Cancer Growth Metastasis 2017 19;10:1179064417713197. Epub 2017 Jun 19.
Department of Pharmaceutical & Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA, USA.
The WASF3 gene facilitates the metastatic phenotype, and its inactivation leads to suppression of invasion and metastasis regardless of the genetic background of the cancer cell. This reliance on WASF3 to facilitate metastasis suggests that targeting its function could serve as an effective strategy to suppress metastasis. WASF3 stability and function are regulated by the WASF Regulatory Complex (WRC) of proteins, particularly CYFIP1 and NCKAP1. Read More
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and one of the most lethal human cancers. Inflammation is a critical component in PDAC initiation and progression. Inflammation also contributes to the aggressiveness of PDAC indirectly via induction of epithelial-mesenchymal transition (EMT), altogether leading to enhanced resistance to chemotherapy and poor survival rates. Read More
Glutathione disulfide (GSSG) is an endogenous peptide and the oxidized form of glutathione. The impacts of GSSG on cell function/dysfunction remain largely unexplored due to a lack of method to specifically increase intracellular GSSG. We recently developed GSSG liposomes that can specifically increase intracellular GSSG. Read More
Cancer metastasis is the major cause of cancer mortality. Despite extensive research efforts, effective treatment for cancer metastasis is still lacking. Cancer metastasis involves 4 essential steps: cell detachment, migration, invasion, and adhesion. Read More
Purpose: Agarose macrobeads containing mouse renal adenocarcinoma cells (RMBs) release factors, suppressing the growth of cancer cells and prolonging survival in spontaneous or induced tumor animals, mediated, in part, by increased levels of myocyte-enhancing factor (MEF2D) via EGFR-and AKT-signaling pathways. The primary objective of this study was to determine the safety of RMBs in advanced, treatment-resistant metastatic cancers, and then its efficacy (survival), which is the secondary objective.
Methods: Thirty-one patients underwent up to four intraperitoneal implantations of RMBs (8 or 16 macrobeads/kg) via laparoscopy in this single-arm trial (FDA BB-IND 10091; NCT 00283075). Read More
For many years, transfusion of allogeneic red blood cells, platelet concentrates, and plasma units has been part of the standard therapeutic arsenal used along the surgical and nonsurgical treatment of patients with malignancies. Although the benefits of these blood products are not a matter of debate in specific pathological conditions associated with life-threatening low blood cell counts or bleeding, increasing clinical evidence is nevertheless suggesting that deliberate transfusion of these blood components may actually lead to negative clinical outcomes by affecting patient's immune defense, stimulating tumor growth, tethering, and dissemination. Rigorous preclinical and clinical studies are needed to dimension the clinical relevance, benefits, and risks of transfusion of blood components in cancer patients and understand the amplitude of problems. Read More
Glioblastoma (GB) is the most common malignant brain tumor. Drug resistance frequently develops in these tumors during chemotherapy. Therefore, predicting drug response in these patients remains a major challenge in the clinic. Read More
Background: Metastatic cells from a primary tumor can occur before the primary cancer is detected. Metastatic cells can also remain in the patient for many years after removal of the primary tumor without proliferating. These dormant malignant cells can awaken and cause recurrent disease decades after the primary treatment. Read More
Pancreatic ductal adenocarcinoma is one of the most aggressive malignancies, characterized by the local invasion into surrounding tissues and early metastasis to distant organs. Oncogenic mutations of the K-RAS gene occur in more than 90% of human pancreatic cancers. The goal of this study was to investigate the functional significance and downstream effectors of mutant K-RAS oncogene in the pancreatic cancer invasion and metastasis. Read More
Despite the considerable progress in understanding the biology of human cancer and technological advancement in drug discovery, treatment failure remains an inevitable outcome for most cancer patients with advanced diseases, including melanoma. Despite FDA-approved BRAF-targeted therapies for advanced stage melanoma showed a great deal of promise, development of rapid resistance limits the success. Hence, the overall success rate of melanoma therapy still remains to be one of the worst compared to other malignancies. Read More
Cancer Growth Metastasis 2015 7;8(Suppl 1):63-80. Epub 2015 Sep 7.
Department of Biomedical Engineering, University of Arizona, Tucson, AZ, USA. ; College of Optical Sciences, University of Arizona, Tucson, AZ, USA. ; University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
Optical coherence tomography (OCT) is a high-resolution, nondestructive imaging modality that enables time-serial assessment of adenoma development in the mouse model of colorectal cancer. In this study, OCT was utilized to evaluate the effectiveness of interventions with the experimental antitumor agent α-difluoromethylornithine (DFMO) and a nonsteroidal anti-inflammatory drug sulindac during early [chemoprevention (CP)] and late stages [chemotherapy (CT)] of colon tumorigenesis. Biological endpoints for drug interventions included OCT-generated tumor number and tumor burden. Read More
Esophageal cancer is the eighth leading cause of cancer and the sixth most common cause of cancer-related death worldwide. Despite recent advances in the development of surgical techniques in combination with the use of radiotherapy and chemotherapy, the prognosis for esophageal cancer remains poor. The cellular and molecular mechanisms that drive the pathogenesis of esophageal cancer are still poorly understood. Read More
Cancer Growth Metastasis 2015 12;8(Suppl 1):29-36. Epub 2015 Aug 12.
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine-South Bend, South Bend, IN, USA. ; Harper Cancer Research Institute, South Bend, IN, USA. ; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, USA. ; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
Ovarian cancer (OC) is the leading cause of death from a gynecological malignancy in the United States. By the time a woman is diagnosed with OC, the tumor has usually metastasized. Mouse models that are used to recapitulate different aspects of human OC have been evolving for nearly 40 years. Read More
Nonmelanoma skin cancer (NMSC) is a major health concern worldwide. With increasing numbers in high-risk groups such as organ transplant recipients and patients taking photosensitizing medications, the incidence of NMSC continues to rise. Mouse models of NMSC allow us to better understand the molecular signaling cascades involved in skin tumor development in order to identify novel therapeutic strategies. Read More
Mouse models of human cancer play a critical role in understanding the molecular and cellular mechanisms of tumorigenesis. Advances continue to be made in modeling human disease in a mouse, though the relevance of a mouse model often relies on how closely it is able to mimic the histologic, molecular, and physiologic characteristics of the respective human cancer. A classic use of a genetically engineered mouse in studying cancer is through the overexpression or deletion of a gene. Read More
Many common cancers have a propensity to metastasize to bone. Although malignancies often go undetected in their native tissues, bone metastases produce excruciating pain that severely compromises patient quality of life. Cancer-induced bone pain (CIBP) is poorly managed with existing medications, and its multifaceted etiology remains to be fully elucidated. Read More
Objective: Plasminogen system plays a crucial role in physiological and pathological events related to tissue regeneration, wound healing, immune response, angiogenesis, invasion and metastasis. It gets activated when plasminogen associates with its cell surface receptors. Latest information on some of the well-explored plasminogen receptors such as annexin II-S100A10, cytokeratin 8, α-enolase, plasminogen receptor (KT) (Plg-R(KT)) and histone H2B has been discussed in the present review. Read More
The innate immune system is an integral component of the inflammatory response to pathophysiological stimuli. Toll-like receptors (TLRs) and inflammasomes are the major sensors and pattern recognition receptors (PRRs) of the innate immune system that activate stimulus (signal)-specific pro-inflammatory responses. Chronic activation of PRRs has been found to be associated with the aggressiveness of various cancers and poor prognosis. Read More
Molecular heterogeneity within primary breast carcinomas and among axillary lymph node (LN) metastases may impact diagnosis and confound treatment. In this study, we used short tandem repeated sequences to assess genomic heterogeneity and to determine hereditary relationships among primary tumor areas and regional metastases from 30 breast cancer patients. We found that primary carcinomas were genetically heterogeneous and sampling multiple areas was necessary to adequately assess genomic variability. Read More
Cancer Growth Metastasis 2015 29;8:1-13. Epub 2015 Jan 29.
Center for Translational Cancer Research, Helen F. Graham Cancer Center, Christiana Care Health Services, Inc., Newark, DE, USA. ; Department of Medical Laboratory Sciences, University of Delaware, Newark, DE, USA.
The relationship between wound healing and cancer has long been recognized. The mechanisms that regulate wound healing have been shown to promote transformation and growth of malignant cells. In addition, chronic inflammation has been associated with malignant transformation in many tissues. Read More
Cancer Growth Metastasis 2014 8;7:43-51. Epub 2014 Dec 8.
Laboratoire d'Oncologie Moléculaire, Département de Chimie, Centre de Recherche BIOMED, Université du Québec à Montreal, Quebec, Canada. ; Département de Physiologie, Faculté de Médecine, Université de Montreal, Montreal, Canada.
Caveolae are specialized cell membrane invaginations known to regulate several cancer cell functions and oncogenic signaling pathways. Among other caveolar proteins, they are characterized by the presence of proteins of the cavin family. In this study, we assessed the impact of cavin-1, cavin-2, and cavin-3 on cell migration in a human HT-1080 fibrosarcoma model. Read More
Myeloma bone disease (MBD) is a devastating complication of multiple myeloma (MM). More than 80% of MM patients suffer from destructive bony lesions, leading to pain, fractures, mobility issues, and neurological deficits. MBD is not only a main cause of disability and morbidity in MM patients but also increases the cost of management. Read More
Cancer Growth Metastasis 2014 19;7:27-32. Epub 2014 Jun 19.
Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA. ; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Pro-oxidative stressors including cigarette smoke (CS) generate novel lipids with platelet-activated factor-receptor (PAF-R) agonistic activity mediate systemic immunosuppression, one of the most recognized events in promoting carcinogenesis. Our previous studies have established that these oxidized-PAF-R-agonists augment murine B16F10 melanoma tumor growth in a PAF-R-dependent manner because of its effects on host immunity. As CS generates PAF-R agonists, the current studies sought to determine the impact of PAF-R agonists on lung cancer growth and metastasis. Read More
The aim of cancer chemoprevention is disruption or delay of the molecular pathways that lead to carcinogenesis. Chemopreventive blocking and/or suppressing agents disrupt the molecular mechanisms that drive carcinogenesis such as DNA damage by reactive oxygen species, increased signal transduction to NF-κB, epigenomic deregulation, and the epithelial mesenchymal transition that leads to metastatic progression. Numerous dietary phytochemicals have been observed to inhibit the initiation phase of carcinogenesis, and therefore are useful in primary chemoprevention. Read More
The presence of abnormal cells with malignant potential or neoplastic characteristics is a relatively common phenomenon. The interaction of these abnormal cells with their microenvironment is essential for tumor development, protection from the body's immune or defence mechanisms, later progression and the development of life-threatening or metastatic disease. The tumor microenvironment is a collective term that includes the tumor's surrounding and supportive stroma, the different effectors of the immune system, blood platelets, hormones and other humoral factors. Read More
In this article, we have reviewed current literature regarding the regulation of hepatocellular carcinoma (HCC) by the interaction of malignant hepatocytes and their tissue environment through cytokine signaling, here represented by transforming growth factor-beta (TGF-β) signaling. We have discussed responses of TGF-β signaling in transition of hepatic stellate cells to myofibroblasts (MFBs), recruitment of tumor-associated macrophages (TAMs), and enrichment of tumor-associated endothelial cells (TECs). The malignant hepatocytes also secrete various factors such as platelet-derived growth factors (PDGFs), vascular endothelial growth factor (VEGF), and TGF-β. Read More
The high mortality rate caused by ovarian cancer has not changed for the past thirty years. Although most patients diagnosed with this disease respond to cytoreductive surgery and platinum-based chemotherapy and undergo remission, foci of cells almost always escape therapy, manage to survive, and acquire the capacity to repopulate the tumor. Repopulation of ovarian cancer cells that escape front-line chemotherapy, however, is a poorly understood phenomenon. Read More
We have previously shown that the antiprogestin and antiglucocorticoid mifepristone inhibits the growth of ovarian cancer cells. In this work, we hypothesized that cellular stress caused by mifepristone is limited to cytostasis and that cell killing is avoided as a consequence of the persistent activity of the PI3K/Akt survival pathway.To investigate the role of this pathway in mifepristone-induced growth inhibition, human ovarian cancer cells of various histological subtypes and genetic backgrounds were exposed to cytostatic doses of mifepristone in the presence or absence of the PI3K inhibitor, LY294002. Read More
Prostate cancer (PC) is one of the most common cancers arising in men and has a high propensity for bone metastasis, particularly to the spine. At this stage, it often causes severe morbidity due to pathological fracture and/or metastatic epidural spinal cord compression which, if untreated, inevitably leads to intractable pain, neurological deficit, and paralysis. Unfortunately, the underlying molecular mechanisms driving growth of secondary PC in the bony vertebral column remain largely unknown. Read More
The link between signaling pathways and diseases suggests the importance of pathway analysis for drug discovery. This includes target identification and validation, compound mode of action and drug candidate optimization. Here, we propose to apply cell signaling pathway panel approaches for oncology drug discovery. Read More
Curcumin, a phytochemical isolated from curcuma plants which are used as coloring ingredient for the preparation of curry powder, has several activities which suggest that it might be an interesting drug for the treatment or prevention of cancer. Curcumin targets different pathways which are involved in the malignant phenotype of tumor cells, including the nuclear factor kappa B (NFKB) pathway. This pathway is deregulated in multiple tumor entities, including Hodgkin's lymphoma (HL). Read More
Cancer Growth Metastasis 2013 1;6:23-34. Epub 2013 Aug 1.
Spinal Biology Research Laboratory, University of Melbourne, Department of Surgery, Austin Health, Heidelberg Victoria 3084, Australia. ; Department of Spinal Surgery, Austin Health, Heidelberg Victoria 3084, Australia.
The bony skeleton is one of the most common sites of metastatic spread of cancer and is a significant source of morbidity in cancer patients, causing pain and pathologic fracture, impaired ambulatory ability, and poorer quality of life. Animal cancer models of skeletal metastases are essential for better understanding of the molecular pathways behind metastatic spread and local growth and invasion of bone, to enable analysis of host-tumor cell interactions, identify barriers to the metastatic process, and to provide platforms to develop and test novel therapies prior to clinical application in human patients. Thus, the ideal model should be clinically relevant, reproducible and representative of the human condition. Read More
Pancreatic adenocarcinoma is an aggressive cancer with a greater than 95% mortality rate and short survival after diagnosis. Chemotherapeutic resistance hinders successful treatment. This resistance is often associated with mutations in codon 12 of the K-Ras gene (K-Ras 12), which is present in over 90% of all pancreatic adenocarcinomas. Read More
Proteases play important roles during tumor angiogenesis, invasion, and metastasis. Various molecular imaging techniques have been employed for protease imaging: optical (both fluorescence and bioluminescence), magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), and positron emission tomography (PET). In this review, we will summarize the current status of imaging proteases in cancer with these techniques. Read More
BACKGROUND: The mechanisms responsible for resistant or recurrent disease in childhood non-Hodgkin lymphoma (NHL) are not yet fully understood. A unique mechanism suggesting the role of the mitochondria as the key energy source responsible for residual cells has been assessed in the clinical setting on specimens from patients on therapy were found to have increased copies of mitochondrial DNA (mtDNA) associated with positive minimal residual disease and/or persistent disease (MRD/PD) status. The potential role of mtDNA in MRD/PD emphasizes queries into the contributions of relevant enzymatic pathways responsible for MRD/PD. Read More