in predicting axillary response
Recommended from our members