The t(1;3) breakpoint-spanning genes LSAMP and NORE1 are involved in clear cell renal cell carcinomas.

By positional cloning, we identified two breakpoint-spanning genes in a familial clear cell renal cell carcinoma (CCRCC)-associated t(1;3)(q32.1;q13.3): LSAMP and NORE1 (RASSF1 homolog). Both genes are downregulated in 9 of 9 RCC cell lines. While the NORE1A promoter predominantly presents partial methylation in 6 of the cell lines and 17/53 (32%) primary tumors, the LSAMP promoter is completely methylated in 5 of 9 cell lines and in 14/53 (26%) sporadic and 4 familial CCRCCs. Expression of LSAMP and NORE1A proteins in CCRCC cell lines inhibited cell proliferation. These characteristics indicate that LSAMP and NORE1A may represent new candidate tumor suppressors for CCRCC.

Gene expression profiling of favorable histology Wilms tumors and its correlation with clinical features.

The aims of this study were to understand the underlying molecular mechanisms of favorable histology Wilms tumors (WTs) and to classify them based on their molecular signatures. We studied a total of 15 favorable histology WTs using microarrays containing 19,968 cDNAs. First, we found commonly altered genes in WT. A total of 267 cDNAs were significantly overexpressed at least 3-fold in all of the tumors compared with noncancerous kidney and contained known WT-related genes such as IGF II and WT1. The gene with the highest expression change compared with noncancerous kidney was topoisomerase IIalpha. By hierarchical clustering, there was a clear distinction between high-stage and low-stage tumors. A total of 30 cDNAs were found differentially expressed between the high- and low-stage groups. One of them, Stathmin 1, which is involved in the microtubule system, was highly expressed in high-stage tumors compared with the low-stage tumors. The present chemotherapy regimens for WT consist mainly of topoisomerase II inhibitors (i.e., actinomycin D, doxorubicin, and etoposide) and antimicrotubule agents (i.e., vincristine and paclitaxel). Our data suggest that high expression of topoisomerase IIalpha and microtubule-related genes such as tubulin and stathmin 1 may be related to the high chemosensitivity of WT. In addition, retinol-related genes such as CRABP2 and retinol-binding protein 1 were overexpressed in WT, and CRABP2 was more highly expressed in the poor outcome patients, which suggests that retinoid acid may be a potential drug. In summary, our findings suggest that the integration of gene expression data and clinical parameters could aid in detecting aggressive tumors among favorable histology WT and lead to the discovery of new drugs for WT.

Gene expression profiling of early- and late-relapse nonseminomatous germ cell tumor and primitive neuroectodermal tumor of the testis.

PURPOSE: To better understand the molecular mechanisms that underlay the development and progression of nonseminomatous germ cell tumor of testis (NSGCTT) as well as malignant transformation of teratoma and primitive neuroectodermal tumor (PNET). EXPERIMENTAL DESIGN: We studied the gene expression profiles of 17 retroperitoneal NSGCTTs (10 yolk sac tumors, 3 embryonal carcinomas, 4 teratomas) and 2 PNETs obtained from patients with two clinical outcomes. Tissue samples were obtained from the Indiana University. One group of NSGCTT and PNET patients developed metastases within 2 years (early-relapse) of initial successful treatment, and the other group developed metastases after 2 years (late-relapse). Gene expression in these groups of patients was quantified using cDNA microarrays and real-time relative quantitative PCR. RESULTS: We demonstrate that the gene expression profiles of these tumors correlate with histological type. In addition, we identify type-specific genes that may serve as novel diagnostic markers. We also identify a gene set that can distinguish between early-relapse and late-relapse yolk sac tumors. The expression differences of these genes may underlie the differences in clinical outcome and drug response of these tumors. CONCLUSION: This is the first study that used gene expression profiling to examine the molecular characteristics of the NSGCTTs and drug response in early- and late-relapse tumors. These results suggest that two molecularly distinct forms of NSGCTTs exist and that the integration of expression profile data with clinical parameters could enhance the diagnosis and prognosis of NSGCTTs. More importantly, the identified genes provide insight into the molecular mechanisms of aggressive NSGCTTs and suggest intervention strategies.

Impact of minimizing diagnostic blood loss in the critically ill.

BACKGROUND: The use of a small-volume phlebotomy tube (SVPT) versus conventional-volume phlebotomy tube (CVPT) has led to a decrease in daily blood loss. Blood loss due to phlebotomy can lead ultimately to decreased rates of anemia and blood transfusions, which can be important in the critically ill patient. METHODS: We compared SVPT vs CVPT retrospectively in critically ill adult patients age ≥18 years admitted to a surgical intensive care unit for ≥48 hours. CVPT were evaluated from January 2011 to May 2011 and SVPT from June 2012 to October 2012. RESULTS: Amount of blood drawn for laboratory tests and transfusions were evaluated in 248 patients (116 SVPT vs 132 CVPT). When compared with CVPT, total blood volume removed (mean ± SD) with SVPT was less overall, 174 ± 182 mL vs 299 ± 355 mL, P = .001. Daily blood draws also were less, 22.5 ± 17.3 mL vs 31.7 ± 15.5 mL, P < .001. The units of packed red blood cells given were not significant, 4.4 ± 3.6 units vs 6.0 ± 8.2 units, P = .16. CONCLUSION: The use of SVPT blood sampling led to a decreased amount of blood drawn. Strategies that use SVPT in a larger cohort also may decrease the number of transfusions in selected patients. Every effort should be made to use SVPT.

Impact of evaluating antibiotic concentrations in abdominal abscesses percutaneously drained.

BACKGROUND: Appropriate antibiotic therapy and prompt drainage are essential for optimal results with abdominal abscesses. METHODS: In this prospective study, 47 abdominal abscesses from 42 patients over 2 years who had percutaneous drainage were evaluated. Antibiotic concentrations were evaluated from the abscess fluid and correlated with clinical and microbiologic cure. RESULTS: Only 23% of patients had appropriate antibiotic selection with optimal concentrations for the bacteria recovered. Piperacillin/tazobactam, cefepime, and metronidazole provided adequate concentrations in all except the largest abscesses, whereas fluconazole required higher doses in all abscesses. Vancomycin and ciprofloxacin levels were inadequate in most abscesses. With gram-negative aerobes, the use of appropriate antibiotics resulted in a relatively higher incidence of presumed eradication (100% [4 of 4] vs 75% [9 of 12], P = .26). With ≥ 3 organisms identified, clinical failure was significant (58% vs 13%, P = .01). CONCLUSIONS: For optimal treatment, abdominal abscesses require prompt drainage and properly selected antibiotics at adequate doses. Essential information can be obtained from abscess cultures and their antibiotic concentrations.