Cancer diagnostics
Provided is a diagnostic comprising a peptide or protein capable of recognizing at least a portion of a tissue section and a fluorescent substance having the below-described characteristics: i) having, in a predetermined excitation wavelength, an emission wavelength not adjacent to a wavelength region of nonspecific autofluorescence which the tissue section has; and ii) permitting simultaneous observation of the image of the peptide or protein and the image of the tissue section. A diagnostic method and diagnostic kit each of which uses the peptide or protein, and the fluorescent substance is provided. A therapeutic agent administered to a disease after selection of the appropriate agent for the disease by using the above-described method. Also, a tissue section stained by the peptide or protein and the fluorescent substance is provided. In addition, a method of analyzing expression and/or behavior of a protein by using the fluorescent substance is provided.
1 . A diagnostic comprising a peptide or protein capable of recognizing at least a portion of a tissue section and a fluorescent substance having the below-described characteristics i) and ii):
i) having, in a predetermined excitation wavelength, an emission wavelength not adjacent to a wavelength region of nonspecific autofluorescence which the tissue section has;
ii) having fluorescence properties permitting simultaneous observation of the image of the peptide or protein and the image of the tissue section.
2 . A diagnostic of claim 1 , wherein in a predetermined excitation wavelength, the fluorescent substance shows a Stokes shift thereof on a long wavelength side not adjacent to the wavelength region of nonspecific autofluorescence which the tissue section has.
3 . A diagnostic of claim 1 , wherein the tissue section is a human-derived paraffin section or human-derived formalin-fixed paraffin section.
4 . A diagnostic of claim 1 , wherein the peptide or protein is an antibody.
5 . A diagnostic of claim 4 , wherein the antibody is a monoclonal antibody.
6 . A diagnostic of claim 5 , wherein the monoclonal antibody is a cancer-reactive monoclonal antibody.
7 . A diagnostic of claim 6 , wherein the cancer is gastric cancer, breast cancer, colorectal cancer or esophagus cancer.
8 . A diagnostic of claim 5 , wherein the monoclonal antibody has amino acid sequences of SEQ. ID NOS. 1, 2 and 3 of Sequence Listing in a hypervariable region of a heavy chain and amino acid sequences of SEQ. ID NOS. 4, 5 and 6 of Sequence Listing in a hypervariable region of a light chain.
9 . A diagnostic of claim 5 , wherein the monoclonal antibody has a heavy chain variable region containing an amino acid sequence of SEQ. ID No. 7 of Sequence Listing and a light chain variable region containing an amino acid sequence of SEQ. ID No. 8 of Sequence Listing.
10 . A diagnostic of claim 5 , wherein the monoclonal antibody is a biotin-labeled monoclonal antibody.
11 . A diagnostic of claim 2 , wherein the Stokes shift of the fluorescent substance has a wavelength longer by at least about 80 nm than that of the tissue section.
12 . A diagnostic of claim 11 , wherein the Stokes shift of the fluorescent substance has a wavelength longer by at least about 150 nm than that of the tissue section.
13 . A diagnostic of claim 1 , wherein the excitation wavelength ranges from about 450 nm to about 500 nm.
14 . A diagnostic of claim 13 , wherein the excitation wavelength ranges from about 480 nm to about 500 nm.
15 . A diagnostic of claim 13 , wherein the excitation wavelength is about 490 nm.
16 . A diagnostic of claim 1 , wherein the fluorescent substance is a peridinin chlorophyll protein or a fragment of the protein containing the fluorescent group portion thereof.
17 . A diagnostic of claim 16 , wherein the peridinin chlorophyll protein is streptavidin-bound peridinin chlorophyll protein.
18 . A diagnostic of claim 1 , which is a diagnostic for pathologic tissue.
19 . A diagnostic method, which comprises performing tissue staining with the diagnostic as claimed in claim 1 .
20 . A diagnostic method of claim 19 , for diagnosing the reactivity between cancer and the diagnostic.
21 . A therapeutic agent appropriate for a disease, which has been selected by using a diagnostic method as claimed in claim 19 .
22 . A therapeutic agent of claim 21 , wherein the disease is cancer.
23 . A therapeutic agent of claim 22 , wherein the cancer is gastric cancer, breast cancer, colorectal cancer or esophagus cancer.
24 . An analysis method, which comprises using a fusion protein available by fusing a fluorescent substance having the below-described characteristics with a protein,
i) having, in a predetermined excitation wavelength, an emission wavelength not adjacent to a wavelength region of nonspecific autofluorescence which a tissue section has;
ii) having fluorescence properties permitting simultaneous observation of the image of the peptide or protein and the image of the tissue section.
25 . An analysis method of claim 24 , wherein in a predetermined excitation wavelength, the fluorescent substance shows a Stokes shift thereof on a long wavelength side not adjacent to the wavelength region of nonspecific autofluorescence which the tissue section has.
26 . An analyzing method of claim 24 , wherein the Stokes shift of the fluorescent substance has a wavelength longer by at least about 80 nm than that of the tissue section.
27 . An analyzing method of claim 24 , wherein the Stokes shift of the fluorescent substance has a wavelength longer by at least about 150 nm than that of the tissue section.
28 . An analyzing method of claim 24 , for analyzing the expression and/or behavior of the protein in a cell.
29 . A tissue section which has been subjected to tissue staining with a diagnostic as claimed in claim 1 .
30 . A diagnostic kit, comprising a diagnostic as claimed in claim 1 .
31 . A diagnostic kit of claim 30 , for judging the reactivity of the therapeutic agent with cancer.
32 . A therapeutic agent for a disease, which is to be administered after selection of a medicament appropriate to the disease by using the diagnostic kit as claimed in claim 30 .
33 . A therapeutic agent of claim 32 , wherein the disease is cancer.
34 . A therapeutic agent of claim 33 , wherein the cancer is gastric cancer, breast cancer, colorectal cancer or esophagus cancer.