Papers by Elizabeth Peralta
Cancer research, 2000
A potent anti-human (hu) p53 CD8+ CTL response develops in HLA A*0201 transgenic (Tg) mice after ... more A potent anti-human (hu) p53 CD8+ CTL response develops in HLA A*0201 transgenic (Tg) mice after immunization with peptides corresponding to HLA A*0201 motifs from hu p53. Mice immunized with the hu P53(149-157) peptide develop a CTL response that is of moderately high affinity and is capable of recognizing hu tumor cells expressing mutated p53. In this report, the mRNAs encoding the predominantly expressed T-cell receptor (TCR) sequences were molecularly cloned from a murine (mu) CTL clone derived from immunized Tg mice, which recognized endogenously processed hu p53 restricted by HLA A*0201. The separate A and B chain TCR cDNAs were transfected in the corresponding TCR A- and B- Jurkat-CD3- mutant T-cell lines, and each rescued CD3 surface expression. Both TCR chains were simultaneously introduced into Jurkat-CD3+ cells, and the transfected Jurkat cells recognized hu T2 cells sensitized with the p53(149-157) CTL epitope but not T2 cells sensitized with a nonspecific CTL epitope. B...
Clinics in Colon and Rectal Surgery, 2009
Several uncommon tumors occur in the anal canal such as gastrointestinal stromal tumors, carcinoi... more Several uncommon tumors occur in the anal canal such as gastrointestinal stromal tumors, carcinoids, and lymphoma. Increased clinical experience and advancements in molecular biology have improved the accuracy of pathologic diagnosis and guided treatment recommendations, which the author addresses in this article.
Annals of Surgical Oncology, 2004
Without Abstract
A potent anti-human (hu) p53 CD81 CTL response develops in HLA A*0201 transgenic (Tg) mice after ... more A potent anti-human (hu) p53 CD81 CTL response develops in HLA A*0201 transgenic (Tg) mice after immunization with peptides corre- sponding to HLA A*0201 motifs from hu p53. Mice immunized with the hu p53149 -157 peptide develop a CTL response that is of moderately high affinity and is capable of recognizing hu tumor cells expressing mutated p53. In this report,
altered protein product that accumulates within the cell. Although the observed endogenous human ... more altered protein product that accumulates within the cell. Although the observed endogenous human CTL response to p53 is weak, high-affinity, human p53-specific CTLs have been generated from HLA A2.1 transgenic mice immunized with human CTL epitope peptides. In this study, we examine the ability of HLA A2.1-restricted and human p53-specific CTLs from HLA A2.1 transgenic mice to suppress the growth of p53-overexpressing human tumors in severe combined immunodeficient (SCID) mice. In vitro, murine p53149_,57-specific CTLs selectively lysed the p53overexpressing pancreatic carcinoma cell line Pane-1 but did not recog nize HLA A2.1~tumor cells or HLA A2.1+ normal human fibroblasts. Furthermore, in vivo, the growth of established human tumor xenografts in SCID mice was significantly reduced and survival was prolonged after the administration of p53-specific CTLs but not after the administration of control CTLs or PBS alone. Following treatment with pS3,49_,S7specific CTLs, regressing Panc-1 tumors were infiltrated by the CD8+ CTLs, as demonstrated by immunohistochemistry.
The American Journal of Surgery, 2000
Risk factors for contralateral breast cancer (CBC) may indicate a benefit for contralateral proph... more Risk factors for contralateral breast cancer (CBC) may indicate a benefit for contralateral prophylactic mastectomy (CPM) at the time of unilateral mastectomy for breast cancer. The purpose of this study is to evaluate the efficacy of CPM in preventing CBC. sixty-four patients undergoing CPM and a control group of 182 patients not undergoing CPM and matched for age, stage, surgery, chemotherapy, and hormonal therapy were retrospectively compared for CBC rate, disease-free survival, and overall survival. Thirty-six CBCs occurred in the control group. In the CPM group, 3 CBCs were found at the time of prophylactic mastectomy, but none occurred subsequently (P = 0.005). Disease-free survival at 15 years in the CPM group was 55% (95% confidence interval [CI] 38% to 69%) versus 28% (95% CI 19% to 36%) in the control group (P = 0.01). Overall survival at 15 years was 64% (95% CI 45% to 78%) CPM versus 48% (95% CI 39% to 58%) in controls (P = 0.26). CPM prevented CBC and significantly prolonged disease-free survival. Future studies will need to address risk assessment and contralateral breast cancer prevention in patients treated for early breast cancer.
Food and Bioprocess Technology, 2014
ABSTRACT An antioxidant active packaging was developed by coextruding two layers of high-density ... more ABSTRACT An antioxidant active packaging was developed by coextruding two layers of high-density polyethylene (HDPE). Bags were made with the film in which the inner layer, designed to be in contact with food, contained marigold flower (Tagetes erecta) extract rich in carotenoids. The outer layer of the film was added with titanium dioxide (TiO2) to decrease the effect of commercial lighting on the degradation of carotenoids. Four bilayer films were produced: added with TiO2 and carotenoids, added with carotenoids, added with TiO2, and with no additives at all (control film). Degradation of color and astaxanthin in the films was delayed by the addition of the TiO2 when they were stored under commercial lighting at 25 °C. Bags made of these films produced an improvement on the soybean oil stability at 25 °C as a result of a synergic effect of light protection by TiO2 and carotenoids release. This release was measured as diffusion coefficients of carotenoids from the films toward soybean oil at 10, 25, and 40 °C (2.10–19.26 × 10−11 cm2 s−1) with activation energy of 53.66 kJ mol−1. In conclusion, the combination of the two layers of HDPE added with TiO2 and carotenoids introduced opacity and permitted to extend the active effect of the films in contact with soybean oil. Moreover, the effect of temperature on the diffusion of carotenoids showed that this new active packaging is able to exert its function in conditions of transport, storage, and commercialization of food.
Food Packaging and Shelf Life, 2014
The American Journal of Surgery, 2013
Triple-negative (TN) breast cancer lacks a known signaling pathway amenable to targeted therapy. ... more Triple-negative (TN) breast cancer lacks a known signaling pathway amenable to targeted therapy. The authors hypothesized that the G protein-coupled receptor GPR30 may be present in TN breast cancer and serve a role for tumor growth. A retrospective pathology study and chart review were conducted. All patients aged ≤49 years from 2000 to 2008 were included (n = 24). Concurrent patients aged ≥50 years were randomly selected. Paraffin sections were stained for GPR30 and reviewed by a pathologist blinded to estrogen receptor and progesterone receptor status. Disease-free survival was analyzed versus age and receptor status. Means were compared using 2-sample t tests and proportions using chi-square analysis. Twenty-seven patients tested GPR30 positive and 21 GPR30 negative. Seventeen of 18 TN cancers tested positive for GPR30 (P < .0001). Recurrence at a mean follow-up of 36 months was 22.2% in the GPR30-positive group and 9.5% in the GPR30-negative group. GPR30 is prevalent in TN breast cancer and associated with young age and possibly recurrence.
Surgery, 1999
Background. Pancreatic cancer is a highly lethal disease that frequently presents in advanced sta... more Background. Pancreatic cancer is a highly lethal disease that frequently presents in advanced stages. For most patients, treatment with great clinical efficacy does not exist. Relevant in vivo models to test novel therapies are highly desirable. Methods. The human pancreatic ductal adenocarcinoma cell line Panc-1 was injected intraperitoneally into SCID mice. The pattern of the resulting peripancreatic as well as metastatic disease was examined. Survival experiments after chemotherapy with gemcitabine or doxorubicin, and after immunotherapy with p53-specific cytotoxic T lymphocytes were performed. Results. All animals developed isolated pancreatic tumor implants within 48 hours after injection. After the formation of invasive pancreatic tumor nodules, peripancreatic and portal adenopathy developed, causing biliary obstruction. All tumor-bearing animals died of disease within 5 to 12 weeks. Survival after gemcitabine treatment and after p53-CTL injection was significantly prolonged, with some animals remaining tumor-free. Doxorubicin treatment did not yield extended survival, but led to significant toxicity.
Surgery, 2006
Induction of apoptosis by tamoxifen has been postulated to involve oxidative stress. Tamoxifen (T... more Induction of apoptosis by tamoxifen has been postulated to involve oxidative stress. Tamoxifen (TAM) may act on estrogen receptors (ER) located in the plasma membrane. Our hypothesis that supplemental antioxidant vitamin E (alpha-tocopherol) acts at the plasma membrane to alter the effectiveness of tamoxifen was tested in ER-positive breast cancer cell lines, MCF-7 and T47D. Cells were treated in vitro with 20-muM TAM alone and in combination with 10-muM alpha-tocopherol (AT). Estrogen growth signals were quantified by immunohistochemical staining for the mitogen-activated protein kinase p-ERK. Rapid changes in intracellular calcium were detected in TAM-treated MCF-7 and T-47D cells by fluorescence microscopy of cells loaded with the calcium-sensitive dye Fluo 4AM. Apoptosis was assayed by flow cytometry. Proliferating cells in normal medium exhibited strong p-ERK staining. Addition of TAM abolished p-ERK staining and caused cell rounding and death. The addition of AT led to the restoration of cell proliferation and p-ERK expression even in the presence of high-dose TAM. Intracellular calcium rapidly increased in MCF-7 and T47D cells upon exposure to TAM, followed by an increase in caspase activation and eventual apoptosis. The increase in intracellular calcium was abolished by the addition of 10muM AT to TAM, and pan-caspase staining decreased at 5 hours from 72% to 41%. These studies suggest that supplemental vitamin E decreases the inhibitory effect of TAM on the proliferation of ER+ breast cancer cells and eliminates the rapid rise in intracellular calcium that leads to apoptosis stimulated by TAM. The use of vitamin E acetate supplements may be inadvisable for women taking tamoxifen.
Packaging Technology and Science, 2013
Four films were extruded in a pilot-plant scale blown extrusion machine: a monolayer low-density ... more Four films were extruded in a pilot-plant scale blown extrusion machine: a monolayer low-density polyethylene (LDPE) film added with 2.90% of marigold (Tagetes erecta) extract, a two-layer high-density polyethylene/ LDPE film added with 3.59% of the extract in the LDPE layer and the corresponding two control films without addition of the extract. More than 64% of astaxanthin contained in the extract was lost during the extrusion process. Spectroscopic, optical and mechanical properties of the films were affected by the addition of the marigold extract. The films showed to be light sensitive when exposed to commercial light at 25 C; however, bags made of the films showed a positive effect on soybean oil stability when used as packaging.
The Journal of Urology, 1999
Superficial bladder cancer is often responsive to immunotherapy with bacillus Calmette-Guerin (BC... more Superficial bladder cancer is often responsive to immunotherapy with bacillus Calmette-Guerin (BCG). However, some tumors progress despite BCG treatment, and most of these have mutations in the p53 tumor suppressor gene resulting in its over-expression. Overexpressed p53 is therefore a potential target for immunotherapy. The objective of this study was to demonstrate whether human bladder cancer xenografts in SCID mice could be eliminated by cytotoxic T cells (CTL) which recognize over-expressed p53. Murine CTL which are specific for human p53 were previously generated in our laboratory by peptide immunization of HLA A2.1 transgenic mice. These CTL recognize and lyse human tumor cell lines which over-express p53 in the context of HLA A2.1. The p53 over-expressing HLA A2.1+ human bladder cancer cell line J82 was used to establish subcutaneous or intravesicular tumors in SCID mice. The mice were then administered tail vein injections of 5 x 10(7) p53-specific CTL, control CTL, or phosphate buffered saline (PBS). The subcutaneous tumor mean volume at 5 weeks for the p53-specific CTL treatment group was significantly lower than for both the control CTL or the PBS group (32 mm.3 versus 185 mm.3, p = 0.04 and 32 mm.3 versus 418 mm.3, p = 0.0001). In the mice with intravesicular tumors, a reduction to nonpalpable tumor size in vivo was seen with specific CTL therapy (14% palpable) versus control CTL treatment (86% palpable), the final tumor volume at necropsy was 127 mm.3 versus 246 mm.3 (N.S.). The overall response of the human bladder tumors in the SCID mouse model suggests the possibility of targeting p53 in patients with bladder cancer.
Ejc Supplements, 2010
Poster Sessions mutations and three variants of indefinite biological effect). Ten frame shift mu... more Poster Sessions mutations and three variants of indefinite biological effect). Ten frame shift mutations were detected, the result of which was production of truncated protein. They included: 5467insT, 6174delT, 6192delAT, 6675delTA, 8141del5, 9152delT, 9326insA and 9631delC. The 8141del5 mutation was detected in 3 patients. The group of pathogenic mutations was completed with the nonsense change E394X and splice site mutation IVS23−2A>G. The presence of 10 missense type mutations was detected: N289H, N372H, T598A, G602R, N991D, D1420O, K1690N, T1915M, I2627F, N3124I. The frequency of N991D, D1420O and N3124I was compared between breast cancer patients and the control group of healthy subjects.
Journal of the American College of Surgeons, 2011
Journal of Surgical Research, 2009
Journal of Surgical Research, 2009
Methods. A prospective study of seven women taking tamoxifen for adjuvant therapy of breast cance... more Methods. A prospective study of seven women taking tamoxifen for adjuvant therapy of breast cancer. Four who were already taking AT supplements had random core biopsies of the normal breast and again 30 days after discontinuing AT. Three who were not on AT had biopsies before and after adding AT 400 mg for 30 days. Biopsies were stained for estrogen receptor (ER) and the mitogen-activated protein kinase p-ERK. Tissue extracts were assayed for p-ERK by enzyme-linked immunosorbent assay. Serum levels of ␣-tocopherol and tamoxifen were measured.
Journal of Surgical Research, 2008
Conclusions: EPC levels are elevated in patients with pancreatic adenocarcinoma, and these levels... more Conclusions: EPC levels are elevated in patients with pancreatic adenocarcinoma, and these levels decline after cancer resection. This is consistent with the idea that pancreatic cancer is a source of EPC-mobilizing angiogenic factors. The results of this study suggest that EPCs are biologically important for the growth of pancreatic adenocarcinoma and may serve as a surrogate marker for tumor neovascularization to guide anti-angiogenic therapy. MD; 4 Duke, Durham, NC; 5 5Brown, Providence, RI MRI patterns have been described which characterize tumor containment in women with locally advanced breast cancer (LABC). Previously, these patterns were shown to predict eligibility for breast conservation therapy (BCT) following neoadjuvant chemotherapy (NACT). Tumors that were more contained at diagnosis tended to achieve BCT eligibility more often. We sought to determine if MRI data from the I-SPY Trial, a correlative science trial in which LABC patients underwent NACT with serial MRI and biopsies, predicted BCT eligibility. Methods: Eligible patients with new primary breast cancer Ͼ3 cm were enrolled. All patients received anthracycline (AC)-based chemotherapy. Some received further treatment with taxane (T) or other agents. All patients had serial MRI at baseline (T1), after 1 cycle AC (T2), intra-regimen (T3), and pre-surgery (T4). MRI patterns were defined by a 5-point loss of containment (LOC) scale using the T1 MRI. Tumor patterns were defined as follows: 1) single, unicentric, 2) multilobular, circumscribed 3) multinodular, 4) diffuse and 5) setpal. Eligibility for BCT following NACT was determined by a longest diameter (LD) Ͻ4 cm on the T4 MRI. Actual surgical treatment was individualized based on surgeon and patient preference. Results: 237 patients were enrolled at 9 institutions between 6/02-3/06. 15 patients withdrew or failed to complete the study. 18 patients had insufficient data at the time of analysis on 5/14/07. 15 patients with tumors 4 cm in LD on either clinical exam or on T1 MRI (deeming them ineligible for BCT prior to NACT) and were included in the analysis. Patients were assigned MRI patterns according to the T1 MR. For patterns 1, 2, 3, 4, and 5 there were 28, 54, 60, 28, and 19 patients. After NACT, 65% patients were eligible to undergo BCT based on a T4 MR LD Ͻ4 cm. For patterns 1, 2, 3, 4, and 5, BCT eligibility was 21/28 (75%), 44/54 (81%), 34/60 (57%), 15/28 (54%), and 9/19 (47%). Only 61/189 (32%) eligible patients underwent BCT. Actual BCT rates by MR pattern were 12/28 (43%), 27/54 (50%), 14/60 (23%), 8/28 (28%), and 0/19 (0%) for patterns 1, 2, 3, 4, and 5. The majority of eligible patients (52%) and those that underwent BCT (61%) were patterns 1 or 2. Conclusions: 65% of patients with tumors Ͼ4 cm at diagnosis became eligible for BCT after NACT. MRI patterns were helpful in predicting who would achieve BCT eligibility. Well-contained lesions (types 1 and 2) tend to undergo a concentric size reduction, thus making these lesions more amenable to BCT. The lesser contained a tumor is on baseline MRI, the lower the likelihood that the tumor will respond so as to allow for BCT. This will help to set patient treatment expectations.
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Papers by Elizabeth Peralta