UMass Memorial Peritoneal Surface Malignancy

Research Program

 

 

Traditionally, peritoneal-based malignancies have been considered an untreatable and terminal condition. Until the recent acceptance of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC), peritoneal-based tumor specimens were not available for investigation because these tumors were usually considered inoperable. Consequently, little is known about the molecular and cellular biology of these tumors. The Peritoneal Surface Malignancy Program at UMass Memorial has a basic and translational research program. This program is dedicated to bringing our clinical knowledge of the unsolved problems faced by patients with peritoneal-based cancers to the laboratory to find less toxic and more effective ways of treating and curing our patients. Some of our on-going projects and future endeavors are listed here.

 

 1. Alternative solutions in hyperthermic intraperitoneal perfusion

 Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IC) are considered the standard of care for patients with peritoneal dissemination of appendiceal cancer, ovarian cancer and peritoneal mesothelioma. Data are also accumulating that show a survival advantage for this approach in selected patients with carcinomatosis for colorectal cancer. However, there is no consensus as to the optimal form of IC. Usage of a wide variety of chemotherapy agents, in various carrier solutions, administered either with or without hyperthermia, for a broad range of times (30 minutes to days), has been reported with remarkably comparable rates of success. Consequently, the optimal form of IC is unknown, while on the other hand, clinically significant systemic side effects are well-documented.The main goal of this project is to investigate alternative peritoneal perfusion techniques that result in tumor –specific cell death with less systemic toxicity. Identification of tumor-specific cytotoxic peritoneal perfusates will improve oncologic outcomes combined with decreased toxicity for patients undergoing CRS and HIPEC.

 

 2. DNA and Protein Microarray Investigation of Appendiceal Cancer

 Because non-carcinoid appendical cancers are extremely rare, little is known about the genetic pathways that are involved in the growth and dissemination of these tumors.  The purpose of this research project is to investigate the genetic and protein expression profiles of non-carcinoid appendiceal cancers. The potential benefits of this project are to identify novel targets for therapy, provide better prognostic information, and identify people at risk for developing appendiceal cancer based upon genetic and protein profiles.

 

 3. Cell cycle-targeted therapy enhances tumor cell death during HIPEC

 The ultimate goal of all cancer therapy is cancer-specific cell death, without harming normal cells. Because all cancer cells lose regulation of their cell cycle, cancer therapies that target the cell cycle are appealing and rational. Recent studies from our laboratory targeted the cell cycle in normal, sarcoma and colon cancer cell lines with a cell cycle inhibitor after exposure to chemotherapy. In these studies, the combined treatment resulted in significantly enhanced cell death in the cancer cell lines, but not in the normal cells.  Based upon these findings, the main hypothesis of this project is that increased cytotoxicity by cell cycle inhibition after chemotherapy specifically enhances cancer cell death while sparing normal cells. Our objective is to translate our preliminary findings of cell cycle-induced cancer cell death in to improved outcomes for patients undergoing HIPEC.

 

4. Cytokine and protein profiles of malignant ascites

 Patients with peritoneal ascites often suffer debilitating symptoms including life-threatening anorexia and cachexia.  Symptom management is challenging and often inadequate, resulting in loss of quality of life (QoL). This study is investigating the cytokine and other protein profiles of malignant and non-malignant ascites for potential targets for palliation.  This is an on-going prospective, observational study at the UMass Memorial Medical Center. Patients with ascites retrieved either at surgery or by paracentesis are asked to complete a brief QoL questionnaire.  Relative intensity of cytokine and protein expression in the ascites fluid is quantified. Significant differences between non-malignant and malignant ascites are determined and correlated with QoL data. Through this study we hope to identify targets for more effective palliation of symptomatic ascites. So far we have identified angiogenin as a potential target for anti-angiogenic therapy in malignant ascites. In addition, the appetite suppressant, leptin, may be a potential target for palliation of ascites-related anorexia.

 

 5. The role of mucin-regulating hormones in pseudomyxoma peritonei (PMP)

Luteinizing hormone (LH) and beta human chorionogranin (b-HCG) have been shown to play a significant role in the production of gynecologic-associated mucins. The role of sex hormones in the production of gastrointestinal mucin, including that produced by the appendix, has never been determined. The purpose of this project is to investigate the role of sex hormones in the production of gastrointestinal mucin. The potential benefit of the results of this study is to identify a hormone-based therapy for the management of PMP.