An Uncommon Presentation of Carcinosarcoma of the Stomach and a Minimally Invasive Approach for Treatment.

Carcinosarcoma is a rare malignant neoplasm that is composed of both epithelial and mesenchymal tumor components. Gastric carcinosarcoma is even more rare and is often diagnosed at a late stage. In this report, we investigate a case of early gastric carcinosarcoma with regional lymph node metastasis in a 78-year-old woman. The patient underwent partial gastrectomy, lymphadenectomy, and splenectomy. The tumor was confined to the gastric submucosa, and a biopsy specimen led to a histological diagnosis of carcinosarcoma with adenocarcinoma, squamous-cell carcinoma, and undifferentiated pleomorphic sarcoma components. Metastasis was present in one lymph node and displayed osteosarcomatous differentiation. Vigilant monitoring for recurrence and metastatic disease will be required for this patient.

Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy.

Overexpression of the B7-H1 (PD-L1) molecule in the tumor microenvironment (TME) is a major immune evasion mechanism in some patients with cancer, and antibody blockade of the B7-H1/PD-1 interaction can normalize compromised immunity without excessive side-effects. Using a genome-scale T cell activity array, we identified Siglec-15 as a critical immune suppressor. While only expressed on some myeloid cells normally, Siglec-15 is broadly upregulated on human cancer cells and tumor-infiltrating myeloid cells, and its expression is mutually exclusive to B7-H1, partially due to its induction by macrophage colony-stimulating factor and downregulation by IFN-γ. We demonstrate that Siglec-15 suppresses antigen-specific T cell responses in vitro and in vivo. Genetic ablation or antibody blockade of Siglec-15 amplifies anti-tumor immunity in the TME and inhibits tumor growth in some mouse models. Taken together, our results support Siglec-15 as a potential target for normalization cancer immunotherapy.

Hormone producing gynecological tumors: pathologic entities and clinical significance.

INTRODUCTION: Due to their derivation from the cell types involved in gynecologic hormonal networks, many gynecologic tumors may produce hormones. In a normal physiological setting, these hormones are essential for regulating the biology and function of gynecological organs, the ovary and uterus in particular. Overproduction of hormones by the tumor may lead to abnormal clinical manifestations of the patients and spillage of excess hormonal products into the blood. Abnormal elevation of serum hormones may be considered as biomarkers that are important to pathologists and clinicians in making precise tumor diagnoses and likely useful in monitoring the tumor burden/recurrence to guide patient treatment options. This review will discuss gynecologic neoplasms that produce hormonal biomarkers and assess their relevance to pathological diagnosis, evaluation for therapeutic response and monitoring disease progression. AREAS COVERED: Studies involving hormonal production by a gynecologic tumor were candidates for inclusion in this review. EXPERT COMMENTARY: Serum hormonal biomarkers have clinical utility both in the diagnosis of gynecologic neoplasms and clinical monitoring of treatment efficacy and recurrence.

Structural studies of the Nudix GDP-mannose hydrolase from E. coli reveals a new motif for mannose recognition.

The Nudix hydrolase superfamily, characterized by the presence of the signature sequence GX(5)EX(7)REUXEEXGU (where U is I, L, or V), is a well-studied family in which relations have been established between primary sequence and substrate specificity for many members. For example, enzymes that hydrolyze the diphosphate linkage of ADP-ribose are characterized by having a proline 15 amino acids C-terminal of the Nudix signature sequence. GDPMK is a Nudix enzyme that conserves this characteristic proline but uses GDP-mannose as the preferred substrate. By investigating the structure of the GDPMK alone, bound to magnesium, and bound to substrate, the structural basis for this divergent substrate specificity and a new rule was identified by which ADP-ribose pyrophosphatases can be distinguished from purine-DP-mannose pyrophosphatases from primary sequence alone. Kinetic and mutagenesis studies showed that GDPMK hydrolysis does not rely on a single glutamate as the catalytic base. Instead, catalysis is dependent on residues that coordinate the magnesium ions and residues that position the substrate properly for catalysis. GDPMK was thought to play a role in biofilm formation because of its upregulation in response to RcsC signaling; however, GDPMK knockout strains show no defect in their capacity of forming biofilms.