Utility of The Paris System for Reporting Urinary Cytology in patients with HPV-positive urinary tract carcinoma.

Background: Human papillomavirus (HPV)-positive urinary tract carcinomas (UTCas) have distinct morphology and molecular features with potential treatment implications. Cytomorphologic analysis of these tumors on urine cytology specimens has not yet been reported. The authors evaluated the cytomorphologic findings of HPV-positive UTCa on urine cytology using The Paris System for Reporting Urinary Cytology (TPS) criteria.

Primary Melanoma of the Urinary Bladder: Clinical, Histopathologic, and Comprehensive Molecular Analysis of a Rare Tumor.

Primary melanoma of the urinary bladder is extremely rare and generally has a poor prognosis. The histopathological diagnosis can be challenging as tumors can be unpigmented and of varying morphology. Here we report a rare example of primary urinary bladder melanoma with clinical, imaging, gross anatomical, histopathologic, immunohistochemical, and molecular findings to illustrate the utility of an integrated approach in establishing the diagnosis and guide therapy.

Clinicopathologic and Molecular Characterization of High-Risk Human Papillomavirus-Positive Carcinomas of the Urinary Tract.

Context.—: Human papillomavirus (HPV) is a well-known cause of squamous cell carcinomas of anogenital and oropharyngeal regions, where treatment strategies and prognosis depend on HPV status. The significance of HPV status in tumors arising along the urinary tract is not well established.

Intact Chorionic Vesicle in Very Early Products of Conception Specimens: Clinicopathologic Features of 26 Cases That May Mimic Complete Hydatidiform Mole.

Among the morphologic mimics of hydatidiform moles, the chorionic vesicle of early first-trimester pregnancy has received scant attention. The chorionic vesicle is the stage of the implanted blastocyst in which the cytotrophoblastic shell is circumferentially lined by primary and secondary villi and envelops the notochord stage embryo, yolk sac, and amniotic sac, ∼5 to 6 weeks since the last menstrual period. Miscarriage specimens at this early gestational age that contain an intact chorionic vesicle may be misinterpreted as a complete hydatidiform mole because of its large size, cistern-like cavity, and circumferentially radiating villi and trophoblast, particularly so when embryonic tissue is absent.

CpG Oligonucleotides as Vaccine Adjuvants.

CpG Oligonucleotides (ODN) are immunomodulatory synthetic oligonucleotides specifically designed to stimulate Toll-like receptor 9. TLR9 is expressed on human plasmacytoid dendritic cells and B cells and triggers an innate immune response characterized by the production of Th1 and pro-inflammatory cytokines. This chapter reviews recent progress in understanding the mechanism of action of CpG ODN and provides an overview of human clinical trial results using CpG ODN to improve vaccines for the prevention/treatment of cancer, allergy, and infectious disease.

PAM3 protects against DSS-induced colitis by altering the M2:M1 ratio.

Inflammation of the gastrointestinal tract contributes to the development of inflammatory bowel disease (IBD). Human IBD is modeled by administering dextran sulfate sodium (DSS) to mice. In humans and mice, inflammatory M1 macrophages contribute to the progression of IBD whereas immunosuppressive M2 macrophages protect against colitis.

Critical Role of B Cells in Toll-Like Receptor 7-Mediated Protection against Listeria monocytogenes Infection.

Toll-like receptors (TLR) trigger the immune system to mount a rapid innate response capable of protecting the host from a wide variety of bacterial and viral pathogens. There is interest in harnessing TLR agonists to reduce the susceptibility of at-risk populations to infection. However, the widespread prophylactic use of TLR agonists has been compromised by the need to administer them by parenteral injection.

PAM3 supports the generation of M2-like macrophages from lupus patient monocytes and improves disease outcome in murine lupus.

Systematic Lupus Erythematosus (SLE) is an autoimmune syndrome of unclear etiology. While T and B cell abnormalities contribute to disease pathogenesis, recent work suggests that inflammatory M1-like macrophages also play a role. Previous work showed that the TLR2/1 agonist PAM3CSK4 (PAM3) could stimulate normal human monocytes to preferentially differentiate into immunosuppressive M2-like rather than inflammatory M1-like macrophages.

Clofarabine inhibits Ewing sarcoma growth through a novel molecular mechanism involving direct binding to CD99.

Ewing sarcoma (ES) is an aggressive bone and soft tissue malignancy that predominantly affects children and adolescents. CD99 is a cell surface protein that is highly expressed on ES cells and is required to maintain their malignancy. We screened small molecule libraries for binding to extracellular domain of recombinant CD99 and subsequent inhibition of ES cell growth.

Effect of Calcium Carbonate Encapsulation on the Activity of Orally Administered CpG Oligonucleotides.

Synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODNs) stimulate immune cells via Toll-like receptor 9 (TLR9). Because oligodeoxynucleotides (ODNs) are susceptible to gastric degradation, clinical trials designed to evaluate their therapeutic utility have relied solely on parenteral routes of administration. A strategy to improve the activity of orally delivered ODNs by reducing their susceptibility to gastrointestinal (GI) digestion via encapsulation in calcium carbonate nanoparticles (ODNcaps) was recently described.