美阿尔贡国家实验室发现217种新抗癌靶子

The  study  centers  on  capillary  formation,  or  angiogenesis,  a  process  shown  to  be  essential  to  tumor  progression  as  tumors  attract  capillaries  to  provide  oxygen  essential  for  growth  and  frequently  use  those  same  vessels  to  send  out  metastatic  cells.  By  zeroing  in  on  these  capillary-forming  proteins,  drug  researchers  may  be  able  to  treat  a  tumor  by  directly  cutting  off  its  blood  supply.

Drug  researchers,  using  tools  available  since  the  human  genome  was  sequenced,  seek  specific  targets  to  develop  more  precise  cancer  drugs  with  fewer  side  effects.  "Once  you  have  a  unique  target,"  explained  biologist  Diane  Rodi,  "you  don't  have  the  side  effects  of  the  drugs  –  most  cancer  drugs  are  anti-growth  drugs  that  kill  all  the  growing  cells  in  the  body.  Most  cancer  therapies  are  not  very  specific  and  that  is  why  they  are  so  toxic."

The  Argonne  biologists  identified  217  proteins  involved  only  in  capillary  formation  --  morphogenesis  --  by  finding  all  the  gene  products  turned  on  during  capillary  formation  and  subtracting  out  those  related  only  to  growth,  or  proliferation,  in  a  novel  process  called  subtractive  transcriptomics.

Argonne  biologists  grew  human  endothelial  cells  –  the  cells  involved  in  blood  vessel  formation  –  on  a  tumor  tissue-mimicking  plate.  As  the  capillaries  grew  over  an  8-hour  period,  researchers  isolated  RNA  samples  at  intervals  –  at  30  minutes,  1  hour,  2  hours,  4  hours  and  8  hours.  To  determine  which  genes  do  not  contribute  specifically  to  blood  vessel  formation,  endothelial  cells  were  grown  on  gelatin-coated  plastic.  RNA  was  isolated  at  the  same  intervals  as  on  the  tumor  tissue-mimicking  plate.

Each  RNA  sample  was  tested  using  microarray  analysis  at  the  University  of  Chicago.  The  microarrays  hold  44,000  samples  of  known  RNA  coded  by  the  human  genome.  A  reaction  reveals  the  RNA  that  is  being  produced  at  each  stage  of  the  biological  process.  RNA  codes  for  proteins.   (责任编辑：泉水)

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美阿尔贡国家实验室发现217种新抗癌靶子