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Immunohistochemical heterogeneity of breast carcinomas negative for estrogen receptors, progesterone receptors and Her2/neu (basal-like breast carcinomas)
被引:61
作者:

Lerma, Enrique
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机构: Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08025, Spain

Peiro, Gloria
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机构: Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08025, Spain

Ramon, Teresa
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h-index: 0
机构: Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08025, Spain

Fernandez, Sonia
论文数: 0 引用数: 0
h-index: 0
机构: Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08025, Spain

Martinez, Daniel
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h-index: 0
机构: Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08025, Spain

Pons, Cristina
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h-index: 0
机构: Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08025, Spain

Munoz, Fina
论文数: 0 引用数: 0
h-index: 0
机构: Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08025, Spain

Sabate, Josep Ma
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h-index: 0
机构: Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08025, Spain

Alonso, Carmen
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h-index: 0
机构: Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08025, Spain

Ojeda, Belen
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h-index: 0
机构: Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08025, Spain

Prat, Jaime
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h-index: 0
机构: Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08025, Spain

Barnadas, Agusti
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h-index: 0
机构: Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08025, Spain
机构:
[1] Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08025, Spain
[2] Gen Hosp, Dept Pathol, Alicante, Spain
[3] Hosp Santa Creu & Sant Pau, Dept Oncol, Barcelona 08025, Spain
[4] Hosp Santa Creu & Sant Pau, Dept Radiol, Barcelona 08025, Spain
关键词:
breast;
carcinoma;
immunohistochemistry;
growth membrane receptors;
IG-FR;
PTEN;
Akt;
D O I:
10.1038/modpathol.3800961
中图分类号:
R36 [病理学];
学科分类号:
100104 ;
摘要:
Basal breast carcinomas triple negative for estrogen receptors, progesterone receptors and Her2/neu breast carcinomas are more aggressive than conventional neoplasms. We studied 64 cases with immunohistochemistry, using 23 antibodies, to characterize diverse pathological pathways. A basal cytokeratin was identified in 81% of tumors and vimentin was identified in 55%. The mean Ki67 index was 46% ( range, 10-90%). Coincident expression of p50 and p65, which suggests an active nuclear factor-kappa B factor, was present in 13% of neoplasms. Epithelial growth factor receptor ( EGFR), insulin-like growth factor-I receptor ( IGF-IR) or c-kit ( CD117) was identified in 77% of tumors. Loss of protein tyrosine phosphatase was found in 14%, whereas Akt activation was present in 28%. Several differences were identified between two subtypes of basal breast carcinomas: the pure variant ( negative S-100 and actin) was more frequently associated with 'in situ carcinoma' ( P = 0.019) and pBad overexpression ( P = 0.098), whereas the myoepithelial variant ( positive S-100 or actin) showed more frequent tumor necrosis ( P = 0.048), vimentin expression ( P = 0.0001), CD117 expression ( P = 0.001) and activated caspase-3 ( P = 0.089). IGF-IR could be as important as EGFR for the growth of these neoplasms. Basal cell carcinoma has at least two subtypes with distinct microscopic and immunohistochemical features.
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页码:1200 / 1207
页数:8
相关论文
共 57 条
[51]
Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications
[J].
Sorlie, T
;
Perou, CM
;
Tibshirani, R
;
Aas, T
;
Geisler, S
;
Johnsen, H
;
Hastie, T
;
Eisen, MB
;
van de Rijn, M
;
Jeffrey, SS
;
Thorsen, T
;
Quist, H
;
Matese, JC
;
Brown, PO
;
Botstein, D
;
Lonning, PE
;
Borresen-Dale, AL
.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,
2001, 98 (19)
:10869-10874

Sorlie, T
论文数: 0 引用数: 0
h-index: 0
机构: Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway

Perou, CM
论文数: 0 引用数: 0
h-index: 0
机构: Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway

Tibshirani, R
论文数: 0 引用数: 0
h-index: 0
机构: Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway

Aas, T
论文数: 0 引用数: 0
h-index: 0
机构: Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway

Geisler, S
论文数: 0 引用数: 0
h-index: 0
机构: Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway

Johnsen, H
论文数: 0 引用数: 0
h-index: 0
机构: Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway

Hastie, T
论文数: 0 引用数: 0
h-index: 0
机构: Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway

Eisen, MB
论文数: 0 引用数: 0
h-index: 0
机构: Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway

van de Rijn, M
论文数: 0 引用数: 0
h-index: 0
机构: Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway

Jeffrey, SS
论文数: 0 引用数: 0
h-index: 0
机构: Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway

Thorsen, T
论文数: 0 引用数: 0
h-index: 0
机构: Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway

Quist, H
论文数: 0 引用数: 0
h-index: 0
机构: Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway

Matese, JC
论文数: 0 引用数: 0
h-index: 0
机构: Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway

Brown, PO
论文数: 0 引用数: 0
h-index: 0
机构: Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway

Botstein, D
论文数: 0 引用数: 0
h-index: 0
机构: Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway

Lonning, PE
论文数: 0 引用数: 0
h-index: 0
机构: Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway

Borresen-Dale, AL
论文数: 0 引用数: 0
h-index: 0
机构:
Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway
[52]
Breast cancer classification and prognosis based on gene expression profiles from a population-based study
[J].
Sotiriou, C
;
Neo, SY
;
McShane, LM
;
Korn, EL
;
Long, PM
;
Jazaeri, A
;
Martiat, P
;
Fox, SB
;
Harris, AL
;
Liu, ET
.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,
2003, 100 (18)
:10393-10398

Sotiriou, C
论文数: 0 引用数: 0
h-index: 0
机构: NCI, Div Clin Sci, Ctr Adv Technol, Gaithersburg, MD 20877 USA

Neo, SY
论文数: 0 引用数: 0
h-index: 0
机构: NCI, Div Clin Sci, Ctr Adv Technol, Gaithersburg, MD 20877 USA

McShane, LM
论文数: 0 引用数: 0
h-index: 0
机构: NCI, Div Clin Sci, Ctr Adv Technol, Gaithersburg, MD 20877 USA

Korn, EL
论文数: 0 引用数: 0
h-index: 0
机构: NCI, Div Clin Sci, Ctr Adv Technol, Gaithersburg, MD 20877 USA

Long, PM
论文数: 0 引用数: 0
h-index: 0
机构: NCI, Div Clin Sci, Ctr Adv Technol, Gaithersburg, MD 20877 USA

Jazaeri, A
论文数: 0 引用数: 0
h-index: 0
机构: NCI, Div Clin Sci, Ctr Adv Technol, Gaithersburg, MD 20877 USA

Martiat, P
论文数: 0 引用数: 0
h-index: 0
机构: NCI, Div Clin Sci, Ctr Adv Technol, Gaithersburg, MD 20877 USA

Fox, SB
论文数: 0 引用数: 0
h-index: 0
机构: NCI, Div Clin Sci, Ctr Adv Technol, Gaithersburg, MD 20877 USA

Harris, AL
论文数: 0 引用数: 0
h-index: 0
机构: NCI, Div Clin Sci, Ctr Adv Technol, Gaithersburg, MD 20877 USA

Liu, ET
论文数: 0 引用数: 0
h-index: 0
机构: NCI, Div Clin Sci, Ctr Adv Technol, Gaithersburg, MD 20877 USA
[53]
Correlation of KIT and EGFR overexpression with invasive ductal breast carcinoma of the solid-tubular subtype, nuclear grade 3, and mesenchymal or myoepithelial differentiation
[J].
Tsuda, H
;
Morita, D
;
Kimura, M
;
Shinto, E
;
Ohtsuka, Y
;
Matsubara, O
;
Inazawa, J
;
Tamaki, K
;
Mochizuki, H
;
Tamai, S
;
Hiraide, H
.
CANCER SCIENCE,
2005, 96 (01)
:48-53

Tsuda, H
论文数: 0 引用数: 0
h-index: 0
机构: Natl Def Med Coll, Dept Pathol 2, Tokorozawa, Saitama 3598513, Japan

Morita, D
论文数: 0 引用数: 0
h-index: 0
机构: Natl Def Med Coll, Dept Pathol 2, Tokorozawa, Saitama 3598513, Japan

Kimura, M
论文数: 0 引用数: 0
h-index: 0
机构: Natl Def Med Coll, Dept Pathol 2, Tokorozawa, Saitama 3598513, Japan

Shinto, E
论文数: 0 引用数: 0
h-index: 0
机构: Natl Def Med Coll, Dept Pathol 2, Tokorozawa, Saitama 3598513, Japan

Ohtsuka, Y
论文数: 0 引用数: 0
h-index: 0
机构: Natl Def Med Coll, Dept Pathol 2, Tokorozawa, Saitama 3598513, Japan

Matsubara, O
论文数: 0 引用数: 0
h-index: 0
机构: Natl Def Med Coll, Dept Pathol 2, Tokorozawa, Saitama 3598513, Japan

Inazawa, J
论文数: 0 引用数: 0
h-index: 0
机构: Natl Def Med Coll, Dept Pathol 2, Tokorozawa, Saitama 3598513, Japan

Tamaki, K
论文数: 0 引用数: 0
h-index: 0
机构: Natl Def Med Coll, Dept Pathol 2, Tokorozawa, Saitama 3598513, Japan

Mochizuki, H
论文数: 0 引用数: 0
h-index: 0
机构: Natl Def Med Coll, Dept Pathol 2, Tokorozawa, Saitama 3598513, Japan

Tamai, S
论文数: 0 引用数: 0
h-index: 0
机构: Natl Def Med Coll, Dept Pathol 2, Tokorozawa, Saitama 3598513, Japan

Hiraide, H
论文数: 0 引用数: 0
h-index: 0
机构: Natl Def Med Coll, Dept Pathol 2, Tokorozawa, Saitama 3598513, Japan
[54]
Large, central acellular zones indicating myoepithelial tumor differentiation in high-grade invasive ductal carcinomas as markers of predisposition to lung and brain metastases
[J].
Tsuda, H
;
Takarabe, T
;
Hasegawa, F
;
Fukutomi, T
;
Hirohashi, S
.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY,
2000, 24 (02)
:197-202

Tsuda, H
论文数: 0 引用数: 0
h-index: 0
机构:
Natl Canc Ctr, Res Inst, Div Pathol, Chuo Ku, Tokyo 1040045, Japan Natl Canc Ctr, Res Inst, Div Pathol, Chuo Ku, Tokyo 1040045, Japan

Takarabe, T
论文数: 0 引用数: 0
h-index: 0
机构: Natl Canc Ctr, Res Inst, Div Pathol, Chuo Ku, Tokyo 1040045, Japan

Hasegawa, F
论文数: 0 引用数: 0
h-index: 0
机构: Natl Canc Ctr, Res Inst, Div Pathol, Chuo Ku, Tokyo 1040045, Japan

Fukutomi, T
论文数: 0 引用数: 0
h-index: 0
机构: Natl Canc Ctr, Res Inst, Div Pathol, Chuo Ku, Tokyo 1040045, Japan

Hirohashi, S
论文数: 0 引用数: 0
h-index: 0
机构: Natl Canc Ctr, Res Inst, Div Pathol, Chuo Ku, Tokyo 1040045, Japan
[55]
Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome
[J].
van de Rijn, M
;
Perou, CM
;
Tibshirani, R
;
Haas, P
;
Kallioniemi, C
;
Kononen, J
;
Torhorst, J
;
Sauter, G
;
Zuber, M
;
Köchli, OR
;
Mross, F
;
Dieterich, H
;
Seitz, R
;
Ross, D
;
Botstein, D
;
Brown, P
.
AMERICAN JOURNAL OF PATHOLOGY,
2002, 161 (06)
:1991-1996

van de Rijn, M
论文数: 0 引用数: 0
h-index: 0
机构: Stanford Univ, Ctr Med, Dept Pathol L235, Stanford, CA 94305 USA

Perou, CM
论文数: 0 引用数: 0
h-index: 0
机构: Stanford Univ, Ctr Med, Dept Pathol L235, Stanford, CA 94305 USA

Tibshirani, R
论文数: 0 引用数: 0
h-index: 0
机构: Stanford Univ, Ctr Med, Dept Pathol L235, Stanford, CA 94305 USA

Haas, P
论文数: 0 引用数: 0
h-index: 0
机构: Stanford Univ, Ctr Med, Dept Pathol L235, Stanford, CA 94305 USA

Kallioniemi, C
论文数: 0 引用数: 0
h-index: 0
机构: Stanford Univ, Ctr Med, Dept Pathol L235, Stanford, CA 94305 USA

Kononen, J
论文数: 0 引用数: 0
h-index: 0
机构: Stanford Univ, Ctr Med, Dept Pathol L235, Stanford, CA 94305 USA

Torhorst, J
论文数: 0 引用数: 0
h-index: 0
机构: Stanford Univ, Ctr Med, Dept Pathol L235, Stanford, CA 94305 USA

Sauter, G
论文数: 0 引用数: 0
h-index: 0
机构: Stanford Univ, Ctr Med, Dept Pathol L235, Stanford, CA 94305 USA

Zuber, M
论文数: 0 引用数: 0
h-index: 0
机构: Stanford Univ, Ctr Med, Dept Pathol L235, Stanford, CA 94305 USA

Köchli, OR
论文数: 0 引用数: 0
h-index: 0
机构: Stanford Univ, Ctr Med, Dept Pathol L235, Stanford, CA 94305 USA

Mross, F
论文数: 0 引用数: 0
h-index: 0
机构: Stanford Univ, Ctr Med, Dept Pathol L235, Stanford, CA 94305 USA

Dieterich, H
论文数: 0 引用数: 0
h-index: 0
机构: Stanford Univ, Ctr Med, Dept Pathol L235, Stanford, CA 94305 USA

Seitz, R
论文数: 0 引用数: 0
h-index: 0
机构: Stanford Univ, Ctr Med, Dept Pathol L235, Stanford, CA 94305 USA

Ross, D
论文数: 0 引用数: 0
h-index: 0
机构: Stanford Univ, Ctr Med, Dept Pathol L235, Stanford, CA 94305 USA

Botstein, D
论文数: 0 引用数: 0
h-index: 0
机构: Stanford Univ, Ctr Med, Dept Pathol L235, Stanford, CA 94305 USA

Brown, P
论文数: 0 引用数: 0
h-index: 0
机构: Stanford Univ, Ctr Med, Dept Pathol L235, Stanford, CA 94305 USA
[56]
A gene-expression signature as a predictor of survival in breast cancer.
[J].
van de Vijver, MJ
;
He, YD
;
van 't Veer, LJ
;
Dai, H
;
Hart, AAM
;
Voskuil, DW
;
Schreiber, GJ
;
Peterse, JL
;
Roberts, C
;
Marton, MJ
;
Parrish, M
;
Atsma, D
;
Witteveen, A
;
Glas, A
;
Delahaye, L
;
van der Velde, T
;
Bartelink, H
;
Rodenhuis, S
;
Rutgers, ET
;
Friend, SH
;
Bernards, R
.
NEW ENGLAND JOURNAL OF MEDICINE,
2002, 347 (25)
:1999-2009

van de Vijver, MJ
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

He, YD
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

van 't Veer, LJ
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

Dai, H
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

Hart, AAM
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

Voskuil, DW
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

Schreiber, GJ
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

Peterse, JL
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

Roberts, C
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

Marton, MJ
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

Parrish, M
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

Atsma, D
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

Witteveen, A
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

Glas, A
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

Delahaye, L
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

van der Velde, T
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

Bartelink, H
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

Rodenhuis, S
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

Rutgers, ET
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

Friend, SH
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

Bernards, R
论文数: 0 引用数: 0
h-index: 0
机构: Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands
[57]
Gene expression profiling predicts clinical outcome of breast cancer
[J].
van't Veer, LJ
;
Dai, HY
;
van de Vijver, MJ
;
He, YDD
;
Hart, AAM
;
Mao, M
;
Peterse, HL
;
van der Kooy, K
;
Marton, MJ
;
Witteveen, AT
;
Schreiber, GJ
;
Kerkhoven, RM
;
Roberts, C
;
Linsley, PS
;
Bernards, R
;
Friend, SH
.
NATURE,
2002, 415 (6871)
:530-536

van't Veer, LJ
论文数: 0 引用数: 0
h-index: 0
机构: Rosetta Inpharmat, Kirkland, WA 98034 USA

Dai, HY
论文数: 0 引用数: 0
h-index: 0
机构: Rosetta Inpharmat, Kirkland, WA 98034 USA

van de Vijver, MJ
论文数: 0 引用数: 0
h-index: 0
机构: Rosetta Inpharmat, Kirkland, WA 98034 USA

He, YDD
论文数: 0 引用数: 0
h-index: 0
机构: Rosetta Inpharmat, Kirkland, WA 98034 USA

Hart, AAM
论文数: 0 引用数: 0
h-index: 0
机构: Rosetta Inpharmat, Kirkland, WA 98034 USA

Mao, M
论文数: 0 引用数: 0
h-index: 0
机构: Rosetta Inpharmat, Kirkland, WA 98034 USA

Peterse, HL
论文数: 0 引用数: 0
h-index: 0
机构: Rosetta Inpharmat, Kirkland, WA 98034 USA

van der Kooy, K
论文数: 0 引用数: 0
h-index: 0
机构: Rosetta Inpharmat, Kirkland, WA 98034 USA

Marton, MJ
论文数: 0 引用数: 0
h-index: 0
机构: Rosetta Inpharmat, Kirkland, WA 98034 USA

Witteveen, AT
论文数: 0 引用数: 0
h-index: 0
机构: Rosetta Inpharmat, Kirkland, WA 98034 USA

Schreiber, GJ
论文数: 0 引用数: 0
h-index: 0
机构: Rosetta Inpharmat, Kirkland, WA 98034 USA

Kerkhoven, RM
论文数: 0 引用数: 0
h-index: 0
机构: Rosetta Inpharmat, Kirkland, WA 98034 USA

Roberts, C
论文数: 0 引用数: 0
h-index: 0
机构: Rosetta Inpharmat, Kirkland, WA 98034 USA

Linsley, PS
论文数: 0 引用数: 0
h-index: 0
机构: Rosetta Inpharmat, Kirkland, WA 98034 USA

Bernards, R
论文数: 0 引用数: 0
h-index: 0
机构: Rosetta Inpharmat, Kirkland, WA 98034 USA

Friend, SH
论文数: 0 引用数: 0
h-index: 0
机构: Rosetta Inpharmat, Kirkland, WA 98034 USA