Biomedical subjects

Jennifer Quinn

Publications and source records attributed to Jennifer Quinn.

6 recordsLinked to original sources

PubMed2006

Incidence and patterns of neuraxis metastases in children with diffuse pontine glioma.

PURPOSE: We performed a retrospective study of patients with diffuse pontine glioma (DPG) who suffered neuraxis metastasis (NM) and characterized the incidence, clinical features, radiologic findings, and patterns of disease dissemination. METHODS: Magnetic resonance imaging (MRI) of brain and spine was used to assess NM. Some patients also underwent magnetic resonance spectroscopy (MRS) (6 patients) and fluorodeoxyglucose positron emission tomography (FDG-PET) scans (13 patients) to further evaluate areas of metastatic disease. Three patients had histologic confirmation of disease at the site of NM. RESULTS: Between 1986 and 2003, 18 of 96 patients (17.3%) with DPG developed NM. The median age at diagnosis was 8 years (range, 4-17). All patients had adjuvant chemotherapy and/or focal radiotherapy at diagnosis. The NM occurred at a median of 15 months from diagnosis of DPG (range, 3-96). Three patterns of NM were seen on MRI of brain and spine in these patients; 8 (39%) had parenchymal (PM), 4 (22%) leptomeningeal (PM), 2 (11%) subependymal, and in 5 a combination of two or more patterns. The MRS and FDG-PET scan of suspected areas of metastatic disease was consistent with tumor in 6 of 6 and 12 of 13 patients who underwent these procedures respectively. Three patients also had histologic confirmation of malignant glioma at the site of NM. Despite salvage therapy, all 18 patients have died of disease at a median of 5 months (range, 0.5-20) from diagnosis of neuraxis spread. CONCLUSION: Our study emphasizes the need for screening patients with DPG for NM at the time of recurrence.

Adolescent↗

PubMed2006

Mouse trophoblast stem cells.

The trophectoderm is one of the earliest cell types to differentiate in the forming mammalian embryo. It is responsible for the initial implantation and the formation of the trophoblast components of the placenta, an organ essential for nutrient and waste exchange between the fetus and its mother. The trophoblast can be modeled in vitro using trophoblast stem cells. Trophoblast stem cells require fibroblast growth factor (FGF)4, heparin, and contact with embryonic fibroblasts, or fibroblast-conditioned medium. They grow as tight epithelial colonies, which express markers of the early trophectoderm and have been shown to contribute to all of the components of the placenta through chimera studies. These cells can be passaged indefinitely and can be differentiated by removal of FGF4 and fibroblasts and will express genetic markers of later placental cell types. This chapter will discuss the initial derivation of trophoblast stem cells from the blastocyst stage, maintenance, differentiation, flow cytometry and transfection techniques that can be used with these cells.

Animals↗

PubMed2005

Survival analysis of presumptive prognostic markers among oligodendrogliomas.

BACKGROUND: Allelic losses of 1p and 19q arms correlate with the oligodendroglial phenotype as well as with sensitivity to radiotherapy and chemotherapy. Furthermore, the DNA repair gene, methylguanine methyltransferase (MGMT), is diminished in 80% of oligodendroglial tumors and represents a possible mechanism for this therapeutic sensitivity. However, the authors questioned the relevance of genetic testing and measuring MGMT levels in tumors that were diagnostic of oligodendroglioma. METHODS: The authors performed a retrospective analysis of 1p, 19q, 9p21, TP53, and MGMT status in 46 patients with oligodendrogliomas to address any relations that may exist among these markers with regard to progression-free survival (PFS) and total survival. Methodologies included comparative genomic hybridization; loss of heterozygosity (LOH) on 1p, 19q, and 9p21; TP53 mutational analysis; and immunohistochemistry for MGMT. RESULTS: The authors found that survival among patients with light microscopically diagnosed oligodendroglial tumors demonstrating LOH of 1p and 19q trended toward statistical significance (P = 0.102 and P = 0.058, respectively). 9p21 LOH was significant as a predictor of PFS only among anaplastic oligodendrogliomas in this cohort (P = 0.033). TP53 mutation was found to be significantly predictive of a shorter survival (P = 0.027) among all patients and exhibited a strong trend toward a shorter PFS (P = 0.060). Low-level MGMT labeling index (LI) (< 20%) was noted in 86% of all oligodendroglial tumors. MGMT LI was not found to correlate with an improved PFS or total survival in this cohort, recognizing that median survival was not reached after a median follow-up of 104 months. CONCLUSIONS: 9p21 and TP53 mutational status assisted in developing a stricter subclassification of these tumors with prognostic significance. MGMT levels were decreased in a majority of oligodendrogliomas.

Biomarkers, Tumor↗

PubMed2003

High-dose chemotherapy with autologous stem-cell rescue in children and adults with newly diagnosed pineoblastomas.

PURPOSE: We evaluated the usefulness of a treatment regimen that included high-dose chemotherapy (HDC) with autologous stem-cell rescue (ASCR) in patients with newly diagnosed pineoblastoma (PBL). PATIENTS AND METHODS: Twelve patients with PBL were initially treated with surgery and induction chemotherapy. All but two patients underwent radiotherapy. Subsequently, all patients received HDC using cyclophosphamide (CTX) + melphalan (MEL) or busulfan (Bu) + MEL regimens and ASCR. RESULTS: A total of six children and six adults with median ages of 4.2 (range, 0.3 to 19.8 years) and 23 years (range, 23 to 43.7 years), respectively, were treated according to this strategy. Four patients had metastatic disease confined to the neuraxis. Five of 12 patients (42%) had a complete tumor resection at diagnosis. Ten patients received radiotherapy at median doses of 36.0 and 59.4 Gy to the neuraxis and pineal region, respectively. Eleven patients received HDC with CTX + MEL, and one patient received BU + MEL followed by ASCR. Nine patients are alive with no evidence of disease recurrence at a median of 62 months from diagnosis (range, 28 to 125 months), including three patients with metastatic disease and two infants who did not receive any radiotherapy. Three patients have died of progressive disease at 19, 32, and 37 months from diagnosis, respectively. The actuarial 4-year progression-free and overall survivals are 69% (95% confidence interval [CI], 39% to 99%) and 71% (95% CI, 43% to 99%), respectively. CONCLUSION: The use of HDC in addition to radiotherapy seems to be an effective treatment for patients with newly diagnosed pineoblastoma.

Adolescent↗

PubMed2003

Progress report of a Phase I study of the intracerebral microinfusion of a recombinant chimeric protein composed of transforming growth factor (TGF)-alpha and a mutated form of the Pseudomonas exotoxin termed PE-38 (TP-38) for the treatment of malignant brain tumors.

TP-38 is a recombinant chimeric targeted toxin composed of the EGFR binding ligand TGF-alpha and a genetically engineered form of the Pseudomonas exotoxin, PE-38. After in vitro and in vivo animal studies that showed specific activity and defined the maximum tolerated dose (MTD), we investigated this agent in a Phase I trial. The primary objective of this study was to define the MTD and dose limiting toxicity of TP-38 delivered by convection-enhanced delivery in patients with recurrent malignant brain tumors. Twenty patients were enrolled in the study and doses were escalated from 25 ng/mL to 100 with a 40 mL infusion volume delivered by two catheters. One patient developed Grade IV fatigue at the 100 ng/mL dose, but the MTD has not been established. The overall median survival after TP-38 for all patients was 23 weeks whereas for those without radiographic evidence of residual disease at the time of therapy, the median survival was 31.9 weeks. Overall, 3 of 15 patients, with residual disease at the time of therapy, have demonstrated radiographic responses and one patient with a complete response and has survived greater than 83 weeks.

Adult↗

PubMed2002

Amount of training and stimulus salience affect associability changes in serial conditioning.

Q. J. Exp. Psychol. 44B (1992) 17 reported that extended training with a serial compound of two conditioned stimuli, S1-->S2, resulted in losses in the rate at which S1-food associations were formed in a subsequent test phase. However, this ability of S1 to participate in new learning (its associability) could be restored by omitting S2 on some trials. Variables that affect performance in this task were examined in five Pavlovian appetitive conditioning experiments with rats. In Experiment 1, the associability of S1 decreased gradually as a function of the number of training sessions with a consistent S1-S2 relation. In Experiment 2, after extended exposure to a consistent S1-S2 relation, the associability of S1 was restored with as few as one training session in which the S1-S2 relation was made inconsistent by omitting S2 on some trials. In Experiments 3-5, test phase conditioning of S1 after inconsistent training was found to be either greater than, less than, or similar to, conditioning of S1 after consistent training, depending on the relative salience of the events used as S1 and S2. The results showed that both intrinsic and extrinsic relations among stimuli must be considered when interpreting the results of experiments in stimulus selection.

Journal Article↗