Discovery of a novel molecule that regulates tumor growth and metastasis.

The heparan sulfate proteoglycan, Glypican-1 (GPC1), significantly impacts the growth of pancreatic cancer cells in vivo and markedly attenuates tumor angiogenesis and metastasis in athymic mice. Interestingly, both cancer cell-derived and host-derived GPC1 play an important role in tumor development and spread. These data suggest that GPC1 may be a valid therapeutic target for pancreatic cancer.

14-3-3sigma Modulates pancreatic cancer cell survival and invasiveness.

Purpose: The purpose of the present study was to investigate the potential role of 14-3-3sigma in pancreatic ductal adenocarcinoma (PDAC).

Experimental Design: 14-3-3 isoform expression was determined by real-time quantitative PCR in laser capture normal pancreatic ductal cells and pancreatic cancer cells and in 5 pancreatic cancer cell lines. PANC-1 cells, with low levels of 14-3-3sigma, were stably transfected with a human 14-3-3sigma cDNA.

The epistemology of patient safety research.

Patient safety has only recently been subjected to wide-spread systematic study. Healthcare differs from other high risk industries in being more diverse and multi-contextual, and less certain and regulated. Also many patient safety problems are low-frequency events associated with many, varied contributing factors.

Silicone breast implants and magnetic resonance imaging screening for rupture: do U.S. Food and Drug Administration recommendations reflect an evidence-based practice approach to patient care?

Regular magnetic resonance imaging has been recommended for the purpose of screening for silicone implant rupture. However, when its use as a screening test is critically examined, it appears that evidence to support its use is lacking. For example, there is no conclusive evidence at this time to show that using magnetic resonance imaging screening of asymptomatic women leads to a reduction in patient morbidity.

Targeting angiogenesis in pancreatic cancer: rationale and pitfalls.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer responsible for over 20% of deaths due to gastrointestinal malignancies. PDAC is usually diagnosed at an advanced stage which, in part, helps to explain its high resistance to chemotherapy and radiotherapy. In addition, the cancer cells in PDAC have a high propensity to metastasize and to aberrantly express several key regulators of angiogenesis and invasion.

Glypican-1 modulates the angiogenic and metastatic potential of human and mouse cancer cells.

Cells isolated from many types of human cancers express heparin-binding growth factors (HBGFs) that drive tumor growth, metastasis, and angiogenesis. The heparan sulfate proteoglycan glypican-1 (GPC1) is a coreceptor for HBGFs. Here we show that both cancer cell-derived and host-derived GPC1 are crucial for efficient growth, metastasis, and angiogenesis of human and mouse cancer cells.

The absolute quantification strategy: application to phosphorylation profiling of human separase serine 1126.

The absolute quantification (AQUA) strategy provides a means to determine the precise protein or modified protein levels directly from cells or tissues. The technique is based on two major principles: stable isotope dilution theory and the use of synthetic peptides containing such stable isotopes to exactly mimic native counterparts after proteolysis. These peptides can be synthesized with modifications such as phosphorylation.

In-Vitro Investigations of Nanoparticle Magnetic Thermotherapy: Adjuvant Effects and Comparison to Conventional Heating.

Thermotherapy, particularly magnetic nanoparticle hyperthermia, is a promising modality both as a direct cancer cell killing and as a radiosensitization technique for adjuvant therapy. Dextran-coated iron oxide nanoparticles were mixed with multiple tumor cell lines in solution and exposed to varying magnetic field regimes and combined with traditional external radiotherapy. Heating of cell lines by water bath in temperature patterns comparable to those achieved by nanoparticle hyperthermia was conducted to assess the relative value of nano-magnetic thermotherapy compared with conventional bulk heating techniques and data.

Pathology of non-infective gastritis.

The discovery of Helicobacter pylori and its intimate role in the development of the most common form of chronic gastritis has elicited a much-needed interest in non-neoplastic gastric pathology. This has been paralleled by an increase in upper endoscopic examinations, which allow recognition of novel patterns and distribution of mucosal injury. Numerous attempts at classification have been made, most based on the acuteness or chronicity of gastric mucosal injury.

Colonoscopy demand and capacity in New Hampshire.

Background: Screening for colorectal cancer has been clearly shown to decrease the incidence and mortality from this disease. Accurate information about the demand and capacity for screening, particularly with colonoscopy, is critical in planning screening strategies. National assessments have recently begun; estimates of smaller geographic regions should improve the accuracy of national estimates, as well as inform strategies for individual states.

Barrett's esophagus with high-grade dysplasia simulating metastatic adenocarcinoma in a fine needle aspiration biopsy.

An endoscopic ultrasound examination, performed to rule out invasive esophageal carcinoma in a patient with a history of Barrett's esophagus with high-grade dysplasia, disclosed an enlarged paraesophageal lymph node which was aspirated. The aspirate contained markedly atypical clustered large cells that displayed prominent nucleoli and mitoses, as well as lymphoid cells, suggestive of adenocarcinoma metastatic to a lymph node. The neoplastic-appearing cells were, in fact, dysplastic glandular cells that the needle traversed en route to a reactive lymph node.

Functional magnetic resonance imaging of the primary somatosensory cortex in piglets.

Object: The piglet is an excellent model for the developing human brain, and has been used increasingly in various centers for studies of traumatic brain injury and other insults. Unlike rodent or primate models, however, there are few behavioral scales for the piglet, and the available ones are used to test general responsiveness rather than specific functional outcome. The differing behavioral repertoires of animals of different ages provide an additional challenge when age-dependent injury responses are compared.

Telephone care management to improve cancer screening among low-income women: a randomized, controlled trial.

Background: Minority and low-income women receive fewer cancer screenings than other women.

Objective: To evaluate the effect of a telephone support intervention to increase rates of breast, cervical, and colorectal cancer screening among minority and low-income women.

Design: Randomized, controlled trial conducted between November 2001 and April 2004.

Disaster research methods: past progress and future directions.

Published results for 225 disaster studies were coded on methodological variables, severity of effects, and event year. Methods varied greatly, but cross-sectional, after-only designs, convenience sampling, and small samples were modal. Samples that were assessed before the disaster, selected for reasons of convenience, or were large tended to show less severe effects than other samples.

Restoration of Smad4 in BxPC3 pancreatic cancer cells attenuates proliferation without altering angiogenesis.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive human malignancy in which the transforming growth factor beta (TGF-beta) signal transducer, Smad4, is commonly mutated or deleted. BxPC3 human pancreatic cancer cells exhibit a homozygous deletion of the Smad4 gene, yet are growth inhibited by TGF-beta1. In the present study, we sought to determine whether reintroduction of Smad4 into BxPC3 cells alters their behavior in vitro and in vivo.

Lymphangioma of the posterior mediastinum in an adult: diagnosis via cytopathologist-assisted fine-needle aspiration biopsy with cell block.

Lymphangiomas are uncommon in the posterior mediastinum. We report a case of a lymphangioma in this location that was diagnosed by computed tomographic-guided fine-needle aspiration biopsy. The cell block of the lesion closely simulated a normal structure immediately adjacent to the target and could have been misdiagnosed as "normal tissue.

Docetaxel in the treatment of esophageal cancer.

Esophageal cancer is the ninth most common malignancy in the world and the seventh leading cause of death in American men. Because symptoms are often intermittent and vague, patients typically present at an advanced stage, with limited survival. In operable patients, standard care includes surgery with or without adjuvant chemotherapy and radiotherapy; chemotherapy and radiotherapy is the standard care for inoperable disease.

Smad7 abrogates transforming growth factor-beta1-mediated growth inhibition in COLO-357 cells through functional inactivation of the retinoblastoma protein.

Smad7 is overexpressed in 50% of human pancreatic cancers. COLO-357 pancreatic cancer cells engineered to overexpress Smad7 are resistant to the actions of transforming growth factor-beta1 (TGF-beta1) with respect to growth inhibition and cisplatin-induced apoptosis but not with respect to modulation of gene expression. To delineate the mechanisms underlying these divergent consequences of Smad7 overexpression, we studied the effects of Smad7 on TGF-beta1-dependent signaling pathways and cell cycle regulating proteins.

Factors affecting the professional image of physicians.

Objective: The purpose of this study was to use an experimental design to determine the effect of selected aspects of dress on the professional image of physicians in an adult outpatient setting by those who use the health care services the most (55+), the least (18 to 22), and other physicians on whom we depend for referrals.

Methods: Ten slides of physicians representing a variety of ages; ethnic and religious affiliations were shown to 3 populations across the United States and Canada. Set 1 (N = 216) was shown to undergraduates and rated on 10 attributes of professional image.

A review of research on residential programs for people with severe mental illness and co-occurring substance use disorders.

Substance use disorder is the most common and clinically significant co-morbidity among clients with severe mental illnesses, associated with poor treatment response, homelessness and other adverse outcomes. Residential programs for clients with dual disorders integrate mental health treatment, substance abuse interventions, housing and other supports. Ten controlled studies suggest that greater levels of integration of substance abuse and mental health services are more effective than less integration.

Intraductal papillary mucinous adenoma that arises from pancreatic heterotopia within a meckel diverticulum.

Neoplasia is an unusual complication of Meckel diverticulum. Most tumors of Meckel diverticulum are neuroendocrine or mesenchymal in origin. Adenocarcinomas represent a minority of the tumors that arise in Meckel diverticulum and are generally thought to develop from either endogenous small intestinal epithelium or heterotopic gastric epithelium.

Initial diagnosis of breast cancer via cytological examination of a pleural effusion: a rare event facilitated by recognition of an unusual morphological pattern.

It is uncommon for breast carcinoma to present as a malignant serous effusion. Here, we describe a case in which the initial diagnosis of an occult invasive ductal carcinoma of the breast was made via cytological examination of a pleural effusion. Recognition of a cribriform architecture with intraluminal necrosis and microcalcifications in a cell block preparation was critical in making that diagnosis.

Update on diabetes mellitus.

Diabetes mellitus is a complex multi-system disorder that may be classified as autoimmune mediated type 1 diabetes, or as insulin resistance associated type 2 diabetes. In type 1 diabetes, there is selective loss of the beta cells within the endocrine islets, as a consequence of T-cell and cytokine mediated destruction of these cells, perhaps in conjunction with destruction of the peri-islet Schwann cells. In type 2 diabetes, the etiology of the resistance ranges from post-receptor defects in the insulin signaling pathway to excessive production of adipocyte derived cytokines that antagonize insulin action to mitochondrial defects that interfere with glucose disposal.

Billing for the Evaluation and Treatment of Adult Depression by the Primary Care Clinician.

Depression is a common problem encountered in primary care practice. There are many barriers that the primary care clinician faces in managing patients with depression. Financial reimbursement is one infrequently addressed barrier that influences how care is provided.