Recoverin, a photoreceptor-specific calcium-binding protein, is expressed by the tumor of a patient with cancer-associated retinopathy.

Recoverin is a member of the EF-hand family of calcium-binding proteins involved in the transduction of light by vertebrate photoreceptors. Recoverin also was identified as an autoantigen in the degenerative disease of the retina known as cancer-associated retinopathy (CAR), a paraneoplastic syndrome whereby immunological events lead to the degeneration of photoreceptors in some individuals with cancer. In this study, we demonstrate that recoverin is expressed in the lung tumor of a CAR patient but not in similar tumors obtained from individuals without the associated retinopathy. Recoverin was identified intially by Western blot analysis of the CAR patient's biopsy tissue by using anti-recoverin antibodies generated against different regions of the recoverin molecule. In addition, cultured cells from the biopsy tissue expressed recoverin, as demonstrated by reverse transcription-PCR using RNA extracted from the cells. The immunodominant region of recoverin also was determined in this study by a solid-phase immunoassay employing overlapping heptapeptides encompassing the entire recoverin sequence. Two linear stretches of amino acids (residues 64-70, Lys-Ala-Tyr-Ala-Gln-His-Val; and 48-52, Gln-Phe-Gln-Ser-Ile) made up the major determinants. One of the same regions of the recoverin molecule (residues 64-70) also was uniquely immunopathogenic, causing photoreceptor degeneration upon immunization of Lewis rats with the corresponding peptide. These data demonstrate that the neural antigen recoverin more than likely is responsible for the immunological events associated with vision loss in some patients with cancer. These data also establish CAR as one of the few autoimmune-mediated diseases for which the specific self-antigen is known.

Preparation and properties of nido-carborane-specific monoclonal antibodies for potential use in boron neutron capture therapy for cancer.

As the first step of a research program aimed at developing a bispecific monoclonal antibody system for the delivery of boron-rich molecules to tumor cells for boron neutron capture therapy, monoclonal antibodies (mAbs) were produced against an anionic nido-carborane derivative, 4-[7,8-dicarbadodecahydroundecaborat(-1)-7-yl]butanoic acid. Two IgG subclass mAbs, designated HAW101 and HAW102, were identified that specifically bound the anionic nido-carborane hapten, as well as a variety of other anionic nido-carborane cage derivatives. By using surface plasmon resonance technology, the affinity constants of HAW101 and HAW102 were determined to be 1.9 x 10(9) and 6.8 x 10(8) M-1, respectively. A diverse array of 7-substituted and 7,8-disubstituted anionic nido-carborane derivatives reacted with the mAb HAW101 in competition ELISA, whereas anionic closo-polyhedral boranes showed negligible binding, suggesting a role for the open nido-carborane cage structure. These results suggest that mAbs such as HAW101, which bind anionic nido-carboranes, are useful in the development of bispecific mAbs for specific targeting and enhanced boron delivery to tumor sites.

Adverse pregnancy outcomes reporting system, item-specific completeness of reporting for 1989.

Cover title.

Adverse pregnancy outcomes in Illinois : county-specific prevalence and related infant mortality, 1989-1998.

"May 2000."

Birth defects and other adverse pregnancy outcomes in Illinois, 2001-2005 : a report on county-specific incidence /

" ... supported by grant/cooperative agreement number U50/CCU523303 from the U.S. Centers for Disease Control and Prevention."--Page ii.

Birth defects and other adverse pregnancy outcomes in Illinois, 1998-2002 : a report on county-specific incidence.

" ... supported by grant/cooperative agreement number U50/CCU523303 from the U.S. Centers for Disease Control and Prevention."--Page ii.

Site-specific annual cancer incidence by sex, race, and hispanic ethnicity, Illinois.

Description based on: 1986-1992.

Information extraction from clinical and radiology notes for liver cancer staging

Thesis (Ph.D.)--University of Washington, 2016-06

Merkel cell polyomavirus-specific CD8 T cells in Merkel cell carcinoma: T cell receptor diversity & novel immune therapies

Thesis (Ph.D.)--University of Washington, 2016-06

Parotidectomy: review of treatment and outcomes

Background: Parotidectomy is a common surgical procedure performed for a wide array of benign and malignant tumours. The aim of the present study was to review a single-institution experience with parotidectomy over a 10 year period. Methods: We retrospectively reviewed 170 patients who had parotidectomy performed. The preoperative investigations, clinicopathological parameters, perioperative morbidity and mortality were assessed. Results: One hundred and six (62%) of the patients were men. The mean age was 54 years (range 21-80). Indications for parotidectomy included benign tumour (44%), malignant tumour (42%), inflammatory parotid disease (7%) and miscellaneous (5%). The most common benign tumour was pleomorphic adenoma (25%). The most common malignant tumour was metastatic cutaneous squamous cell carcinoma (SCC) (19%). Fine needle aspiration cytology was performed in 83% patients with a sensitivity and specificity for benign tumours of 76% and 97%, respectively. The sensitivity and specificity for malignant tumours was 90% and 99%, respectively. One (0.6%) patient died in the postoperative period. Postoperative complications included wound infection (2.3%), wound haematoma (3.5%) and seroma (6.6%). Six patients (3.5%) developed temporary complete facial paresis, while 33 patients (20%) developed temporary partial facial palsy in the immediate postoperative period. The 2-year disease-free and disease-specific survival for those patients with metastatic cutaneous SCC were 75% and 76%, respectively. Conclusions: The most common indications for parotidectomy were pleomorphic adenoma and metastatic cutaneous SCC. Our perioperative morbidity and survival for patients with malignant parotid disease compare favourably with other institutional series.

Kallikrein 4 (hK4) and prostate-specific antigen (PSA) are associated with the loss of E-cadherin and an epithelial-mesenchymal transition (EMT)-like effect in prostate cancer cells

Prostate-specific antigen (PSA) and the related kallikrein family of serine proteases are current or emerging biomarkers for prostate cancer detection and progression. Kallikrein 4 (KLK4/hK4) is of particular interest, as KLK4 mRNA has been shown to be elevated in prostate cancer. In this study, we now show that the comparative expression of hK4 protein in prostate cancer tissues, compared with benign glands, is greater than that of PSA and kallikrein 2 (KLK2/hK2), suggesting that hK4 may play an important functional role in prostate cancer progression in addition to its biomarker potential. To examine the roles that hK4, as well as PSA and hK2, play in processes associated with progression, these kallikreins were separately transfected into the PC-3 prostate cancer cell line, and the consequence of their stable transfection was investigated. PC-3 cells expressing hK4 had a decreased growth rate, but no changes in cell proliferation were observed in the cells expressing PSA or hK2. hK4 and PSA, but not hK2, induced a 2.4-fold and 1.7-fold respective increase, in cellular migration, but not invasion, through Matrigel, a synthetic extracellular matrix. We hypothesised that this increase in motility displayed by the hK4 and PSA-expressing PC-3 cells may be related to the observed change in structure in these cells from a typical rounded epithelial-like cell to a spindle-shaped, more mesenchymal-like cell, with compromised adhesion to the culture surface. Thus, the expression of E-cadherin and vimentin, both associated with an epithelial-mesenchymal transition (EMT), was investigated. E-cadherin protein was lost and mRNA levels were significantly decreased in PC-3 cells expressing hK4 and PSA (10-fold and 7-fold respectively), suggesting transcriptional repression of E-cadherin, while the expression of vimentin was increased in these cells. The loss of E-cadherin and associated increase in vimentin are indicative of EMT and provides compelling evidence that hK4, in particular, and PSA have a functional role in the progression of prostate cancer through their promotion of tumour cell migration.

Isoform specific changes in PPAR alpha and beta in colon and breast cancer with differentiation

To investigate the role of peroxisome proliferator-activated receptors (PPARs) chi and beta in the differentiation of colon cancer cells, we differentiated HT-29 cells using sodium butyrate (NaB) and culturing post-confluence and assessed differentiation using the marker intestinal alkaline phosphatase. While PPAR chi levels only changed with culturing post confluence, PPAR beta levels increased independent of the method of differentiation. To explore further the differences induced by NaB. we assessed changes in both PPAR isoforms in MCF-7 breast cancer cells cultured in the presence of NaB over 48 h. Again a very different expression pattern was observed with PPAR-1 increasing after 4 h and remaining elevated, while PPAR beta increased transiently. Our studies suggest that the expression of PPARs is dependent upon both the method of differentiation and on time. Moreover, these studies show that changes in levels are not required for the differentiation of colon cancer cell lines, whereas changes in PPAR beta are more closely associated with differentiation. (c) 2005 Elsevier Inc. All rights reserved.

Cognitive deficits associated with cancer: A model of subjective and objective outcomes

Cancer and its treatment can affect many different aspects of quality of life. As a construct measured subjectively, quality of life shows an inconsistent relationship with objective outcome measures. That is, sometimes subjective and objective outcomes correspond with each other and sometimes they show little or no relationship. In this article, we propose a model for the relationship between subjective and objective outcomes using the example of cognitive function in people with cancer. The model and the research findings on which it is based help demonstrate that, in some circumstances, subjective measures of cognitive function correlate more strongly with psychosocial variables such as appraisal, coping, and emotions than with objective cognitive function. The model may provide a useful framework for research and clinical practice in quality of life for people with cancer.

Skin cancer medicine in primary care: towards an agenda for quality health outcomes

The number of skin cancer clinics functioning within Australia's primary care environment is increasing rapidly, and significant concerns have been raised about the type and quality of work done by some doctors in some clinics. Mainstream general practice is threatened by perceived fragmentation, and specialist practice in dermatology and plastic surgery is threatened by encroachment into their domains of practice. We propose an agenda of training, standards, accreditation, audit and research to ensure that skin cancer clinics provide optimal health outcomes for patients.