statement of the problem: recurrent aphthous stomatitis (ras) is one of the most common lesions in the oral cavity. due to its multifactorial nature, there is no definitive treatment for ras. laser therapy is one of the suggested treatments to reduce patient’s discomfort. purpose: the purpose of the present clinical trial is to assess the effect of low and high level laser therapy on pain contr...

4. 3.1. 3.2. 3.3. 3.4. The Renin Angiotensin System (RAS) . . . . . . . . . . . . . . . . . . . . . . . . . . In Vitro Assays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Renin Inhibitor Design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Novel Transition-State Analogues . . . . . . . . . . . . . . . . . . . ....

The brain renin-angiotensin system (RAS) has been highlighted as having a pathological role in stroke, dementia, and neurodegenerative disease. Particularly, in dementia, epidemiological studies indicate a preventive effect of RAS blockade on cognitive impairment in Alzheimer disease (AD). Moreover, basic experiments suggest a role of brain angiotensin II in neural injury, neuroinflammation, an...

Monoclonal antibodies (mAbs) against the extracellular domain of the epidermal growth factor receptor (EGFR) have been introduced for the treatment of metastatic colorectal cancer (mCRC).We have reported recently that increased copy number of the EGFR can predict response to anti-EGFR mAbs and that patients might be selected for treatment based on EGFR copy number. Here, we show that mutations ...

Mutations that activate RAS proto-oncogenes and their effectors are common in acute myeloid leukemia (AML); however, efforts to therapeutically target Ras or its effectors have been unsuccessful, and have been hampered by an incomplete understanding of which effectors are required for AML proliferation and survival. We investigated the role of Ras effector pathways in AML using murine and human...

Rhabdomyosarcoma (RMS) is a childhood malignant soft tissue cancer that is derived from myogenic progenitors trapped in a permanent mode of growth. Here, we report that miR-214 is markedly down-regulated in human RMS cell lines. Although not required for embryogenesis in mice, miR-214 suppresses mouse embryonic fibroblast (MEF) proliferation. When re-introduced into RD cells, a line of human em...

Oncogenic RAS mutations are present in 15-30% of thyroid carcinomas. Endogenous expression of mutant Ras is insufficient to initiate thyroid tumorigenesis in murine models, indicating that additional genetic alterations are required. We used Sleeping Beauty (SB) transposon mutagenesis to identify events that cooperate with HrasG12V in thyroid tumor development. Random genomic integration of SB ...

OBJECTIVE Placental activation of the renin-angiotensin system (RAS) plays an important role in pathogenesis of preeclampsia. RAS induces reactive oxygen species (ROS) production by activating NADPH oxidases. Keap1-Nrf2 system is a critical regulator for cellular anti-oxidative stress response through controlling transcription of antioxidant genes. This study has explored the relationship betwe...

Activation of K-ras and inactivation of p16 are the most frequently identified genetic alterations in human pancreatic epithelial adenocarcinoma (PDAC). Mouse models engineered with mutant K-ras and deleted p16 recapitulate key pathological features of PDAC. However, a human cell culture transformation model that recapitulates the human pancreatic molecular carcinogenesis is lacking. In this st...

In the early 1980s, the oncogene field was in transition. The biological properties of more than 20 oncogenes had been described in animal tumor models and cell transformation assays. Attention was shifting to the question of how these genes actually function. In a few cases, it was obvious. The v-Sis protein (encoded by the transforming gene of simian sarcoma virus) was shown to be related to ...