Medullary carcinoma of the breast: a population-based perspective

Prognostic factors specific to medullary carcinoma of the breast (MCB) are unknown. Our objective was to identify patient and tumor factors predictive of overall survival (OS) in a large cohort of MCB patients. The Surveillance, Epidemiology, and End Results database was used to identify patients with MCB diagnosed from 1988 to 2004. Patient, tumor, and treatment factors were compared by univariate analysis via the Kaplan–Meier method and survival differences detected using the log-rank test. A multivariate Cox proportional hazards model controlled for patient age, race, type of surgery, radiotherapy, tumor size, number of lymph node metastases (LNM), lymph node yield (LNY), estrogen receptor (ER) and progesterone receptor (PR) status, and extent of disease. On univariate analysis of 3,348 patients, factors influencing OS included age, race, tumor size, ER status, type of surgery, radiotherapy, LNM, LNY, and extent of disease (P < 0.001). On multivariate analysis, advancing age (P < 0.001), black race (P < 0.001), regional metastases (P < 0.001), distant metastases (P < 0.001), increasing tumor size (P < 0.001), ER positivity (P = 0.003), and increasing LNM (P < 0.001) were associated with decreased OS. An OS benefit was seen in PR-positive patients (P = 0.002) and in those with increasing LNY (P < 0.001). Even among node-negative patients, increasing LNY was associated with improved OS (P < 0.001). Tumor size, LNM, regional and distant metastases, PR status, age, and race are important prognostic factors in MCB. ER positivity was associated with decreased OS, which may reflect inaccuracy in diagnosing MCB or a significant biologic variant. The improved OS seen with increasing LNY in node-negative patients suggests MCB may be currently understaged.     

Gel core liposomes: an advanced carrier for improved vaccine delivery

Many sub-unit vaccines are successful in preventing the occurrence of disease, but their use is largely restrained due to low immunogenicity. Novel carrier-based vaccine could serve as a vaccine adjuvant to overcome low immunogenicity of sub-unit vaccines. The use of liposomes as a delivery system for antigen is well recognized but they are unstable and release of antigen from them cannot be controlled over a prolonged period of time. To overcome the limitation of liposomes, this study has developed gel core liposomes in which a core of polymer was incorporated inside the liposomal vesicles, which serve the function of skeleton and provide mechanical strength to vesicles. In the present investigation BSA-loaded gel core liposomes were prepared by reverse phase evaporation method and characterized for vesicles size, shape, entrapment efficiency, in vitro release and stability studies. The in vivo studies to evaluate antigen presenting potential of the gel-core liposomes was performed in Balb/c mice by measuring the immune response elicited by intramuscular administration of BSA-loaded gel core liposomes and compared with intramuscularly administered BSA-loaded conventional liposomes, alum adsorbed BSA and plain antigen. Results indicate that intramuscular immunization with gel core liposomes induces efficient systemic antibody responses against BSA as compared to other formulations. The gel core liposomal formulation provides good entrapment efficiency, enhanced in vitro stability, prolonged antigen release and effective immunoadjuvant property, justifying its potential for improved vaccine delivery.     

Stable synaptic retention of serine-880-phosphorylated GluR2 in hippocampal neurons

Phosphorylation of S880 within the GluR2 C-terminus has been reported to promote endocytosis of AMPA receptors (AMPARs) by preventing GluR2 interaction with the putative synaptic anchoring proteins GRIP and ABP. It is not yet established however, whether S880 phosphorylation induces removal of AMPARs from synaptic sites, and the trafficking of phosphorylated GluR2 subunits with surface and endocytosed GluR2 has not been directly compared within the same intact neurons. Here we show that phosphorylation of GluR2 subunits by PKC activated with phorbol esters is compartmentally restricted to receptors located at the cell surface. Endogenous AMPARs containing S880-phosphorylated GluR2 remained highly synaptic and colocalized with postsynaptic markers to the same extent as AMPARs which did not contain S880-phosphorylated GluR2. Moreover, following S880 phosphorylation, exogenous GluR2 homomers were found specifically at the cell surface and did not co-traffic with the internalized endosomal GluR2 population. We also show that GluR2 is endogenously phosphorylated by a constitutively active kinase pharmacologically related to PKC, and this phosphorylation is opposed by the protein phosphatase PP1. Our results demonstrate a population of hippocampal AMPARs which do not require interaction with GRIP/ABP for synaptic anchorage.     

284 press-fit Kinemax total knee arthroplasties followed for 10 years: poor survival of uncemented prostheses

BACKGROUND AND PURPOSE: Our institution began using the Kinemax total knee arthroplasty system in 1988, both with and without cement fixation. We report 10-year survival figures. METHODS: Theater records showed that 284 Kinemax total knee arthroplasties had been performed 1988 through 1993. Life-table survival estimates were used to determine the probability of survivorship 10 years after surgery for the total group and by age, sex, diagnosis, and mode of fixation. Median follow-up was 11 (0.8-15) years for unrevised knees in patients who were still alive. RESULTS: The 10-year cumulative survivorship was higher (93%, 95% CI: 81-97) when both components had been cemented than if either, or both, were uncemented (77%, CI: 67-83; p < 0.001). There was an increased incidence of failure in patients who were less than 60 years of age at the time of surgery (p = 0.004). INTERPRETATION: The smooth-backed Kinemax knee without cement was found to be associated with a high failure rate at 10 years. The 10-year cumulative survival results of the cemented prosthesis are acceptable.     

Gastric cancer: D2 dissection or low Maruyama Index-based surgery--a debate

This article provides perspectives on the surgical approaches required optimally to manage patients with respectable gastric adenocarcinoma. The status of techniques of surgical resection in the management of gastric cancer is reviewed. The premise of this approach is that extended gastrectomy with D2 lymph node dissection is good. Also addressed are prognostic and predictive factors in the surgical treatment of stomach cancer.     

Broadening of transgenic adenocarcinoma of the mouse prostate (TRAMP) model to represent late stage androgen depletion independent cancer

BACKGROUND: The transgenic adenocarcinoma of the mouse prostate (TRAMP) model closely mimics PC-progression as it occurs in humans. However, the timing of disease incidence and progression (especially late stage) makes it logistically difficult to conduct experiments synchronously and economically. The development and characterization of androgen depletion independent (ADI) TRAMP sublines are reported. METHODS: Sublines were derived from androgen-sensitive TRAMP-C1 and TRAMP-C2 cell lines by androgen deprivation in vitro and in vivo. Epithelial origin (cytokeratin) and expression of late stage biomarkers (E-cadherin and KAI-1) were evaluated using immunohistochemistry. Androgen receptor (AR) status was assessed through quantitative real time PCR, Western blotting, and immunohistochemistry. Coexpression of AR and E-cadherin was also evaluated. Clonogenicity and invasive potential were measured by soft agar and matrigel invasion assays. Proliferation/survival of sublines in response to androgen was assessed by WST-1 assay. In vivo growth of subcutaneous tumors was assessed in castrated and sham-castrated C57BL/6 mice. RESULTS: The sublines were epithelial and displayed ADI in vitro and in vivo. Compared to the parental lines, these showed (1) significantly faster growth rates in vitro and in vivo independent of androgen depletion, (2) greater tumorigenic, and invasive potential in vitro. All showed substantial downregulation in expression levels of tumor suppressor, E-cadherin, and metastatis suppressor, KAI-1. Interestingly, the percentage of cells expressing AR with downregulated E-cadherin was higher in ADI cells, suggesting a possible interaction between the two pathways. CONCLUSIONS: The TRAMP model now encompasses ADI sublines potentially representing different phenotypes with increased tumorigenicity and invasiveness.     

Atrial myxoma demonstrated by cine gradient refocused echo magnetic resonance imaging

A case of atrial myxoma presenting with syncope evaluated by echocardiography and MRI is described. Cine gradient‐echo MRI demonstrated atrial myxoma as a very low signal intensity mass indicating the presence of haemosiderin.