Effectiveness of lexico-syntactic pattern matching for ontology enrichment with clinical documents.

Objective: To evaluate the effectiveness of a lexico-syntactic pattern (LSP) matching method for ontology enrichment using clinical documents.

Methods: Two domains were separately studied using the same methodology. We used radiology documents to enrich RadLex and pathology documents to enrich National Cancer Institute Thesaurus (NCIT).

Robotic liver surgery.

Although minimally invasive hepatic resection surgery has shown decreased morbidity in select patients, conventional laparoscopic liver resection has inherent limitations with reduced freedom of movement within the abdominal cavity and 2-dimensional view of the operative field. Robotic liver surgery allows surgeons to perform advanced procedures with a potential for improved precision and ergonomics as well as a 3-dimensional view of the surgical site. However, use of the robot entails a steep learning curve and additional equipment.

Factors associated with Type I and Type II endometrial cancer.

Objective: We investigated risk factors for Type II (n = 176) vs. Type I (n = 1,576) endometrial cancer (EC) in cases treated at Magee-Womens Hospital between 1996 and 2008.

Methods: Clinical data were available from the University of Pittsburgh Medical Center (UPMC) Network Cancer Registry.

Temporal and demographic patterns of non-Hodgkin's lymphoma incidence in Pennsylvania.

Our study analyzed temporal and demographic patterns of non-Hodgkin's lymphoma (NHL) incidence in Pennsylvania and compared Pennsylvania time trends with national trends. Joinpoint and age-period-cohort analyses summarized sex- and race-specific NHL incidence time trends between 1985 and 2004. Ecologic analysis identified demographic factors associated with age-adjusted county-specific NHL incidence.

Mifepristone: pharmacology and clinical impact in reproductive medicine, endocrinology and oncology.

Importance Of The Field: Mifepristone is a synthetic selective progesterone-receptor modulator (SPRM) that is widely used around the globe in the field of reproductive medicine. At present mifepristone is approved in a number of countries for early termination of pregnancy (TOP), cervical dilatation before surgical TOP, and management of early embryonic loss or fetal death. A number of new clinical applications are being developed in gynecology, endocrinology and oncology.

Surgical techniques in visceral resection and peritonectomy procedures.

Peritoneal surface malignancies may now be approached with curative intent using a strategy of cytoreductive surgery combined with intraperitoneal chemotherapy. Complete cytoreduction to tumor nodules less than 2.5 mm is considered critical to the efficacy of the local chemotherapy and achieving complete cytoreduction impacts long-term survival.

Interleukin-15 enhances natural killer cell cytotoxicity in patients with acute myeloid leukemia by upregulating the activating NK cell receptors.

Interleukin-15 (IL-15) has a major role in NK-cell homeostasis. Modulation of the relative frequency and expression intensity of the NK-cell receptors by IL-15 may increase NK cell-mediated cytotoxicity in cancer patients. We investigated the receptor repertoire and measured NK-cell activity in newly diagnosed AML patients and evaluated the ex vivo effects of IL-15.

Factors affecting feeling-of-knowing in a medical intelligent tutoring system: the role of immediate feedback as a metacognitive scaffold.

Previous studies in our laboratory have shown the benefits of immediate feedback on cognitive performance for pathology residents using an intelligent tutoring system (ITS) in pathology. In this study, we examined the effect of immediate feedback on metacognitive performance, and investigated whether other metacognitive scaffolds will support metacognitive gains when immediate feedback is faded. Twenty-three participants were randomized into intervention and control groups.

Early development of the Toll-like receptor 9 agonist, PF-3512676, for the treatment of patients with advanced cancers.

Background: Unmethylated oligodeoxynucleotides (ODNs) with cytosine-phosphate-guanine (CpG) motifs can potently activate the immune system through Toll-like receptor (TLR) 9. PF-3512676 is a synthetic CpG ODN that induces strong Th1-type immune responses through TLR9 and is now in clinical development.

Objective: To review discovery and development of synthetic CpG ODNs and their effects on immune cells and to relate preclinical and early clinical development of PF-3512676.

The Supercourse of fisheries: importance of sharing educational materials and implications for cancer and chronic disease research.

Epidemiologic research has demonstrated that fish is an important component of human nutrition. Existing information for the public about the benefits vs dangers of fish consumption is often contradictory and unclear. Education in the field of human nutrition, especially in the area of fish consumption could be markedly enhanced if there were better mechanisms for the development of customized high quality, low cost educational lectures Researchers from the Department of Epidemiology, University of Pittsburgh, in collaboration with the members of the Global Health Network Supercourse project are developing a library of lectures on nutrition, environmental health, and fisheries, for the use and share among the scientists of the world.

The association of bone mineral density with prostate cancer risk in the Osteoporotic Fractures in Men (MrOS) Study.

We investigated the association of bone mineral density (BMD) measures with prostate cancer (PCa) risk in older men enrolled in the Osteoporotic Fractures in Men Study. We hypothesized that men with higher BMD, a marker of exposure to endogenous sex hormones, would have an increased incidence of PCa. The cohort included 4,597 men (89% White, 65 years or older) with no prior history of PCa.

Tremelimumab (CP-675,206): a fully human anticytotoxic T lymphocyte-associated antigen 4 monoclonal antibody for treatment of patients with advanced cancers.

Tremelimumab, a fully human monoclonal IgG2 antibody targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA4), is being developed by Pfizer for treatment of patients with advanced cancers. Treatment with an anti-CTLA4 mAb prevents normal downregulation of T cells and prolongs T cell activation, thereby enhancing immune function. In Phase I and II studies, tremelimumab was well tolerated with predictable and manageable side effects.

Oncolytic vaccinia virus: from bedside to benchtop and back.

The field of oncolytic viral therapy has undergone a major shift in focus in the last few years. Less research has been directed at making incremental improvements in original vectors based mainly on strains of adenovirus and HSV; instead a variety of different viral strains have been suggested as potential backbones for future oncolytic viruses (including Newcastle disease virus, reovirus, vesicular stomatitis virus, polio virus, retrovirus, Sindbis virus, picornavirus, mumps and measles virus), with many of these progressing to clinical trials. Of these, vaccinia virus represents a particularly promising candidate.

KD5170, a novel mercaptoketone-based histone deacetylase inhibitor, exerts antimyeloma effects by DNA damage and mitochondrial signaling.

Histone deacetylase inhibitors have emerged as promising anticancer drugs. Using an unbiased ultrahigh throughput screening system, a novel mercaptoketone-based histone deacetylase inhibitor series was identified that was optimized to the lead compound, KD5170. KD5170 inhibited the proliferation of myeloma cell lines and the viability of CD138(+) primary myeloma cells by induction of apoptosis, accompanied by an increase of acetylation of histones and activation of caspase-3, caspase-8, and caspase-9.

Endometrial cancer: multiplexed Luminex approaches for early detection.

Background: Endometrial carcinoma is the most common gynecologic cancer. Despite the advances that have been made in other cancers, both the annual incidence of and the death rate associated with endometrial cancer appear to be rising, both in the US and around the world. In the US, ∼ 41,000 cases are diagnosed and about 7000 women die from the disease each year.

Pathophysiology of myeloma bone disease.

Multiple myeloma is a tumor of terminally differentiated plasma cells that home to and expand in the bone marrow. It is the second most common hematologic malignancy, with approximately 16,000 new cases per year, and accounts for an estimated 11,000 deaths in the USA. It is the most common cancer to metastasize to bone, with up to 90% of patients developing bone lesions.

Hematopoietic stem cell transplantation for chronic lymphocytic leukemia: potential cure for an incurable disease.

Hematopoietic stem cell transplantation (HSCT) has been used as a treatment modality in patients with chronic lymphocytic leukemia (CLL). Allogeneic HSCT is the only therapy at present that has curative potential in patients with CLL. Allogeneic HSCT using standard myeloablative regimens has been generally associated with high treatment mortality rates and autologous HSCT with high relapse rates.

The expanding role of rituximab and radioimmunotherapy in the treatment of B-cell lymphomas.

The role of rituximab in the treatment of B-cell lymphomas has rapidly emerged from the relapsed setting to first-line combination regimens across the broad range of histologic subtypes. The role of maintenance rituximab in indolent lymphomas after first-line therapy needs to be defined along with the integration of radioimmunotherapy into the first-line therapeutic regimens. As mechanisms of action/resistance to monoclonal antibody therapy are better understood, approaches to predicting response and optimizing combination therapy to overcoming primary and acquired resistance may be developed.

Tremelimumab, a fully human monoclonal IgG2 antibody against CTLA4 for the potential treatment of cancer.

Pfizer Inc is developing tremelimumab, a fully human monoclonal IgG2 antibody against cytotoxic T-lymphocyte-associated antigen, for the potential intravenous treatment of cancer. Phase III clinical trials to confirm the role of tremelimumab in the treatment of metastatic melanoma are ongoing, as are phase II trials in patients with NSCLC and colorectal cancer.

Yttrium ibritumomab tiuxetan in the treatment of non-Hodgkin's lymphoma: current status and future prospects.

After nearly three decades with little change in the treatment for B-cell non-Hodgkin's lymphoma, the addition of immunotherapy has had a profound effect on the treatment of this group of diseases. A more subtle addition to the armentarium has been the radiolabeled monoclonal antibodies, (90)yttrium ibritumomab tiuxetan and (131)iodine tositumomab. Unfortunately these drugs have been underutilized.

Oblimersen in the treatment of metastatic melanoma.

Oblimersen (Genasense is a Bcl-2 antisense compound that selectively targets Bcl-2 RNA for degradation by RNase H and thereby decreases Bcl-2 protein production. Bcl-2 protein plays a major role in preventing apoptosis and has been linked to chemotherapy resistance in melanoma. Preclinical studies with oblimersen in melanoma cell lines and xenograft models of melanoma have demonstrated downregulation of Bcl-2 protein, induction of apoptosis and enhanced tumor response when combined with chemotherapy.

User-centered semantic harmonization: a case study.

Semantic interoperability is one of the great challenges in biomedical informatics. Methods such as ontology alignment or use of metadata neither scale nor fundamentally alleviate semantic heterogeneity among information sources. In the context of the Cancer Biomedical Informatics Grid program, the Biomedical Research Integrated Domain Group (BRIDG) has been making an ambitious effort to harmonize existing information models for clinical research from a variety of sources and modeling agreed-upon semantics shared by the technical harmonization committee and the developers of these models.

Effects of polycyclic aromatic hydrocarbons (PAHs) in environmental pollution on exogenous and oxidative DNA damage (EXPAH project): description of the population under study.

The EXPAH project was a molecular epidemiology study whose aims were to evaluate the hypothesis that polycyclic aromatic hydrocarbons (PAHs) are a major source of genotoxic activities of organic mixtures associated with air pollution. Biomarkers of exposure, effects and susceptibility, and oxidative DNA damage were measured in three PAH-exposed populations from Prague (Czech Republic), Kosice (Slovakia) and Sofia (Bulgaria). Control populations were included from each city.