Clinical Application of Induced Hepatocyte-like Cells Produced from Mesenchymal Stromal Cells: A Literature Review.

Liver disease is a leading cause of mortality worldwide, resulting in 1.3 million deaths annually. The vast majority of liver disease is caused by metabolic disease (i.e., NASH) and alcohol-induced hepatitis, and to a lesser extent by acute and chronic viral infection. Furthermore, multiple insults to the liver is becoming common due to the prevalence of metabolic and alcohol-related liver diseases. Despite this rising prevalence of liver disease, there are few treatment options: there are treatments for viral hepatitis C and there is vaccination for hepatitis B. Aside from the management of metabolic syndrome, no direct liver therapy has shown clinical efficacy for metabolic liver disease, there is very little for acute alcohol-induced liver disease, and liver transplantation remains the only effective treatment for late-stage liver disease. Traditional pharmacologic interventions have failed to appreciably impact the pathophysiology of alcohol-related liver disease or end-stage liver disease. The difficulties associated with developing liver-specific therapies result from three factors that are common to late-stage liver disease arising from any cause: hepatocyte injury, inflammation, and aberrant tissue healing. Hepatocyte injury results in tissue damage with inflammation, which sensitizes the liver to additional hepatocyte injury and stimulates hepatic stellate cells and aberrant tissue healing responses. In the setting of chronic liver insults, there is progressive scarring, the loss of hepatocyte function, and hemodynamic dysregulation. Regenerative strategies using hepatocyte-like cells that are manufactured from mesenchymal stromal cells may be able to correct this pathophysiology through multiple mechanisms of action. Preclinical studies support their effectiveness and recent clinical studies suggest that cell replacement therapy can be safe and effective in patients with liver disease for whom there is no other option.

Circulating tumor cell data: integration with imaging and serum tumor markers for metastatic breast cancer patient management.

Management of metastatic breast cancer is critical to maximizing survival with good quality of life. Circulating tumor cell (CTC) levels in the peripheral blood hold promise for enabling improved patient care. We describe a case of a 47-year-old female with infiltrating ductal carcinoma who developed metastatic disease. Serum tumor markers were discordant with imaging studies at several time points. CTC levels were used to support decision making in light of the discordant data. The use of this tool enabled prompt changes in therapy with progressive disease and supported suspending therapy to enable recovery from treatment adverse effects when a significant response was detected by imaging and CTCs were absent from the peripheral circulation. The additional information provided by CTC enumeration helped clarify disease status and provided support for treatment decisions.

Integrating circulating tumor cell data with imaging and serum prostate-specific antigen measurement for metastatic prostate cancer therapy management.

Optimal management of therapy can improve quality of life, and potentially survival, of patients with metastatic prostate cancer. Circulating tumor cell (CTC) enumeration in the peripheral blood holds promise for facilitating optimal therapy management based on high cancer specificity and prompt response to changes in disease status. We present the case of a 54-year-old male diagnosed with metastatic prostate cancer. The patient's disease status was monitored radiographically and by serial determinations of serum prostate-specific antigen concentration, performance status, and CTC enumeration. At multiple visits, the disease status was not clear due to discordance between standard assessments. The additional information provided by CTC enumeration helped clarify disease status and provided support for treatment decisions.

Progress in using circulating tumor cell information to improve metastatic breast cancer therapy.

Circulating tumor cells (CTCs) were discovered nearly 150 years ago but have only recently been recognized as a feature of most solid tumors due to their extremely low concentration in the peripheral circulation. Several technologies have been developed to isolate and analyze CTCs, which can now be routinely accessed for clinical information. The most mature of these (the CELLSEARCH system) uses immunomagnetic selection of epithelial cell adhesion molecule to isolate CTCs for analysis. Studies using this system have demonstrated that categorization of patients into high and low CTC groups using a validated decision point is prognostic in patients with metastatic breast, colorectal, or prostate cancer. Initial attempts to use CTC counts to guide therapeutic decisions appeared to yield positive results and key concepts in clinical application of CTC information, including the CTC cutoff, predictive value in disease subtypes, and comparison to current evaluation methods, have been demonstrated. Clinical studies of the impact of CTC counts in routine clinical practice are ongoing; however, recent published evidence on the clinical use of CTCs in metastatic breast cancer continues to support these concepts, and experience in the community oncology setting also suggests that CTC enumeration can be useful for therapy management.