A Rare Case of Clival Metastasis in a Patient with Gastric Cancer

We report a rare case of clival metastasis from gastric cancer. A 73-year-old man with advanced gastric cancer treated with nivolumab as a third-line chemotherapy experienced headache, tongue deviation, and difficulties in speaking clearly. We suspected stroke or brain metastasis, but brain contrast-enhanced magnetic resonance imaging demonstrated a clival mass, diagnosed as clival metastasis from gastric cancer. The tumor could not be identified by plain computed tomography and plain magnetic resonance imaging alone. He received palliative radiotherapy (30 Gy/10 fr); his symptoms improved gradually. Although metastasis from gastric cancer to other organs is common, bone metastases are rare.     

Granulomatous lobular mastitis: difficulty of diagnosis

We report a case of a rare inflammatory disease, granulomatous lobular mastitis. Two weeks prior to admission the patient, a 43 year-old woman, (gravida 1, para 1) had noticed a left breast mass associated with tenderness. Palpation, gross inspection, and clinical examination, as well as the rapid growth of the mass lesion led us to believe that it was highly suspicious of malignant neoplasm. Mammography, ultrasonography, and computed tomography did not differentiate it from a malignant neoplasm. Aspiration cytology revealed an inflammatory lesion with a few clusters of epithelial cells it was diagnosed as borderline malignancy(class III) by a prudent pathologist, and thus mastectomy was performed. However, the final histologi-cal diagnosis was granulomatous lobular mastitis with no evidence of malignancy. As the clinical manifestations of granulomatous mastitis are similar to those of mammary carcinoma and, as it is an inflammatory lesion of uncertain etiology and pathogenesis, it has often been mistaken clinically for carcinoma and treated as such. Our review of the literature indicated that granulomatous mastitis most often occurs in young patients with a history of childbirth or oral contraceptive usage. Recurrence was documented in 38% of patients, and, accordingly long-term follow-up by aspiration cytology, complete resection, and adequate drug treatment with corticosteroids are recommended. Received: January 6, 1999 / Accepted: September 22, 1999     

Activated cAMP receptors switch encystation into sporulation

Metazoan embryogenesis is controlled by a limited number of signaling modules that are used repetitively at successive developmental stages. The development of social amoebas shows similar reiterated use of cAMP-mediated signaling. In the model Dictyostelium discoideum, secreted cAMP acting on 4 cAMP receptors (cARs1-4) coordinates cell movement during aggregation and fruiting body formation, and induces the expression of aggregation and sporulation genes at consecutive developmental stages. To identify hierarchy in the multiple roles of cAMP, we investigated cAR heterogeneity and function across the social amoeba phylogeny. The gene duplications that yielded cARs 2-4 occurred late in evolution. Many species have only a cAR1 ortholog that duplicated independently in the Polysphondylids and Acytostelids. Disruption of both cAR genes of Polysphondylium pallidum (Ppal) did not affect aggregation, but caused complete collapse of fruiting body morphogenesis. The stunted structures contained disorganized stalk cells, which supported a mass of cysts instead of spores; cAMP triggered spore gene expression in Ppal, but not in the cAR null mutant, explaining its sporulation defect. Encystation is the survival strategy of solitary amoebas, and lower taxa, like Ppal, can still encyst as single cells. Recent findings showed that intracellular cAMP accumulation suffices to trigger encystation, whereas it is a complementary requirement for sporulation. Combined, the data suggest that cAMP signaling in social amoebas evolved from cAMP-mediated encystation in solitary amoebas; cAMP secretion in aggregates prompted the starving cells to form spores and not cysts, and additionally organized fruiting body morphogenesis. cAMP-mediated aggregation was the most recent innovation.     

Simplified Preparation of αvβ3 Integrin-Targeted Microbubbles Based on a Clinically Available Ultrasound Contrast Agent: Validation in a Tumor-Bearing Mouse Model

The usefulness of ultrasound molecular imaging with α_vβ₃ integrin-targeted microbubbles for detecting tumor angiogenesis has been demonstrated. Recently, we developed α_vβ₃ integrin-targeted microbubbles by modifying clinically available microbubbles (Sonazoid, Daiichi-Sankyo Pharmaceuticals, Tokyo, Japan) with a secreted glycoprotein (lactadherin). The aims of our present study were to simplify the preparation of lactadherin-bearing Sonazoid and to examine the diagnostic utility of lactadherin-bearing Sonazoid for α_vβ₃ integrin-expressing tumor vessels by using SK-OV-3-tumor–bearing mice. By incubating 1.2?×?10⁷ Sonazoid microbubbles with 1.0?µg lactadherin, the complicated washing and centrifugation steps during the microbubble preparation could be omitted with no significant reduction in labeling ratio of lactadherin-bearing Sonazoid. In addition, the number of Sonazoid microbubbles accumulated in the SK-OV-3 tumor was significantly increased by modifying Sonazoid with lactadherin. Our data suggest that the lactadherin-bearing Sonazoid is an easily prepared and potentially clinically translatable targeted microbubble for α_vβ₃ integrin-expressing vessels.     

Immunomodulatory effects of phosphorylated dextrin in mouse spleen cell cultures

Corn dextrin preparations with average degradation degrees of 16.7 and 167, or average molecular masses of 2,700 and 27,000, were covalently introduced with 4.5 and 11.2 to 35.4 mol of phosphoric acid, respectively, per mole by dry-heating at 110 to 140 degrees C for 24 h with sodium phosphate, and their effects on cell proliferation and production of immunoglobulin A (IgA) were investigated in C3H/HeN mouse spleen cell cultures. All the phosphorylated dextrin had mitogenic effects and stimulated proliferative responses induced by lipopolysaccharide (LPS) and concanavalin A (ConA). The phosphorylated dextrin with an average degradation degree of 16.7 was divided into 3 fractions, which had 3.6, 4.0 and 6.5 mol of phosphoric acid per mole when the molecular mass of each dextrin was postulated to be 2,700. LPS-induced proliferation was greatest with the preparation having 3.6 mol of phosphoric acid per mole of dextrin, whereas ConA-induced proliferation was strongest with 6.5 mol of phosphoric acid. On the other hand, the divided dextrin enhanced production of IgA by approximately 1.2-, 2.0- and 2.2-fold in accordance with the increasing amount of phosphoric acid. These results indicate that phosphorylated dextrin stimulates humoral immune responses in mouse spleen cell cultures.