Clinical Significance of Disseminated Pluripotent Tumor Cell Signature Expression in the Bone Marrow from Patients with Colorectal Cancer.

Purpose: Disseminated tumor cells (DTCs) are critically involved in tumor relapse and survival in several invasive tumors. We previously showed that the ATP-binding cassette (ABC) transporter, , is a chemoresistance mediator expressed on specific cell subsets in colorectal cancer (CRC) and other malignancies. This study evaluated the molecular signature expression and its clinical relevance of DTCs in bone marrow from patients with colon cancer.

Ten-year follow-up of a prospective trial for the targeted therapy of gastric cancer with the human monoclonal antibody PAT-SC1.

The fully human monoclonal antibody PAT-SC1 is specific for an isoform of CD55 (decay-accelerating factor) designated CD55PAT-SC1. This antigen is expressed in the majority (80%) of gastric cancers (GCs), and the antibody induces tumour cell-specific apoptosis in vitro as well as in vivo. PAT-SC1, therefore, has been deemed promising as a therapeutic agent.

Differential effects of PPARgamma activation by the oral antidiabetic agent pioglitazone in Barrett's carcinoma in vitro and in vivo.

Background And Purpose: The nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is a key transcription factor regulating genes involved in adipogenesis, glucose homeostasis and cell differentiation. Moreover, PPARgamma has been demonstrated to control proliferation and apoptosis in various cancer cells. We investigated the biological effects of PPARgamma activation by the oral antidiabetic agent pioglitazone in Barrett's adenocarcinoma cells in vitro and in vivo.

The intraportal injection model: a practical animal model for hepatic metastases and tumor cell dissemination in human colon cancer.

Background: The development of new therapeutic strategies for treatment of metastasized colorectal carcinoma requires biologically relevant and adequate animal models that generate both reproducible metastasis and the dissemination of tumor cells in the form of so-called minimal residual disease (MRD), an expression of the systemic character of neoplastic disease.

Methods: We injected immunoincompetent nude mice intraportally with different numbers (1 x 10(5), 1 x 10(6) and 5 x 10(6) cells) of the human colon carcinoma cell lines HT-29 and SW-620 and investigated by histological studies and CK-20 RT-PCR the occurrence of hematogenous metastases and the dissemination of human tumor cells in bone marrow.

Results: Only the injection of 1 x 10(6) cells of each colon carcinoma cell line produced acceptable perioperative mortality with reproducible induction of hepatic metastases in up to 89% of all animals.

Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides.

Background: Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT).

Methods: Twenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87.

Neoadjuvant therapy of gastric cancer with the human monoclonal IgM antibody SC-1: impact on the immune system.

Adjuvant therapies for minimal residual disease are a promising approach to improve the poor survival rates after surgery of gastric tumors. A pilot study of a neoadjuvant therapy was performed using a human monoclonal IgM antibody (SC-1) specifically inducing apoptosis in signet ring cell stomach carcinomas. However, scarce information exists on how such a treatment affects the immune system, in particular what are the effects of apoptosis induction and infusion of large amounts of IgM.

Who benefits from gastric banding?

Background: In the present study, criteria were investigated to predict major benefit after laparoscopic adjustable gastric banding (LAGB).

Materials And Methods: 85 morbidly obese patients were operated with LAGB between 1999 and 2005. Seventy-one of these patients were analyzed according to several possible predictive characteristics for success as the primary endpoint.

Feasibility and limits of an orthotopic human colon cancer model in nude mice.

We sought to develop an accurate colorectal cancer model in nude mice with stable local growth, tumor cell dissemination, and reproducible metastatic capacity. To this end, we orthotopically transplanted histologically intact human colorectal cancer tissue from 10 human patients into nude mice. After successful local tumor growth, tumor tissues were retransplanted as many as 9 times in serial passage.

Disseminated tumor cells in the blood of patients with gastric cancer are an independent predictive marker of poor prognosis.

Objective: Gastric cancer carries a poor prognosis even after curative resection (R0). Tumor progression in gastric cancer patients has been attributed to the persistence of disseminated tumor cells (DTC) in various body compartments as a sign of minimal residual disease, although the prognostic relevance of DTC is still unclear. In this study the prognostic relevance of DTC in the blood of gastric cancer patients was investigated.

Human antibody SC-1 reduces disseminated tumor cells in nude mice with human gastric cancer.

Advanced gastric cancer is a systemic disease that requires adjuvant therapy targeted at eliminating disseminated tumor cells (DTCs). We investigated whether the apoptosis-inducing human monoclonal IgM antibody SC-1 was able to reduce the number of disseminated gastric cancer cells in blood and bone marrow. Human gastric tumor specimens with positive expression of the SC-1 receptor were transplanted in nude mice with metastasizing gastric cancer.

Tumor induction by activated JNK occurs through deregulation of cellular growth.

Activation of the cytoplasmic (Ras-Raf-MEK-ERK) signaling cascade was shown to be both, necessary and sufficient for transformation in vitro as well as in vivo. However, over the last years the involvement of stress-activated protein kinases (SAPKs)/Jun N-terminal kinases (JNKs), and their substrate c-Jun in the process of cellular transformation has been suggested. To dissect the mechanisms through which JNK signaling contributes to the transformation process we employed a recently generated constitutively active version of this kinase, SAPKbeta-MKK7, which behaves like a weakly transforming oncogene in vitro.

Expression profiling and genetic alterations of the selenoproteins GI-GPx and SePP in colorectal carcinogenesis.

The trace element selenium is discussed as a chemopreventive agent in colorectal carcinogenesis. Selenocysteine-containing proteins, so-called selenoproteins, represent potential molecular targets for nutritive selenium supplementation. Due to their antioxidative potential, the selenoproteins gastrointestinal glutathione peroxidase (GI-GPx) and selenoprotein P (SePP) are considered to provide protection against reactive oxygen species (ROS), thereby reducing DNA damage and preventing development of colon cancer.

Detection of disseminated tumor cells in nude mice with human gastric cancer.

Disseminated tumor cells (DTC) are a potential contributor to relapse of cancer. In the present study we developed a model for induction of disseminated tumor cells in nude mice, which can aid in the search for therapeutic approaches as well as improve our understanding of metastasizing gastric cancer. To detect DTC in blood and bone marrow we established a modified animal model of orthotopic transplantation.

Optimization of a metastasizing human gastric cancer model in nude mice.

Our purpose was to optimize the surgical orthotopic implantation (SOI) technique to create a reproducible gastric cancer model in nude mice with stable tumor growth and metastasizing course. We performed xenotransplantation of primary human tumor specimens from patients with gastric cancer (series 1) and orthotopic transplantation of tumor specimens originating from the gastric cancer cell line 23132/87 (series 2). All specimens were transplanted using microsurgical techniques.

Short-term immunosuppression after rat parathyroid allotransplantation.

The aim of this study was to evaluate whether short-term postoperative immunosuppression is able to sufficiently prolong graft survival after experimental allogeneic parathyroid transplantation. Heterotopic parathyroid transplantation was performed in 6 groups: 1) syngeneic control Lewis (LEW) to LEW; 2) allogeneic control Wistar-Furth (WF) to LEW; 3-5) WF to LEW plus short-term immunosuppression, postoperative days 1-13 (cyclosporine 5/10/20 mg/kg); and 6) WF to LEW plus 10 mg/kg CyA from preoperative day 7 to postoperative day 7. Graft function was examined up to 60 days; histological and immunohistological examination was performed on all grafts with impaired function.

Human monoclonal IgM antibodies with apoptotic activity isolated from cancer patients.

Monoclonal antibodies are accepted as ideal adjuvant therapeutic reagents for all kinds of diseases. Polyvalent (cross-linking) and low-mutated IgM antibodies (less immunogenic) are believed to be the most effective weapons against cancer. The best sources for these types of antibodies are the cancer patients themselves.

Ultrastructural alterations of primary human liver sinusoidal cells in patients treated for peritonitis.

Acute peritonitis is still associated with a high mortality rate. Bacterial toxins are rapidly cleared from the peritoneal cavity and may induce general sepsis. The hepatic sinusoidal cells are part of the primary defence against these toxins.

Constitutive JNK activation in NIH 3T3 fibroblasts induces a partially transformed phenotype.

The c-Jun N-terminal kinases (JNKs) (also known as stress-activated protein kinases or SAPKs), members of the mitogen-activated protein kinase (MAPK) family, regulate gene expression in response to a variety of physiological and unphysiological stimuli. Gene knockout experiments and the use of dominant interfering mutants have pointed to a role for JNKs in the processes of cell differentiation and survival as well as oncogenic transformation. Direct analysis of the transforming potential of JNKs has been hampered so far by the lack of constitutively active forms of these kinases.