Silibinin attenuates ionizing radiation-induced pro-angiogenic response and EMT in prostate cancer cells.
Biochem Biophys Res Commun. 2015 Jan 02;456(1):262-8
Authors: Nambiar DK, Rajamani P, Singh RP
Radiotherapy of is well established and frequently utilized in prostate cancer (PCa) patients. However, recurrence following therapy and distant metastases are commonly encountered problems. Previous studies underline that, in addition to its therapeutic effects, ionizing radiation (IR) increases the vascularity and invasiveness of surviving radioresistant cancer cells. This invasive phenotype of radioresistant cells is an upshot of IR-induced pro-survival and mitogenic signaling in cancer as well as endothelial cells. Here, we demonstrate that a plant flavonoid, silibinin can radiosensitize endothelial cells by inhibiting expression of pro-angiogenic factors. Combining silibinin with IR not only strongly down-regulated endothelial cell proliferation, clonogenicity and tube formation ability rather it strongly (p<0.001) reduced migratory and invasive properties of PCa cells which were otherwise marginally affected by IR treatment alone. Most of the pro-angiogenic (VEGF, iNOS), migratory (MMP-2) and EMT promoting proteins (uPA, vimentin, N-cadherin) were up-regulated by IR in PCa cells. Interestingly, all of these invasive and EMT promoting actions of IR were markedly decreased by silibinin. Further, we found that potentiated effect was an end result of attenuation of IR-activated mitogenic and pro-survival signaling, including Akt, Erk1/2 and STAT-3, by silibinin.
PMID: 25446081 [PubMed - indexed for MEDLINE]
"Spooky actions at a distance": physics, psi, and distant healing.
J Altern Complement Med. 2005 Oct;11(5):923-30
Authors: Leder D
Over decades, consciousness research has accumulated evidence of the real and measureable existence of "spooky actions at a distance"--modes of telepathy, telekinesis, clairvoyance, and the like. More recently scientists have begun rigorous study of the effects of distant healing intention and prayer vis-a-vis nonhuman living systems and patients in clinical trials. A barrier to taking such work seriously may be the belief that it is fundamentally incompatible with the scientific world view. This article suggests that it need not be; contemporary physics has generated a series of paradigms that can be used to make sense of, interpret, and explore "psi" and distant healing. Four such models are discussed, two drawn from relativity theory and two from quantum mechanics. First is the energetic transmission model, presuming the effects of conscious intention to be mediated by an as-yet unknown energy signal. Second is the model of path facilitation. As gravity, according to general relativity, "warps" space-time, easing certain pathways of movement, so may acts of consciousness have warping and facilitating effects on the fabric of the surrounding world. Third is the model of nonlocal entanglement drawn from quantum mechanics. Perhaps people, like particles, can become entangled so they behave as one system with instantaneous and unmediated correlations across a distance. Last discussed is a model involving actualization of potentials. The act of measurement in quantum mechanics collapses a probabilistic wave function into a single outcome. Perhaps conscious healing intention can act similarly, helping to actualize one of a series of possibilities; for example, recovery from a potentially lethal tumor. Such physics-based models are not presented as explanatory but rather as suggestive. Disjunctions as well as compatibilities between the phenomena of modern physics and those of psi and distant healing are explored.
PMID: 16296928 [PubMed - indexed for MEDLINE]
Pancreas: healing response in critical illness.
Crit Care Med. 2003 Aug;31(8 Suppl):S582-9
Authors: Bentrem DJ, Joehl RJ
OBJECTIVE: The pathophysiology of acute pancreatitis represents a diverse mix of congenital, hereditary, and acquired problems associated with or causing acute pancreatic inflammation. Acute pancreatitis is characterized by acinar cell injury that may involve regional and systemic inflammatory responses. The systemic manifestations of acute pancreatitis are responsible for the majority of pancreatitis-associated morbidity and are due to the actions of specific inflammatory cytokines. This report summarizes this pancreatic injury, the role of cytokines in the pathogenesis of acute pancreatitis, and the pancreatic healing response that follows.
DESIGN: A comprehensive literature review of experimental pancreatitis as well as reports of cytokine involvement and healing response during clinical pancreatitis was performed.
RESULTS: Histamine release, bradykinin generation, and cytokine release play a significant role during acute pancreatic inflammation. Following an experimental insult, there is rapid expression of tumor necrosis factor-alpha, interleukin-6, interleukin-1, and chemokines by pancreatic acinar cells and/or transmigrated leukocytes. Preventing the action of these mediators has a profound beneficial effect in experimental animals. Pancreatic fibrosis is a central histologic response after pancreatitis. Transient collagen deposition with acinar necrosis occurs in acute pancreatitis; in chronic pancreatitis, permanent and disorganized pancreatic fibrosis and parenchymal cell atrophy occur.
CONCLUSIONS: Inflammatory mediators are responsible for the systemic manifestations of acute pancreatitis and the associated distant organ dysfunction. After the acute injury, regeneration or pancreatic repair is characterized by decreased release of proinflammatory mediators and decreased infiltrating inflammatory cells. Differentiation and proliferation of pancreatic myofibroblasts or "stellate" cells may be responsible for increased extracellular matrix production. The predictable nature in which the inflammation and fibrosis are produced may stimulate novel approaches to disease treatment.
PMID: 12907888 [PubMed - indexed for MEDLINE]
Investigation of the growth and metastasis of malignant melanoma in a murine model: the role of supplemental vitamin A.
Plast Reconstr Surg. 2003 Jul;112(1):152-8; discussion 159-61
Authors: Weinzweig J, Tattini C, Lynch S, Zienowicz R, Weinzweig N, Spangenberger A, Edstrom L
Vitamin A possesses both wound-healing and antitumor actions. Vitamin A-induced fibroplasia results in subsequent increased collagen production and deposition. This effect of vitamin A has been shown to result in the production of collagenous capsules around several murine breast and lung tumor systems. This tumor encapsulation process can potentially convert a systemic disease to a local one that can be easily treated by tumor excision. The goal of the present study was to determine whether supplemental vitamin A could promote the encapsulation of a murine melanoma. Sixty DBA/2J male mice were inoculated intracutaneously with 1 x 106 Cloudman S91 melanoma cells using a 30-gauge needle. The mice were divided into three groups: a control group, a pre-vitamin A group, and a post-vitamin A group. The control mice were fed a commercial chow containing 15,000 IU of vitamin A and 6.4 mg of beta-carotene per kilogram diet, considerably more than the National Research Council's recommended daily allowance of vitamin A for normal mice. The control diet was, therefore, not vitamin A-deficient. The pre-vitamin A mice were fed the basal chow supplemented with 150,000 IU of vitamin A per kilogram diet for 10 days before inoculation and for the remainder of the study. The post-vitamin A mice were fed the vitamin A-supplemented diet beginning on the day of inoculation and continuing for the remainder of the study. Sixty days after inoculation, tumor growth was assessed and the five mice remaining in each group were euthanized. Ventral skin at the site of inoculation was harvested for histologic assessment of local tumor growth and invasiveness. The liver and lungs of each of these mice were also harvested for histologic assessment of tumor metastasis. Sixty days after tumor inoculation, a 60 percent survival rate was observed in the control group as opposed to the vitamin A-supplemented animals, which demonstrated a 100 percent survival rate in both groups (n = 5 in each group). Decreased mean tumor size and gross tumor in most vitamin A-supplemented animals were statistically significant when compared with the control animals. The control animals had a mean tumor size of 26.1 mm, whereas the post-vitamin A group had a mean tumor size of 5.7 mm. One hundred percent of the control group exhibited tumor; one animal had distant metastases. The pre-vitamin A group did not exhibit any tumor growth, and the post-vitamin A group exhibited tumor growth in 40 percent of animals. Neither vitamin A-supplemented group showed any evidence of distant metastases. The animals supplemented with vitamin A demonstrated decreased tumor growth and metastasis. This in vivo model may indicate a potential prophylactic and therapeutic role for supplemental vitamin A in the treatment of malignant melanoma.
PMID: 12832888 [PubMed - indexed for MEDLINE]