Effect of dietary GLA+/-tamoxifen on the growth, ER expression and fatty acid profile of ER positive human breast cancer xenografts

Gamma linolenic acid (GLA) possesses a number of selective anti-tumour properties including modulation of steroid receptor structure and function. We have investigated the effect of dietary GLA on the growth, oestrogen receptor (ER) expression and fatty acid profile of ER+ve human breast cancer xenografts. Experimental diets A, B, C, D were commenced after subcutaneous implantation of 40 female nude mice with the MCF-7 B1M cell line (Group A = control diet: B = control diet + GLA supplement: C = control diet + tamoxifen: D = control diet + GLA + tamoxifen; 10 mice/group). The mice were terminated when tumour cross-sectional area reached 250 mm(2). ER H-scores were assessed by immunohistochemical assay and fatty acid profiles by gas-liquid chromatography of termination tumour samples. Groups C and D displayed significantly slower tumour growth (p =.0002, p =.0006) with trend for slower growth in B (p =.065) compared to control Group A. ER was significantly reduced in all groups compared to A (p <.0001) with Group D (combined therapy) displaying markedly lower ER expression than with either therapy alone (p =.0002). There were significantly raised levels of tumour GLA and metabolites in the two groups (B and D) receiving GLA (p <.0001). This xenograft model of ER+ve breast cancer has demonstrated significantly lower tumour ER expression in those groups receiving GLA, an effect which appears to be additive to the reduced ER expression resulting from tamoxifen alone. The effects of GLA on ER function and the possibility of synergistic inhibitory action of GLA with tamoxifen via enhanced down-regulation of the ER pathway require further investigation.     

The conacher memorial lecture: “100 years of effort”

The academic goals of the Centennial Conference on Laryngeal Cancer are, the provision of a forum for a full and frank discussion among experts in the field of laryngeal cancer covering all aspects of the management of this disease; the review of clinical investigation in this field; to identify areas in which research appears to be fruitful, and, finally, the dissemination of the transactions, discussions and conclusions of this Conference by means of the medical literature, audiovisual tapes and television tapes of special interviews and discussions. The Conference is dedicated to the human larynx and to Charlie Conacher whose Memorial Fund has strongly supported investigation in this field in the Toronto area. With the help of the Conacher Research Fund, extensive investigation, including serial whole organ sectioning of the larynx, has been carried on in Toronto for six years. Increase in knowledge of the laryngeal anatomy in the spread of tumors as a result of serial sectioning has led to improvements in conservation surgery and in the planning of fields for radiotherapeutic treatment. The efforts of surgeons, clinicians and radiotherapists in the past 100 years, has transformed laryngeal cancer from one of the least favorable to one of the most favorable of human malignant diseases. We have improved the preservation of life for people suffering from this disease, and, indeed, we have also increased the number of cases in which the voice may be preserved by radiotherapy or by conservation surgery. The Laryngeal Conference is convened to stimulate our clinic and basic research in the field of laryngeal cancer. Our survival figures for patients with this disease have changed little in the past 20 years, and new ideas and the development of new therapeutic approaches are essential. The Conference is designed to stimulate interest, research and new methods of therapy and earlier diagnosis and to distribute this knowledge as widely as possible to doctors working in the field so that the patients with laryngeal cancer will ultimately benefit.     

Psychometric Properties of a Scale on Judgmental Communication with Peers About Sex Among YMSM and Their Close Friends in Lebanon

AIDS and Behavior - We are not aware of any validated sexual health communication scales for use with young men who have sex with men (YMSM). We used data from an HIV prevention study in Lebanon...     

The prospects for renal xenotransplantation

Summary: Xenotransplantation of non-human organs into human recipients has long been proposed as a possible strategy to overcome the acute shortage of donor organs. However, vascular organ transplants to humans from phylogenetically disparate species such as the pig are not currently possible due to a rapid rejection process termed hyperacute rejection. This process is initiated by the binding of host pre-formed 'natural antibodies' to the donor vascular endothelium, activation of the host complement system and activation or injury of the donor endothelial cells, leading to intravascular coagulation and loss of the graft due to ischaemic necrosis within minutes to hours of engraftment. Prevention of natural antibody binding and complement activation is viewed as paramount to preventing hyperacute rejection. Even if hyperacute rejection can be prevented, further barriers to successful discordant xenografts such as delayed xenograft rejection and a donor-directed cell-mediated rejection process will still represent major obstacles. This review examines recent advances being made in the various areas of xenograft research and the potential clinical application of pig-to-human xenografts that these strategies may bring.     

The Effects of Brief Mindfulness Training on Caregivers' Well-Being

This study investigated the effects of brief mindfulness training on caregivers for family members with dementia. Eleven caregivers completed 4 hours of mindfulness training. Using mixed methods in a parallel model, survey data were gathered preintervention, postintervention, and 1 month postintervention; qualitative interviews were conducted 1 month postintervention. Findings include increased acceptance, presence, peace, and hope, and decreased reactivity and caregiver burden resulting from brief mindfulness training. Activity professionals working with dementia caregivers can be of service through delivery of or referrals for mindfulness training. This intervention appeared to balance caregivers' doing, being, and becoming.     

Cardiac Operations for North American Children with Rheumatic Diseases: 1985–2005

Certain pediatric rheumatic diseases are known to affect the heart, sometimes requiring surgical intervention. The Pediatric Cardiac Care Consortium database was used to characterize cardiac surgical intervention among children with rheumatic diseases from 1985 to 2005. From this large database, the records for patients younger than 21 years who underwent cardiac surgery for any rheumatic disorder were extracted. The data collected included the type of procedure performed, the age at the time of the procedure, and the year the procedure was performed. The 261 pediatric patients identified underwent 361 cardiac surgical procedures for complications of rheumatic heart disease (RHD; 160 patients), neonatal lupus (NLE; 53 patients), Kawasaki disease (KD; 28 patients), systemic lupus erythematosus (SLE; 13 patients), and juvenile rheumatoid arthritis (JRA; 7 patients). Multiple procedures were performed for 23% of the patients. The most common procedures included pacemaker implantations among infants with NLE, coronary artery bypass grafts for KD primarily in 5- to 15-year-olds, and cardiac valve operations among adolescents with RHD, SLE, and JRA. Six perioperative deaths occurred. The proportion of annual pediatric cardiac surgical volume attributable to rheumatic diseases did not change during the period studied. Despite advances in their medical care, children with rheumatic diseases continue to sustain measurable morbidity and mortality due to the cardiovascular manifestations of their disease.     

AAV1/2-mediated CNS Gene Delivery of Dominant-negative CCL2 Mutant Suppresses Gliosis, ��-amyloidosis, and Learning Impairment of APP/PS1 Mice

Accumulation of aggregated amyloid-β (Aβ) peptide was studied as an initial step for Alzheimer''s disease (AD) pathogenesis. Following amyloid plaque formation, reactive microglia and astrocytes accumulate around plaques and cause neuroinflammation. Here brain chemokines play a major role for the glial accumulation. We have previously shown that transgenic overexpression of chemokine CCL2 in the brain results in increased microglial accumulation and diffuse amyloid plaque deposition in a transgenic mouse model of AD expressing Swedish amyloid precursor protein (APP) mutant. Here, we report that adeno-associated virus (AAV) serotype 1 and 2 hybrid efficiently deliver 7ND gene, a dominant-negative CCL2 mutant, in a dose–response manner and express >1,000-fold higher recombinant CCL2 than basal levels after a single administration. AAV1/2 hybrid virus principally infected neurons without neuroinflammation with sustained expression for 6-months. 7ND expressed in APP/presenilin-1 (APP/PS1) bigenic mice reduced astro/microgliosis, β-amyloidosis, including suppression of both fibrillar and oligomer Aβ accumulation, and improved spatial learning. Our data support the idea that the AAV1/2 system is a useful tool for CNS gene delivery, and suppression of CCL2 may be a therapeutic target for the amelioration of AD-related neuroinflammation.     

Squamous cell carcinoma of the larynx

A patient with a moderately advanced squamous cell carcinoma of the larynx (T2, glottic) is presented. The consultants discuss their preferred diagnostic and treatment options. All consultants agree that the chances for cure (5-yr survival) are 80-85%, but they differ as to the preferred treatment approach to preserve phonation. Drs. Biller and Pearson predict that 80-90% of patients would be alive and have usable voice, with surgical treatment, whereas Dr. Bryce believes the chances of voice preservation are 65% after radiotherapy only. In his opinion an additional 10% would be helped by conservation partial laryngeal surgery.     

Phase I study of Caelyx (doxorubicin HCL, pegylated liposomal) in recurrent or metastatic head and neck cancer

Background:Pegylated liposome technology represents a favourabledrug-carrier system, since stealth liposomal drugs have a reduced clearancewith prolonged circulation half-life and selective drug accumulation intissues with increased vascular permeability, such as tumor tissues. Caelyxis a pegylated liposome containing doxorubicin, which has been developed totarget drug delivery to cancer cells, thus reducing toxicities.Biodistribution studies have shown a selective tumor uptake in patients withadvanced head and neck cancer (HNC), thus justifying the present phase Istudy. Patients and methods:Patients with recurrent or metastatic HNCwere treated with Caelyx administered at the starting dose of 30mg/m² every three weeks and escalated by 5 mg/m² perstep. Dose escalation was stopped if more than a third of patients of a givencohort had dose-limiting toxicity (DLT), which was defined as grade 4neutropenia or thrombocytopenia, grade 3 febrile neutropenia, grade 3thrombocytopenia with bleeding, grade 3 non-hematologic toxicity (except fornausea and alopecia), or >2 week delay in chemotherapy recycling. The abovedose level was defined as maximum tolerated dose (MTD) and the dose levelimmediately below was recommended for phase II evaluation. Response wasevaluated after three courses of chemotherapy. Results:Twenty-four patients were treated at five dose levels.At 50 mg/m², three out of six patients had grade 3 stomatitis;therefore, this level was defined as MTD and 45 mg/m² was theselected dose for phase II. Stomatitis occurred in 11 patients across all doselevels, considering all delivered cycles. Neutropenia occurred in 10 of 24patients, but reached grade 4 in only 2 patients at fourth dose level. Skintoxicity, mainly appearing in the form of palmar-plantar erythrodysestesia,was the most frequent toxicity, occurring in 14 patients. Other side effectswere mild. One complete response (4%) and seven partial responses(29%) were observed, for an overall response rate of 33%(95% confidence interval (95% CI): 16%–55%). Conclusions:Caelyx is a safe and promising new treatment in HNC,that deserves further evaluation both alone and integrated withinchemo-radiotherapy strategies.