Gastric cancer with radiographically occult metastatic disease: Biology, challenges, and diagnostic approaches

Gastric adenocarcinoma is an aggressive cancer that demonstrates heterogeneous biology depending on patient ethnicity, tumor location, tumor type, and genetic profile. It remains the third leading cause of cancer deaths worldwide and was estimated to result in 782,000 deaths in 2018. Challenges exist in accurately assessing the disease burden, as available radiological staging often underestimates metastatic disease. This diagnostic handicap, along with the poor understanding of the heterogeneous biology of gastric cancer, has hindered the development of effective therapeutic solutions and thus halted improvement in patient outcomes over the last few decades. The management of occult peritoneal disease is complicated, as most patients are understaged by standard imaging studies and therefore thought to have local diseases. In this article, we systematically review recent literature on the limitations that are associated with standard radiographic staging, discuss recent molecular biology advances to better identify and diagnose occult peritoneal disease, and propose possible management strategies to approach this complicated clinical problem

Ral signaling pathway in health and cancer

The Ral (Ras-Like) signaling pathway plays an important role in the biology of cells. A plethora of effects is regulated by this signaling pathway and its prooncogenic effectors. Our team has demonstrated the overactivation of the RalA signaling pathway in a number of human malignancies including cancers of the liver, ovary, lung, brain, and malignant peripheral nerve sheath tumors. Additionally, we have shown that the activation of RalA in cancer stem cells is higher in comparison with differentiated cancer cells. In this article, we review the role of Ral signaling in health and disease with a focus on the role of this multifunctional protein in the generation of therapies for cancer. An improved understanding of this pathway can lead to development of a novel class of anticancer therapies that functions on the basis of intervention with RalA or its downstream effectors

Gastric Cancer with Radiographically Occult Metastatic Disease: Biology, Challenges, and Diagnostic Approaches

Gastric adenocarcinoma is an aggressive cancer that demonstrates heterogeneous biology depending on patient ethnicity, tumor location, tumor type, and genetic profile. It remains the third leading cause of cancer deaths worldwide and was estimated to result in 782,000 deaths in 2018. Challenges exist in accurately assessing the disease burden, as available radiological staging often underestimates metastatic disease. This diagnostic handicap, along with the poor understanding of the heterogeneous biology of gastric cancer, has hindered the development of effective therapeutic solutions and thus halted improvement in patient outcomes over the last few decades. The management of occult peritoneal disease is complicated, as most patients are understaged by standard imaging studies and therefore thought to have local diseases. In this article, we systematically review recent literature on the limitations that are associated with standard radiographic staging, discuss recent molecular biology advances to better identify and diagnose occult peritoneal disease, and propose possible management strategies to approach this complicated clinical problem

The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection