Baton Rouge, LA, United States
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Serrero G.,A And G Pharmaceutical, Inc. | Serrero G.,University of Maryland, Baltimore | Hawkins D.M.,University of Minnesota | Yue B.,A And G Pharmaceutical, Inc. | And 9 more authors.
Breast Cancer Research | Year: 2012

Introduction: GP88 (progranulin) has been implicated in tumorigenesis and resistance to anti-estrogen therapies for estrogen receptor positive (ER +) breast cancer. Previous pathological studies showed that GP88 is expressed in invasive ductal carcinoma (IDC), but not in normal mammary epithelial tissue, benign lesions or lobular carcinoma. Based on these results, the present study examines GP88 prognostic significance in association with recurrence and death risks for ER +IDC patients.Methods: Two retrospective multi-site clinical studies examined GP88 expression by immunohistochemistry (IHC) analysis of paraffin-embedded breast tumor tissue sections from ER +IDC patients (lymph node positive and negative, stage 1 to 3) in correlation with patients' survival outcomes. The training study established a GP88 cut-off value associated with decreased disease-free (DFS) and overall (OS) survivals. The validation study verified the GP88 cut-off value and compared GP88 prognostic information with other prognostic factors, particularly tumor size, grade, disease stage and lymph node status in multivariate analysis.Results: GP88 expression is associated with a statistically significant increase in recurrence risk for ER +IDC patients. The training study established that GP88 3+ score was associated with decreased DFS (P = 0.0004) and OS (P = 0.0036). The independent validation study verified that GP88 3+ score was associated with a 5.9-fold higher hazard of disease recurrence and a 2.5-fold higher mortality hazard compared to patients with tumor GP88 < 3+. GP88 remained an independent risk predictor after considering age, ethnicity, nodal status, tumor size, tumor grade, disease stage, progesterone receptor expression and treatments.Conclusions: The survival factor GP88 is a novel prognostic biomarker, predictive of recurrence risk and increased mortality for non-metastatic ER +IDC patients. Of importance, our data show that GP88 continues to be a prognostic factor even after five years. These results also provide evidence that GP88 provides prognostic information independent of tumor and clinical characteristics and would support prospective study to examine whether GP88 expression could help stratify patients with ER +tumors for adjuvant therapy. © 2012 Serrero et al.; licensee BioMed Central Ltd.


Jiang X.-P.,Breast Cancer Research and Treatment Center | Elliott R.L.,Breast Cancer Research and Treatment Center | Head J.F.,Breast Cancer Research and Treatment Center
Breast Cancer Research and Treatment | Year: 2015

We hypothesized that normal mitochondria inhibited cancer cell proliferation and increased drug sensitivity by the mechanism of suppression of cancer aerobic glycolysis. To demonstrate the mechanism, we used real-time PCR and glycolysis cell-based assay to measure gene expression of glycolytic enzymes and glucose transporters, and extracellular lactate production of human breast cancer cells. We found that isolated fluorescent probe-stained mitochondria of MCF-12A (human mammary epithelia) could enter into human breast cancer cell lines MCF-7, T47D, and MDA-MB-231, confirmed by fluorescent and confocal microscopy. Mitochondria from the untransformed human mammary epithelia increased drug sensitivity of MCF-7 cells to paclitaxel. Real-time PCR showed that exogenous normal mitochondria of MCF-12A suppressed gene expression of glycolytic enzymes, lactate dehydrogenase A, and glucose transporter 1 and 3 of MCF-7 and MDA-MB-231 cells. Glycolysis cell-based assay revealed that normal mitochondria significantly suppressed lactate production in culture media of MCF-7, T47D, and MDA-MB-231 cells. In conclusion, normal mitochondria suppress cancer proliferation and increase drug sensitivity by the mechanism of inhibition of cancer cell glycolysis and glucose uptake. © 2015, Springer Science+Business Media New York.


Elliott R.L.,Breast Cancer Research and Treatment Center | Deland M.,Breast Cancer Research and Treatment Center | Head J.F.,Breast Cancer Research and Treatment Center | Elliott M.C.,Breast Cancer Research and Treatment Center
Surgical Oncology | Year: 2011

Failure after breast conserving surgery (BCS) and total breast irradiation usually occurs at the site of the original tumor. This has caused an increased interest in accelerated partial breast irradiation (APBI), because if radiation is delivered directly to the tumor bed there should be better local control. Patients greater than age 50 with core biopsy confirmed invasive ductal carcinoma were enrolled. They had preoperative ultrasound defining margins of less than 3.5 cm. Intraoperative ultrasound was also performed in an effort to ensure good surgical margins. After excision of the tumor, intraoperative radiotherapy (IORT) with the Intrabeam System was delivered to the tumor bed. The procedure has been performed on 67 patients. Sixty-one patients had it with the original surgery, while 6 had the procedure after re-exploration of the segmental mastectomy site. Because of the final pathology (surgical margins, tumor biology, and nodal status) 4 patients later had total mastectomy and 11 received total breast irradiation. When total breast irradiation is done the IORT serves as the radiation boost. The cosmetic results have been good to excellent, and there have been no serious surgical or radiation complications. To date there have been no local failures. IORT with the Intrabeam System is feasible, user friendly, versatile, with few complications, good cosmetic results, and great patient acceptance. It is practical and excellent for breast IORT in the community setting. © 2009 Elsevier Ltd. All rights reserved.


PubMed | Breast Cancer Research and Treatment Center
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

11581 Local failure after breast conserving surgery (BCS) and breast radiation usually occurs at the tumor site. This has increased interest in accelerated partial breast irradiation (APBI), because better local control should be achieved if radiation is delivered directly to the tumor bed. The interstitial catheter and Mammosite balloon brachytherapy procedures require multiple visits to the radiation center and another procedure to remove the devices. Veronesis intraoperative radiotherapy technique (IORT) and the Mobetron require a special operating room (OR), expensive equipment, and are not very mobile. The IntraBeam IORT system is ideal for APBI. It is inexpensive, safe, easy to use, mobile and can be used in any standard OR. The system also can be used at multiple sites. The photon radiation unit, control console, and applicators all fit easily in cases, requiring only a stand at another site. This makes the system versatile and cost effective. It is convenient for the patient because it requires no further surgery or visits to the radiation center. The procedure is very practical for the community setting. We have performed the procedure to compliment BCS in 54 patients, 49 as part of the original surgery, while 5 had re-exploration of the previous segmental mastectomy site. Because of the final pathology, 3 patients had total mastectomies and 8 went on to have total breast irradiation. When total breast radiation is required, the IntraBeam IORT serves as the radiation boost. There have been no serious surgical or radiation complications, however, most patients developed seromas, managed by aspiration. There were no wound infections. One patient had re-excision of the segmental mastectomy site after 22 months because of severe induration. The pathology report was only radiation fibrosis and fat necrosis. Patient satisfaction has been great and there have been no local recurrences. However, our follow-up is not long enough to determine the true efficacy of preventing local recurrence. No significant financial relationships to disclose.


PubMed | Breast Cancer Research and Treatment Center
Type: Journal Article | Journal: Breast cancer research and treatment | Year: 2015

We hypothesized that normal mitochondria inhibited cancer cell proliferation and increased drug sensitivity by the mechanism of suppression of cancer aerobic glycolysis. To demonstrate the mechanism, we used real-time PCR and glycolysis cell-based assay to measure gene expression of glycolytic enzymes and glucose transporters, and extracellular lactate production of human breast cancer cells. We found that isolated fluorescent probe-stained mitochondria of MCF-12A (human mammary epithelia) could enter into human breast cancer cell lines MCF-7, T47D, and MDA-MB-231, confirmed by fluorescent and confocal microscopy. Mitochondria from the untransformed human mammary epithelia increased drug sensitivity of MCF-7 cells to paclitaxel. Real-time PCR showed that exogenous normal mitochondria of MCF-12A suppressed gene expression of glycolytic enzymes, lactate dehydrogenase A, and glucose transporter 1 and 3 of MCF-7 and MDA-MB-231 cells. Glycolysis cell-based assay revealed that normal mitochondria significantly suppressed lactate production in culture media of MCF-7, T47D, and MDA-MB-231 cells. In conclusion, normal mitochondria suppress cancer proliferation and increase drug sensitivity by the mechanism of inhibition of cancer cell glycolysis and glucose uptake.

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