ノート/テキストマイニング
訪問者数 643      最終更新 2010-09-03 (金) 17:41:37

以下、未完成。

Trial 1 (2010-8-31)

SEED 〜 Start with "Trastuzumab" 〜 Search PubMed

背景知識: ウィキペディアから
トラスツズマブ(Trastuzumab)はヒト癌遺伝子HER2/neu(c-erbB-2)の遺伝子産物であるHER2蛋白に特異的に結合する事で抗腫瘍効果を発揮する抗がん剤。癌の増殖などに関係する特定の分子を狙い撃ちする分子標的治療薬の一種である。

同じような原理で作用するものはないか? つまりTrastuzumabそのものではなくて、 その作用原理のようなところに興味がある、とする。

PubMed "Trastuzumab" Search --> 3573 listed.

初期の論文(PubMed Searchで時間順の最後のページ)を見てみた。http://www.ncbi.nlm.nih.gov/pubmed

Results: 3561 to 3573 of 3573

3561.  Progress in breast cancer treatment: prevention, new therapies come to forefront.
Miller JL.
Am J Health Syst Pharm. 1998 Nov 15;55(22):2326, 2328, 2330. No abstract available.
PMID: 9825027 [PubMed - indexed for MEDLINE]Related citations

3562.  Trastuzumab and capecitabine for metastatic breast cancer.
[No authors listed]
Med Lett Drugs Ther. 1998 Nov 6;40(1039):106-8. No abstract available.
PMID: 9814369 [PubMed - indexed for MEDLINE]Related citations
 
3563.  New breast cancer drug.
[No authors listed]
Harv Womens Health Watch. 1998 Nov;6(3):7. No abstract available.
PMID: 9814134 [PubMed - indexed for MEDLINE]Related citations
 
3564.  Novel approaches in development for the treatment of pancreatic cancer.
Butera J, Malachovsky M, Rathore R, Safran H.
Front Biosci. 1998 Nov 1;3:E226-9. Review.
PMID: 9792896 [PubMed - indexed for MEDLINE]Related citations

3565.  Pharmacogenomics at work.
[No authors listed]
Nat Biotechnol. 1998 Oct;16(10):885. No abstract available. 
PMID: 9788323 [PubMed - indexed for MEDLINE]Related citations

3566.  [Cancerology: search for better therapeutic schemes]
Mabro M.
Presse Med. 1998 Jul 4-11;27(24):1228-30. French. No abstract available.
PMID: 9767784 [PubMed - indexed for MEDLINE]Related citations

3567.  HER-2 breast assay, linked to Herceptin, wins FDA's okay.
Graziano C.
CAP Today. 1998 Oct;12(10):1, 14-6. No abstract available. 
PMID: 10187049 [PubMed - indexed for MEDLINE]Related citations

3568.  Phase II study of receptor-enhanced chemosensitivity using recombinant humanized
anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with
HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment.
Pegram MD, Lipton A, Hayes DF, Weber BL, Baselga JM, Tripathy D, Baly D,
Baughman SA, Twaddell T, Glaspy JA, Slamon DJ.
J Clin Oncol. 1998 Aug;16(8):2659-71.
PMID: 9704716 [PubMed - indexed for MEDLINE]Related citations

3569.  [New antibody for breast cancer therapy. Interview by Brigitte Schalhorn.]
Eiermann W.
Fortschr Med. 1998 Jun 30;116(18-19):18. German. No abstract available. 
PMID: 9691532 [PubMed - indexed for MEDLINE]Related citations

3570.  Breast cancer biology blossoms in the clinic.
Nass SJ, Hahm HA, Davidson NE.
Nat Med. 1998 Jul;4(7):761-2. No abstract available.
PMID: 9662357 [PubMed - indexed for MEDLINE]Related citations

3571.  Recombinant humanized anti-HER2 antibody (Herceptin) enhances the antitumor
activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts.
Baselga J, Norton L, Albanell J, Kim YM, Mendelsohn J.
Cancer Res. 1998 Jul 1;58(13):2825-31. Erratum in: Cancer Res 1999 Apr 15;59(8):2020.
PMID: 9661897 [PubMed - indexed for MEDLINE]Free ArticleRelated citations

3572.  Genentech's anticancer Mab expected by November.
Robertson D.
Nat Biotechnol. 1998 Jul;16(7):615. No abstract available.
PMID: 9661186 [PubMed - indexed for MEDLINE]Related citations

3573.  Herceptin raises its sights beyond advanced breast cancer.
McNeil C.
J Natl Cancer Inst. 1998 Jun 17;90(12):882-3. No abstract available.
PMID: 9637135 [PubMed - indexed for MEDLINE]Free ArticleRelated citations

さてここで1つだけ論文を選んでみる(たとえばなるべく初期の提案レベルの論文?)。それの Abstract を取り出す

http://www.ncbi.nlm.nih.gov/pubmed/9661897

Cancer Res. 1998 Jul 1;58(13):2825-31.
Recombinant humanized anti-HER2 antibody (Herceptin) enhances the antitumor activity
of paclitaxel and doxorubicin against HER2/neu overexpressing human breast
cancer xenografts.

Baselga J, Norton L, Albanell J, Kim YM, Mendelsohn J.

Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. baselga@hg.vhebron.es

Erratum in:
    * Cancer Res 1999 Apr 15;59(8):2020. 

Abstract
Recombinant humanized anti-HER2 antibody, rhuMAb HER2, inhibits the growth of
breast cancer cells overexpressing HER2 and has clinical activity. We explored
in preclinical models its capacity to enhance the tumoricidal effects of
paclitaxel and doxorubicin. In cultures of naturally HER2-overexpressing
cancer cells, rhuMAb HER2 inhibited growth and enhanced the cytotoxic effects
of paclitaxel. Treatment of well established BT-474 breast cancer xenografts
overexpressing HER2 in athymic mice with rhuMAb HER2 resulted in a
dose-dependent antitumor activity. In combination studies, treatment with
paclitaxel and rhuMAb HER2 or doxorubicin and rhuMAb HER2 resulted in greater
inhibition of growth than that observed with any agent alone. The combination
of paclitaxel and rhuMAb HER2 resulted in the highest tumor growth inhibition
and had a significantly superior complete tumor regression rate when compared
with either paclitaxel or rhuMAb HER2 alone. Clinical trials that are built on
these results are under way.

PMID: 9661897 [PubMed - indexed for MEDLINE]Free Article

このAbstractの言っていること(意味の論理構造?)を追いかけてみる。〜訳す?

ここから、次のように考えてみる。

この論文では、rhuMAb HER2 がどういうものか・どういう効果があるかを論じている。
(そのことは、おそらくキーワード抽出をすればrhuMAb HER2がキーワードとして採れるだろう)
rhuMAb HER2を含むdependency関係を抽出して、何が言えるか?
つまり、一般化して考えるとして、多数の例について、
最重要キーワード(どうやって見つけるかは別の大きな問題だが)を中心にして
そのキーワードを含むdependency関係を羅列してみて、何らかの欲しい性向が無いか見る、
という実験ができるだろう。

で、やってみよう。

Depencency関係の(Stanford Parserによる)抽出

(ROOT
  (S
    (NP
      (NP
        (JJ Recombinant)
        (JJ humanized)
        (JJ anti-HER2)
        (NN antibody))
      (, ,)
      (NP (JJ rhuMAb) (NN HER2))
      (, ,))
    (VP
      (VP
        (VBZ inhibits)
        (NP
          (NP (DT the) (NN growth))
          (PP (IN of) (NP (NN breast) (NN cancer) (NNS cells))))
        (S (VP (VBG overexpressing) (NP (NN HER2)))))
      (CC and)
      (VP (VBZ has) (NP (JJ clinical) (NN activity))))
    (. .)))
(ROOT
  (S
    (NP (PRP We))
    (VP
      (VBD explored)
      (PP (IN in) (NP (JJ preclinical) (NNS models)))
      (NP
        (PRP$ its)
        (NN capacity)
        (S
          (VP
            (TO to)
            (VP
              (VB enhance)
              (NP
                (NP (DT the) (JJ tumoricidal) (NNS effects))
                (PP
                  (IN of)
                  (NP (NN paclitaxel) (CC and) (NN doxorubicin)))))))))
    (. .)))
(ROOT
  (S
    (PP
      (IN In)
      (NP
        (NP (NNS cultures))
        (PP
          (IN of)
          (NP
            (ADJP (RB naturally) (JJ HER2-overexpressing))
            (NN cancer)
            (NNS cells)))))
    (, ,)
    (NP (NN rhuMAb) (NN HER2))
    (VP
      (VP (VBD inhibited) (NP (NN growth)))
      (CC and)
      (VP
        (VBD enhanced)
        (NP
          (NP (DT the) (JJ cytotoxic) (NNS effects))
          (PP (IN of) (NP (NN paclitaxel))))))
    (. .)))
(ROOT
  (S
    (NP
      (NP (NNP Treatment))
      (PP
        (IN of)
        (NP
          (NP
            (ADJP (RB well) (JJ established))
            (NN BT-474)
            (NN breast)
            (NN cancer)
            (NNS xenografts))
          (VP
            (VBG overexpressing)
            (NP (NN HER2))
            (PP
              (IN in)
              (NP
                (NP (JJ athymic) (NNS mice))
                (PP (IN with) (NP (JJ rhuMAb) (NN HER2)))))))))
    (VP
      (VBD resulted)
      (PP
        (IN in)
        (NP (DT a) (JJ dose-dependent) (NN antitumor) (NN activity))))
    (. .)))
(ROOT
  (S
    (PP (IN In) (NP (NN combination) (NNS studies)))
    (, ,)
    (NP
      (NP (NN treatment))
      (PP
        (IN with)
        (NP
          (ADJP (JJ paclitaxel) (CC and) (JJ rhuMAb))
          (NN HER2)
          (CC or)
          (NN doxorubicin)
          (CC and)
          (NN rhuMAb)
          (NN HER2))))
    (VP
      (VBD resulted)
      (PP
        (IN in)
        (NP
          (NP (JJR greater) (NN inhibition))
          (PP (IN of) (NP (NN growth)))))
      (SBAR
        (IN than)
        (S
          (NP (DT that))
          (VP
            (VBD observed)
            (PP (IN with) (NP (DT any) (NN agent)))
            (ADVP (RB alone))))))
    (. .)))
(ROOT
  (S
    (NP
      (NP (DT The) (NN combination))
      (PP
        (IN of)
        (NP (ADJP (JJ paclitaxel) (CC and) (JJ rhuMAb)) (NN HER2))))
    (VP
      (VP
        (VBD resulted)
        (PP
          (IN in)
          (NP
            (DT the)
            (ADJP (JJS highest) (NN tumor))
            (NN growth)
            (NN inhibition))))
      (CC and)
      (VP
        (VBD had)
        (NP
          (NP
            (DT a)
            (ADJP (RB significantly) (JJ superior))
            (JJ complete)
            (NN tumor)
            (NN regression)
            (NN rate))
          (SBAR
            (WHADVP (WRB when))
            (S
              (VP
                (VBN compared)
                (PP
                  (IN with)
                  (NP
                    (DT either)
                    (ADJP (JJ paclitaxel) (CC or) (JJ rhuMAb))
                    (NN HER2))
                  (ADVP (RB alone)))))))))
    (. .)))
(ROOT
  (S
    (NP
      (NP (JJ Clinical) (NNS trials))
      (SBAR
        (WHNP (WDT that))
        (S
          (VP
            (VBP are)
            (VP
              (VBN built)
              (PP (IN on) (NP (DT these) (NNS results))))))))
    (VP (VBP are) (PP (IN under) (NP (NN way))))
    (. .)))
===
   amod / antibody / Recombinant *** antibody-4  Recombinant-1
   amod / antibody / humanize *** antibody-4  humanized-2
   amod / antibody / anti-HER2 *** antibody-4  anti-HER2-3
   nsubj / inhibits / antibody *** inhibits-9  antibody-4
   nsubj / ha / antibody *** has-19  antibody-4
   amod / HER2 / rhuMAb *** HER2-7  rhuMAb-6
   appos / antibody / HER2 *** antibody-4  HER2-7
   dobj / inhibits / growth *** inhibits-9  growth-11
   nn / cell / breast *** cells-15  breast-13
   nn / cell / cancer *** cells-15  cancer-14
   prep_of / growth / cell *** growth-11  cells-15
   xcomp / inhibits / overexpressing *** inhibits-9  overexpressing-16
   dobj / overexpressing / HER2 *** overexpressing-16  HER2-17
   conj_and / inhibits / ha *** inhibits-9  has-19
   amod / activity / clinical *** activity-21  clinical-20
   dobj / ha / activity *** has-19  activity-21
---
   nsubj / explore / We *** explored-2  We-1
   amod / model / preclinical *** models-5  preclinical-4
   prep_in / explore / model *** explored-2  models-5
   poss / capacity / it *** capacity-7  its-6
   dobj / explore / capacity *** explored-2  capacity-7
   aux / enhance / to *** enhance-9  to-8
   infmod / capacity / enhance *** capacity-7  enhance-9
   amod / effect / tumoricidal *** effects-12  tumoricidal-11
   dobj / enhance / effect *** enhance-9  effects-12
   prep_of / effect / paclitaxel *** effects-12  paclitaxel-14
   prep_of / effect / doxorubicin *** effects-12  doxorubicin-16
   conj_and / paclitaxel / doxorubicin *** paclitaxel-14  doxorubicin-16
---
   prep_in / inhibit / culture *** inhibited-11  cultures-2
   advmod / HER2-overexpressing / naturally *** HER2-overexpressing-5  n aturally-4
   amod / cell / HER2-overexpressing *** cells-7  HER2-overexpressing-5
   nn / cell / cancer *** cells-7  cancer-6
   prep_of / culture / cell *** cultures-2  cells-7
   nn / HER2 / rhuMAb *** HER2-10  rhuMAb-9
   nsubj / inhibit / HER2 *** inhibited-11  HER2-10
   nsubj / enhance / HER2 *** enhanced-14  HER2-10
   dobj / inhibit / growth *** inhibited-11  growth-12
   conj_and / inhibit / enhance *** inhibited-11  enhanced-14
   amod / effect / cytotoxic *** effects-17  cytotoxic-16
   dobj / enhance / effect *** enhanced-14  effects-17
   prep_of / effect / paclitaxel *** effects-17  paclitaxel-19
---
   nsubj / result / Treatment *** resulted-17  Treatment-1
   advmod / established / well *** established-4  well-3
   amod / xenograft / establish *** xenografts-8  established-4
   nn / xenograft / BT-474 *** xenografts-8  BT-474-5
   nn / xenograft / breast *** xenografts-8  breast-6
   nn / xenograft / cancer *** xenografts-8  cancer-7
   prep_of / Treatment / xenograft *** Treatment-1  xenografts-8
   partmod / xenograft / overexpressing *** xenografts-8  overexpressing-9
   dobj / overexpressing / HER2 *** overexpressing-9  HER2-10
   amod / mouse / athymic *** mice-13  athymic-12
   prep_in / overexpressing / mouse *** overexpressing-9  mice-13
   amod / HER2 / rhuMAb *** HER2-16  rhuMAb-15
   prep_with / mouse / HER2 *** mice-13  HER2-16
   amod / activity / dose-dependent *** activity-22  dose-dependent-20
   nn / activity / antitumor *** activity-22  antitumor-21
   prep_in / result / activity *** resulted-17  activity-22
---
   nn / study / combination *** studies-3  combination-2
   prep_in / result / study *** resulted-16  studies-3
   nsubj / result / treatment *** resulted-16  treatment-5
   amod / HER2 / paclitaxel *** HER2-10  paclitaxel-7
   conj_and / paclitaxel / rhuMAb *** paclitaxel-7  rhuMAb-9
   amod / HER2 / rhuMAb *** HER2-10  rhuMAb-9
   prep_with / treatment / HER2 *** treatment-5  HER2-10
   prep_with / treatment / doxorubicin *** treatment-5  doxorubicin-12
   conj_or / HER2 / doxorubicin *** HER2-10  doxorubicin-12
   nn / HER2 / rhuMAb *** HER2-15  rhuMAb-14
   prep_with / treatment / HER2 *** treatment-5  HER2-15
   conj_and / HER2 / HER2 *** HER2-10  HER2-15
   amod / inhibition / greater *** inhibition-19  greater-18
   prep_in / result / inhibition *** resulted-16  inhibition-19
   prep_of / inhibition / growth *** inhibition-19  growth-21
   mark / observe / than *** observed-24  than-22
   nsubj / observe / that *** observed-24  that-23
   advcl / result / observe *** resulted-16  observed-24
   prep_with / observe / agent *** observed-24  agent-27
   advmod / observe / alone *** observed-24  alone-28
---
   nsubj / result / combination *** resulted-8  combination-2
   nsubj / have / combination *** had-16  combination-2
   amod / HER2 / paclitaxel *** HER2-7  paclitaxel-4
   conj_and / paclitaxel / rhuMAb *** paclitaxel-4  rhuMAb-6
   amod / HER2 / rhuMAb *** HER2-7  rhuMAb-6
   prep_of / combination / HER2 *** combination-2  HER2-7
   dep / tumor / highest *** tumor-12  highest-11
   amod / inhibition / tumor *** inhibition-14  tumor-12
   nn / inhibition / growth *** inhibition-14  growth-13
   prep_in / result / inhibition *** resulted-8  inhibition-14
   conj_and / result / have *** resulted-8  had-16
   advmod / superior / significantly *** superior-19  significantly-18
   amod / rate / superior *** rate-23  superior-19
   amod / rate / complete *** rate-23  complete-20
   nn / rate / tumor *** rate-23  tumor-21
   nn / rate / regression *** rate-23  regression-22
   dobj / have / rate *** had-16  rate-23
   advmod / rate / when *** rate-23  when-24
   rel / rate / when *** rate-23  when-24
   amod / HER2 / paclitaxel *** HER2-31  paclitaxel-28
   conj_or / paclitaxel / rhuMAb *** paclitaxel-28  rhuMAb-30
   amod / HER2 / rhuMAb *** HER2-31  rhuMAb-30
   prep_compared_with / rate / HER2 *** rate-23  HER2-31
   dep / rate / alone *** rate-23  alone-32
---
   amod / trial / Clinical *** trials-2  Clinical-1
   nsubjpass / build / trial *** built-5  trials-2
   nsubj / are / trial *** are-9  trials-2
   auxpass / build / are *** built-5  are-4
   rcmod / trial / build *** trials-2  built-5
   prep_on / build / result *** built-5  results-8
   prep_under / are / way *** are-9  way-11
---
===

キーワードに関係するDepencency関係を詳細に見てみる

これらのうち、キーワードとの意味的つながりが「重要(ここでの意味合いで)」と考えられるdependency関係をリストしてみる。

第1文では、

HER2-7  (amod)  rhuMAb-6          "rhuMAb HER2"
antibody-4 (appos) HER2-7         "antibody, ...HER2, "
inhibits-9 (nsubj) antibody-4     "antibody ... inhibits"
(inhibitsの対象)
inhibits-9 (dobj) growth-11       "inhibits growth ... "
(growthの対象)
growth-11 (prep_of) cell-15       " growth of cells"

構文木で見れば

(ROOT
  (S
    (NP
      (NP
        (JJ Recombinant)
        (JJ humanized)
        (JJ anti-HER2)
        (NN antibody))
      (, ,)
      (NP (JJ rhuMAb) (NN HER2))
      (, ,))
    (VP
      (VP
        (VBZ inhibits)
        (NP
          (NP (DT the) (NN growth))
          (PP (IN of) (NP (NN breast) (NN cancer) (NNS cells))))
        (S (VP (VBG overexpressing) (NP (NN HER2)))))
      (CC and)
      (VP (VBZ has) (NP (JJ clinical) (NN activity))))
    (. .)))

第2文では、rhuMAb HER2 という語は陽には出てきておらず、it (its capacity to enhance ... ) という形で言われている。どうするべきか?

もし it = rhuMAb HER2 が判定できるなら(難しいかもしれない)、

capacity-7  (poss)  its-6          "its capacity"
explored-2  (dobj)  capacity-7     "explored ... its capacity"
capacity-7  (infmod)  enhance-9    "capacity to enhance ..."
enhance-9  (dobj)  effects-12      "enhance ... effect ..."
effect-12  (prep_of)  paclitaxel-14  "effect of paclitaxel and doxorubicin"
effect-12  (prep_of)  doxorubicin-16

第3文では、再度 rhuMAb HER2 という語があって、

HER2-10  (nn)  rhuMAb-9          "rhuMAb HER2"
inhibited-11  (nsubj)  HER2-10     "rhuMAb HER2 inhibited growth"
enhanced-14   (nsubj)  HER2-10     "rhuMAb HER2 ... enhanced the cytotoxic effects"
inhibited-11  (dobj)  growth-12
enhanced-14  (dobj)  effect-17
effect-17  (prep_of)  paclitaxel-19  "effects of paclitaxel"

第4文では、

HER2-16  (amod)  rhuMAb-15       "rhuMAb HER2"
mice-13  (prep_with)  HER2-16    "mice with rhuMAb HER2"
ここで欲しい構文になっていない? "overexpressing HER2"は"xenografts"を修飾すると考えるべきで?
xenografts-8 in mice-13が、"Treatments of xenografts in mice with rhuMAb HER2"と
つながって欲しいのではないか?
そうすれば、"Treatments with rhuMAb HER2 resulted in a dose-dependent antitumor activity"
が得られる。

第5文では、(まだ書きかけ途中)

重要なdependency関係とは?

横道だが、キーワード抽出プログラムで何が採れるか試す

キーワード抽出 --> たとえばGenSen Web (for English) を利用〜抽出原理は何か? http://gensen.dl.itc.u-tokyo.ac.jp/gensenweb_eng.html

結果 (score値〜non-Perplexity modeを併記)

HER2                                                                     9.00
rhuMAb                                                                   7.00
paclitaxel                                                               4.00
growth                                                                   3.00
growth of breast cancer cell                                             2.81
tumor growth inhibition                                                  2.45
inhibition of growth                                                     2.45
BT-474 breast cancer xenograft                                           2.21
HER2-overexpressing cancer cell                                          2.14
cytotoxic effect of paclitaxel                                           2.04
tumoricidal effect of paclitaxel                                         2.04
doxorubicin                                                              2.00
combination of paclitaxel                                                1.86
superior complete tumor regression rate                                  1.81
dose-dependent antitumor activity                                        1.70
combination study                                                        1.57
clinical activity                                                        1.57
Recombinant humanized                                                    1.41
Clinical trial                                                           1.41
anti-HER2 antibody                                                       1.41
preclinical model                                                        1.41
athymic mice                                                             1.41
way                                                                      1.00
Treatment                                                                1.00
culture                                                                  1.00
capacity                                                                 1.00
treatment                                                                1.00
inhibit                                                                  1.00
agent                                                                    1.00
result                                                                   1.00

確かに、rhuMAbとHER2が採れている。ただし、別々になっている。HER2単独では、意味(意図)的には逆向きなことに注意。

比較 〜 PubMed上でキーワード検索((単独のキーワード、複数キーワードのAND条件)

PubMed上で、同じキーワードセットを含む論文を検索し、結果がどれだけ残るかテスト。
たとえば、先頭3つのキーワードの組み合せについて、検索結果。

<1語のみ>

HER2rhuMAbpaclitaxelgrowthgrowth of breast
cancer cell
tumor growth inhibition
ヒトEGFR関連物質2
(human EGFR-related 2)
薬剤taxolの一般名
58311151859914304742520948989

<2語のAND>

HER2rhuMAbpaclitaxelgrowth of breast
cancer cell
tumor growth inhibition
HER2263321140443
rhuMAb41113
paclitaxel568793
growth of breast
cancer cell
5659
tumor growth inhibition

<3語のAND>


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Last-modified: 2010-09-03 (金) 17:41:37 (2575d)