Publications by authors named "Marcia Wills"

Mast cell sarcoma is a rare, aggressive neoplasm composed of cytologically malignant mast cells presenting as a solitary mass. Previous descriptions of mast cell sarcoma have been limited to single case reports, and the pathologic features of this entity are not well known. Here, we report three new cases of mast cell sarcoma and review previously reported cases.

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Mycophenolate mofetil (MMF) is an immunosuppressive medication utilized in the management of both autoimmune and solid organ transplant patients. Diarrhea is a common gastrointestinal side effect of MMF, but more severe forms of GI symptoms are described in renal transplant patients with a distinct pattern of histopathologic change, similar to graft-versus-host disease or Crohn's disease. This rare entity, commonly referred to as "MMF-related enterocolitis," has been described in adult patients, mostly in renal transplant patients, and in only two pediatric renal transplant patients.

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Adult-type sarcomas are, as the name indicates, rare tumors in the pediatric population. Although soft tissue sarcomas as a group are not uncommon diagnoses, nonrhabdomyosarcoma soft tissue sarcomas are much rarer and encompass a wide range of diagnoses. A few of these tumors are commonly found in the adult population and are thus referred to as adult-type sarcomas.

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A case of a very low birthweight premature infant with a clinical presentation of necrotising enterocolitis that was found to have malrotation and midgut volvulus at autopsy is presented.

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Mutational inactivation of the RB1 tumor suppressor gene initiates retinoblastoma and other human cancers. RB1 protein (pRb) restrains cell proliferation by binding E2f transcription factors and repressing the expression of cell cycle target genes. It is presumed that loss of pRb/E2f interaction accounts for tumor initiation, but this has not been directly tested.

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Introduction: Human tails and pseudotails are rare sacrococcygeal lesions that are associated with a wide variety of anomalies and syndromes. Anorectal malformations are also relatively uncommon congenital defects that often occur in conjunction with syndromes or other congenital abnormalities. The anomalies associated with both disorders determine the timing and approach to surgical correction.

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Purpose: Whole mount processing is more resource intensive than routine systematic sampling of radical retropubic prostatectomy specimens. We compared whole mount and systematic sampling for detecting pathological outcomes, and compared the prognostic value of pathological findings across pathological methods.

Materials And Methods: We included men (608 whole mount and 525 systematic sampling samples) with no prior treatment who underwent radical retropubic prostatectomy at Vanderbilt University Medical Center between January 2000 and June 2008.

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Purpose: To evaluate whether selected high-risk matrix metalloproteinase-7 single nucleotide polymorphisms influence clinicopathologic outcomes in patients with early-stage prostate cancer.

Methods And Materials: Two hundred twelve prostate cancer patients treated with radical prostatectomy were evaluated with a median follow-up of 9.8 years.

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We report the identification and characterization of three Staphylococcus aureus isolates recovered from throat and vaginal cultures, as well as from an axillary abscess, of a 17-year-old female who died of tampon-related toxic shock syndrome. The three S. aureus isolates were unrelated as determined by pulsed-field gel electrophoresis.

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Purpose: Prognostic biomarkers are needed to optimize treatment decisions for prostate cancer. Single nucleotide polymorphisms participate in the individual genetic background modulating risk and clinical outcomes of cancer. We tested whether EGFR polymorphisms are associated with prostate cancer clinical outcomes.

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Background: Hepsin is a cell surface protease that is over-expressed in more than 90% of human prostate cancer cases. The previously developed Probasin-hepsin/Large Probasin-T antigen (PB-hepsin/LPB-Tag) bigenic mouse model of prostate cancer demonstrates that hepsin promotes primary tumors that are a mixture of adenocarcinoma and neuroendocrine (NE) lesions, and metastases that are NE in nature. However, since the majority of human prostate tumors are adenocarcinomas, the contribution of hepsin in the progression of adenocarcinoma requires further investigation.

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Purpose: Bladder fibrosis is an undesired end point of partial bladder outlet obstruction. In fibrotic disease of the lung, kidney, skin and heart chemokines recruit bone marrow derived cells to injured tissue. Blockade of chemokines like CCL2 results in decreased fibrosis in other organs.

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Purpose: Transforming growth factor-beta is a potent stimulator of extracellular matrix production. Several studies show that loss of transforming growth factor-beta signaling decreases kidney, liver and lung fibrosis. However, the role of transforming growth factor-beta signaling in bladder fibrosis is not entirely understood.

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Extraadrenal pheochromocytomas and paragangliomas are rare entities within the pediatric population. We report the presentation of three synchronous extra-adrenal abdominal paragangliomas in an adolescent boy who carries a germline mutation in the succinate dehydrogenase B (SDHB) gene. Loss of heterozygosity of this allele was demonstrated by direct sequencing of DNA from two of his tumors, confirming loss of tumor suppressor function in the pathogenesis of these paragangliomas.

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Objectives: Mouse double-minute 2 (MDM2) SNP309 polymorphism (T>G) has been correlated with an increased risk of cancer in multiple tumor types. MDM2 overexpression has shown to be weakly associated with distant tumor metastases, and down-regulation of MDM2 via antisense oligonucleotides in vitro has resulted in the radiosensitization of prostate cancer cell lines. Based on these results, we decided to evaluate the role of MDM2 SNP309 in the context of histopathologic parameters and clinical outcomes in prostate cancer tumors.

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Background: The role of Wnt/beta-Catenin signaling in embryogenesis and carcinogenesis has been extensively studied in organs such as colon, lung and pancreas, but little is known about Wnt/beta-Catenin signaling in the prostate. Although stabilizing mutations in APC and beta-Catenin are rare in primary prostate tumors, recent studies suggest that cytoplasmic/nuclear beta-Catenin is associated with advanced, metastatic, hormone-refractory prostate carcinoma.

Methods: To better understand the role of beta-Catenin in prostatic development and carcinogenesis, we studied Wnt expression during prostate development and activated Wnt/beta-Catenin signaling in the developing and adult prostate.

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Purpose: Identifying developmental proteins could lead to markers of bladder progenitor cells, which could be used to investigate bladder diseases. We recently reported a novel embryonic stem cell model in which to study differential protein expression patterns during bladder development. Differential and temporal expressions of the endodermal proteins known as forkhead box (Foxa1 and Foxa2) were observed.

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Purpose: We have previously reported that embryonic rat bladder mesenchyma has the appropriate inductive signals to direct pluripotent mouse embryonic stem cells toward endodermal derived urothelium and develop mature bladder tissue. We determined whether nonembryonic stem cells, specifically bone marrow derived mesenchymal stem cells, could serve as a source of pluripotent or multipotent progenitor cells.

Materials And Methods: Epithelium was separated from the mesenchymal shells of embryonic day 14 rat bladders.

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p57(Kip2) has been considered a candidate tumor suppressor gene because of its location in the genome, biochemical activities, and imprinting status. However, little is known about the role of p57(Kip2) in tumorigenesis and cancer progression. Here, we show that the expression of p57(Kip2) is significantly decreased in human prostate cancer, and the overexpression of p57(Kip2) in prostate cancer cells significantly suppressed cell proliferation and reduced invasive ability.

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Background: Neuroendocrine (NE) prostate cancer develops as an aggressive disease that does not respond to androgen ablation therapy. It has been demonstrated that the paracrine action of NE cells facilitates the progression of androgen dependent adenocarcinoma to an androgen independent state, suggesting a significant role for NE cells during failure of androgen ablation therapy.

Methods: To investigate the pathways that are involved in NE differentiation of prostate cancer, we have looked at the expression of genes known to be involved in endocrine differentiation of beta-cells in the pancreas.

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HSV causes serious complications in immunocompromised patients, especially SCT recipients. Although ACV is an effective antiviral prophylaxis, the emergence of ACV resistance is a growing problem. The authors describe two cases of fatal ACV-resistant HSV in two pediatric patients following unrelated donor SCT.

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Wilms' tumors, or nephroblastomas, are thought to arise from abnormal postnatal retention and dysregulated differentiation of nephrogenic progenitor cells that originate as a condensed metanephric mesenchyme within embryonic kidneys. We have previously shown that the transcriptional regulator CITED1 (CBP/p300-interacting transactivators with glutamic acid [E]/aspartic acid [D]-rich C-terminal domain) is expressed exclusively in these nephrogenic progenitor cells and is downregulated as they differentiate to form nephronic epithelia. In the current study, we show that CITED1 expression persists in blastemal cell populations of both experimental rat nephroblastomas and human Wilms' tumors, and that primary human Wilms' tumors presenting with disseminated disease show the highest level of CITED1 expression.

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Purpose: We examined the role of transforming growth factor-beta in urothelial and bladder development. Transforming growth factor-beta signaling was attenuated in the urothelial compartment and the subsequent effects were examined in a tissue recombination model.

Materials And Methods: Urothelium was cultured from adult rat bladders and transfected with control vector C7Delta or mutant DNIIR (dominant negative transforming growth factor-beta receptor II).

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