Effect of matrigel on the tumorigenicity of human breast and ovarian carcinoma cell lines

The effect of Matrigel, a solubilised tissue basement membrane extract, has been investigated on the tumorigenicity of 3 breast (MCF-7, T47D and MDA.MB.231) and 5 ovarian [PEO1, PEO1 cDDPr, PEO4, PEO14 and OV(hyg)CAR3] carcinoma cell lines. In the absence of Matrigel, the PEO14 and MDA.MB.231 cell lines produced take rates of 30% and 50%, respectively, while the other cell lines either did not develop or only occasionally developed as tumours. With Matrigel, 100% take rates were achieved for 7 of the 8 cell lines (MCF-7, T47D, MDA.MB.231, PEO1, PEO1 cDDPr, PEO4 and PEO14); in the remaining cell line [OV(hyg)CAR3] 2/6 (33%) tumours grew. Xenografts established with Matrigel could be transferred into recipient animals and grown in the absence of Matrigel, suggesting that Matrigel is necessary only for initial establishment of tumours. Furthermore, cells which had been re-established from a T47D xenograft and then inoculated into mice without Matrigel showed a take rate greater than that of the original cell line but less than that of the xenograft. In conclusion, Matrigel has proven to be extremely useful in establishing a variety of cell lines as xenografts. © 1996 Wiley-Liss, Inc.     

Insight in Alzheimer's disease

Increasing interest in insight and anosognosia in neuropsychiatric illness has been accompanied by growing academic study of such awareness phenomena in Alzheimer's disease. This article reviews the current status of knowledge of this topic and makes the case that insight and anosognosia are concepts with direct clinical relevance to Alzheimer's disease. The associated symptomatology, and implications for patient management, are emphasized. Such relevance should form the basis for future research.     

The vcop scale: A measure of overprotection in parents of physically vulnerable children

A scale is developed for measuring the overprotecting vs. optimal developmental stimulation tendencies for parents of physically “vulnerable” children. A series of items were administered to parents whose parenting techniques had been rated as either highly overprotective or as optimal by a group of MDs and other professionals. Correlations were estimated between each of the items and parental tendencies as rated by professionals. Twenty-eight items were selected that provided maximum prediction of overprotection. The resulting R² was extraordinarily high (.94). Coefficient alpha and test-retest coefficients were acceptable. It is hoped that release of the new instrument (VCOPS) at this time will allow others to join in determining the clinical and experimental validity of this scale.     

Inherited RORB pathogenic variants: Overlap of photosensitive genetic generalized and occipital lobe epilepsy

Variants in RORB have been reported in eight individuals with epilepsy, with phenotypes ranging from eyelid myoclonia with absence epilepsy to developmental and epileptic encephalopathies. We identified novel RORB variants in 11 affected individuals from four families. One was from whole genome sequencing and three were from RORB screening of three epilepsy cohorts: developmental and epileptic encephalopathies (n = 1021), overlap of generalized and occipital epilepsy (n = 84), and photosensitivity (n = 123). Following interviews and review of medical records, individuals' seizure and epilepsy syndromes were classified. Three novel missense variants and one exon 3 deletion were predicted to be pathogenic by in silico tools, not found in population databases, and located in key evolutionary conserved domains. Median age at seizure onset was 3.5 years (0.5-10 years). Generalized, predominantly absence and myoclonic, and occipital seizures were seen in all families, often within the same individual (6/11). All individuals with epilepsy were photosensitive, and seven of 11 had cognitive abnormalities. Electroencephalograms showed generalized spike and wave and/or polyspike and wave. Here we show a striking RORB phenotype of overlap of photosensitive generalized and occipital epilepsy in both individuals and families. This is the first report of a gene associated with this overlap of epilepsy syndromes.     

A soluble form of B cell maturation antigen, a receptor for the tumor necrosis factor family member APRIL, inhibits tumor cell growth

A proliferation-inducing ligand (APRIL) is a ligand of the tumor necrosis factor (TNF) family that stimulates tumor cell growth in vitro and in vivo. Expression of APRIL is highly upregulated in many tumors including colon and prostate carcinomas. Here we identify B cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI), two predicted members of the TNF receptor family, as receptors for APRIL. APRIL binds BCMA with higher affinity than TACI. A soluble form of BCMA, which inhibits the proliferative activity of APRIL in vitro, decreases tumor cell proliferation in nude mice. Growth of HT29 colon carcinoma cells is blocked when mice are treated once per week with the soluble receptor. These results suggest an important role for APRIL in tumorigenesis and point towards a novel anticancer strategy.     

A Multi-institutional Analysis of Duodenal Neuroendocrine Tumors: Tumor Biology Rather than Extent of Resection Dictates Prognosis

Introduction

Duodenal neuroendocrine tumors (NETs) are rare neoplasms with poorly defined management. We sought to evaluate the outcomes of patients undergoing resection of duodenal NETs.

Methods

Using a multi-institutional database, 146 patients who underwent resection for duodenal NETs between 1993 and 2015 were identified. Data on clinicopathologic characteristics and outcomes were collected and analyzed.

Results

Local surgical resection (LR) was performed in 57 (39.0 %) patients, while 50 (34.3 %) patients underwent pancreaticoduodenectomy (PD) and 39 (26.7 %) patients an endoscopic resection (ER). Factors associated with worse RFS included advanced tumor grade and metastasis at diagnosis (both P?<?0.05) but not procedure type (P?>?0.05). Among patients who had at least one lymph node examined (n?=?85), 50 (58.8 %) had a metastatic lymph node; lymph node metastasis (P?=?0.04) and advanced tumor grade (P?=?0.04) were more common among patients with tumors >1.5 cm. Median length-of-stay was longer for PD versus LR (P?<?0.001). PD patients were at increased risk for severe postoperative complications (P?=?0.01).

Conclusion

Recurrence of duodenal NETs was dependent on tumor biology rather than procedure type. PD was associated with a longer hospital stay and higher risk of perioperative complications. For patients with tumors ≤1.5 cm, LR or ER may be appropriate with PD reserved for larger lesions and those not amenable to a more local approach.

     

Translating Cancer Prevention and Control Research into the Community Setting: Workforce Implications

A gap exists between cancer prevention research and its translation into community practice. Two strategies to reduce this gap are community-based participatory research (CBPR) and dissemination research. CBPR offers an avenue to engage academic and community partners, thereby providing mechanisms for joint learning and application of knowledge. Dissemination research examines the movement of evidence-based public health and clinical innovations to practice settings. While applying these approaches may reduce the gap between research and practice, the cancer prevention workforce may be inadequate in size, insufficiently trained, lack resources and incentives, or face structural barriers to effectively participate in CBPR and disseminate evidence-based research findings into practice. Information on translating cancer prevention information to communities and workforce implications was obtained from a panel of experts and through a review of the literature on CBPR and dissemination research. The expert panel and literature review identified major barriers to successfully conducting CBPR and dissemination research in community settings. Barriers included inadequate policies; insufficient networking and communication infrastructures; unsupportive research cultures, climates, and mindsets; inadequate researcher and practitioner education; and limited CBPR and dissemination research with adequate study designs. No specific estimates of the cancer prevention workforce were found; however, indirect evidence for a shortfall were identified. We recommend expanding CBPR training for academic and community partners; increasing funding for dissemination research and practice; supporting proven partnerships; and providing strategic coordination for government agencies, research institutions, nongovernmental organizations, and the private sector to foster better dissemination of information and integration of community-based cancer prevention and control programs and practices. Specific challenges and needs that must be addressed to improve the translation of cancer prevention research into community settings were identified.     

The management of epilepsy in pregnancy

While most women with epilepsy can expect a normal pregnancy outcome, epilepsy remains a significant contributor to both maternal and perinatal morbidity. Pre-pregnancy planning must address reliable contraception and optimisation of antiepileptic drug (AED) regimens to minimise teratogenic risk while maintaining seizure control. The most recent data from the AED registries regarding malformations is presented in this review, as is the limited data on the newer AEDs and studies linking neurocognitive outcomes to AED exposure. During pregnancy, important considerations include; therapeutic drug monitoring, surveillance for obstetric complications and vigilance for seizures during the intrapartum and postpartum period.     

Fever and neutropenia in pediatric hematopoietic stem cell transplant patients

The objective of this study was to identify patterns of fever and neutropenia in pediatric patients undergoing initial hospitalization for hematopoietic stem cell transplantation. A retrospective review of 75 HSCTs over a 4-year period at a single institution was performed, of which 68% were allogeneic and 32% were autologous. Stem cell sources included bone marrow (29%), PBSC (52%) and umbilical cord blood (16%). Fever occurred in 74 (98%) of the episodes. Unexplained fever (FUO) occurred in 43%. Bacteremia without an anatomic focus occurred in 29%, while CVC associated infections occurred in 17%. In 49% of transplants at least one blood culture was positive. The incidence of bacteremia was higher in allogeneic HSCTs (58%) than in autologous transplants (29%). Gram-positive bacteria accounted for 71% of the isolates. Lower rates of bacteremia were observed in patients receiving oral fluoroquinolone prophylaxis. The median duration of fever was 12.5 days and time to engraftment 14 days. Regression analysis demonstrated that duration of fever was strongly associated with time to engraftment, and that time to engraftment was associated with source of cells and number of CD34+ cells/kg administered. Recipients of autologous PBSC had the shortest durations of fever and time to engraftment, while recipients of allogeneic umbilical cord blood had the longest. Bone Marrow Transplantation (2000) 25, 59-65.