Primary Signet Ring Cell Carcinoma of the Duodenum: Case Report

Introduction: Primary carcinoma of the duodenum is an infrequent malignancy; it represents 0.3-0.5% of all carcinomas of the GI tract and 33-45% of all carcinomas of the small intestine. Clinical case: A 57-year-old female patient with nonspecific GI symptoms and unintentional weight loss was diagnosed with diffuse, infiltrating, and ulcerated adenocarcinoma in the duodenum. Surgical management with duodenopancreatectomy was considered; however, it could not be performed due to deteriorating nutritional status. She later died due to abdominal sepsis. Conclusion: The clinical manifestations of adenocarcinoma of the duodenum are variable and nonspecific. It is a challenge to make an early diagnosis. We recommend considering the diagnostic possibility in patients with nausea, emesis, abdominal pain, and weight loss, which requires esophagogastroduodenoscopy and histological and immunohistochemical confirmation.

Introducción: el carcinoma primario de duodeno es una neoplasia maligna infrecuente; representa el 0,3%-0,5% de todos los carcinomas del tracto gastrointestinal y el 33%-45% de todos los carcinomas de intestino delgado. Caso clínico: paciente de sexo femenino de 57 años, con sintomatología gastrointestinal inespecífica y pérdida de peso no intencional a quien se le diagnosticó un adenocarcinoma difuso, infiltrante y ulcerado en el duodeno. Se planteó el manejo quirúrgico con duodenopancreatectomía; sin embargo, no pudo realizarse debido al deterioro del estado nutricional y posteriormente falleció como consecuencia de una sepsis abdominal. Conclusión: las manifestaciones clínicas del adenocarcinoma de duodeno son variables e inespecíficas, es un reto realizar un diagnóstico precoz. Se recomienda considerar la posibilidad diagnóstica en pacientes con síntomas de náuseas, emesis, dolor abdominal y pérdida de peso, que requiere la realización de esofagogastroduodenoscopia y confirmación histológica e inmunohistoquímica.

Collagen I provides a survival advantage to MD-1483 head and neck squamous cell carcinoma cells through phosphoinositol 3-kinase signaling.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) has a 50% relapse rate. The tumor microenvironment has been linked to resistance of cancer cells to chemotherapy. We hypothesized that the tumor matrix proteins collagen and fibronectin play protective roles in HNSCC. MATERIALS AND METHODS: We investigated the effects of collagen I, collagen IV and fibronectin on growth, 2-D and 3-D clonogenic potential, resistance to paclitaxel, apoptosis and activation of phosphoinositol-3 kinase (PI3K) in MD-1483 HNSCC cells. RESULTS: Collagen I, collagen IV and fibronectin specifically increased the efficiency of 2-D colony formation through binding integrins α2ß1 and α5ß1, respectively, and provided resistance to paclitaxel-induced colony elimination and apoptosis. Collagen I, but not fibronectin, increased the efficiency of 3-D colony formation and induced resistance to paclitaxel. Activation of protein kinase-B by collagen I was necessary for the protective effect. CONCLUSION: These data support the potential contribution of fibronectin and collagen to chemotherapy resistance in HNSCC, with effects of collagen mediated by PI3K.

Dual FGF-2 and intergrin alpha5beta1 signaling mediate GRAF-induced RhoA inactivation in a model of breast cancer dormancy.

Interactions with the bone marrow stroma regulate dormancy and survival of breast cancer micrometastases. In an in vitro model of dormancy in the bone marrow, we previously demonstrated that estrogen-dependent breast cancer cells are partially re-differentiated by FGF-2, re-express integrin alpha5beta1 lost with malignant transformation and acquire an activated PI3K/Akt pathway. Ligation of integrin alpha5beta1 by fibronectin and activation of the PI3K pathway both contribute to survival of these dormant cells. Here, we investigated mechanisms responsible for the dormant phenotype. Experiments demonstrate that integrin alpha5beta1 controls de novo cytoskeletal rearrangements, cell spreading, focal adhesion kinase rearrangement to the cell perimeter and recruitment of a RhoA GAP known as GRAF. This results in the inactivation of RhoA, an effect which is necessary for the stabilization of cortical actin. Experiments also demonstrate that activation of the PI3K pathway by FGF-2 is independent of integrin alpha5beta1 and is also required for cortical actin reorganization, GRAF membrane relocalization and RhoA inactivation. These data suggest that GRAF-mediated RhoA inactivation and consequent phenotypic changes of dormancy depend on dual signaling by FGF-2-initiated PI3K activation and through ligation of integrin alpha5beta1 by fibronectin.

Expression of FGF-2 alters focal adhesion dynamics in migration-restricted MDA-MB-231 breast cancer cells.

Basic fibroblast growth factor (FGF-2) expression takes place during morphogenic differentiation of mammary ducts and is lost in breast cancer. Forced re-expression of FGF-2 in breast cancer cell lines induces a more differentiated phenotype and inhibits motility by unknown mechanisms. Here we demonstrate that MDA-MB-231 cells with encumbered motility due to forced re-expression of FGF-2 have activated focal complexes as determined by immunoprecipitation/western blotting and immunofluorescence staining with antibodies to FAK, p130Cas, paxillin, vinculin and phosphotyrosine. The activation of the focal adhesion complexes results in loss of stress fibers associated with malignant transformation of mammary epithelial cells and the formation of circumferentially-distributed actin bundles associated with non-transformed mammary epithelial cells. These effects require continuous FGF-2 expression, as the effects of exogenous recombinant FGF-2 are only small and transient. FGF-2 expression results in an increase in integrin alpha 3 expression and decreases in integrin beta 1 and beta 4 expression. These changes, however, induce only a small decrease in adhesion to uncoated and fibronectin-coated tissue culture dishes suggesting that the primary cause of impaired motility is due to intrinsic signaling. These data suggest that FGF-2-inhibits motility in breast cancer cells by stabilization of focal complexes and induction of a more differentiated phenotype with disruption of stress fiber formation and a characteristic cortical actin distribution.

A phenotype-sensitizing Apoe-deficient genetic background reveals novel atherosclerosis predisposition loci in the mouse.

Therapeutic intervention for atherosclerosis has predominantly concentrated on regulating cholesterol levels; however, these therapeutics are not efficacious for all patients, suggesting that other factors are involved. This study was initiated to identify mechanisms that regulate atherosclerosis predisposition in mice other than cholesterol level regulation. To do so we performed quantitative trait locus analysis using two inbred strains that each carry the atherosclerosis phenotype-sensitizing Apoe deficiency and that have been shown to have widely disparate predilection to atherosclerotic lesion formation. One highly significant locus on chromosome 10 (LOD = 7.8) accounted for 19% of the variance in lesion area independent of cholesterol. Two additional suggestive loci were identified on chromosomes 14 (LOD = 3.2) and 19 (LOD = 3.2), each accounting for 7-8% of the lesion variance. In all, five statistically significant and suggestive loci affecting lesion size but not lipoprotein levels were identified. Many of these were recapitulated in an independent confirmatory cross. In summary, two independently performed crosses between C57BL/6 and FVB/N Apoe-deficient mice have revealed several previously unreported atherosclerosis susceptibility loci that are distinct from loci linked to lipoprotein levels.