Vatalanib

Vatalanib (INN, codenamed PTK787 or PTK/ZK) is a small molecule protein kinase inhibitor that inhibits angiogenesis. It is being studied as a possible treatment for several types of cancer, particularly cancer that is at an advanced stage or has not responded to chemotherapy. Vatalanib is orally active, that is, it is effective when taken by mouth.

Vatalanib is being developed by Bayer Schering and Novartis. It inhibits all known VEGF receptors, as well as platelet-derived growth factor receptor-beta and c-kit, but is most selective for VEGFR-2.

Development

Vatalanib was discovered through high-throughput screening. It has been extensively investigated in Phase I, II and III clinical trials. Two large, randomized controlled Phase III trials have studied the effect of adding vatalanib to the FOLFOX chemotherapy regimen in people with metastatic colorectal cancer: CONFIRM-1, whose participants had not yet received any treatment for their cancer; and CONFIRM-2, in which participants had received first-line treatment with irinotecan and fluoropyrimidines. Vatalanib produced no significant improvement in overall survival (the primary endpoint of the studies), although it did significantly increase progression-free survival in CONFIRM-2. Both trials found that progression-free survival was improved in people with high levels of lactate dehydrogenase, an enzyme used as a marker of tissue breakdown; the reasons for and implications of this difference are still unclear.

PTK2

PTK2 protein tyrosine kinase 2 (PTK2), also known as Focal Adhesion Kinase (FAK), is a protein that, in humans, is encoded by the PTK2 gene. PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion (how cells stick to each other and their surroundings) and spreading processes (how cells move around). It has been shown that when FAK was blocked, breast cancer cells became less metastatic due to decreased mobility.

Function

This gene encodes a cytosolic protein tyrosine kinase that is found concentrated in the focal adhesions that form among cells attaching to extracellular matrix constituents. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases that included PYK2, but lacks significant sequence similarity to kinases from other subfamilies. With the exception of certain types of blood cells, most cells express FAK. FAK tyrosine kinase activity can be activated, which plays a key important early step in cell migration. FAK activity elicits intracellular signal transduction pathways that promote the turn-over of cell contacts with the extracellular matrix, promoting cell migration. FAK is required during development, with loss of FAK resulting in lethality. It seems to be a paradox that FAK is not absolutely required for cell migration, and may play other roles in the cell, including the regulation of the tumor suppressor p53. At least four transcript variants encoding four different isoforms have been found for this gene, but the full-length natures of only two of them have been determined.

PTK6

Tyrosine-protein kinase 6 is an enzyme that in humans is encoded by the PTK6 gene.

Function

Tyrosine-protein kinase 6 (also known as Breast Tumor Kinase, Brk) is a cytoplasmic non-receptor protein kinase which may function as an intracellular signal transducer in epithelial tissues. The encoded protein has been shown to undergo autophosphorylation.

Clinical significance

Overexpression of this gene in mammary epithelial cells leads to sensitization of the cells to epidermal growth factor and results in a partially transformed phenotype. Expression of this gene has been detected at low levels in some breast tumors but not in normal breast tissue.

Interactions

PTK6 has been shown to interact with STAP2 and KHDRBS1.

References

Further reading

Movement

Movement may refer to:

Society and the arts

Music

She Wolf

She Wolf (Spanish: Loba) is the eighth studio album by Colombian singer-songwriter Shakira. It was released on 9 October 2009, by Epic Records and Sony Music Latin. As executive producers, Shakira and Amanda Ghost enlisted collaborators including The Neptunes, John Hill, Wyclef Jean, Lukas Burton, Future Cut, Jerry Duplessis and Timbaland. Musically, the record shifts from her traditional Latin pop and pop rock musical styles, instead exploring electropop, with influences of folk and world music. The lyrical themes of the album mostly focus on love and relationships and were based on the conversations Shakira had with her friends.

She Wolf reached number one on the charts of Argentina, Ireland, Italy, Mexico and Switzerland. It also charted inside the top five in Spain, Germany and the United Kingdom. It debuted at number fifteen on the Billboard 200. She Wolf was certified double-platinum in Colombia and Mexico, platinum in Italy and Spain, and gold in numerous countries including France and the United Kingdom.

Movement (clockwork)

In horology, a movement, also known as a caliber, is the mechanism of a clock or watch, as opposed to the case, which encloses and protects the movement, and the face which displays the time. The term originated with mechanical timepieces, whose clockwork movements are made of many moving parts. It is less frequently applied to modern electronic or quartz timepieces, where the word module is often used instead.

In modern mass-produced clocks and watches, the same movement is often inserted into many different styles of case. When buying a quality pocketwatch from the mid-19th to the mid-20th century, for example, the customer would select movement and case individually. Mechanical movements get dirty and the lubricants dry up, so they must periodically be disassembled, cleaned, and lubricated. One source recommends servicing intervals of: 3–5 years for watches, 15–20 years for grandfather clocks, 10–15 years for wall or mantel clocks, 15–20 years for anniversary clocks, and 7 years for cuckoo clocks, with the longer intervals applying to antique timepieces.