Upregulation of sphingosine kinase 1 in response to doxorubicin generates an angiogenic response via stabilization of Snail.

Sphingosine kinase 1 (SK1) converts the pro-death lipid sphingosine to the pro-survival sphingosine-1-phosphate (S1P) and is upregulated in several cancers. DNA damaging agents, such as the chemotherapeutic doxorubicin (Dox), have been shown to degrade SK1 protein in cancer cells, a process dependent on wild-type p53. As mutations in p53 are very common across several types of cancer, we evaluated the effects of Dox on SK1 in p53 mutant cancer cells.

Bioactive sphingolipids: Advancements and contributions from the laboratory of Dr. Lina M. Obeid.

Sphingolipids and their synthetic enzymes have emerged as critical mediators in numerous diseases including inflammation, aging, and cancer. One enzyme in particular, sphingosine kinase (SK) and its product sphingosine-1-phosphate (S1P), has been extensively implicated in these processes. SK catalyzes the phosphorylation of sphingosine to S1P and exists as two isoforms, SK1 and SK2.

Transcriptional Regulation of Sphingosine Kinase 1.

Once thought to be primarily structural in nature, sphingolipids have become increasingly appreciated as second messengers in a wide array of signaling pathways. Sphingosine kinase 1, or SK1, is one of two sphingosine kinases that phosphorylate sphingosine into sphingosine-1-phosphate (S1P). S1P is generally pro-inflammatory, pro-angiogenic, immunomodulatory, and pro-survival; therefore, high SK1 expression and activity have been associated with certain inflammatory diseases and cancer.

A role for caspase-2 in sphingosine kinase 1 proteolysis in response to doxorubicin in breast cancer cells - implications for the CHK1-suppressed pathway.

Sphingosine kinase 1 (SK1) is a lipid kinase whose activity produces sphingosine 1-phosphate, a prosurvival lipid associated with proliferation, angiogenesis, and invasion. SK1 overexpression has been observed in numerous cancers. Recent studies have demonstrated that SK1 proteolysis occurs downstream of the tumor suppressor p53 in response to several DNA-damaging agents.

Novel Metabolic Abnormalities in the Tricarboxylic Acid Cycle in Peripheral Cells From Huntington's Disease Patients.

Metabolic dysfunction is well-documented in Huntington's disease (HD). However, the link between the mutant huntingtin (mHTT) gene and the pathology is unknown. The tricarboxylic acid (TCA) cycle is the main metabolic pathway for the production of NADH for conversion to ATP via the electron transport chain (ETC).

Abnormalities in the tricarboxylic Acid cycle in Huntington disease and in a Huntington disease mouse model.

Glucose metabolism is reduced in the brains of patients with Huntington disease (HD). The mechanisms underlying this deficit, its link to the pathology of the disease, and the vulnerability of the striatum in HD remain unknown. Abnormalities in some of the key mitochondrial enzymes involved in glucose metabolism, including the pyruvate dehydrogenase complex (PDHC) and the tricarboxylic acid (TCA) cycle, may contribute to these deficits.

History of pain concepts and pain therapy.

The development of the concept of pain and its treatment constitutes one of the most interesting and fascinating chapters in the history of medicine. The concept proposed by Aristotle and other ancient Greek philosophers that pain was a passion of the soul remained widely accepted for some 22 centuries, and treatment remained empirical and often ineffective. For a century after the scientific study of pain began, several theories were proposed, and these theories prompted the development of various therapeutic modalities.

The prevalence of pain in four cancers.

Although pain is widely recognized as a major problem in cancer patients, most studies have concentrated on pain among those with advanced or terminal cancer in specialized treatment settings. The study reported here gives a more complete picture of the problem of pain among cancer patients by providing data generalizable to those in early as well as late stages of the disease, and receiving care in the community as well as specialized treatment centers. Having included measures of several distinct features of pain, this study also provides a more complete understanding of the cancer patient's day-to-day pain problem than earlier investigations.

Importance of effective pain control.

Although the scientific study of pain in the modern sense was initiated 150 years ago, and a number of theories were subsequently proposed, until two decades ago pain research remained conceptually stagnant and the meager amount done was not commensurate with the magnitude and clinical importance of pain. Consequently, pain treatment remained somewhat empirical and ineffective. Moreover, the knowledge and effective therapeutic modalities that were available were not properly applied, primarily because medical students and physicians were not taught the basic principles of pain management.

Cardiovascular and subjective central nervous system effects of long-acting local anaesthetics in man.

Intravenous infusions of etiodocaine 50, 75 and 100 mg and bupivacaine 75 mg were carried out over ten minutes in healthy young adult males. Cardiovascular sequelae were generally trivial at all doses. A collection of subjective central nervous system symptoms were described which may be regarded as early warning of impending local anaesthetic toxicity.

Illness behavior and depression compared in pain center and private practice patients.

Recent descriptions of illness behavior and personality factors in chronic pain patients reflect patient populations at clinics dealing with refractory, multiple referral pain problems. Pain patients from the University of Washington Pain Center were compared with patients from a private practice clinic with regard to illness behavior and depression. Private practice patients were significantly less depressed, showed less conviction of disease, general hypochondriasis, affect disturbance and were less somatically focussed than the Pain Center patients.