Long-term Kidney Transplantation Outcomes Network (APOLLO): Design and Rationale.

Introduction: Much of the higher risk for end-stage kidney disease (ESKD) in African American individuals relates to ancestry-specific variation in the apolipoprotein L1 gene (). Relative to kidneys from European American deceased-donors, kidneys from African American deceased-donors have shorter allograft survival and African American living-kidney donors more often develop ESKD. The National Institutes of Health (NIH)-sponsored Long-term Kidney Transplantation Outcomes Network (APOLLO) is prospectively assessing kidney allograft survival from donors with recent African ancestry based on donor and recipient genotypes.

Donor-derived myeloid sarcoma in two kidney transplant recipients from a single donor.

We report the rare occurrence of donor-derived myeloid sarcoma in two kidney transplant patients who received organs from a single deceased donor. There was no evidence of preexisting hematologic malignancy in the donor at the time of organ recovery. Both recipients developed leukemic involvement that appeared to be limited to the transplanted organ.

Genetic markers associated with early cancer-specific mortality following prostatectomy.

Background: This study sought to identify novel effectors and markers of localized but potentially life-threatening prostate cancer (PCa), by evaluating chromosomal copy number alterations (CNAs) in tumors from patients who underwent prostatectomy and correlating these with clinicopathologic features and outcome.

Methods: CNAs in tumor DNA samples from 125 patients in the discovery cohort who underwent prostatectomy were assayed with high-resolution Affymetrix 6.0 single-nucleotide polymorphism microarrays and then analyzed using the Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm.

CBFB and MYH11 in inv(16)(p13q22) of acute myeloid leukemia displaying close spatial proximity in interphase nuclei of human hematopoietic stem cells.

To gain a better understanding of the mechanism of chromosomal translocations in cancer, we investigated the spatial proximity between CBFB and MYH11 genes involved in inv(16)(p13q22) found in patients with acute myeloid leukemia. Previous studies have demonstrated a role for spatial genome organization in the formation of tumorigenic abnormalities. The nonrandom localization of chromosomes and, more specifically, of genes appears to play a role in the mechanism of chromosomal translocations.

p53-Dependent anticancer effects of leptomycin B on lung adenocarcinoma.

Purpose: Leptomycin B (LMB) and/or its derivatives are considered a novel class of cancer therapeutics through blocking chromosome maintenance region 1, which mediates p53 nuclear export. The objectives of the present study were to first evaluate the cytotoxic effects of LMB on a normal human lung epithelial cell line (BEAS-2B) and three human lung adenocarcinoma cell lines with various p53 status (wild type: A549, mutant: NCI-H522, and null: NCI-H358) and then to identify LMB-induced gene expression alterations in human p53 signaling pathway.

Methods: Cells were treated with 0.

Sonographic findings in trisomy 9.

Objective: The purpose of this study was to identify the most common prenatal sonographic findings in fetuses with complete trisomy 9.

Methods: A retrospective review of all cases of trisomy 9 at 5 participating institutions over a 15-year interval was conducted. Indications for referral and sonographic findings in each case were reviewed to identify characteristic fetal structural anomalies.

Ultrasound findings in trisomy 22.

We sought to identify the characteristic sonographic findings of fetal trisomy 22 by performing a retrospective review of nine cases of fetal trisomy 22. All cases of chromosomal mosaicism were excluded, as were first-trimester losses. Indications for sonography, gestational age, and sonographically detected fetal anomalies were analyzed.

X-linked chronic granulomatous disease secondary to skewed X chromosome inactivation in a female with a novel CYBB mutation and late presentation.

Chronic granulomatous disease (CGD) is characterized by defects in the superoxide producing enzyme NADPH oxidase causing phagocytes to improperly clear invading pathogens. Here we report findings of a late presenting 16-year-old female with X-linked CGD. The patient presented with community-acquired pneumonia, but symptoms persisted for 2 weeks during triple antimicrobial coverage.

Rapid group B streptococci screening using a real-time polymerase chain reaction assay.

Objective: To estimate the clinical performance characteristics of a real-time polymerase chain reaction (PCR) assay using vaginal/rectal swabs from antepartum (35-37 weeks of gestation) and intrapartum women.

Methods: The assay evaluated is a qualitative, automated, real-time PCR test for the detection of group B streptococci, with results available in approximately 75 minutes. Enrollment in this multicenter clinical study occurred between October 2005 and January 2006.

Deletion of a small consensus region at 6q15, including the MAP3K7 gene, is significantly associated with high-grade prostate cancers.

Purpose: Chromosome 6q14-21 is commonly deleted in prostate cancers, occurring in approximately 22% of all tumors and approximately 40% of metastatic tumors. However, candidate prostate tumor suppressor genes in this region have not been identified, in part due to the large and broad nature of the deleted region implicated in previous studies.

Experimental Design: We first used high-resolution Affymetrix single nucleotide polymorphism arrays to examine DNA from malignant and matched nonmalignant cells from 55 prostate cancer patients.

Recurring translocation (10;17) and deletion (14q) in clear cell sarcoma of the kidney.

Context: Clear cell sarcoma of the kidney (CCSK) is a prognostically unfavorable renal neoplasm of childhood. Previous cytogenetic studies of CCSK have reported balanced translocations t(10;17)(q22;p13) and t(10;17)(q11;p12). Although the tumor suppressor gene p53 is located at the chromosome 17p13 breakpoint, p53 abnormalities are rarely present in these tumors.

Fas-associating death domain protein overexpression induces apoptosis in lung cancer cells.

Objectives: Non-small cell lung cancers commonly develop resistance to radiation and chemotherapy, and they often present at stages beyond surgical resectability. Because current treatment modalities are inadequate, novel therapies are necessary to reduce the effects of the increasing incidence in pulmonary neoplasms. Fas-associating death domain protein is a central mediator of death receptor-initiated apoptosis that directly activates the caspase-8 protease.

Depletion of Bcl-2 by an antisense oligonucleotide induces apoptosis accompanied by oxidation and externalization of phosphatidylserine in NCI-H226 lung carcinoma cells.

Oxidant-induced apoptosis involves oxidation of many different and essential molecules including phospholipids. As a result of this non-specific oxidation, any signaling role of a particular phospholipid-class of molecules is difficult to elucidate. To determine whether preferential oxidation of phosphatidylserine (PS) is an early event in apoptotic signaling related to PS externalization and is independent of direct oxidant exposure, we chose a genetic-based induction of apoptosis.

In vivo expression of p53 and Bcl-2 and their role in programmed cell death in premalignant and malignant lung lesions.

Forty-four specimens of non-malignant and malignant human lung tissue, taken from patients with non-small cell lung cancer (NSCLC), were examined for the expression of wild-type p53, mutant p53, and bcl-2 and the occurrence of programmed cell death (apoptosis). Wild-type p53 expression peaked in peritumoral and metaplastic samples, whereas mutant p53, bcl-2 and apoptosis were first detected in metaplasia and increased with progression to carcinoma. Bcl-2 positive samples had lower levels of apoptosis than bcl-2 negative samples and was independent of wild-type or mutant p53 expression.