The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer

The most devastating aspect of cancer is the emergence of metastases. Thus, identification of potentially metastatic cells among a tumor cell population and the underlying molecular changes that switch cells to a metastatic state are among the most important issues in cancer biology. Here we show that, although normal human colonic epithelial cells lack the glycosphingolipid globotriaosylceramide (Gb3), this molecule is highly expressed in metastatic colon cancer. In addition, a subpopulation of cells that are greatly enriched in Gb3 and have an invasive phenotype was identified in human colon cancer cell lines. In epithelial cells in culture, Gb3 was necessary and sufficient for cell invasiveness. Transfection of Gb3 synthase, resulting in Gb3 expression in noncancerous polarized epithelial cells lacking endogenous Gb3, induced cell invasiveness. Furthermore, Gb3 knockdown by small inhibitory RNA in colon cancer epithelial cells inhibited cell invasiveness. Gb3 is the plasma membrane receptor for Shiga toxin 1. The noncatalytic B subunit of Shiga toxin 1 causes apoptosis of human colon cancer cells expressing Gb3. Injections of the B subunit of Shiga toxin 1 into HT29 human colon cancer cells engrafted into the flanks of nude mice inhibited tumor growth. These data demonstrate the appearance of a subpopulation of Gb3 containing epithelial cells in the metastatic stage of human colon cancer and suggest their possible role in colon cancer invasiveness

Transitoriness in cancer patients: a cross-sectional survey of lung and gastrointestinal cancer patients

Objective: Despite earlier diagnosis and advancements in treatment, cancer remains a leading cause of death in the world (13% of all deaths according to the World Health Organization) among men and women. Cancer accounts for approximately 20% of the deaths in the USA every year. Here, we report the findings from a cross-sectional survey of psychosocial factors in lung and gastrointestinal cancer patients. The aim of the study was to explore the associations among transitoriness, uncertainty, and locus of control (LOC) with quality of life. Transitoriness is defined as a person's confrontation with life's finitude due to a cancer diagnosis. Methods: A total of 126 patients with lung or gastrointestinal cancer completed eight self-reporting questionnaires addressing demographics, spiritual perspective, symptom burden, transitoriness, uncertainty, LOC, and quality of life. Results: Transitoriness, uncertainty, and LOC were significantly associated with one another (r = 0.3267, p = 0.0002/r = 0.1994, p = 0.0252, respectively). LOC/belief in chance has a significant inverse relationship with patients' quality of life (r = −0.2505, p = 0.0047). Transitoriness, uncertainty, and LOC were found to have a significant inverse relationship with patients' quality of life (transitoriness state: r = −0.5363, p = 0.0000/trait: r = −0.4629, p = 0.0000/uncertainty: r = −0.4929, p = 0.0000/internal LOC: r = 0.1759, p = 0.0489/chance LOC: r = −0.2505, p = 0.0047). Conclusion: Transitoriness, uncertainty, and LOC are important concepts as they adversely influence patients' quality of life. Incorporating this finding into the care of cancer patients may provide them with the support they need to cope with treatment and maintenance of a positive quality of lif

Lattice Boltzmann Method For Fast Patient-Specific Simulation of Liver Tumor Ablation from CT Images

International audienceRadio-frequency ablation (RFA), the most widely used minimally invasive ablative therapy of liver cancer, is challenged by a lack of patient-specifi c planning. In particular, the presence of blood vessels and time varying thermal di ffusivity makes the prediction of the extent of the ablated tissue diffi cult. This may result in incomplete treatments and increased risk of recurrence. We propose a new model of the physical mechanisms involved in RFA of abdominal tumors based on Lattice Boltzmann Method to predict the extent of ablation given the probe location and the biological parameters. Our method relies on patient images, from which level set representations of liver geometry, tumor shape and vessels are extracted. Then a computational model of heat diff usion, cellular necrosis and blood flow through vessels and liver is solved to estimate the extent of ablated tissue. After quantitative verifi cations against an analytical solution, we apply our framework to 5 patients datasets which include pre- and post-operative CT images, yielding promising correlation between predicted and actual ablation extent (mean point to mesh errors of 8.7 mm). Implemented on graphics processing units, our method may enable RFA planning in clinical settings as it leads to near real-time computation: 1 minute of ablation is simulated in 1.14 minutes,which is almost 60 faster than standard fi nite element method

The Impact of Postoperative Complications on the Administration of Adjuvant Therapy Following Pancreaticoduodenectomy for Adenocarcinoma

ABSTRACT Background. The impact of postoperative complications on the administration of adjuvant therapy following pancreaticoduodenectomy (PD) for adenocarcinoma is still unclear. Methods. A retrospective review of all patients undergoing PD at our institution between 1995 and 2011 was performed. Clinicopathological data, including ClavienDindo complication grade, time to adjuvant therapy (TTA), and survival, were analyzed. Approximately 45,200 cases of pancreatic cancer (PC) are diagnosed yearly in the US, with 38,500-attributable cancer-related deaths. 1 The overall 5-year survival rate for PC is only 6 %, 1 and even for resectable cancers, the 5-year survival rate following pancreaticoduodenectomy (PD) is less than 20 %. 2-7 Local and systemic recurrence are common following PD, suggesting both systemic and local adjuvant therapy are necessary to improve outcomes