Early-Stage Metastasis Requires Mdm2 and Not p53 Gain of Function
Metastasis of cancer cells to distant organ systems is a complex process that is initiated with the programming of cells in the primary tumor. The formation of distant metastatic foci is correlated with poor prognosis and limited effective treatment options. We and others have correlated Mouse double minute 2 (Mdm2) with metastasis; however, the mechanisms involved have not been elucidated. Here, it is reported that shRNA-mediated silencing of Mdm2 inhibits epithelial–mesenchymal transition (EMT) and cell migration. In vivo analysis demonstrates that silencing Mdm2 in both post-EMT and basal/triple-negative breast cancers resulted in decreased primary tumor vasculature, circulating tumor cells, and metastatic lung foci. Combined, these results demonstrate the importance of Mdm2 in orchestrating the initial stages of migration and metastasis. Implication: Mdm2 is the major factor in the initiation of metastasis. Mol Cancer Res; 15(11); 1598–607. ©2017 AACR.
CONCLUSIONS: High YES1 cytoplasmic expression in EOC patient tissue is significantly correlated with favorable prognosis. Patients with high YES1 expression tend to be sensitive to platinum-based chemotherapy. PMID: 31970720 [PubMed - as supplied by publisher]
Despite aggressive upfront treatment with a combination of surgery and chemotherapy, most women with advanced epithelial malignancy will experience disease recurrence. The goal of treatment in the recurrent setting shifts away from a curative approach towards palliation of symptoms. In an attempt to delay time to first recurrence, the concept of maintenance chemotherapy emerged. This paper reviews the available literature evaluating the use of maintenance chemotherapy in the primary treatment setting and its effect on progression-free survival and overall survival.
A diagnosis of recurrent epithelial ovarian cancer carries with it a very poor prognosis despite aggressive chemotherapy with or without secondary surgical cytoreduction. Recently, maintenance treatment after second-line chemotherapy has gained momentum given promising results of antiangiogenics and PARP inhibitors used in this setting. When used appropriately, these agents may provide a meaningful survival benefit with minimal effects on quality of life. This paper reveals the current literature evaluating the use of maintenance therapy in the recurrent setting for the epithelial ovarian, fallopian tube, or primary peritoneal cancers.
Some of the patients with epithelial ovarian cancer will not respond to initial therapy. These patients have a poor prognosis. Our aim was to identify patients with a worse prognosis by integrating clinical, pathologic, and genomic data. Using publicly available genomic data and integrating it with clinical data, we significantly improved the prediction of patients with worse surgical outcomes and those who do not respond to initial chemotherapy. We further improved these models with more precise data collection and better understanding of the genetic background of the studied population. Better prediction will lead to bet...
Patients with inflammatory bowel disease demonstrate selenium nutritional deficiencies and are at increased risk for colon cancer. Previously, we determined that global loss of the selenium-containing antioxidant protein, Selenoprotein P (SELENOP), exacerbates experimental colitis-associated cancer (CAC). Using a variety of tissue-specific knockout mouse lines, we further determined that epithelial-derived SELENOP served as the primary mediator of disease severity, and Villin-Cre; Selenop f/f (Selenop ΔIEC) mice have increased tumor incidence, number, size, and dysplasia as compared to WT cohorts.
Toll-like receptor 4 (TLR4), the receptor for gram negative lipopolysaccharide, is upregulated in biopsies of ulcerative colitis and colorectal cancer (CRC) patients, particularly in intestinal epithelial cells (IECs). We have demonstrated that activation of TLR4 promotes redox activity in IECs and induces susceptibility to colitis, colitis-associated cancer (CAC) and CRC. Furthermore, we have shown that TLR4-induced susceptibility to colitis is transmissible by simple cohousing, suggesting that the microbiota plays a key role in TLR4-driven effects.
In conclusion, the expression levels of WWOX, Elf5, Snail1 and EMT related factors in epithelial ovarian cancer tissues are consistent and different. The expression levels of WWOX and Elf5 are related to the survival and prognosis of patients with epithelial ovarian cancer. PMID: 31966058 [PubMed]
Authors: Li D, Li L, Cao Y, Chen X Abstract Breast cancer (BC) is one of the most dangerous malignant diseases among women. A growing amount of evidence has suggested that long non-coding RNAs participate in the development and progression of BC and may potentially serve as therapeutic targets or prognostic markers for the disease. A previous study demonstrated that long intergenic non-protein coding RNA 01140 (LINC01140) was prominently correlated with overall survival in patients with gastric cancer. However, the function of LINC01140 in BC has not yet been elucidated. Therefore, the present study aimed to invest...
ConclusionsLinc00662 was significantly upregulated in CRC, and mediated CRC progression and metastasis by competing with miR-497-5p to modulate the expression of AVL9. Therefore, our result sheds light on the potential application of linc00662 in CRC diagnosis and therapy.