FOXC2 Expression is Associated with Tumor Proliferation and Invasion Potential in Oral Tongue Squamous Cell Carcinoma

Forkhead box protein C2 (FOXC2) is a gene encoding a transcription factor that controls the generation of mesodermal tissue including vascular and lymphatic tissues. FOXC2 has previously been associated with EMT and tumor angiogenesis in various cancers. Moreover, a relationship between the expression of FOXC2 and poor prognosis has been reported in various cancers. We herein examined the clinicopathological significance of FOXC2 in oral tongue squamous cell carcinoma (OTSCC) and attempted to clarify the function of FOXC2 in OTSCC cell lines in vitro. The overexpression of FOXC2 was more frequent in cancers with higher grades according to the pattern of invasion (grade 4 vs. 1?3; p < 0.05). A correlation was observed between the expression of FOXC2 and that of VEGF-A and -C (VEGF-A; p < 0.05, VEGF-C; p < 0.001). The high-FOXC2 expression group had a significantly poorer prognosis than that of the low-expression group (p < 0.001). Multivariate analysis indicated that the overexpression of FOXC2 may also be an independent prognostic factor, similar to N classification (N0 vs 1/2; p < 0.05), stage classification (stage I/II vs III/IV; p < 0.05), pattern of invasion (grade 1-3vs 4; p < 0.05), local recurrence (local recurrence (+) vs (?); p < 0.01), and the overexpression of FOXC2 (FOXC2 overexpression (?) vs.(+); p < 0.05). In the OTSCC cell line analysis, the expression of FOXC2 was also associated with proliferation and invasion potential. These results strongly suggest that the overexpression of FOXC2 may be a potent predictor of survival in OTSCC patients

Inflammatory pseudo-tumor of the liver: a rare pathological entity

Inflammatory pseudo-tumor (IPT) of the liver is a rare benign neoplasm and is often mistaken as a malignant entity. Few cases have been reported in the literature and the precise etiology of inflammatory pseudotumor remains unknown. Patients usually present with fever, abdominal pain and jaundice. The proliferation of spindled myofibroblast cells mixed with variable amounts of reactive inflammatory cells is characteristics of IPT. We reviewed the literature regarding possible etiology for IPT with a possible suggested etiology

Co-expression of nuclear and cytoplasmic HMGB1 is inversely associated with infiltration of CD45RO+ T cells and prognosis in patients with stage IIIB colon cancer

<p>Abstract</p> <p>Background</p> <p>The intratumoral infiltration of T cells, especially memory T cells, is associated with a favorable prognosis in early colorectal cancers. However, the mechanism underlying this process remains elusive. This study examined whether high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) molecule, is involved in the infiltration of T cells and disease progression in locally advanced colon cancer.</p> <p>Methods</p> <p>Seventy-two cases of pathologically-confirmed specimens were obtained from patients with stage IIIB (T3N1M0) colon cancer who underwent radical resection between January 1999 and May 2002 at the Cancer Center of Sun Yat-Sen University. The density of tumor-infiltrating lymphocytes (TILs) within the tumor tissue and the expression of HMGB1 in the cancer cells were examined via immunohistochemical analysis. The phenotype of CD45RO+ cells was confirmed using a flow cytometric assay. The association between HMGB1 expression, the density of TILs, and the 5-year survival rate were analyzed.</p> <p>Results</p> <p>The density of CD45RO+ T cells within the tumor was independently prognostic, although a higher density of CD3+ T cells was also associated with a favorable prognosis. More importantly, the expression of HMGB1 was observed in both the nucleus and the cytoplasm (co-expression pattern) in a subset of colon cancer tissues, whereas nuclear-only expression of HMGB1 (nuclear expression pattern) existed in most of the cancer tissues and normal mucosa. The co-expression pattern of HMGB1 in colon cancer cells was inversely associated with the infiltration of both CD3+ and CD45RO+ T cells and 5-year survival rates.</p> <p>Conclusions</p> <p>This study revealed that the co-expression of HMGB1 is inversely associated with the infiltration of CD45RO+ T cells and prognosis in patients with stage IIIB colon cancer, indicating that the distribution patterns of HMGB1 might contribute to the progression of colon cancer via modulation of the local immune response.</p

Differential disruption of cell cycle pathways in small cell and non-small cell lung cancer

Lung cancer is the leading cause of cancer-related mortality in the world, with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) comprising the two major cell types. Although these cell types can be distinguished readily at the histological level, knowledge of their underlying molecular differences is very limited. In this study, we compared 14 SCLC cell lines against 27 NSCLC cell lines using an integrated array comparative genomic hybridisation and gene expression profiling approach to identify subtype-specific disruptions. Using stringent criteria, we have identified 159 of the genes that are responsible for the different biology of these cell types. Sorting of these genes by their biological functions revealed the differential disruption of key components involved in cell cycle pathways. Our novel comparative combined genome and transcriptome analysis not only identified differentially altered genes, but also revealed that certain shared pathways are preferentially disrupted at different steps in these cell types. Small cell lung cancer exhibited increased expression of MRP5, activation of Wnt pathway inhibitors, and upregulation of p38 MAPK activating genes, while NSCLC showed downregulation of CDKN2A, and upregulation of MAPK9 and EGFR. This information suggests that cell cycle upregulation in SCLC and NSCLC occurs through drastically different mechanisms, highlighting the need for differential molecular target selection in the treatment of these cancers

Strategies to Target Tumor Immunosuppression

The tumor microenvironment is currently in the spotlight of cancer immunology research as a key factor impacting tumor development and progression. While antigen-specific immune responses play a crucial role in tumor rejection, the tumor hampers these immune responses by creating an immunosuppressive microenvironment. Recently, major progress has been achieved in the field of cancer immunotherapy, and several groundbreaking clinical trials demonstrated the potency of such therapeutic interventions in patients. Yet, the responses greatly vary among individuals. This calls for the rational design of more efficacious cancer immunotherapeutic interventions that take into consideration the “immune signature” of the tumor. Multimodality treatment regimens that aim to enhance intratumoral homing and activation of antigen-specific immune effector cells, while simultaneously targeting tumor immunosuppression, are pivotal for potent antitumor immunity