Differential and Overlapping Pattern of Foxp1 and Foxp2 Expression in the Striatum of Adult Mouse Brain.

Genetic mutations of FOXP1 and FOXP2 are associated with neurodevelopmental diseases. It is important to characterize the cell types that express Foxp1 and Foxp2 in the brain. Foxp1 and Foxp2 are expressed at high levels in the striatum of mouse brains. There are two populations of striatal projection neurons (SPNs), dopamine D1 receptor (D1R)-expressing striatonigral neurons and D2 receptor (D2R)-expressing striatopallidal neurons. In addition to SPNs, there are different types of striatal interneurons. Here, we quantitatively analyze the expression pattern of Foxp1 and Foxp2 with respect to specific cell types of projection neurons and interneurons in the striatum of adult mouse brains. Double immunostaining and in situ hybridization showed that Foxp1 and Foxp2 were specifically expressed in SPNs, but not in interneurons. For Foxp1, 50-57% of Foxp1-positive neurons co-expressed D1R mRNA, and 45-52% of Foxp1-positive neurons co-expressed D2R mRNA in the striatum at rostrocaudal levels. For Foxp2, 65-77% of Foxp2-positive neurons co-expressed D1R mRNA, and 21-26% of Foxp2-positive neurons co-expressed D2R mRNA in the striatum at rostrocaudal levels. Neither Foxp1 nor Foxp2 was found to co-localize with parvalbumin, somatostatin, nNOS, calretinin and ChAT in interneurons of the striatum. Moreover, none of parvalbumin-, somatostatin-, nNOS-, and calretinin-positive interneurons co-expressed Foxp1 or Foxp2 in the cerebral cortex. As Foxp1 and Foxp2 can form heterodimers for transcriptional regulation, the differential and overlapping expression pattern of Foxp1 and Foxp2 in SPNs implicates coordinate and distinct roles of Foxp1 and Foxp2 in developmental construction and physiologic functions of striatal circuits in the brain.

Apolipoprotein C1 (APOC1) as a novel diagnostic and prognostic biomarker for lung cancer: A marker phase I trial.

BACKGROUND: Tumor cells continuously evolve over time in response to host pressures. However, explanations as to how tumor cells are influenced by the inflammatory tumor microenvironment over time are, to date, poorly defined. We hypothesized that prognostic biomarkers could be obtained by exploring the expression of inflammation-associated genes between early and late stage lung cancer tumor samples. METHODS: Candidate inflammation-associated genes, apolipoprotein C-1 (APOC1), MMP1, KMO)1, CXCL5, CXCL)7, IL-1α, IL-1ß, TNF-α and IL-6 were verified by real-time quantitative polymerase chain reaction. Gene expression profiles and immunofluorescence staining of 30 lung cancer tissues were compared. RESULTS: Expressions of APOC1 and IL-6 mRNA on tumor tissues in late stage disease were significantly higher than in early stage lung cancer samples. Immunofluorescence staining of tumor samples showed that the expression of APOC1 gradually increased from early to late stage in lung cancer patients. The expression levels of IL-6 and APOC1 in tumor samples were positively correlated; however, no prognostic value of APOC1 can be identified in serum samples. CONCLUSIONS: We found that the level of tumor APOC1 was highly expressed in late stage lung cancer. Further research is warranted to determine the molecular mechanisms underlying the cross talk of APOC1 and IL-6 in tumor progression. An expanded sample size marker phase II study may lead to the discovery of new lung cancer therapeutics targeting APOC1.

Recombinant heat shock protein 70 in combination with radiotherapy as a source of tumor antigens to improve dendritic cell immunotherapy.

Local radiotherapy (RT) plus intratumoral dendritic cell (DC) injection can mediate immunological response. We hypothesized that co-injection of exogenous recombinant heat shock protein 70 (rHsp70) in combination with RT-DC could be as effective as co-injection of HSP-peptide for evoking specific immune response. rHsp70-prostate-specific antigen (rHSP70C'-PSA) and α-fetoprotein (rHSP70C'-AFP) were used to compare specific response. Growth inhibition of the tumor and the systemic anti-tumor immune response were measured on CT26/PSA and CT26/AFP mice model. Intratumoral co-injection of rHsp70 and DC into the irradiated tumor site induced a more potent anti-tumor immune response than injection of DC alone. rHsp70 was as effective as rHsp70C'-PSA or rHsp70C'-AFP in inducing a tumor-specific cytotoxic T lymphocyte response or tumor growth delay. These results demonstrate that co-administration with rHsp70 and RT could be a simple and effective source of tumor antigens to achieve RT-DC immunotherapy protocol and easy to apply in clinical use.