BackgroundThe goal of our study was to investigate the molecular underpinnings associated with the relatively aggressive clinical behavior of prostate cancer (PCa) in African American (AA) compared to Caucasian American (CA) patients using a genome-wide approach.MethodsAA and CA patients treated with radical prostatectomy (RP) were frequency matched for age at RP, Gleason grade, and tumor stage. Array-CGH (BAC SpectralChip2600) was used to identify genomic regions with significantly different DNA copy number between the groups. Gene expression profiling of the same set of tumors was also evaluated using Affymetrix HG-U133 Plus 2.0 arrays. Concordance between copy number alteration and gene expression was examined. A second aCGH analysis was performed in a larger validation cohort using an oligo-based platform (Agilent 244K).ResultsBAC-based array identified 27 chromosomal regions with significantly different copy number changes between the AA and CA tumors in the first cohort (Fisher's exact test, P < 0.05). Copy number alterations in these 27 regions were also significantly associated with gene expression changes. aCGH performed in a larger, independent cohort of AA and CA tumors validated 4 of the 27 (15%) most significantly altered regions from the initial analysis (3q26, 5p15-p14, 14q32, and 16p11). Functional annotation of overlapping genes within the 4 validated regions of AA/CA DNA copy number changes revealed significant enrichment of genes related to immune response.ConclusionsOur data reveal molecular alterations at the level of gene expression and DNA copy number that are specific to African American and Caucasian prostate cancer and may be related to underlying differences in immune response.
Introduction Intra-articular distal radius fractures with volar and dorsal comminution present a special challenge to the hand surgeon. Methods Ten patients formed the study cohort. All plates were low profile and stainless steel. Radiographic parameters, range of motion, and strength compared to the uninjured side were recorded. Functional outcome was evaluated by Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and Gartland and Werley scoring system. Results Median age at surgery was 58 years (range, 24 to 86). Mean follow-up was 17 months (range, 12 to 28). According to the AO classification system, there were three type C2 and seven type C3 fractures. Median preoperative dorsal angulation was 24 deg; median postoperative dorsal angulation was 3 deg. Eighty percent (8) of the fractures also had an intra-articular step-off or gap, all of which were corrected to neutral by the procedure. Compared with the contralateral side, mean extension and flexion were 73 and 75%, respectively, pronation and supination were 95 and 88%, respectively, and grip strength and thumb pinch were 72 and 87%, respectively. Mean postoperative DASH score was 16 points, and 70% (7) of the patients had Gartland and Werley scores of good or excellent. None of the patients needed to have their plates removed, and no extensor tendon rupture was reported. Conclusions The "sandwich" plating technique is an effective method of regaining near-anatomic reconstruction of intra-articular, volarly and dorsally comminuted distal radius fractures. Results from this study demonstrate that patients can expect to regain about 80% of their range of motion and strength. Moreover, 70% of the patients will have good to excellent functional outcomes. This is the first study to examine range of motion and functional outcome of low-profile "sandwich" plating without plate removal.
Objective-The role of socioeconomic factors in the worse outcome of black men with prostate cancer remains unclear. To determine if socioeconomic factors affect prostate cancer outcomes, we studied a cohort of only black patients to minimize known confounding factors Methods-Black men treated with radical prostatectomy at New York Veterans Administration Medical Center and Memorial Sloan-Kettering Cancer Center between 1990 and 2005 were studied. A centralized pathology review process determined the Gleason score of all cases. PSA recurrence at both sites was defined as PSA ≥ 0.2 with a confirmatory rise. By matching patients' home zip codes to the U.S. Census Bureau database, corresponding socioeconomic data regarding median household income (income) and percentage of population having graduated from high school (education) was obtained. Income, education, clinical and pathological parameters were analyzed for the whole cohort.Results-430 black patients were studied. They resided in neighborhoods where median household income was $41,498.10 and mean percentage of high school graduates was 73.4%. Eighty-eight (20.9%) patients had PSA recurrence. Median follow-up for survivors was 37 months. Neither income nor education evaluated as continuous or categorical variables were predictors of PSA recurrence. When evaluated as composite categorical variable, the combination of greater income and education did not predict disease free survival.Conclusions-Data suggest that socioeconomic factors have limited impact on PSA recurrence in black men treated with radical prostatectomy. Thus, biologic factors might play a role in the poor outcomes in this population.
Primitive neuroectodermal tumor (PNET) is a pathologic diagnosis that encompasses several different tumor types, including central nervous system tumors and Ewing’s sarcomas. Teratoma, a common element of germ cell tumor (GCT), has the ability to transform to malignant PNET in a small number of patients. Making a definitive diagnosis of PNET is difficult given its deviation from elements of GCT and its non-specific pathologic findings. Establishing the diagnosis is crucial as PNETs respond poorly to standard platinum-based chemotherapy used for treatment of GCT. Primary treatment for PNET is surgical, though this is often not feasible in many patients due to extensive disease at diagnosis. As an alternative, chemotherapy regimens traditionally used for Ewing’s sarcoma, such as vincristine, doxorubicin and cyclophosphamide alternating with ifosfamide and etoposide, have shown limited efficacy in the neoadjuvant, adjuvant, and palliative settings. Future research should delineate the genetic underpinnings of PNET and develop therapeutic options accordingly.
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