HER2 - human epidermal growth factor receptor 2
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http://ft-patho.net/index.php?HER2%20-%20human%20epidermal%20growth%20factor%20receptor%202
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-- ¿÷·Á¤È¤¹¤ë¥Ú¡¼¥¸ --
'''ALK'''-rearranged lung adenocarcinoma with partially squamous differentiation(adenosquamous carcinoma)--CHUBU1339
(Ǿ¸¶È¯)Malignant melanoma-SPSJohnan226-Case07
100Îã¤ÎMPN¾ÉÎ㥹¥é¥¤¥É¤ò¤ß¤ë²ñ---Âè10²óÅìµþ¹ü¿ñÉÂÍý¸¦µæ²ñ
221SPS/case01- Angiomyolipoma of the liver
221SPS/case04
30ºÐÃËÀ¤ÎÇÙ¼ðáç-¿ÇÃǺ¤Æñ¾ÉÎã
3q27
A07-11
AILD-Angioimmunoblastic lymphadenopathy with dysproteinemia
ALK-positive ALCL-Case02
ALK-positive large B-cell lymphoma
ALK-positive lymphoma, variant of ALCL?
ALL
AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); '''CBFB-MYH11'''
AML-M1, Acute myeloblastic leukaemia without maturation
AML-M5
APC (adenoma polyposis coli)°äÅÁ»Ò¤ÈÂçIJ´â
ASD/Giemsa À÷¿§--¹ü¿ñ¥¯¥í¥Ã¥È¡¦À¸¸¡ÁÈ¿¥¤ÎÀ÷¿§
ActiveX¤¬Í¸ú
Acute promyelocytic leukaemia - Case 01
Acute promyelocytic leukaemia - Case 02
Acute promyelocytic leukaemia - Case 03
Acute promyelocytic leukaemia(APL), AML-M3
Adenocarcinoma of the uterine cervix
Adult T cell leukaemia/lymphoma
Age related clonal hematopoiesis/ clonal hematopoiesis of indeterminate potential
Algorithm for diagnosis of MDS (Myelodysplastic syndrome)
Alveolar rhabdomyosaroma
Anaplastic large cell lymphoma (ALCL)
Anaplastic large cell lymphoma(ALCL), ALK-positive
Anaplastic large cell lymphoma, small cell variant
Anaplastic lymphoma receptor tyrosine kinase( ALK )
Angioimmunoblastic T cell lymphoma (AITL)
Angioimmunoblastic T-cell lymphoma/case01
Aplastic anemia (AA)
Apocrine hidradenoma, clear cell type
Askin tumor
Autoimmune pancreatitis (¼«¸ÊÌȱÖÀç¹±ê)
B-cell malignancy_Expert2019
B-cell receptor signaling BºÙ˦¥·¥°¥Ê¥ëÅÁã
Barrett esophagus¤Î¿ÇÃÇ
Behcet disease
Birt-Hogg-Dube¾É¸õ·²
Blimp-1
Blimp-1/PRDM1 B-cell ½ªËöʬ²½
Blimp1/PRDM1
Bone marrow cellularity
BracketName
Breast cancer--Æý´â¤Î´ðÁÃ
Breast cancer--Æý´â¤Î¿ÇÃǤȼ£ÎÅ
Breast cancer--Æý´â¤Îʬ»ÒʬÎà¤È¥×¥í¥Æ¥ª¡¼¥à¤Î°Û¾ï
Burkitt lymphoma
Burkitt's lymphoma of the small intestine
Burkitt's lymphoma--case01
Burkitt's lymphoma--case03
Burkitt's+lymphoma--case01
BºÙ˦
CA-125
CA19-9
CAR-TºÙ˦ÎÅË¡--¥¥á¥é¹³¸¶¼õÍÆÂΰäÅÁ»ÒƳÆþTºÙ˦ÎÅË¡
CD25
CD30 - TNFRmember 8
CD4+,CD56+ Hematodermal tumor_SPS227-Case08
CD44
CD45; protein tyrosine phosphatase, receptor type Cprotein tyrosine phosphatase, receptor type C (PTPRC)
CD5-positive diffuse large B-cell lymphoma with discordant expression of CD20 by FCM and IHC
CD56-positive hematolymphoid diseases
CHUB1085
CHUB1251 uterine tumors in a TSC patient
CHUBU10-Case01
CHUBU10-Case02
CHUBU10-Lecture01
CHUBU10-Lecture02
CHUBU1015
CHUBU1016
CHUBU1017
CHUBU1034
CHUBU1042
CHUBU1043
CHUBU1045
CHUBU1054
CHUBU1056
CHUBU1064
CHUBU1080
CHUBU1082
CHUBU1094-Solitary fibrous tumor
CHUBU1105--Collecting duct carcinoma of Bellini
CHUBU1142
CHUBU1159-histiocytoid/signet-ring cell carcinoma of the eyelid
CHUBU1166- Marburg type acute multiple sclerosis
CHUBU1174
CHUBU1206
CHUBU1215
CHUBU1248-Extraskeletal myxoid chondrosarcoma
CHUBU1250
CHUBU1252 Rosai-Dorfman disease of the dura mater
CHUBU1258 Papilloma of the lung
CHUBU1266_Fibrolamellar carcinoma
CHUBU1269
CHUBU1308
CHUBU1309
CHUBU1310
CHUBU1359 ÍñÁã¼ðáç
CHUBU1369
CHUBU1387-brain tumor
CHUBU57/Case943-VS
CHUBU57/Case944-VS
CHUBU57/Case945-VS
CHUBU57/Case946-VS
CHUBU58/Case967-VS
CHUBU61/Case1042-VS
CHUBU992
CHUBUs2009-case01
CHUBUs2012-Case04_salivary duct carcinoma
CLL/SLL
CPC cases
CPC¾ÉÎãÊó¹ð
Cancer stem cell ¤¬¤ó´´ºÙ˦
Carcinoma showing thymus-like differentiation-SPSJohnan226-Case08
Castleman disease
Castleman disease with increasing in IgG4-positive plasma cells
Castleman+disease
Chemokine¡¡¥±¥â¥«¥¤¥ó
Choriocarcinoma
Chronic myelomonocytic leukaemia (CMML)
Chronic neutrophilic leukemia (CNL)
Churg-Strauss Sx, case01
Churg-Strauss Syndrome
Churg-Strauss syndrome case01
Claudin¤ÈºÙ˦´Ö¥¸¥ã¥ó¥¯¥·¥ç¥ó
Cluster Differentiation
Colon Cancer
Colorectal cancer - ÂçIJľIJ´â
ComputerMemo
Crohn's disease
Crow-Fukase Syndrome SPS222-Case08
Crow-Fukase+Syndrome+SPS222-Case08
Cryptorchidism ÄäαâдÝ
Cutaneous vasculitis and vasculitis-like syndromes ÈéÉæ·ì´É±ê¤È·ì´É±êÎà»÷¼À´µ
Cytokeratin ¥µ¥¤¥È¥±¥é¥Á¥ó
Cytokine¥µ¥¤¥È¥«¥¤¥ó
DIC
DLBCL, Anaplastic large cell type
DNA
DNMT3A
Dedifferentiated liposarcoma of the peritoneum
Dendritic cells ¼ù¾õºÙ˦
Desmoplastic melanoma and desmoplastic neurotropic melanoma--Àþ°Ý·ÁÀ®À¹õ¿§¼ð¤ÈÀþ°Ý·ÁÀ®À¿À·Ð¸þÀ¹õ¿§¼ð
Diffuse astrocytic and oligodendroglial tumors-WHO2016 CNS tumor
Diffuse large B cell lymphoma, not otherwise specified (DLBCL, NOS)
Diffuse large B-cell lymphoma
Diffuse large B-cell lymphoma (DLBCL) WHO 4th revised
Diffuse large B-cell lymphoma, anaplastic and extranodal
Disorder of ocular movement
EBV positive DLBCL of the elderly
EBV positive DLBCL of the elderly-233SPS-Case04
EBV-associated smooth muscle tumor (CHUBU1401)
EGFR ¾åÈéÀ®Ä¹°ø»Ò¼õÍÆÂÎ
EML4-ALK adenocarcinoma of the lung--CHUBU1090
EML4-ALK non small cell lung cancer
EML4-ALK positive lung cancer-228SPS-09
EML4-ALK+adenocarcinoma+of+the+lung--CHUBU1090
Endocrine pancreas ç¹ÆâʬÈçÁÈ¿¥
Endometrial stromal tumor »ÒµÜÆâËì´Ö¼Á¼ðáç
Enteropathy T-cell lymphoma
Enteropathy-associated T-cell lymphoma
Eosiophilia ¹¥»ÀµåÁý¿¾É
Epigenetics ¥¨¥Ô¥¸¥§¥Í¥Æ¥£¥Ã¥¯¥¹
Epstein-Barr virus
Essential thromobocythemia ËÜÂÖÀ·ì¾®ÈÄ·ì¾É
Ewing's sarcoma
Ewing's sarcoma and pPNET
Extranodal Natural Killer(NK)/T-Cell Lymphoma, Nasal Type
Extrarenal malignant rhabdoid tumor ¿Õ³°À°À¥é¥Ö¥É¥¤¥É¼ðáç
FDCS(Follicular dendritic cell sarcoma)
FLT3
Fc receptor
Fertility-Spairing Management in young endometrial cancer patients
Fertilization to implantation
Fibrolamellar carcinoma of the liver
Fibrosarcoma Àþ°ÝÆù¼ð
Floral variant of follicular lymphoma
Follicle
Follicle and Follicular lymphoma 2018
Follicular dendritic cell sarcoma--Cases
Follicular lymphoma
Follicular lymphoma- various cases
FormattingRules
Four cases of ALK-positive adenocarcinoma of the lung--234SPS-Case07
FrontPage
GIST with PDGFRA D842V mutation
GIST¤Î¿ÇÃǤȼ£ÎÅ
GNAS, GNAS complex locus
Gastric cancer
Gastric cancer/Gastric carcinoma with lymphoid stroma
Gastric cancer/Gastric endcrine cell carcinoma
Gastric cancer/Hepatoid carcinoma of the stomach
Gastric cancer°ß´â molecular subtypes
Gastric type Adenocarcinoma of the cervix uteri
Gastric ulcer with CMV infection
Gastric+cancer
Gaucher disease
Gestational sac
Glassy cell carcinoma-228SPS-Case03
Granular lymphocyte-proliferative disorders--ðùγ¥ê¥ó¥ÑµåÁý¿¾É(GLPD)
HER2 - human epidermal growth factor receptor 2
HLA; Human Leukocyte Antigen-¥µ¥Ö¥¿¥¤¥Ô¥ó¥°
Help
Hemangioblastoma
Hematological neoplasm-Case report-01
Hematopathology Expert
Hepatocellular carcinoma, clear cell type
Herpes Simplex Encephalitis ñ½ã¥Ø¥ë¥Ú¥¹Ç¾±ê
High grade B-cell lymphoma (HGBCL) ¹â°ÀÅÙBºÙ˦¥ê¥ó¥Ñ¼ð
Histiocytic necrotizing lymphadenitis, Kikuchi-Fujimoto Disease case02
Histon modifications ¥Ò¥¹¥È¥ó½¤¾þ
Hodgkin lymphoma
Hodgkin lymphoma, lymphocyte-rich (LRCHD)
Hodgkin lymphoma-Nodular sclerosis
Homeobox
Human papilloma virus
IDCS(Interdigitating cell sarcoma) etc
IDCS-cases
IL-2 receptor, CD25, CD122 and CD132
IRF4/ MUM-1
IWT-A06-8
IgD and IgE myeloma --unusual myelomas
IgG4 related lymphadenopathy--SPS223-Case01
Immunoglobulin gene Ìȱ֥°¥í¥Ö¥ê¥ó°äÅÁ»Ò
Infectious mononucleosis--lymphadenopathy, pathological findings
Inflammatory pseudotumor of the brain--SPS235-Case05
Inflammatory pseudotumor-like follicular dendritic cell tumor--SPS-Johnan217case01
Integrated diagnosis of diffuse gliomas
InterWiki
InterWikiName
InterWikiSandBox
Intraepithelial sebaseous carcinoma(sebaseous carcinoma in situ)-230SPS-case02
Invasive cribriform carcinoma
Invasive cribriform carcinoma of the breast
JAK/STAT¥·¥°¥Ê¥ê¥ó¥°
Japanese History
Juvenile granulosa cell tumor-SPS222-Case01
Juvenile myelomonocytic leukemia ¼ãǯÀ¹ü¿ññµåÀÇò·ìÉÂ
KMT2A; lysine methyltrasferase 2A, former MLL
Kidney tumors-WHO2016
Kikuchi-Fujimoto disease
Kikuchi-Fujimoto disease case01
Kimura's disease
Kuettner's tumor
Lag time consulation-Iwata City Hospital/Iwata-jaw
Lag time consultaion-Free version/IwataBreast-07
Lag time consultaion-Iwata City Hospital/IwataBreast-04
Lag time consultaion-Iwata City Hospital/IwataBreast-05
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Lag time consultation-Free version/IwataBreast-01
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Lag time consultation-Iwata City Hospital
Lag time consultation-Iwata City Hospital/ Iwata-skin-05
Lag time consultation-Iwata City Hospital/ Iwata-uterus-17
Lag time consultation-Iwata City Hospital/CHUBU998
Lag time consultation-Iwata City Hospital/Iwata-Breast-27
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Lag time consultation-Iwata City Hospital/Iwata-Breast-29
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Lag time consultation-Iwata City Hospital/Iwata-Breast-32
Lag time consultation-Iwata City Hospital/Iwata-CaUO-01
Lag time consultation-Iwata City Hospital/Iwata-Head and Neck-01
Lag time consultation-Iwata City Hospital/Iwata-Head and Neck-02
Lag time consultation-Iwata City Hospital/Iwata-Head and Neck-03
Lag time consultation-Iwata City Hospital/Iwata-Lung-01;malignant round cell tumor
Lag time consultation-Iwata City Hospital/Iwata-Skin-04
Lag time consultation-Iwata City Hospital/Iwata-Skin03
Lag time consultation-Iwata City Hospital/Iwata-Uterus-15
Lag time consultation-Iwata City Hospital/Iwata-Uterus-16
Lag time consultation-Iwata City Hospital/Iwata-breast-33
Lag time consultation-Iwata City Hospital/Iwata-breast-34
Lag time consultation-Iwata City Hospital/Iwata-breast-35
Lag time consultation-Iwata City Hospital/Iwata-breast-36
Lag time consultation-Iwata City Hospital/Iwata-breast-37
Lag time consultation-Iwata City Hospital/Iwata-breast-38
Lag time consultation-Iwata City Hospital/Iwata-breast-39
Lag time consultation-Iwata City Hospital/Iwata-breast-40
Lag time consultation-Iwata City Hospital/Iwata-breast-41
Lag time consultation-Iwata City Hospital/Iwata-breast-42
Lag time consultation-Iwata City Hospital/Iwata-lymph node-04
Lag time consultation-Iwata City Hospital/Iwata-lymph node03
Lag time consultation-Iwata City Hospital/Iwata-maxillary tumor
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Lag time consultation-Iwata City Hospital/IwataBreast-03
Lag time consultation-Iwata City Hospital/IwataBreast-08
Lag time consultation-Iwata City Hospital/IwataBreast-09
Lag time consultation-Iwata City Hospital/IwataBreast-10
Lag time consultation-Iwata City Hospital/IwataBreast-11
Lag time consultation-Iwata City Hospital/IwataBreast-12
Lag time consultation-Iwata City Hospital/IwataBreast-13
Lag time consultation-Iwata City Hospital/IwataBreast-14
Lag time consultation-Iwata City Hospital/IwataBreast-15
Lag time consultation-Iwata City Hospital/IwataBreast-16
Lag time consultation-Iwata City Hospital/IwataBreast-17
Lag time consultation-Iwata City Hospital/IwataBreast-18
Lag time consultation-Iwata City Hospital/IwataBreast-19
Lag time consultation-Iwata City Hospital/IwataBreast-20
Lag time consultation-Iwata City Hospital/IwataBreast-21
Lag time consultation-Iwata City Hospital/IwataBreast-22
Lag time consultation-Iwata City Hospital/IwataBreast-23
Lag time consultation-Iwata City Hospital/IwataBreast-24
Lag time consultation-Iwata City Hospital/IwataBreast-25
Lag time consultation-Iwata City Hospital/IwataBreast-26
Lag time consultation-Iwata City Hospital/IwataBreast02
Lag time consultation-Iwata City Hospital/IwataFNA-01
Lag time consultation-Iwata City Hospital/IwataGItract-03
Lag time consultation-Iwata City Hospital/IwataGItract01
Lag time consultation-Iwata City Hospital/IwataHeadneck-01
Lag time consultation-Iwata City Hospital/IwataHeadneck-02
Lag time consultation-Iwata City Hospital/IwataLung-01
Lag time consultation-Iwata City Hospital/IwataOral-01
Lag time consultation-Iwata City Hospital/IwataOvary-01
Lag time consultation-Iwata City Hospital/IwataProstata-01
Lag time consultation-Iwata City Hospital/IwataSkin-01
Lag time consultation-Iwata City Hospital/IwataSkin02
Lag time consultation-Iwata City Hospital/IwataTonsil-01
Lag time consultation-Iwata City Hospital/IwataUterus-02
Lag time consultation-Iwata City Hospital/IwataUterus-03
Lag time consultation-Iwata City Hospital/IwataUterus-04
Lag time consultation-Iwata City Hospital/IwataUterus-05
Lag time consultation-Iwata City Hospital/IwataUterus-06
Lag time consultation-Iwata City Hospital/IwataUterus-07
Lag time consultation-Iwata City Hospital/IwataUterus-08
Lag time consultation-Iwata City Hospital/IwataUterus-10
Lag time consultation-Iwata City Hospital/IwataUterus-11
Lag time consultation-Iwata City Hospital/IwataUterus-12
Lag time consultation-Iwata City Hospital/IwataUterus-13
Lag time consultation-Iwata City Hospital/IwataUterus-14
Lag time consultation-Limit version
Lag time consultation-Limit version/No.08Feb07-01
Lag time consultation/IwataUterus-09
Lag time consultation/ShizCHB071253
Lagtime consultation-Iwata City Hospital/ Bone marrow
Langerhans cell histiocytoma/ Langerhans cell sarcoma--SPS225-Case07
Langerhans cell histiocytosis
Langerhans cell histiocytosis¾ÉÎã²òÀâ
Langerhans cell sarcoma-231SPS-Case03
Langerhans+cell+histiocytosis
LectureNote
Lues lymphadenopathy-SPSJOHNAN(232SPS)-Case01
Lung
Lung cancer- adenocarcinoma and neuroendocrine tumors
Lung cancer-adenocarcinoma, WHO2015
Lung-epithelioid hemangioendothelioma
Lymphomatoid granulomatosis SPS218-Case01
Lynch Syndrome
MALT lymphoma of the esophagus
MALT lymphoma of the lung
MALT lymphoma of the stomach
MDS associated with isolated del(5q)
MDS/MPN, atyical CML
MDS¤Ëǧ¤á¤é¤ì¤ëÀ÷¿§Âΰ۾ï
MDS¤Î°äÅÁ»Ò°Û¾ï-pre-mRNA¥¹¥×¥é¥¤¥·¥ó¥°µ¡¹½¤Ë´Ø¤ï¤ë°äÅÁ»Ò·²¤Î°Û¾ï
MDS¤Î°äÅÁ»Ò°Û¾ï-¥¨¥Ô¥¸¥§¥Í¥Æ¥£¥Ã¥¯À©¸æ°ø»Ò¤ò¥³¡¼¥É¤¹¤ë°äÅÁ»Ò¤Î°Û¾ï
MDS¿ÇÃǤˤª¤±¤ëring sideroblasts
MET met proto-oncogene MET °äÅÁ»Ò
MPL and CALR gene mutation in patients with Myeloproliferative neoplasm
MPL proto-oncogene, thrombopoietin receptor (MPL)
MYD88
Mafž¼Ì°ø»Ò¤È¼À´µ¡¢È¯´â--¹ü¿ñ¼ð¤Îȯ´â°ø»Ò
Malignant Fibrous histiocytoma
Malignant lymphoma of digestive tube
Mantle cell lymphoma
Mantle cell lymphoma--Case02
Mantle cell lymphoma--Case03
Mantle cell lymphoma--Cases
Marginal zone lymphoma of MALT type
Mastocytosis ÈîËþºÙ˦¾É
Medical links
Medical+links
MenuBar
Methotrexate-associated lymphoproliferative disease-231SPS-Case02
Mixed ductal-endocrine carcinoma--CHUBU1091
Mixed germ cell tomor of the testis
Mixed germ cell tumor of the testis--CHUBU1096
Mixed germ cell tumor-SPS225-Case01
Monocyte and macrophage ñµå¡¦¥Þ¥¯¥í¥Õ¥¡¡¼¥¸
Mucin
Mucosal melanoma of the upper pharynx-S100 negative case
Mucosal melanoma Ç´Ëì°À¹õ¿§¼ð
Multiple myeloma - up date
Multiple myeloma--Clinical diagnsosis and Pathology
Multiple myeloma--molecular pathogenesis
Myc
Mycosis fungoides, Sezary syndrome
Myelodysplastic syndromes (MDS) ¹ü¿ñ°Û·ÁÀ®¾É¸õ·²
Myeloid sarcoma-SPS223-Case05
NF-¦ÊB ¥·¥°¥Ê¥ê¥ó¥°
NTKR--Neurotrophic tyrosine kinase receptors
NUT midline carcinoma
Nanopore sequencer--¥Ê¥Î¥Ý¥¢¥·¡¼¥¯¥¨¥ó¥µ¡¼
Natural killer cells (NK cells)
Neruroendocrine cell carcinoma of the penile urethra-234SPS-Case01
NeuralCrest
No.6 Åìµþ¹ü¿ñÉÂÍý¸¦µæ²ñ-Case04
No11 TokyoBM-Case03
No215SPS-Case08 ALK-positive anaplastic large cell lymphoma of the small intestine
Nodal marginal zone lymphoma ÀáÀÊÕ±ïÂÓ¥ê¥ó¥Ñ¼ð
Nodular lymphocyte predominant Hodgkin's lymphoma(NLPHL)
Non tuberculous mycobacterial infection
Notch and Notch signaling
Nuclear receptor, estrogen and estrogen receptor
Nucleolus ³Ë¾®ÂÎ
Oct-2 and BOB.1 transcription factors
Oncocytic carcinoma of the minor salivary gland-JOHNAN_SPS conference 26Sep 2009_Case 02
Ovarian carcinoma
PCFCL
PCR-based TCR clonality studies in lymphoproliferations
PHP
PI3K-Akt signaling pathway¤È ¤¬¤ó
POEMS syndrome; POEMS¾É¸õ·²
PTEN
Paediatric lymphoma-¾®»ù¤Î°À¥ê¥ó¥Ñ¼ð
PathologyAtlas
PathologyAtlas-ALK-positive ALCL
PathologyAtlas-Follicular lymphoma
PathologyAtlas-Follicular lymphoma02
PathologyAtlas-Follicular+lymphoma
Pineal body ¾¾²ÌÂÎ
PlacentaAccreta
Plasmablastic leukemia
Pneumocystis Jirovecii
Polycomb group protein¡¡complex
Polycythemia vera ¿¿À¿·ì¾É
Poorly differentiated neuroendocrine cell carcinoma of the rectum
Precursor B-lymphoblastic lymphoma/leukaemia
Precursor T lymphoblastic lymphoma
Primary cutaneous folicle center lymphoma
Programmed cell death 1
Progressive mesenteric lymphadenopathy related with Gaucher disease-CHUBU slide seminar S2013-Case01
Progressive multifocal leukoencephalopathy; PML
Progressive transformation of germinal center(PTGC)
Pseudomonas aeruginosa necrotizing fascitis-233SPS-Case02
PukiWiki
PukiWiki/1.4
PukiWiki/1.4/Manual
PukiWiki/1.4/Manual/Plugin
PukiWiki/1.4/Manual/Plugin/A-D
PukiWiki/1.4/Manual/Plugin/E-G
PukiWiki/1.4/Manual/Plugin/H-K
PukiWiki/1.4/Manual/Plugin/L-N
PukiWiki/1.4/Manual/Plugin/O-R
PukiWiki/1.4/Manual/Plugin/S-U
PukiWiki/1.4/Manual/Plugin/V-Z
Pulmonary thromboembolism
RAF¡ÊBRAF) ÊѰۤȼðáç
Ras--¤¬¤ó²½¤Ë´Ø¤ï¤ë½ÅÍפʥ·¥°¥Ê¥ëʬ»Ò
RecentDeleted
Regulatory T-cell and Th17
Renal cell neoplasm--¿ÕºÙ˦À¼ðáç, 2016WHO¿·Ê¬Îà
RhoA
RhoA mutation in gastric cancer,diffuse type
SPS-218-06
SPS-Johnan217case05
SPS-Johnan217case06a
SPS-Johnan217case06b
SPS-¾ëÆîÉÂÍý
SPS216-Case01
SPS216-Case02
SPS216-Case03 late metastasis of adult granulosa cell tumor
SPS216-Case04
SPS216-Case05
SPS216Case6and7
SPS218-Case03
SPS219-Case01
SPS219-Case04
SPS219-Case06
SPS220-Case01
SPS220-Case03
SPS220-Case04
SPS220-Case06
SPS220-Case07
SPS220-Case08
SPS222-Case02
SPS222-Case04
SPS222-Case05
SPS223-Case02
SPS223-Case03
SPS223-Case07a, b
SPS225-Case05; mesenteric phlebosclerosis
SPS225-Case05;+mesenteric+phlebosclerosis
SPS239-Case01-A case of colonic neuroendocrine carcinoma
SPS239-Case01-A case of lung tumor
SPS241-Case07 Encapsulated liver cell tumor
SPS¾ëÆîÉÂÍýº©Ã̲ñ 2018_follicular lymphoma
SPSÀŲ¬ÉÂÍý°å²ñ·Ç¼¨ÈÄ
SandBox
Senduit¤Î»È¤¤Êý
Sepsis
Sex cord/stromal cell tumor
Shizuoka Survey 2018
Shizuoka Survey 2019
Soft tissue sarcoma with epithelioid morphorogy
Solitary fibrous tumor of the chest
Solitary fibrous tumors (SFTs)
Spleen--2¼¡¥ê¥ó¥ÑÁÈ¿¥
Splicing abnormalities ¥¹¥×¥é¥¤¥·¥ó¥°°Û¾ï
Staff
Staff's page
Staff's page/CHUBU57
Staff's page/CHUBU58
Staff's page/ÉÂÍý¤Î¤ªÊÙ¶¯_01
Subcutaneous panniculitis-like T-cell lymphoma
Subependymoma
Subependymoma of the rt. lateral ventricle-236SPS-Case05
Subependymoma with intraventricular hemorrhage--SPS269-case02
T-cell receptor signaling --TºÙ˦³èÀ²½¥·¥°¥Ê¥ë
T-cell receptor(TCR) gene
TET2 mutation
TTF1/ NKX2.1
Temporary Case Archives
Textforwikipathologica
The peripheral B-cell repertoire in humans
Thymic well differentiated neuroendocrine carcinoma(carcinoid)-237SPS
Thymus¡¡¶»Á£
Toxoplasmic lymphadenitis
Treatment and clinical practice for renal cell carcinoma
Tubular carcinoma of the breast
TºÙ˦
TºÙ˦¤ÈMHC
Undifferentiated small round cell tumors of the sinonasal tract
Update on IHC
UploadÍÑ¥Ú¡¼¥¸
Uterine cervical carcinosarcoma with neuroectodermal differentiation--SPS229-Case01
Uterine tumors resembling ovarian sex cord tumor (UTROSCT)
VATS¾ÉÎã-ÈØÅÄ»ÔΩÁí¹çɱ¡
VEGF
VEGF-vascular endothelial growth factor ·ì´ÉÆâÈéÁý¿£°ø»Ò
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Vulvovaginal Mesenchymal Tumors-Pathological diagnosis
WHO2016 classification of lymphoid neoplasms
WHO2016 Ǿ¼ðáçʬÎà
Waldenstroem macroglobulinemia
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Wegener's granulomatosis
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a large hepatic tumor of a young adult
acute megakaryoblastic leukaemia AML-M7
acute necrotizing eosinophilic myocarditis- SPS218-Case04
adenocarcinoma of the lung with diverse histology and progression--SPS229-Case04
adenoma malignum °ÀÁ£¼ð
adenosquamous cell carcinoma of the salivary gland--SPS229-Case06
adrenal glands
aggressive natural killer cell leukemia
anaplastic bilineage lymphoma ?
angiomyofibroblastoma--SPSJohnan2011-case01
angiomyolipoma of the kidney
bcl2-negative follicular lymphoma
bone marrow stroma
brain
breast cancer, invasive ductal carcinoma with squamous cell carcinoma component
cancer immunotherapy ¤¬¤óÌȱÖÎÅË¡¡¡
carcinoma of the uterine corpus »ÒµÜÂδâ
carcinosarcoma of the liver
cholangiocellular carcinoma with diffuse vascular intimal carcinomatosis-236SPS-Case03
choroid plexus carcinoma--SPS220-Case02
chromatin remodeling factor ¥¯¥í¥Þ¥Á¥ó¥ê¥â¥Ç¥ê¥ó¥°°ø»Ò
chronic active EB virus infection(CAEBV)
cohesin (¥³¥Ò¡¼¥·¥ó)Ê£¹çÂÎ
combined hepatocellular and cholangiocarcinoma of the liver
complement system
consultation case-cervical lymph node, Apr 2018
cyst wall of the lower jaw
desmoplastic round cell tumor--SPS229-Case07
desmoplastic small round cell tumor--Cases
development of hematopoiesis
effusion lymphoma
eosinophilia¤¬ÃøÌÀ¤Ê¹ü¿ñÁý¿£À¼ðáç
epithelioid trophoblastic tumor(ETT)-CHUBU1342
erythroid cells
extramedullary plasmacytoma of the sinonasal tract
fibroblastic osteosarcoma of the lt. ethomoidal sinuses, low grade
gastrinoma
glassy cell carcinoma_CHUB814
hemophagocytic Lymphohistiocytosis(HLH)/hemophagocytic syndrome(HS)
hemophagocytosis-221SPS/case05
hepatosplenic T-cell lymphoma ´Î磷¿TºÙ˦¥ê¥ó¥Ñ¼ð
histiocytoid/signet-ring cell carcinoma of the skin ( face )
human chorionic gonadotropin(hCG)
hydatidiform mole
information page
information page/primary aldosteronism
intravascular large B-cell lymphoma
islets of Langerhans-pancreas
java scripts
large B-cell lymphoma special types
lobular endocervical glandular hyperplasia
low-grade fibromyxoid sarcoma
lymph node01
lymph node02
lymphangioleiomyomatosis (LAM) of the lung
lymphoma of the thyroid with follicular growth pattern
lymphomania¤Ë¤Ê¤ë¤¿¤á¤Î¥ê¥ó¥Ñ¼ðÉÂÍý¿ÇÃÇ¥³¡¼¥¹
lymphomatoid gastropahty--SPS235-Case04
lymphomatous polyposis, MALT lymphoma type, ²óIJ
lymphoplasmacytic lymphoma(LPL)
lysosomal storage disease
malignant melanoma of the anal canal
mammary fibromatosis (inclusion body fibromatosis of the breast)-233SPS Case03
mature B-cell development
melanoma °À¹õ¿§¼ð
melanoma °À¹õ¿§¼ð/Nodular Melanoma ·ëÀá·¿°À¹õ¿§¼ð
methotrexate-associated lymphoproliferative disease
microRNA
minute meningothelial-like nodules
mixed phenotypic acute leukemia (MPAL) and acute undifferentiated leukaemia
monosomy 7-À÷¿§ÂÎ7È֤ΰ۾ï
mucin-producing bile duct neoplasm
multiple myeloma associated with hypersiderinemia
myxoid type malignant fibrous histiocytoma
neuroendocrine carcinoma, well-differentiated (carcinoid tumor) of the thymus
non-coding RNA
nucleosome and chromatin ¥Ì¥¯¥ì¥ª¥½¡¼¥à¤È¥¯¥í¥Þ¥Á¥ó¡¢À÷¿§ÂÎ
obstructive granulomatous vasculitis of the lung
p16/INK4a-INK4 family
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pancreas cancer
pancreatic acinar cell carcinoma
paraganglioma ˵¿À·ÐÀá¼ðáç
paroxysmal nocturnal hemoglobinuria-PNH
peripheral T-cell lymphoma --pathological diagnosis
peripheral T/NK cell lymphomas- WHO 4th Ed. 2016
placental mesencymal dysplasia-231SPS-Case01
polycythemia vera (primary erythrocytosis)
primary cutaneous diffuse large B-cell lymphoma, Leg type
primary cutaneous follicle center lymphoma
primary sclerosing cholangitis with high level of serum IgG4 consentration-228SPS-06
primary splenic large B cell lymphoma-236SPS-Case06
proteasome
renal tubular dysgenesis--SPS229-Case02
rhabdomyosarcoma-Iwata City Hospital
ruptured dissecting aneurysm of the vertebral artery--Iwata Case08
sialoadenoma papilliferum-236SPS-Case01
signet-ring stromal tumor(SRST)-CHUBU1343
sinonasal malignant melanoma
small GTPase (G-proteins) Äãʬ»ÒÎÌG¥¿¥ó¥Ñ¥¯¼Á
somatostatinoma
stromal cell sarcoma
synovial sarcoma
synovial sarcoma of the esophagus--234SPS-Case03
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syphilitic pharyngitis
telomere and telomerase ¥Æ¥í¥á¥¢¤È¥Æ¥í¥á¥é¡¼¥¼
thrombopoietin receptor (MPL) gene mutation in patients with Myeloproliferative neoplasm
tick bite --¥Þ¥À¥ËÒû½ý
toxoplasmosis-233SPS Case01
ubiquitin signaling
undifferentiated carcinoma with osteoclast-like giant cells
unicystic ameloblastoma
urothelial carcinoma - Ǣϩ¾åÈé´â
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Oncogene 2007; 26: 6469-6487.}; #br #ref(HERfamily01.jpg,around,right,60%) #br '''HER2'''°äÅÁ»Ò¤Ï''17ÈÖÀ÷¿§ÂÎĹÏÓ(17q12-q21)''¤Ë¶Éºß¤·, °äÅÁ»Ò»ºÊª¤ÎHER2¤Ï185kD¤Î ''I·¿Ëì´ÓÄÌ·¿Åü¥¿¥ó¥Ñ¥¯''¤Ç¤¢¤ë. NËöü¦¤ÎºÙ˦³°¥É¥á¥¤¥ó, Ëì´ÓḀ̈إê¥Ã¥¯¥¹, ºÙ˦Æâ¥Á¥í¥·¥ó¥¥Ê¡¼¥¼¥É¥á¥¤¥ó¤è¤ê¤Ê¤ë HER family¥¿¥ó¥Ñ¥¯¼Á¤ÎºÙ˦³°¥É¥á¥¤¥ó¤Ïµ¤«¤é¸¤Þ¤Ç¤ï¤±¤é¤ì, ¥É¥á¥¤¥ó¶¤È¸¤Ï¥·¥¹¥Æ¥¤¥ó¤ËÉÙ¤ß, ¤½¤ì¤¾¤ì10¸Ä¤ÎS-S·ë¹ç¤ò¤â¤Ã¤Æ¤¤¤ë. Ëì¶á˵Îΰè¤ÇÀÚÃǤµ¤ì¤Æ, ²ÄÍÏÀHER2ECD(extracellular domain)(90-110kD)¤òÀ¸À®¤¹¤ë. ºÙ˦Æâ¥É¥á¥¤¥ó¤Ï¥Á¥í¥·¥ó¥¥Ê¡¼¥¼¥É¥á¥¤¥ó¤ª¤è¤ÓCËöü¥É¥á¥¤¥ó¤Ë¤ï¤±¤é¤ì, ³èÀ²½¤·¤¿¥Á¥í¥·¥ó¥¥Ê¡¼¥¼¤Ë¤è¤êCËöü¥É¥á¥¤¥ó¤Ë¤¢¤ë¤¤¤¯¤Ä¤«¤Î¥Á¥í¥·¥ó»Ä´ð¤Ë¥ê¥ó»À²½¤¬¤ª¤³¤ë(¼«¸Ê¥ê¥ó»À²½) ¼«¸Ê¥ê¥ó»À²½¤·¤¿¥Á¥í¥·¥ó»Ä´ð¤Ë''SH2¥É¥á¥¤¥ó¤äPTB(phosphotyrosine binding)¥É¥á¥¤¥ó''¤ò¤â¤Ä¥·¥°¥Ê¥ëÅÁãʬ»Ò¤¬·ë¹ç¤·¤Æ²¼Î®¤Ø¥·¥°¥Ê¥ë¤òÁ÷¤ë. #br #br HER family¼õÍÆÂΤϥꥬ¥ó¥É¤Î·ë¹ç¤Ë¤è¤êΩÂι½Â¤¤¬ÊѲ½¤·¤½¤ì¤¾¤ì¥Û¥â¥À¥¤¥Þ¡¼, ¥Ø¥Æ¥í¥À¥¤¥Þ¡¼¤ò·ÁÀ®¤¹¤ë. HER1(EGFR), HER3, HER4¤Ï, ¥ê¥¬¥ó¥É¤¬¤Ê¤¤¾õÂ֤ǤÏÊĺ¿¹½Â¤¤ò¤È¤ë¤¿¤á, ¥À¥¤¥Þ¡¼¤ò·ÁÀ®¤Ç¤¤Ê¤¤¤¬, ¥ê¥¬¥ó¥É¤¬·ë¹ç¤¹¤ë¤ÈΩÂι½Â¤¤¬ÊѲ½¤·, ¥À¥¤¥Þ¡¼·ÁÀ®¤¬²Äǽ¤È¤Ê¤ë¡£ ´ûÃΤΥꥬ¥ó¥É¤Ï¡¡ #ref(HERdimer01.jpg,around,right,70%) >EGFR--EGR, TGF-¦Á, heparin-binding EGF-like ligand(HB-EGF), amphiregulin, epiregulin(EPR)¤Ê¤É > HER3--neuregulin(NRG1) > HER4--NRG1, NRG2, NRG3, NRG4, HB-EFG, EPR¤Ê¤É¤¬¤¢¤ë. HER2¤Ø¤ÎľÀܤΥꥬ¥ó¥É¤ÏÃΤé¤ì¤Æ¤¤¤Ê¤¤. ''HER2¤Ï³«Êü·¿(active extended)¹½Â¤¤Ç¸ºß¤¹¤ë¤¿¤á, ¥ê¥¬¥ó¥É¤¬¤Ê¤¯¤Æ¤â¾ï¤Ë¥À¥¤¥Þ¡¼·ÁÀ®¤¬²Äǽ¤Ç¤¢¤ë''. ¸½ºßHER2¤Ï, ¼«¿È¤Ë¥ê¥¬¥ó¥É¤¬·ë¹ç¤·¤Ê¤¯¤Æ¤â, ¥ê¥¬¥ó¥É·ë¹ç¤¹¤ß¤ÎHER family¤Î¾¤Îʬ»Ò¤È¥Ø¥Æ¥íÆóÎÌÂΤò·ÁÀ®¤¹¤ë¤³¤È¤Ç³èÀ²½¤·¥·¥°¥Ê¥ë¤òÁ÷¤ë¤È¹Í¤¨¤é¤ì¤Æ¤¤¤ë. &color(crimson){HER2¤¬HER family¤ÎÃæ¤Ç¤ÏºÇ¤â¶¯¤¤¥¥Ê¡¼¥¼¿¨ÇÞ³èÀ¤ò¤â¤Á, HER2¤ò´Þ¤à¥Ø¥Æ¥í¥À¥¤¥Þ¡¼¤¬ºÇ¤â¶¯¤¤¥·¥°¥Ê¥ë³èÀ¤ò¤â¤Ã¤Æ¤¤¤ë};¡£ Ä̾ïÁý¿£°ø»Ò¤Î¥·¥°¥Ê¥ë¤Ï, ¥ê¥¬¥ó¥É-¼õÍÆÂÎÊ£¹çÂΤβòÎ¥, ¼õÍÆÂΤÎæ¥ê¥ó»À²½, ¥ê¥½¥½¡¼¥àÆâ¤Ç¤Îʬ²ò¤Ë¤è¤êµÞ®¤ËÉԳ貽¤¹¤ë¤¬, HER2¤¬²á¾ê¤Ëȯ¸½¤¹¤ë¤È¤³¤ÎÉԳ貽¤¬¸ºÂ®¤¹¤ë. ¤Þ¤¿, ¤µ¤Þ¤¶¤Þ¤Êµ¡½ø¤ÇHER2¤¬ºÙ˦ɽÌ̤ËÄäÂÚ¤·¤Æ¥Û¥â/¥Ø¥Æ¥í¥À¥¤¥Þ¡¼¤ò·ÁÀ®, ¥·¥°¥Ê¥ëÅÁã´ü´Ö¤¬±äŤµ¤ì¤ë¬e{Karunagaran:Karunagaran D, et al E-erbB2 is a common auxiliary subunit of NDF and EGF receptors: implication for breast cancer EMBO J 1996;15: 254-264}; #br #br #ref(HERsignal02.jpg,around,left,70%) #br ''HER dimer¤Î²¼Î®¥·¥°¥Ê¥ë'' HER2¤Î²¼Î®¥·¥°¥Ê¥ë¤È¤·¤Æ¤Ï, Ras/Raf/MEK/MAPK·ÐÏ©¤ÈPI3K/Akt·ÐÏ©¤¬ºÇ¤â½ÅÍפǤ¢¤ê, ¤³¤ì¤é¤Î¥·¥°¥Ê¥ë¤Î³èÀ²½¤Ë¤è¤êºÙ˦Áý¿£, ºÙ˦¼þ´ü¿Ê¹Ô, ¥¢¥Ý¥È¡¼¥·¥¹ÍÞÀ©, ºÙ˦À¸Â¸¤Ê¤É¤¬Ð¶¿Ê¤¹¤ë¡£¬e{Arteaga:Arteaga CL, et alTreatment of HER2-positive breast cancer: current status and future perspectives. Nat Rev Clin Oncol. 2011 Nov 29;9(1):16-32.};¬e{Rosen:Rosen LS, et al Targeting signal transduction pathways in metastatic breast cancer: a comprehensive review. Oncologist. 2010;15(3):216-35. }; ''EGFR-HER2 ¥Ø¥Æ¥í¥À¥¤¥Þ¡¼¤äHER2-HER2 ¥Û¥â¥À¥¤¥Þ¡¼''¤Î²¼Î®¤Ç¤Ï¼ç¤ËRas/Raf/MEK/MAPK·ÐÏ©¤¬, ''HER2-HER3 ¥Ø¥Æ¥í¥À¥¤¥Þ¡¼''¤Î²¼Î®¤Ç¤Ï¼ç¤ËPI3K/Akt·ÐÏ©¤¬³èÀ²½¤µ¤ì¤Æ¤¤¤ë¡£¬e{Arteaga:Arteaga CL, et alTreatment of HER2-positive breast cancer: current status and future perspectives. Nat Rev Clin Oncol. 2011 Nov 29;9(1):16-32.};¬e{Rosen:Rosen LS, et al Targeting signal transduction pathways in metastatic breast cancer: a comprehensive review. Oncologist. 2010;15(3):216-35. }; ''HER3''¤ÏPI3K¤Îp85¥µ¥Ö¥æ¥Ë¥Ã¥È·ë¹ç¥â¥Á¡¼¥Õ¤òͤ·, HER2¤Ë¤è¤ëÁý¿£°ø»Ò¤ò²ð¤·¤¿&color(crimson){PI3K/Akt¤Î³èÀ²½¤ÏHER3¤Î¥ê¥ó»À²½¤Ë¤è¤êºÇ¤â¶¯¤¯Í¶Æ³¤µ¤ì¤ë};. ¬e{Karunagaran:Karunagaran D, et al E-erbB2 is a common auxiliary subunit of NDF and EGF receptors: implication for breast cancer EMBO J 1996;15: 254-264};¬e{:Hellyer NJ, et al. Heregulin-dependent activation of phosphoinositide 3-kinase and Akt via the ErbB2/ErbB3 co-receptor.J Biol Chem. 2001 Nov 9;276(45):42153-61.}; HER2¤Î²á¾êȯ¸½¤·¤Æ¤¤¤ëºÙ˦¤äÆý´â¤Ç¤ÏHER3¤Î¥ê¥ó»À²½¤¬Áý²Ã¤·, PI3K/Akt¤¬³èÀ²½¤·¤Æ¤¤¤ë¤³¤È¤¬Êó¹ð¤µ¤ì¤Æ¤¤¤ë. ¬e{:Wallasch C, et al. Heregulin-dependent regulation of HER2/neu oncogenic signaling by heterodimerization with HER3. EMBO J. 1995 Sep 1;14(17):4267-75.}; ¬e{: Alimandi M, et al.Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas. Oncogene. 1995 May 4;10(9):1813-21.}; ¬e{:Tokunaga E, et al.Akt is frequently activated in HER2/neu-positive breast cancers and associated with poor prognosis among hormone-treated patients. Int J Cancer. 2006 Jan 15;118(2):284-9.}; ¬e{:Zhou X, et al. Activation of the Akt/mammalian target of rapamycin/4E-BP1 pathway by ErbB2 overexpression predicts tumor progression in breast cancers. Clin Cancer Res. 2004 Oct 15;10(20):6779-88.}; ''Akt''¤ÏºÙ˦Áý¿£, ¥¢¥Ý¥È¡¼¥·¥¹ÍÞÀ©, ºÙ˦À¸Â¸¤À¤±¤Ç¤Ï¤Ê¤¯, ±ÉÍÜ, ÅüÂå¼Õ, ¾åÈé´ÖÍշϰܹÔ, ºÙ˦¿»½á, ¥²¥Î¥à°ÂÄêÀ, ·ì´É¿·À¸¤Ê¤É¤µ¤Þ¤¶¤Þ¤Ê¥·¥°¥Ê¥ë·ÐÏ©¤Îʬ´ôÅÀ¤Ë°ÌÃÖ¤¹¤ë½ÅÍפÊʬ»Ò¤Ç¤¢¤ë. ¬e{:Tokunaga E, et al. Deregulation of the Akt pathway in human cancer. Curr Cancer Drug Targets. 2008 Feb;8(1):27-36.}; #br #br #br #clear #br #ref(HER2molecule01.jpg,around,left,70%) ''HER2¤òɸŪ¤È¤·¤¿¹³Âμ£ÎÅ'' ''Trastuzumab'', Herceptin HER2²á¾êȯ¸½ºÙ˦¤ÎÁý¿£ÍÞÀ©¸ú²Ì¤ÎºÇ¤â¹â¤¤¹³HER2¥â¥Î¥¯¥í¥Ê¡¼¥ë¹³ÂΤǤ¢¤ë4D5¤Î¥Ò¥È²½¥â¥Î¥¯¥í¥Ê¡¼¥ë¹³ÂÎ(¥Ò¥È²½IgG1¹³ÂÎ)¤¬ºîÀ®¤µ¤ìTrastuzumab¤È̿̾¤µ¤ì¤¿. Trastuzumab¤Ï4D5¤ÈƱ¤¸¿ÆÏÂÀ¤Ç, &color(crimson){ºÙ˦³°¥É¥á¥¤¥ó¸¤Ë·ë¹ç¤¹¤ë};. ¾¤ÎHER¼õÍÆÂΤȤϷë¹ç¤·¤Ê¤¤. HER2¤ÏºÙ˦³°¥É¥á¥¤¥ó¤ÇÀÚÃǤµ¤ì, ¥ê¥ó»À²½¤µ¤ì¤¿³èÀ·¿¤ÎËì·ë¹çÀÃÇÊÒ p95HER2¤¬À¸¤¸¤ë. Trasutuzumab¤Ï¤³¤ÎÀÚÃǤÈp95HER2¤Î»ºÀ¸¤òÍÞÀ©¤¹¤ë¤³¤È¤Ç²¼Î®¤Ø¤Î¥·¥°¥Ê¥ëÅÁã¤òÍÞÀ©¤¹¤ë. Trasutuzumab¤Ï, HER2¤È¾¤ÎHER¥Õ¥¡¥ß¥ê¡¼¼õÍÆÂΤȤΥۥâ/ ¥Ø¥Æ¥íÆóÎÌÂηÁÀ®¤òÁ˳²¤·²¼Î®¥·¥°¥Ê¥ë³èÀ²½¤òÍÞÀ©¤¹¤ë. Trasutuzumab¤ÏÌȱֺÙ˦¤òÉê³è²½¤·¹³Âΰ͸ÀºÙ˦¾ã³²(antibody-dependent cellular cytotoxicity; ADCC)¤òµ¯¤³¤¹. Trasutuzumab¤Î·ë¹ç¤·¤¿HER2¤Ï¥¨¥ó¥É¥µ¥¤¥È¡¼¥·¥¹¤Ë¤è¤êºÙ˦Æâ¤Ë¼è¤ê¹þ¤Þ¤ìʬ²ò¤¬Â¥¿Ê¤µ¤ì¤ë. °Ê¾å¤«¤éTrastuzumab¤ÎºÙ˦Æâ¸ú²Ì¤Ë¤è¤ê Ras/Raf/MEK/MAPK·ÐÏ©, PI3K/Akt·ÐÏ©¤òÍÞÀ©¤·, apoptosisͶƳ, ºÙ˦Áý¿£Äã²¼, HER2¤Îdownregulation¤äæ¥ê¥ó»À²½, VEGF»ºÀ¸Äã²¼, ¼ðáç·ì´É¿·À¸ÍÞÀ©, ²½³ØÎÅË¡¤Î´¶¼õÀÁý¶¯, ¤ò¤¤¿¤¹. ¤Þ¤¿²¼Î®¥·¥°¥Ê¥ë¤Î½¤¾þ¤ä¾¤Î¥¯¥í¥¹¥È¡¼¥¯¤ÎÊѲ½¤Ê¤É¤â¸ú²Ì¤È¤·¤Æ¹Í¤¨¤é¤ì¤ë¡£ #clear ''Pertuzumab'' 2C4¡¡¾¦ÉÊ̾ ''¥Ñ¡¼¥¸¥§¥¿ Perjeta'' HER dimer·ÁÀ®Á˳²ºÞ(HER-dimerization inhibitor)¤È¤·¤ÆÃΤé¤ì¤ë¿·¥¿¥¤¥×¤Î¹³ÂÎ. 2C4¤Ï4D5¤ÈƱ»þ´ü¤ËºîÀ®¤µ¤ì¤¿. HER2²á¾êȯ¸½ºÙ˦³ô¤Ø¤ÎÁý¿£ÍÞÀ©¸ú²Ì¤Ï4D5¤è¤ê¤â¤«¤Ê¤êÄ㤫¤Ã¤¿¤¬pertuzumab¤Ï&color(red){''HER2¤Î¥É¥á¥¤¥ó¶¤Ë·ë¹ç¤·, HER2¤È¾¤ÎHER¼õÍÆÂΤȤΥÀ¥¤¥Þ¡¼·ÁÀ®¤ò¶¯ÎϤËÁ˳²¤¹¤ë. ÆÃ¤Ë, HER2-HER3 dimer¤Î¸º¾¯''};¤Ë¤è¤ê²¼Î®¤ÎAkt¤äMAPK¥·¥°¥Ê¥ë¤òÍÞÀ©¤¹¤ë¤³¤È¤¬ÌÀ¤é¤«¤Ë¤µ¤ì¤¿. ¬e{Lin:Lin NU, et al Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2008 Apr 20;26(12):1993-9.}; Pertuzumab¤Ïtrasutuzumab¤È·ë¹çÉô°Ì¤¬°Û¤Ê¤ë¤¬ADCC¤ò³èÀ²½¤¹¤ë. HER2²á¾êȯ¸½Æý´â¤Ë¤ª¤¤¤ÆHER2-HER3¥Ø¥Æ¥í¥À¥¤¥Þ¡¼¤Ï¥ê¥¬¥ó¥É¤ÎNGR¸ºß²¼¤Ç¤ÏÃøÌÀ¤Ë³èÀ²½¤¬Áý¶¯¤µ¤ì¤ë¤¬¥ê¥¬¥ó¥ÉÈó°Í¸À¤Ë¤â³èÀ²½¤µ¤ì¤ë¤³¤È¤¬¼¨¤µ¤ì¤Æ¤¤¤ë. Pertuzumab¤Ï¥ê¥¬¥ó¥É°Í¸À¤Î, trasutuzumab¤Ï¥ê¥¬¥ó¥ÉÈó°Í¸À¤ÎHER2-HER3Áê¸ßºîÍѤòÍÞÀ©¤¹¤ë¤³¤È¤¬Êó¹ð¤µ¤ì¤Æ¤¤¤ë. ¬e{:Junttila TT et al, Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941.Cancer Cell. 2009 May 5;15(5):429-40.}; PertuzumabñÆÈÅêÍ¿¤Î͸úÀ, °ÂÁ´À¤Ï³ÎΩ¤µ¤ì¤Æ¤¤¤Ê¤¤. Herceptin°Ê³°¤Î¹³°À¼ðáçÌôÃæ»ß¸å¤Ë»È¤¦¤È¤¤Ïɬ¤ºtrastuzumab(Herceptin)¤ÈÊ»ÍѤ¹¤ë. 2018ǯ10·î10Æü¤Ë&color(#e2041b){''HER2ÍÛÀÆý´â½ÑÁ°½Ñ¸åÎÅË¡¤Ø¤ÎÅêÍ¿¤¬ÄɲþµÇ§''};¤È¤Ê¤êŬ±þ¤ÏHER2ÍÛÀÆý´â¤È¤Ê¤Ã¤¿. (¤³¤ì¤Þ¤Ç¤Ï¡ÖHER2ÍÛÀ¤Î¼ê½ÑÉÔǽËô¤ÏºÆÈ¯Æý´â¡×¡Ë #br ''Lapatinib'' ¾¦ÉÊ̾ ''¥¿¥¤¥±¥ë¥×''¡¡¥°¥é¥¯¥½¥¹¥ß¥¹¥¯¥é¥¤¥ó Lapatinib¤Ï¾®Ê¬»Ò²½¹çʪ¤Ç, EGFR¤ª¤è¤ÓHER2¤ÎºÙ˦Æâ¥É¥á¥¤¥ó¤Ë¸ºß¤¹¤ëATP·ë¹çÉô°Ì¤Ë¶¥¹çŪ¤Ë·ë¹ç¤¹¤ë²ÄµÕŪ¥Á¥í¥·¥ó¥¥Ê¡¼¥¼Á˳²ºÞ. Lapatinib¤ÏHER2ÍÛÀÆý´â¤Ç¤Ï, HER2¤Î¥ê¥ó»À²½¤òÁ˳²¤·, ²¼Î®¤ÎPI3K/Akt·ÐÏ©, MAPK·ÐÏ©¤òÍÞÀ©¤¹¤ë. EGFR¤Ø¤ÎÍÞÀ©¸ú²Ì¤ÏÉÔÌÀ¤Î¤Þ¤Þ¤Ç¤¢¤ë¤¬, in vitro¤ª¤è¤Ó¥Þ¥¦¥¹°Ü¿¢¼ðáçºÙ˦¤ò»È¤Ã¤¿Á°Î×¾²¸¦µæ¤Ç¤Ï, HER2²á¾êȯ¸½Æý´â¥â¥Ç¥ë¤Ë¸ú²Ì¤¬¤¢¤ë¤³¤È¤¬¼¨¤µ¤ì¤Æ¤¤¤ë. Lapatinib¤Î¹³¼ðáç¸ú²Ì¤Ë¤Ï, p95HER2¥ê¥ó»À²½ÍÞÀ©¤ätrastuzmabÂÑÀHER2²á¾êȯ¸½ºÙ˦³ô¤ÎÍÞÀ©, trastuzumab¤È¤ÎÁê¾è¸ú²Ì¤Ê¤É¤¬¤¢¤ë. Lapatinib¤Ï¾®Ê¬»Ò²½¹çʪ¤Î¤¿¤áǾ·ì±Õ´ØÌç¤òÄ̲ᤷ, Ǿž°ÜͽËɤ伣ÎŤË͸ú¤Ç¤¢¤ë²ÄǽÀ¤¬¤¢¤ë¬e{:Esteva FJ, et al. Molecular predictors of response to trastuzumab and lapatinib in breast cancer. Nat Rev Clin Oncol. 2010 Feb;7(2):98-107.}; ¬e{Lin:Lin NU, et al Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2008 Apr 20;26(12):1993-9.}; #br ''Trastuzumab-emtansin (T-DM1)'' ¾¦ÉÊ̾''¥«¥É¥µ¥¤¥é'' trastuzumab¤Ë(N-maleimidometyl) cyclohexane-1-carboxylate(MCC)¤È¤¤¤¦¥ê¥ó¥«¡¼¤ò²ðºß¤·, Èù¾®´ÉÁ˳²ºÞ¤Î¹³¤¬¤óºÞemtansine ¥¨¥à¥¿¥ó¥·¥ó¤¬·ë¹ç¤·¤Æ¤¤¤ë. antibody-drug conjugate(ADC). T-DM1¤ÏHER2¤Ë·ë¹ç¤¹¤ë¤È, ¥¨¥ó¥É¥µ¥¤¥È¡¼¥·¥¹¤Ë¤è¤êºÙ˦Æâ¤Ë¼è¤ê¹þ¤Þ¤ì¥ê¥½¥¾¡¼¥à¤Ë¤è¤êʬ²ò¤µ¤ì¤ë. ·ë²ÌDM1¤ò´Þ¤à°Û²½Âå¼Õ»ºÊª¤¬ºÙ˦¼ÁÆâ¤ËÊü½Ð¤µ¤ìÈù¾®´É¤Ë·ë¹ç, ¤½¤Î½Å¹ç¤òÁ˳²¤¹¤ë. 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(3ǯiDFS Ê»ÍÑ92.8%, ¥×¥é¥»¥Ü91.2%) > 3) °Ê¾å¤«¤é''¥ê¥ó¥ÑÀឰܤ¬±¢À¤Ç¥Û¥ë¥â¥ó¼õÍÆÂΤ¬ÍÛÀ¤Î´µ¼Ô¤µ¤ó¤Ë¤ÏÊݸ±Å¬±þ¤Ë¤Ê¤Ã¤Æ¤â½Ñ¸åPertzumabÊ»ÍѤϹԤï¤Ê¤¤''¡£ > 4) ''¥ê¥ó¥ÑÀឰܤ¬¤¢¤ê, ¥Û¥ë¥â¥ó¼õÍÆÂΤ¬±¢À¤Ç¤¢¤ì¤Ð, Ê»ÍÑÅêÍ¿¤ò¸¡Æ¤¤¹¤ë''. ǯÎð¤Ë¤è¤ê, »È¤¦»È¤ï¤Ê¤¤¤È¤¤¤¦ÁªÂò¤Ï¼ÂÎ×¾²¤ÎÃæ¤Ç¤Ï¤ª¤½¤é¤¯¤Ê¤¤. > 5) ¥ê¥ó¥ÑÀឰܱ¢À, ¥Û¥ë¥â¥ó¼õÍÆÂα¢À¤Î¾ì¹ç¤Ï¡©¡¡¡¡»ÈÍѤÏÈù̯. -&color(red){¥ê¥ó¥ÑÀឰܱ¢À, ¼ðáç·Â<2cm¤ÎÆý´â¤Ç¤Ïweekly ¥Ñ¥¯¥ê¥¿¥¥»¥ë¡ÜTrastuzumab¤Î½Ñ¸åÎÅË¡¤¬ÂçÊÑ͸ú¤Ç7ǯÁ´À¸Â¸´ü´Ö¤Ï96%¤Ç¤¢¤Ã¤¿.(¼ðáç·Â¤¬2cm°Ê²¼¤Ç¤¢¤ì¤Ð, ¥¢¥É¥ê¥¢¥Þ¥¤¥·¥ó¤Ï»È¤ï¤Ê¤¯¤Æ¤è¤¤¤È¤¤¤¦°ÕÌ£¤Ë¤Ê¤ë)}; #br -·ë¶É, %%%¥ê¥ó¥ÑÀឰܱ¢À¤Ç, ¼ðáç·Â<2cm¤Ç¤¢¤ì¤ÐPertzumab»ÈÍѤϤ¢¤ê¤¨¤Ê¤¤%%%. ¼ðáç·Â>3cm¤Î¾ì¹ç¤Ï¥ê¥¹¥¯¤ò¹Í¤¨¤ÆÊ»ÍѤˤʤë¤È»×¤ï¤ì¤ë. #br **µþÂç¶»Éô³°²Ê ¹âÅÄÀµÂÙÀèÀ¸¤Î¹Ö±é¤«¤é¡Ê2018ǯ10·î15Æü¡÷IWT¡Ë [#n6b34fa5] ''Pertuzumab¤Î¸ú²Ì'' >½Ñ¸åPertuzumabÊ»ÍѤˤè¤êºÆÈ¯¥ê¥¹¥¯¤¬20%(hazardÈæca 0.80)¤Û¤É¸º¾¯¤¹¤ë. ¥ê¥ó¥ÑÀáž°ÜÍÛÀÎ㤬¸ú²ÌÂç. (APHINITY»î¸³¬e{:von Minckwitz G, et al, Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N Engl J Med. 2017 Jul 13;377(2):122-131.PMID:28581356};¡¨É¸½à¼£ÎŤǤ¢¤ë¡Ö²½³ØÎÅË¡¡Ü¥È¥é¥¹¥Ä¥º¥Þ¥Ö¡×¤Ë¥Ú¥ë¥Ä¥º¥Þ¥Ö1ǯÅêÍ¿¤ò²Ã¤¨¤ë¼£ÎŤλî¤ß) >½ÑÁ°¤ËPertuzumabÊ»ÍѤ¹¤ë¤ÈpCR¤Î³ä¹ç¤¬Áý²Ã¤¹¤ë. (NeoSphere»î¸³¡§¶É½ê¿Ê¹ÔÀ¡¤±ê¾ÉÀ¡¤¤Þ¤¿¤ÏÁá´üHER2ÍÛÀÆý´â´µ¼Ô¤Ë¤ª¤±¤ë½ÑÁ°Êä½õ¥Ú¥ë¥Ä¥º¥Þ¥Ö¤ª¤è¤Ó¥È¥é¥¹¥Ä¥º¥Þ¥Ö¤Ë´Ø¤¹¤ë5ǯ´Ö¤Î²òÀÏ¡§Â¿»ÜÀß¶¦Æ±¡¤¥ª¡¼¥×¥ó¥é¥Ù¥ë¡¤ÂèIIÁê¥é¥ó¥À¥à²½»î¸³¬e{:Gianni L, et al., 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016 Jun;17(6):791-800 PMID 27179402};) >PertuzumabÅêÍ¿¤Ë¤è¤ëÉûºîÍѤˤϽÅÂç¤Ê¤â¤Î¤Ï¾¯¤Ê¤«¤Ã¤¿. ²¼Î¡.¡Ê¥Ú¥ë¥Ä¥º¥Þ¥Ö¤Î½Ñ¸å1ǯÅêÍ¿¤Ë¤ª¤±¤ëÉûºîÍѤϡ¢È鿾¤ÎÉÑÅÙ¤¬5.5¡óÁý¤¨¡¢½ÅÅ٤β¼Î¡¡Ê¥°¥ì¡¼¥É3°Ê¾å¡Ë¤¬6.1¡óÁý¤¨¤ë¤¬¡¢²½³ØÎÅË¡½ªÎ»¸å¤Î¥°¥ì¡¼¥É3°Ê¾å¤Î²¼Î¡¤Ï0.5¡ó¤Ç¤¢¤ê¡¢¿´ÆÇÀ¤ÎÉÑÅÙ¤ÏÄ㤫¤Ã¤¿¡£¡Ë ''HER2ÍÛÀÆý´â¤Î½ÑÁ°ÎÅË¡¤Î°ÕµÁ ½ÑÁ° vs ½Ñ¸å'' >herceptin¤¬»È¤ï¤ì¤ëÁ°¤Î»î¸³(NSABP B-18: ACÎÅË¡. ¤¤¤í¤¤¤í¤Ê¾ÉÎ㤬Æþ¤Ã¤Æ¤¤¤ë)¤Ç¤Ï ½ÑÁ°¤Îͽ¸å¡á½Ñ¸å¤Îͽ¸å. >HER2ÍÛÀÆý´â¤Ë¸Â¤ë¤È½ÑÁ°, ½Ñ¸åÅêÍ¿¤Î¸ú²Ì, ¤É¤Á¤é¤¬¤è¤¤¤«¤Ï¤ï¤«¤Ã¤Æ¤¤¤Ê¤¤. ͽ¸å¤Î²þÁ±·ë²Ì¤Ç¤Ï½ÑÁ°ÎÅË¡¤Î»î¸³¤Î¥Ç¡¼¥¿¤Î¤Û¤¦¤¬Îɤ«¤Ã¤¿. ''¾¯¤Ê¤¯¤È¤â½ÑÁ°ÅêÍ¿¤Î¥Ç¥á¥ê¥Ã¥È¤Ï¤Ê¤¤.'' >¥Û¥ë¥â¥ó¼õÍÆÂα¢À¤Î¥Ò¥È¤Ï, herceptinÅêÍ¿¤ÇpCR¤È¤Ê¤ë³ä¹ç¤¬¹â¤¤. PertuzumabÅêÍ¿¤âƱ¤¸¤Ç 46%. 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Oncogene 2007; 26: 6469-6487.}; #br #ref(HERfamily01.jpg,around,right,60%) #br '''HER2'''°äÅÁ»Ò¤Ï''17ÈÖÀ÷¿§ÂÎĹÏÓ(17q12-q21)''¤Ë¶Éºß¤·, °äÅÁ»Ò»ºÊª¤ÎHER2¤Ï185kD¤Î ''I·¿Ëì´ÓÄÌ·¿Åü¥¿¥ó¥Ñ¥¯''¤Ç¤¢¤ë. NËöü¦¤ÎºÙ˦³°¥É¥á¥¤¥ó, Ëì´ÓḀ̈إê¥Ã¥¯¥¹, ºÙ˦Æâ¥Á¥í¥·¥ó¥¥Ê¡¼¥¼¥É¥á¥¤¥ó¤è¤ê¤Ê¤ë HER family¥¿¥ó¥Ñ¥¯¼Á¤ÎºÙ˦³°¥É¥á¥¤¥ó¤Ïµ¤«¤é¸¤Þ¤Ç¤ï¤±¤é¤ì, ¥É¥á¥¤¥ó¶¤È¸¤Ï¥·¥¹¥Æ¥¤¥ó¤ËÉÙ¤ß, ¤½¤ì¤¾¤ì10¸Ä¤ÎS-S·ë¹ç¤ò¤â¤Ã¤Æ¤¤¤ë. Ëì¶á˵Îΰè¤ÇÀÚÃǤµ¤ì¤Æ, ²ÄÍÏÀHER2ECD(extracellular domain)(90-110kD)¤òÀ¸À®¤¹¤ë. ºÙ˦Æâ¥É¥á¥¤¥ó¤Ï¥Á¥í¥·¥ó¥¥Ê¡¼¥¼¥É¥á¥¤¥ó¤ª¤è¤ÓCËöü¥É¥á¥¤¥ó¤Ë¤ï¤±¤é¤ì, ³èÀ²½¤·¤¿¥Á¥í¥·¥ó¥¥Ê¡¼¥¼¤Ë¤è¤êCËöü¥É¥á¥¤¥ó¤Ë¤¢¤ë¤¤¤¯¤Ä¤«¤Î¥Á¥í¥·¥ó»Ä´ð¤Ë¥ê¥ó»À²½¤¬¤ª¤³¤ë(¼«¸Ê¥ê¥ó»À²½) ¼«¸Ê¥ê¥ó»À²½¤·¤¿¥Á¥í¥·¥ó»Ä´ð¤Ë''SH2¥É¥á¥¤¥ó¤äPTB(phosphotyrosine binding)¥É¥á¥¤¥ó''¤ò¤â¤Ä¥·¥°¥Ê¥ëÅÁãʬ»Ò¤¬·ë¹ç¤·¤Æ²¼Î®¤Ø¥·¥°¥Ê¥ë¤òÁ÷¤ë. #br #br HER family¼õÍÆÂΤϥꥬ¥ó¥É¤Î·ë¹ç¤Ë¤è¤êΩÂι½Â¤¤¬ÊѲ½¤·¤½¤ì¤¾¤ì¥Û¥â¥À¥¤¥Þ¡¼, ¥Ø¥Æ¥í¥À¥¤¥Þ¡¼¤ò·ÁÀ®¤¹¤ë. HER1(EGFR), HER3, HER4¤Ï, ¥ê¥¬¥ó¥É¤¬¤Ê¤¤¾õÂ֤ǤÏÊĺ¿¹½Â¤¤ò¤È¤ë¤¿¤á, ¥À¥¤¥Þ¡¼¤ò·ÁÀ®¤Ç¤¤Ê¤¤¤¬, ¥ê¥¬¥ó¥É¤¬·ë¹ç¤¹¤ë¤ÈΩÂι½Â¤¤¬ÊѲ½¤·, ¥À¥¤¥Þ¡¼·ÁÀ®¤¬²Äǽ¤È¤Ê¤ë¡£ ´ûÃΤΥꥬ¥ó¥É¤Ï¡¡ #ref(HERdimer01.jpg,around,right,70%) >EGFR--EGR, TGF-¦Á, heparin-binding EGF-like ligand(HB-EGF), amphiregulin, epiregulin(EPR)¤Ê¤É > HER3--neuregulin(NRG1) > HER4--NRG1, NRG2, NRG3, NRG4, HB-EFG, EPR¤Ê¤É¤¬¤¢¤ë. HER2¤Ø¤ÎľÀܤΥꥬ¥ó¥É¤ÏÃΤé¤ì¤Æ¤¤¤Ê¤¤. 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Nat Rev Clin Oncol. 2011 Nov 29;9(1):16-32.};¬e{Rosen:Rosen LS, et al Targeting signal transduction pathways in metastatic breast cancer: a comprehensive review. Oncologist. 2010;15(3):216-35. }; ''EGFR-HER2 ¥Ø¥Æ¥í¥À¥¤¥Þ¡¼¤äHER2-HER2 ¥Û¥â¥À¥¤¥Þ¡¼''¤Î²¼Î®¤Ç¤Ï¼ç¤ËRas/Raf/MEK/MAPK·ÐÏ©¤¬, ''HER2-HER3 ¥Ø¥Æ¥í¥À¥¤¥Þ¡¼''¤Î²¼Î®¤Ç¤Ï¼ç¤ËPI3K/Akt·ÐÏ©¤¬³èÀ²½¤µ¤ì¤Æ¤¤¤ë¡£¬e{Arteaga:Arteaga CL, et alTreatment of HER2-positive breast cancer: current status and future perspectives. Nat Rev Clin Oncol. 2011 Nov 29;9(1):16-32.};¬e{Rosen:Rosen LS, et al Targeting signal transduction pathways in metastatic breast cancer: a comprehensive review. Oncologist. 2010;15(3):216-35. }; ''HER3''¤ÏPI3K¤Îp85¥µ¥Ö¥æ¥Ë¥Ã¥È·ë¹ç¥â¥Á¡¼¥Õ¤òͤ·, HER2¤Ë¤è¤ëÁý¿£°ø»Ò¤ò²ð¤·¤¿&color(crimson){PI3K/Akt¤Î³èÀ²½¤ÏHER3¤Î¥ê¥ó»À²½¤Ë¤è¤êºÇ¤â¶¯¤¯Í¶Æ³¤µ¤ì¤ë};. ¬e{Karunagaran:Karunagaran D, et al E-erbB2 is a common auxiliary subunit of NDF and EGF receptors: implication for breast cancer EMBO J 1996;15: 254-264};¬e{:Hellyer NJ, et al. Heregulin-dependent activation of phosphoinositide 3-kinase and Akt via the ErbB2/ErbB3 co-receptor.J Biol Chem. 2001 Nov 9;276(45):42153-61.}; HER2¤Î²á¾êȯ¸½¤·¤Æ¤¤¤ëºÙ˦¤äÆý´â¤Ç¤ÏHER3¤Î¥ê¥ó»À²½¤¬Áý²Ã¤·, PI3K/Akt¤¬³èÀ²½¤·¤Æ¤¤¤ë¤³¤È¤¬Êó¹ð¤µ¤ì¤Æ¤¤¤ë. ¬e{:Wallasch C, et al. Heregulin-dependent regulation of HER2/neu oncogenic signaling by heterodimerization with HER3. EMBO J. 1995 Sep 1;14(17):4267-75.}; ¬e{: Alimandi M, et al.Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas. Oncogene. 1995 May 4;10(9):1813-21.}; ¬e{:Tokunaga E, et al.Akt is frequently activated in HER2/neu-positive breast cancers and associated with poor prognosis among hormone-treated patients. Int J Cancer. 2006 Jan 15;118(2):284-9.}; ¬e{:Zhou X, et al. Activation of the Akt/mammalian target of rapamycin/4E-BP1 pathway by ErbB2 overexpression predicts tumor progression in breast cancers. Clin Cancer Res. 2004 Oct 15;10(20):6779-88.}; ''Akt''¤ÏºÙ˦Áý¿£, ¥¢¥Ý¥È¡¼¥·¥¹ÍÞÀ©, ºÙ˦À¸Â¸¤À¤±¤Ç¤Ï¤Ê¤¯, ±ÉÍÜ, ÅüÂå¼Õ, ¾åÈé´ÖÍշϰܹÔ, ºÙ˦¿»½á, ¥²¥Î¥à°ÂÄêÀ, ·ì´É¿·À¸¤Ê¤É¤µ¤Þ¤¶¤Þ¤Ê¥·¥°¥Ê¥ë·ÐÏ©¤Îʬ´ôÅÀ¤Ë°ÌÃÖ¤¹¤ë½ÅÍפÊʬ»Ò¤Ç¤¢¤ë. ¬e{:Tokunaga E, et al. Deregulation of the Akt pathway in human cancer. Curr Cancer Drug Targets. 2008 Feb;8(1):27-36.}; #br #br #br #clear #br #ref(HER2molecule01.jpg,around,left,70%) ''HER2¤òɸŪ¤È¤·¤¿¹³Âμ£ÎÅ'' ''Trastuzumab'', Herceptin HER2²á¾êȯ¸½ºÙ˦¤ÎÁý¿£ÍÞÀ©¸ú²Ì¤ÎºÇ¤â¹â¤¤¹³HER2¥â¥Î¥¯¥í¥Ê¡¼¥ë¹³ÂΤǤ¢¤ë4D5¤Î¥Ò¥È²½¥â¥Î¥¯¥í¥Ê¡¼¥ë¹³ÂÎ(¥Ò¥È²½IgG1¹³ÂÎ)¤¬ºîÀ®¤µ¤ìTrastuzumab¤È̿̾¤µ¤ì¤¿. Trastuzumab¤Ï4D5¤ÈƱ¤¸¿ÆÏÂÀ¤Ç, &color(crimson){ºÙ˦³°¥É¥á¥¤¥ó¸¤Ë·ë¹ç¤¹¤ë};. ¾¤ÎHER¼õÍÆÂΤȤϷë¹ç¤·¤Ê¤¤. HER2¤ÏºÙ˦³°¥É¥á¥¤¥ó¤ÇÀÚÃǤµ¤ì, ¥ê¥ó»À²½¤µ¤ì¤¿³èÀ·¿¤ÎËì·ë¹çÀÃÇÊÒ p95HER2¤¬À¸¤¸¤ë. Trasutuzumab¤Ï¤³¤ÎÀÚÃǤÈp95HER2¤Î»ºÀ¸¤òÍÞÀ©¤¹¤ë¤³¤È¤Ç²¼Î®¤Ø¤Î¥·¥°¥Ê¥ëÅÁã¤òÍÞÀ©¤¹¤ë. Trasutuzumab¤Ï, HER2¤È¾¤ÎHER¥Õ¥¡¥ß¥ê¡¼¼õÍÆÂΤȤΥۥâ/ ¥Ø¥Æ¥íÆóÎÌÂηÁÀ®¤òÁ˳²¤·²¼Î®¥·¥°¥Ê¥ë³èÀ²½¤òÍÞÀ©¤¹¤ë. 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ÆÃ¤Ë, HER2-HER3 dimer¤Î¸º¾¯''};¤Ë¤è¤ê²¼Î®¤ÎAkt¤äMAPK¥·¥°¥Ê¥ë¤òÍÞÀ©¤¹¤ë¤³¤È¤¬ÌÀ¤é¤«¤Ë¤µ¤ì¤¿. ¬e{Lin:Lin NU, et al Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2008 Apr 20;26(12):1993-9.}; Pertuzumab¤Ïtrasutuzumab¤È·ë¹çÉô°Ì¤¬°Û¤Ê¤ë¤¬ADCC¤ò³èÀ²½¤¹¤ë. HER2²á¾êȯ¸½Æý´â¤Ë¤ª¤¤¤ÆHER2-HER3¥Ø¥Æ¥í¥À¥¤¥Þ¡¼¤Ï¥ê¥¬¥ó¥É¤ÎNGR¸ºß²¼¤Ç¤ÏÃøÌÀ¤Ë³èÀ²½¤¬Áý¶¯¤µ¤ì¤ë¤¬¥ê¥¬¥ó¥ÉÈó°Í¸À¤Ë¤â³èÀ²½¤µ¤ì¤ë¤³¤È¤¬¼¨¤µ¤ì¤Æ¤¤¤ë. Pertuzumab¤Ï¥ê¥¬¥ó¥É°Í¸À¤Î, trasutuzumab¤Ï¥ê¥¬¥ó¥ÉÈó°Í¸À¤ÎHER2-HER3Áê¸ßºîÍѤòÍÞÀ©¤¹¤ë¤³¤È¤¬Êó¹ð¤µ¤ì¤Æ¤¤¤ë. ¬e{:Junttila TT et al, Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941.Cancer Cell. 2009 May 5;15(5):429-40.}; PertuzumabñÆÈÅêÍ¿¤Î͸úÀ, °ÂÁ´À¤Ï³ÎΩ¤µ¤ì¤Æ¤¤¤Ê¤¤. 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Nat Rev Clin Oncol. 2010 Feb;7(2):98-107.}; ¬e{Lin:Lin NU, et al Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2008 Apr 20;26(12):1993-9.}; #br ''Trastuzumab-emtansin (T-DM1)'' ¾¦ÉÊ̾''¥«¥É¥µ¥¤¥é'' trastuzumab¤Ë(N-maleimidometyl) cyclohexane-1-carboxylate(MCC)¤È¤¤¤¦¥ê¥ó¥«¡¼¤ò²ðºß¤·, Èù¾®´ÉÁ˳²ºÞ¤Î¹³¤¬¤óºÞemtansine ¥¨¥à¥¿¥ó¥·¥ó¤¬·ë¹ç¤·¤Æ¤¤¤ë. antibody-drug conjugate(ADC). T-DM1¤ÏHER2¤Ë·ë¹ç¤¹¤ë¤È, ¥¨¥ó¥É¥µ¥¤¥È¡¼¥·¥¹¤Ë¤è¤êºÙ˦Æâ¤Ë¼è¤ê¹þ¤Þ¤ì¥ê¥½¥¾¡¼¥à¤Ë¤è¤êʬ²ò¤µ¤ì¤ë. ·ë²ÌDM1¤ò´Þ¤à°Û²½Âå¼Õ»ºÊª¤¬ºÙ˦¼ÁÆâ¤ËÊü½Ð¤µ¤ìÈù¾®´É¤Ë·ë¹ç, ¤½¤Î½Å¹ç¤òÁ˳²¤¹¤ë. 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N Engl J Med. 2017 Jul 13;377(2):122-131.PMID:28581356};¡¨É¸½à¼£ÎŤǤ¢¤ë¡Ö²½³ØÎÅË¡¡Ü¥È¥é¥¹¥Ä¥º¥Þ¥Ö¡×¤Ë¥Ú¥ë¥Ä¥º¥Þ¥Ö1ǯÅêÍ¿¤ò²Ã¤¨¤ë¼£ÎŤλî¤ß) >½ÑÁ°¤ËPertuzumabÊ»ÍѤ¹¤ë¤ÈpCR¤Î³ä¹ç¤¬Áý²Ã¤¹¤ë. (NeoSphere»î¸³¡§¶É½ê¿Ê¹ÔÀ¡¤±ê¾ÉÀ¡¤¤Þ¤¿¤ÏÁá´üHER2ÍÛÀÆý´â´µ¼Ô¤Ë¤ª¤±¤ë½ÑÁ°Êä½õ¥Ú¥ë¥Ä¥º¥Þ¥Ö¤ª¤è¤Ó¥È¥é¥¹¥Ä¥º¥Þ¥Ö¤Ë´Ø¤¹¤ë5ǯ´Ö¤Î²òÀÏ¡§Â¿»ÜÀß¶¦Æ±¡¤¥ª¡¼¥×¥ó¥é¥Ù¥ë¡¤ÂèIIÁê¥é¥ó¥À¥à²½»î¸³¬e{:Gianni L, et al., 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016 Jun;17(6):791-800 PMID 27179402};) >PertuzumabÅêÍ¿¤Ë¤è¤ëÉûºîÍѤˤϽÅÂç¤Ê¤â¤Î¤Ï¾¯¤Ê¤«¤Ã¤¿. ²¼Î¡.¡Ê¥Ú¥ë¥Ä¥º¥Þ¥Ö¤Î½Ñ¸å1ǯÅêÍ¿¤Ë¤ª¤±¤ëÉûºîÍѤϡ¢È鿾¤ÎÉÑÅÙ¤¬5.5¡óÁý¤¨¡¢½ÅÅ٤β¼Î¡¡Ê¥°¥ì¡¼¥É3°Ê¾å¡Ë¤¬6.1¡óÁý¤¨¤ë¤¬¡¢²½³ØÎÅË¡½ªÎ»¸å¤Î¥°¥ì¡¼¥É3°Ê¾å¤Î²¼Î¡¤Ï0.5¡ó¤Ç¤¢¤ê¡¢¿´ÆÇÀ¤ÎÉÑÅÙ¤ÏÄ㤫¤Ã¤¿¡£¡Ë ''HER2ÍÛÀÆý´â¤Î½ÑÁ°ÎÅË¡¤Î°ÕµÁ ½ÑÁ° vs ½Ñ¸å'' >herceptin¤¬»È¤ï¤ì¤ëÁ°¤Î»î¸³(NSABP B-18: ACÎÅË¡. ¤¤¤í¤¤¤í¤Ê¾ÉÎ㤬Æþ¤Ã¤Æ¤¤¤ë)¤Ç¤Ï ½ÑÁ°¤Îͽ¸å¡á½Ñ¸å¤Îͽ¸å. >HER2ÍÛÀÆý´â¤Ë¸Â¤ë¤È½ÑÁ°, ½Ñ¸åÅêÍ¿¤Î¸ú²Ì, ¤É¤Á¤é¤¬¤è¤¤¤«¤Ï¤ï¤«¤Ã¤Æ¤¤¤Ê¤¤. ͽ¸å¤Î²þÁ±·ë²Ì¤Ç¤Ï½ÑÁ°ÎÅË¡¤Î»î¸³¤Î¥Ç¡¼¥¿¤Î¤Û¤¦¤¬Îɤ«¤Ã¤¿. ''¾¯¤Ê¤¯¤È¤â½ÑÁ°ÅêÍ¿¤Î¥Ç¥á¥ê¥Ã¥È¤Ï¤Ê¤¤.'' >¥Û¥ë¥â¥ó¼õÍÆÂα¢À¤Î¥Ò¥È¤Ï, herceptinÅêÍ¿¤ÇpCR¤È¤Ê¤ë³ä¹ç¤¬¹â¤¤. PertuzumabÅêÍ¿¤âƱ¤¸¤Ç 46%. 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