Selective modification of fluciclovine (18F) transport in prostate carcinoma xenografts.

We investigated if previously demonstrated inhibition of fluciclovine (18F) in vitro could be replicated in a PC3-Luc xenograft mouse model. Following intratumoral injection of 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), alpha-(methylamino)isobutyric acid (MeAIB) or saline, fluciclovine PET tumor-to-background activity was 43.6 (± 5.4)% and 25.3 (± 5.2)% lower in BCH (n = 6) and MeAIB (n = 5) injected PC3 Luc xenografts, respectively, compared to saline-injected controls (n = 2). Partial inhibition of fluciclovine uptake by BCH and MeAIB can be demonstrated in vivo similar to previous in vitro modeling.

Intratumor C-reactive protein as a biomarker of prognosis in localized renal cell carcinoma.

PURPOSE: Serum C-reactive protein has been shown to have prognostic value in localized and metastatic renal cell carcinoma. However, the prognostic value of intratumor C-reactive protein remains unknown. MATERIALS AND METHODS: A total of 95 patients with resected, clinically localized (T1-T4N0M0) clear cell renal cell carcinoma were followed postoperatively. Intratumor C-reactive protein expression was assessed in surgical specimens using immunohistochemical analysis. Patients were categorized by staining intensity into low risk (staining 0 to 1), intermediate risk (staining 2) and high risk (staining 3) groups. Kaplan-Meier and multivariate Cox regression analyses were used to examine overall survival across patient and disease characteristics. Variables examined in multivariate Cox regression analysis included T stage, Fuhrman nuclear grade, tumor size, preoperative serum C-reactive protein and intratumor C-reactive protein staining. RESULTS: Followup extended up to 46 months with a mean (SD) of 29.8 (11.0) months. Twelve patients (12.6%) died during followup. Of all tumors 49.5%, 25.3% and 25.3% were graded by intratumor C-reactive protein staining as low risk (0 to 1), intermediate risk (2) and high risk (3), respectively. After controlling for variables significant on univariate analysis, patients in the high risk (3) group experienced a 27-fold increased risk of overall mortality compared to those in the low risk (0-1) group (HR 27.767, 95% CI 1.488-518.182). After adjusting for tumor staining, preoperative serum C-reactive protein was not a significant predictor of overall survival (p = 0.741). CONCLUSIONS: Intratumor C-reactive protein may be a robust biomarker of prognosis in patients with localized renal cell carcinoma.

Pattern of fatal head injuries in Ibadan--a 10 year review.

Head injury is an important cause of mortality worldwide. The objective of the present study was to analyse the pattern of fatal head injury among patients seen in University College Hospital, Ibadan. The study was based on retrospective investigation of cases of fatal head injury referred by the coroner to the Department of Pathology, University College Hospital, between 1991 and 2000. Pertinent clinical and postmortem findings were extracted from available coroner's autopsy records. There were 529 cases (402 males and 127 females). Their ages ranged from <1 year to 90 years (mean=33 years), the average age of females (27.8) being less than that of males (34.6) (p=0.00003). 83.8% were road traffic accidents, 8.9% falls from a height, 3.8% assault, and 3% gunshot injuries. 79.1% had a GCS of 8 or less at presentation. The mean survival period of children aged less than 15 years was 2 days while that of adolescents and adults aged 15 years and above was 5.6 days (p=0.02). Subdural (62.4%), subarachnoid (24.6%), epidural (10.2%), and intracerebral (10%) haemorrhages were the major causes of death. Skull fractures occurred in 38.2%, while cerebral contusions occurred in 22.1%. Intracranial infection was relatively uncommon in these patients. The present study has shown that young adults, predominantly males in their most productive years of life, are especially prone to fatal head injury.

A comprehensive review of incidence and survival in patients with rare histological variants of prostate cancer in the United States from 1973 to 2008.

BACKGROUND: The American Joint Commission on Cancer (AJCC) identifies five rare variants of prostate adenocarcinoma: mucinous, ductal, signet ring cell, adenosquamous and neuroendocrine including small cell. No prior study has comprehensively detailed incidence and outcomes for all AJCC variants of prostate cancer. METHODS: We used the Surveillance, Epidemiology and End Results (SEER) program to analyze prostate cancers diagnosed from 1973 to 2008. Cases of mucinous, ductal, signet ring cell, adenosquamous and neuroendocrine carcinoma were identified, along with cases of non-variant adenocarcinoma for comparison. Age-adjusted incidence rates (IRs) and overall survival (OS) were evaluated and stratified by race, age, stage and PSA. All IRs represent the number of cases per million people per year. RESULTS: Each variant is rare, with IRs between 0.03 (adenosquamous) and 0.61 (mucinous). There was a significant difference in incidence between Caucasian and African American patients with mucinous adenocarcinoma. Median OS varied ranged from 10.0 months in neuroendocrine carcinoma to 125.0 months in mucinous adenocarcinoma. In all, 5-year OS ranged from 12.6% in neuroendocrine carcinoma to 75.1% in mucinous adenocarcinoma. There was a significant difference in survival between Caucasian and African American patients for mucinous adenocarcinoma (median survival 144.0 vs 99.0 months, P<0.01). African American patients with mucinous adenocarcinoma also presented with more advanced stage disease compared with Caucasian patients. Multivariate analysis demonstrated that African American race was not associated with worse survival when corrected for stage. CONCLUSIONS: There are differences in IRs and OS among rare variants of prostate cancer. For mucinous adenocarcinoma, there are significant differences in incidence and survival between Caucasian and African American patients. These differences should be considered in clinical decision making for patients with these malignancies.

EPLIN downregulation promotes epithelial-mesenchymal transition in prostate cancer cells and correlates with clinical lymph node metastasis.

Epithelial-mesenchymal transition (EMT) is a crucial mechanism for the acquisition of migratory and invasive capabilities by epithelial cancer cells. By conducting quantitative proteomics in experimental models of human prostate cancer (PCa) metastasis, we observed strikingly decreased expression of EPLIN (epithelial protein lost in neoplasm; or LIM domain and actin binding 1, LIMA-1) upon EMT. Biochemical and functional analyses demonstrated that EPLIN is a negative regulator of EMT and invasiveness in PCa cells. EPLIN depletion resulted in the disassembly of adherens junctions, structurally distinct actin remodeling and activation of ß-catenin signaling. Microarray expression analysis identified a subset of putative EPLIN target genes associated with EMT, invasion and metastasis. By immunohistochemistry, EPLIN downregulation was also demonstrated in lymph node metastases of human solid tumors including PCa, breast cancer, colorectal cancer and squamous cell carcinoma of the head and neck. This study reveals a novel molecular mechanism for converting cancer cells into a highly invasive and malignant form, and has important implications in prognosis and treating metastasis at early stages.

Postoperative better than preoperative C-reactive protein at predicting outcome after potentially curative nephrectomy for renal cell carcinoma.

OBJECTIVES: Preoperative C-reactive protein (CRP) predicts metastasis and mortality in localized renal cell carcinoma (RCC). However, the predictive potential of after resection of localized RCC remains unclear. Therefore, we assessed the absolute ability of postoperative CRP to predict metastases and mortality as a continuous variable. METHODS: Patients with clinically localized (T1-T3N0M0) clear-cell RCC were followed for 1 year postoperatively. Metastases were identified radiologically and mortality by death certificate. Univariate and multivariate binary logistic regression analyses examined 1 year relapse-free survival (RFS) and overall survival (OS) across patient and disease characteristics. RESULTS: Of the 110 patients in this study, 16.4% developed metastases and 6.4% died. Mean (SD) postoperative CRP for patients who did and did not develop metastases were 69.06 (73.55) mg/L and 5.27 (7.80), respectively. Mean (SD) postoperative CRP for patients who did and did not die were 89.31 (69.51) mg/L and 10.88 (30.32), respectively. In multivariate analysis, T-stage (OR: 12.452, 95% CI: 2.889-53.660) and postoperative CRP ((B: .080, SE: .025; P < .001) were significant predictors of RFS. T-Stage (OR: 11.715; 95% CI: 1.102-124.519) and postoperative CRP (B: .017; SE: .007; P < .001) were also significant predictors of OS. After adjusting for postoperative CRP, preoperative CRP was not predictive of these outcomes. CONCLUSIONS: Postoperative, not preoperative, CRP is the better predictor of metastasis and mortality following nephrectomy for localized RCC. Clinicians should consider absolute postoperative CRP to identify high-risk patients for closer surveillance or additional therapy. Predictive algorithms should consider incorporating postoperative CRP as a continuous variable to maximize predictive ability.

Expression of the vascular endothelial growth factor receptors 1 and 2 in acute myeloid leukemia: incidence and feasibility of immunohistochemical staining.

Vascular endothelial growth factor (VEGF) and its receptor tyrosine kinases, VEGFR-1 and VEGFR-2, are important therapeutic targets for various cancers including AML. Paraffin-embedded bone marrow samples (PE-BM) are, in most cases, the only tissue accessible to perform retrospective analyses of novel targets such as VEGF and/or its receptors. As a result, it limits our options to immunohistochemistry (IHS), or more expensive and less practical techniques such as enzyme-linked immunosorbent assay (ELISA) or fluorescence in situ hybridization (FISH). We analyzed the feasibility of IHS to measure VEGFR-1 and VEGFR-2 expression in 28 AML samples using monoclonal antibodies (moAbs) against Flt-1 (VEGFR-1) and KDR/Flk-1 (VEGFR-2). Medical records were reviewed for relevant clinical information. Expression of VEGFR-1 (+) and VEGFR-2 (+) were seen in 25% (7/28) and 43% (12/28) respectively. Forty-six percent (13/28) were dual-negatives for VEGFR-1 and VEGFR-2; 14% (4/28) were dual-positives for VEGFR-1 and VEGFR-2. An inferior survival was observed in patients whose myeloblasts express either VEGFR-1 (+) or VEGFR-2 (+), or both. Determination of expression of VEGF receptors (1 and 2) by IHS in PE-BM tissue is feasible. Prospective comparison of IHC to flow cytometry or other molecular techniques, and assessment of the prognostic significance of VEGF receptors in AML patients is warranted.