WO2018181880A1 - Compound for improving sensitivity of olfactory perception of nematode - Google Patents
Compound for improving sensitivity of olfactory perception of nematode Download PDFInfo
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- WO2018181880A1 WO2018181880A1 PCT/JP2018/013568 JP2018013568W WO2018181880A1 WO 2018181880 A1 WO2018181880 A1 WO 2018181880A1 JP 2018013568 W JP2018013568 W JP 2018013568W WO 2018181880 A1 WO2018181880 A1 WO 2018181880A1
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- behavior
- cineole
- nematode
- nematodes
- chemotaxis
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Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/033—Rearing or breeding invertebrates; New breeds of invertebrates
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K3/00—Materials not provided for elsewhere
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
Definitions
- running behavior means attracting behavior or avoidance behavior. Attracting behavior means behavior that shortens the physical distance from a certain substance, and repelling behavior means behavior that widens the physical distance from a certain substance. Substances that induce attraction behavior are called attractants, and substances that induce repellent behavior are called repellent substances. Nematodes have the property of attracting attractants by olfaction and repelling repellents. The act of attracting an attracting substance is called an attracting action (sometimes referred to as “positive” in the present specification), and an action repelling from a repellent substance is referred to as a repelling action (sometimes referred to as “negative” in this specification). . In addition, attracting behavior and repelling behavior are collectively referred to as chemotaxis behavior.
- Cineol (eg, 1,8-cineole and / or 1,4-cineole) need not be in direct contact with the nematode.
- Cineol eg, 1,8-cineole and / or 1,4-cineole
- cineole is applied somewhere on the inner wall of the culture vessel where the nematode is bred to increase the olfactory sensitivity of the nematode. be able to.
- it can be attached to an inner wall such as a lid of a culture vessel.
- Cineol (for example, 1,8-cineole and / or 1,4-cineole) may be added to the medium.
- bornyl acetate, D-camphor, camphene, linalool, linalyl acetate, graniol, phenylethyl alcohol, citronellol, pinene, limonene, benzyl acetate, vanillin, eugenol, and myrcene are similarly given to the behavior of nematodes. Although the effects were examined, no significant effects were observed for these.
- Example 2 Analysis using odr-3 mutant
- the responsiveness to the odorant observed in the above example is based on olfaction
- there is an abnormality in the AWC nerve which is the olfactory nerve involved in the attraction behavior
- cineol was confirmed.
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Environmental Sciences (AREA)
- Organic Chemistry (AREA)
- Materials Engineering (AREA)
- Animal Behavior & Ethology (AREA)
- Zoology (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Engineering & Computer Science (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
Provided is a compound for improving the sensitivity of the olfactory perception of a nematode.
Description
本発明は、線虫の嗅覚の感度を向上させる化合物を提供する。
The present invention provides a compound that improves the olfactory sensitivity of nematodes.
線虫は、がん患者の尿に対して誘引行動を示し、健常者の尿に対して忌避行動を示す。従って、線虫の走性行動に基づいて尿が由来する対象が、がん患者であるのか、健常者であるのかを判別することができる(特許文献1)。より具体的には、特許文献1には、242検体の中規模試験により、がん患者を100%の感度および95%の特異度で検出することができたことが記載されている。
Nematodes show attracting behavior against the urine of cancer patients and repelling behavior against the urine of healthy individuals. Therefore, it can be determined whether the subject from which urine is derived is a cancer patient or a healthy person based on the chemotactic behavior of the nematode (Patent Document 1). More specifically, Patent Literature 1 describes that a cancer patient could be detected with 100% sensitivity and 95% specificity by a medium-scale test of 242 specimens.
本発明者らは、走性行動評価において、走性行動をより増強させる方法を模索した。その結果、本発明者らは、シネオールが、線虫の嗅覚の感受性を向上させること、および線虫の走性行動を増強することを明らかにした。本発明はこのような知見に基づく発明である。
The present inventors sought a method for further enhancing the chemotaxis behavior in the chemotaxis behavior evaluation. As a result, the present inventors have clarified that cineole improves the olfactory sensitivity of nematodes and enhances the chemotactic behavior of nematodes. The present invention is based on such knowledge.
すなわち、本発明によれば以下の発明が提供される。
(1)シネオールを含む、線虫の嗅覚の感受性を増強させることに用いるための組成物。
(2)シネオールを含む、線虫の嗅覚に基づく走性行動を増強させることに用いるための組成物。
(3)走性行動が、遊走行動および/または忌避行動である、上記(2)に記載の組成物。
(4)線虫の嗅覚の感受性を増強させる方法であって、
シネオール、またはシネオールを含む組成物と線虫とを接触させることを含む、方法。
(5)線虫の嗅覚に基づく走性行動を増強させる方法であって、
シネオール、またはシネオールを含む組成物と線虫とを接触させることを含む、方法。
(6)走性行動が、遊走行動および/または忌避行動である、上記(5)に記載の方法。 That is, according to the present invention, the following inventions are provided.
(1) A composition for use in enhancing the olfactory sensitivity of a nematode, comprising cineole.
(2) A composition for use in enhancing chemotaxis behavior based on the olfactory sense of nematodes, including cineole.
(3) The composition according to the above (2), wherein the chemotaxis behavior is idle running behavior and / or repellent behavior.
(4) A method for enhancing the olfactory sensitivity of a nematode,
Contacting cineole or a composition containing cineole with a nematode.
(5) A method for enhancing chemotaxis behavior based on the olfactory sense of nematodes,
Contacting cineole or a composition containing cineole with a nematode.
(6) The method according to (5) above, wherein the chemotaxis behavior is idle movement and / or repelling behavior.
(1)シネオールを含む、線虫の嗅覚の感受性を増強させることに用いるための組成物。
(2)シネオールを含む、線虫の嗅覚に基づく走性行動を増強させることに用いるための組成物。
(3)走性行動が、遊走行動および/または忌避行動である、上記(2)に記載の組成物。
(4)線虫の嗅覚の感受性を増強させる方法であって、
シネオール、またはシネオールを含む組成物と線虫とを接触させることを含む、方法。
(5)線虫の嗅覚に基づく走性行動を増強させる方法であって、
シネオール、またはシネオールを含む組成物と線虫とを接触させることを含む、方法。
(6)走性行動が、遊走行動および/または忌避行動である、上記(5)に記載の方法。 That is, according to the present invention, the following inventions are provided.
(1) A composition for use in enhancing the olfactory sensitivity of a nematode, comprising cineole.
(2) A composition for use in enhancing chemotaxis behavior based on the olfactory sense of nematodes, including cineole.
(3) The composition according to the above (2), wherein the chemotaxis behavior is idle running behavior and / or repellent behavior.
(4) A method for enhancing the olfactory sensitivity of a nematode,
Contacting cineole or a composition containing cineole with a nematode.
(5) A method for enhancing chemotaxis behavior based on the olfactory sense of nematodes,
Contacting cineole or a composition containing cineole with a nematode.
(6) The method according to (5) above, wherein the chemotaxis behavior is idle movement and / or repelling behavior.
本明細書では、「対象」とは、哺乳動物を意味し、例えば、霊長類(例えば、サル、チンパンジー、ゴリラ、ボノボ、オランウータン、マーモセット、およびヒト)、例えば、ヒトを意味する。本明細書では、対象は好ましくはヒトである。また、本明細書では、「対象」には、健常者、がんであると疑われる対象およびがんに罹患している対象が含まれる意味で用いられる。
As used herein, “subject” means a mammal, for example, a primate (eg, monkey, chimpanzee, gorilla, bonobo, orangutan, marmoset, and human), eg, a human. As used herein, the subject is preferably a human. Further, in the present specification, “subject” is used in a sense that includes healthy subjects, subjects suspected of having cancer, and subjects suffering from cancer.
本明細書では、「がん」は、悪性腫瘍を意味する。がんには、造血器腫瘍、上皮癌(カルシノーマ)、および非上皮性の肉腫(サルコーマ)に大きく分類され得る。造血器腫瘍としては、白血病、悪性リンパ腫、および骨髄腫などが挙げられる。上皮癌としては、肺がん、乳がん、胃がん、大腸がん、子宮がん、卵巣がん、頭頸部がん、および舌がんが挙げられる。肉腫としては、骨肉腫、軟骨肉腫、横紋筋肉腫、平滑筋肉腫、線維肉腫、脂肪肉腫、および血管肉腫が挙げられる。本明細書では、「がん」は、ステージ0の早期がん、およびステージ1の早期がんなどの早期がんを含む。
In the present specification, “cancer” means a malignant tumor. Cancers can be broadly classified into hematopoietic tumors, epithelial cancers (carcinoma), and non-epithelial sarcomas (sarcoma). Examples of hematopoietic tumors include leukemia, malignant lymphoma, and myeloma. Epithelial cancers include lung cancer, breast cancer, stomach cancer, colon cancer, uterine cancer, ovarian cancer, head and neck cancer, and tongue cancer. Sarcomas include osteosarcoma, chondrosarcoma, rhabdomyosarcoma, leiomyosarcoma, fibrosarcoma, liposarcoma, and angiosarcoma. As used herein, “cancer” includes early stage cancers such as stage 0 early stage cancer and stage 1 early stage cancer.
本明細書では、「がん診断に用いるための組成物」を単に「がんの診断薬」ということがある。
In the present specification, the “composition for use in cancer diagnosis” is sometimes simply referred to as “cancer diagnostic agent”.
本明細書では、「線虫」とは、カエノラブディチス・エレガンス(Caenorhabditis elegans)を意味する。線虫は、米国ミネソタ大学の生物科学部のCaenorhabditis Genetics Center (CGC)に様々な環境から単離された株が登録および公開され、分譲可能である。従って、当業者であれば、知られているほとんどの株をCGCから入手することができる。自家受精により繁殖できるという観点では、雌雄同体が好ましく用いられ得る。
As used herein, “nematode” means Caenorhabditis elegans . Nematodes can be transferred to the Caenorhabditis Genetics Center (CGC) at the University of Minnesota's Department of Biological Sciences. Thus, those skilled in the art can obtain most known strains from CGC. From the viewpoint of being able to reproduce by self-fertilization, hermaphrodite can be preferably used.
本明細書では、「走性行動」とは、誘引行動または忌避行動を意味する。誘引行動とは、ある物質からの物理的距離を縮める行動を意味し、忌避行動とは、ある物質からの物理的距離を広げる行動を意味する。誘引行動を誘発する物質を誘引物質といい、忌避行動を誘発する物質を忌避物質という。線虫は嗅覚により誘引物質に対して誘引し、忌避物質から忌避するという性質を有している。誘引物質に対して誘引する行動を誘引行動(本明細書では「陽性」ということがある)といい、忌避物質から忌避する行動を忌避行動(本明細書では「陰性」ということがある)という。また、誘引行動と忌避行動とを合わせて走性行動という。
In this specification, “running behavior” means attracting behavior or avoidance behavior. Attracting behavior means behavior that shortens the physical distance from a certain substance, and repelling behavior means behavior that widens the physical distance from a certain substance. Substances that induce attraction behavior are called attractants, and substances that induce repellent behavior are called repellent substances. Nematodes have the property of attracting attractants by olfaction and repelling repellents. The act of attracting an attracting substance is called an attracting action (sometimes referred to as “positive” in the present specification), and an action repelling from a repellent substance is referred to as a repelling action (sometimes referred to as “negative” in this specification). . In addition, attracting behavior and repelling behavior are collectively referred to as chemotaxis behavior.
本明細書では、「野生株」とは、線虫の野生株であり、例えば、一般的な野生株であるN2 Bristol株が挙げられる。本明細書における野生株は、がんを有する対象から得られた尿には誘引行動を示し、がんを有しない対象から得られた尿には忌避行動を示す株とすることができる。
In this specification, the “wild strain” is a wild strain of a nematode, and includes, for example, a general wild strain N2 Bristol strain. The wild strain in the present specification can be a strain that exhibits attracting behavior in urine obtained from a subject having cancer and exhibits repellent behavior in urine obtained from a subject not having cancer.
線虫の走性行動評価系を用いた尿の分析方法
線虫の走性行動評価系を用いた尿の分析方法は、対象から得られた被検試料(例えば、尿)と線虫とを一定距離離して配置し、線虫が被検試料に対して誘引行動を示すか、忌避行動を示すかを観察することによって行うことができる。そして、誘引行動を示した場合には、対象は、がんに罹患している、またはその可能性があると評価することができる。このようにして、WO2015/088039では、242検体の中規模試験により、がん患者を100%の感度および95%の特異度で検出することができた。 Method of analyzing urine using the nematode chemotaxis behavior evaluation system The method of analyzing urine using the nematode chemotaxis behavior evaluation system is to analyze a test sample (eg, urine) obtained from a subject and a nematode. It can be performed by locating a certain distance and observing whether the nematode exhibits an attracting action or a repelling action with respect to the test sample. If the attracting behavior is shown, the subject can be evaluated as having or possibly having cancer. In this way, WO2015 / 088039 was able to detect cancer patients with 100% sensitivity and 95% specificity by a medium-scale test of 242 specimens.
線虫の走性行動評価系を用いた尿の分析方法は、対象から得られた被検試料(例えば、尿)と線虫とを一定距離離して配置し、線虫が被検試料に対して誘引行動を示すか、忌避行動を示すかを観察することによって行うことができる。そして、誘引行動を示した場合には、対象は、がんに罹患している、またはその可能性があると評価することができる。このようにして、WO2015/088039では、242検体の中規模試験により、がん患者を100%の感度および95%の特異度で検出することができた。 Method of analyzing urine using the nematode chemotaxis behavior evaluation system The method of analyzing urine using the nematode chemotaxis behavior evaluation system is to analyze a test sample (eg, urine) obtained from a subject and a nematode. It can be performed by locating a certain distance and observing whether the nematode exhibits an attracting action or a repelling action with respect to the test sample. If the attracting behavior is shown, the subject can be evaluated as having or possibly having cancer. In this way, WO2015 / 088039 was able to detect cancer patients with 100% sensitivity and 95% specificity by a medium-scale test of 242 specimens.
より詳細には、線虫の走性行動評価系を用いた尿の分析方法は例えば、
シャーレ(例えば、固形培地を導入したシャーレ)に対象から得られた被検試料(例えば、尿)を配置することと、
被検試料が配置されたシャーレに、被検試料と一定距離離れた位置に線虫を配置することと、
配置後、線虫に行動させることと、
線虫が被検試料に対して走性行動を示した場合には、対象ががんに罹患している、またはがんに罹患している可能性があると評価することと、
を含みうる。 More specifically, a method for analyzing urine using a nematode chemotaxis behavior evaluation system is, for example,
Placing a test sample (eg, urine) obtained from a subject in a petri dish (eg, a petri dish into which a solid medium has been introduced);
Placing nematodes in a petri dish where the test sample is placed at a position away from the test sample;
After placement, make the nematode act,
If the nematode exhibits chemotaxis behavior on the test sample, assess that the subject is or may be affected by cancer,
Can be included.
シャーレ(例えば、固形培地を導入したシャーレ)に対象から得られた被検試料(例えば、尿)を配置することと、
被検試料が配置されたシャーレに、被検試料と一定距離離れた位置に線虫を配置することと、
配置後、線虫に行動させることと、
線虫が被検試料に対して走性行動を示した場合には、対象ががんに罹患している、またはがんに罹患している可能性があると評価することと、
を含みうる。 More specifically, a method for analyzing urine using a nematode chemotaxis behavior evaluation system is, for example,
Placing a test sample (eg, urine) obtained from a subject in a petri dish (eg, a petri dish into which a solid medium has been introduced);
Placing nematodes in a petri dish where the test sample is placed at a position away from the test sample;
After placement, make the nematode act,
If the nematode exhibits chemotaxis behavior on the test sample, assess that the subject is or may be affected by cancer,
Can be included.
線虫の走性行動は、被検試料に近づいた線虫数と被検試料から遠のいた線虫数の差や比により評価することができる。線虫数の差に基づく評価の場合には、差が正の値である場合には、全体として被検試料は、誘引行動を誘発するものであり、がん患者に由来するものであると評価することができ、負の値である場合には、全体として被検試料は、忌避行動を誘発するものであり、健常者に由来するものであると評価することができる。また、線虫の走性行動は、例えば、以下のように走性インデックスを指標として評価することができる。
{式中、Aは、被検試料に対して誘引行動を示した線虫の数であり、Bは、被検試料に対して忌避行動を示した線虫の数である。}
The chemotactic behavior of a nematode can be evaluated by the difference or ratio between the number of nematodes approaching the test sample and the number of nematodes far from the test sample. In the case of evaluation based on the difference in the number of nematodes, if the difference is a positive value, the test sample as a whole induces attracting behavior and is derived from a cancer patient. If it can be evaluated and is a negative value, the test sample as a whole induces repellent behavior and can be evaluated to be derived from a healthy person. Moreover, the chemotaxis behavior of a nematode can be evaluated using, for example, the chemotaxis index as an index as follows.
{In the formula, A is the number of nematodes that have attracted the test sample, and B is the number of nematodes that have repelled the test sample. }
走性インデックスが正の値である場合には、全体として被検試料は、誘引行動を誘発するものであり、がん患者に由来するものであると評価することができ、負の値である場合には、全体として被検試料は、忌避行動を誘発するものであり、健常者に由来するものであると評価することができる。
If the chemotaxis index is a positive value, the test sample as a whole induces attracting behavior and can be evaluated to be derived from a cancer patient and is a negative value In some cases, the test sample as a whole induces repellent behavior and can be evaluated to be derived from a healthy person.
走性インデックスは、1に近いほど線虫が誘引行動を示す比率が大きいことを意味し、-1に近いほど線虫が忌避行動を示す比率が大きいことを意味し、0に近いほど線虫は誘引行動も忌避行動も示さないことを意味する。走性インデックスの絶対値が大きいほど、行動評価結果は明確になる。
The chemotaxis index means that the ratio of nematodes indicating attracting behavior is larger as it is closer to 1, the ratio of nematodes indicating repellent behavior is larger as it is closer to -1, and the nematode is closer to 0. Means no attracting or avoiding behavior. The larger the absolute value of the chemotaxis index, the clearer the action evaluation result.
本発明者らは、シネオール(例えば、1,8-シネオールおよび/または1,4-シネオール)が線虫の嗅覚に影響し、走性インデックスの絶対値を増大させることを発見した。
The present inventors have discovered that cineole (eg, 1,8-cineole and / or 1,4-cineole) affects the olfactory sense of nematodes and increases the absolute value of the chemotaxis index.
本発明によれば、線虫の嗅覚の感度を増強させることに用いるための組成物であって、シネオール(例えば、1,8-シネオールおよび/または1,4-シネオール)を含む組成物が提供される。本発明によれば、線虫の嗅覚の感度を増強させる方法であって、線虫を前記シネオール存在下で培養することを含む、方法が提供される。
According to the present invention, there is provided a composition for use in enhancing the olfactory sensitivity of nematodes, comprising cineol (eg, 1,8-cineole and / or 1,4-cineole). Is done. According to the present invention, there is provided a method for enhancing the olfactory sensitivity of a nematode, comprising culturing the nematode in the presence of the cineole.
本発明によればまた、線虫の嗅覚に基づく走性行動評価において誘引行動を強めることに用いるための組成物であって、シネオール(例えば、1,8-シネオールおよび/または1,4-シネオール)を含む組成物が提供される。本発明によればまた、線虫の嗅覚に基づく走性行動評価において誘引行動を強める方法であって、線虫を前記シネオール存在下で培養することを含む、方法が提供される。
According to the present invention, there is also provided a composition for use in enhancing attracting behavior in the evaluation of chemotaxis behavior based on the olfactory sense of a nematode, comprising cineole (for example, 1,8-cineole and / or 1,4-cineole). Is provided. According to the present invention, there is also provided a method for enhancing attraction behavior in evaluation of chemotaxis behavior based on the sense of smell of nematodes, comprising culturing nematodes in the presence of cineole.
シネオール(例えば、1,8-シネオールおよび/または1,4-シネオール)は、線虫に直接接触させる必要は無い。シネオール(例えば、1,8-シネオールおよび/または1,4-シネオール)は揮発性であり、離れたところから線虫の嗅覚神経を刺激して線虫の嗅覚の感度を高めることができる。従って、シネオール(例えば、1,8-シネオールおよび/または1,4-シネオール)は、培養容器の内壁のどこかに塗布し、そこで線虫を繁殖させることで、線虫の嗅覚の感度を高めることができる。例えば、培養容器の蓋などの内壁に付着させることができる。また、シネオール(例えば、1,8-シネオールおよび/または1,4-シネオール)は、培地に添加してもよいのである。
Cineol (eg, 1,8-cineole and / or 1,4-cineole) need not be in direct contact with the nematode. Cineol (eg, 1,8-cineole and / or 1,4-cineole) is volatile and can stimulate the nematode's olfactory nerve from a distance to increase the sensitivity of the nematode's olfaction. Accordingly, cineole (eg, 1,8-cineole and / or 1,4-cineole) is applied somewhere on the inner wall of the culture vessel where the nematode is bred to increase the olfactory sensitivity of the nematode. be able to. For example, it can be attached to an inner wall such as a lid of a culture vessel. Cineol (for example, 1,8-cineole and / or 1,4-cineole) may be added to the medium.
本発明では、シネオール(例えば、1,8-シネオールおよび/または1,4-シネオール)は、原液または水で希釈したものを用いることができる。例えば、希釈倍率は、100万倍~1万倍として用いることができる。本発明では、線虫を例えば、2~4日、1~2日、および1~24時間のいずれかの期間、シネオール(例えば、1,8-シネオールおよび/または1,4-シネオール)存在下で培養することができる。シネオール(例えば、1,8-シネオールおよび/または1,4-シネオール)は、検査時に評価系に導入されてもよいであろう。例えば、シネオール(例えば、1,8-シネオールおよび/または1,4-シネオール)は、走性行動評価系に用いるシャーレの内壁、その蓋の内壁、固形培地の表面および固形培地中から選択されるいずれか1以上に付着または含有させることができる。
In the present invention, cineole (for example, 1,8-cineole and / or 1,4-cineole) diluted with a stock solution or water can be used. For example, the dilution factor can be used as 1 million times to 10,000 times. In the present invention, nematodes are present in the presence of cineol (eg, 1,8-cineole and / or 1,4-cineole) for any period of, for example, 2-4 days, 1-2 days, and 1-24 hours. Can be cultured. Cineol (eg, 1,8-cineol and / or 1,4-cineole) may be introduced into the evaluation system at the time of testing. For example, cineole (eg, 1,8-cineole and / or 1,4-cineole) is selected from the inner wall of a petri dish used for the chemotaxis behavior evaluation system, the inner wall of its lid, the surface of the solid medium, and the solid medium Any one or more can be attached or contained.
本発明では、がん患者の尿に対する走性行動の評価にシネオール(例えば、1,8-シネオールおよび/または1,4-シネオール)を用いることもできる。
In the present invention, cineole (for example, 1,8-cineole and / or 1,4-cineole) can also be used to evaluate the chemotaxis behavior of urine of cancer patients.
以下、実施例に基づいて本発明を説明する。
Hereinafter, the present invention will be described based on examples.
実施例1:シネオールを嗅がせた線虫による走性行動の評価
本実施例では、シネオールが線虫の嗅覚の感受性を向上させることを示す。 Example 1: Evaluation of chemotaxis behavior by nematodes smelled with cineole In this example, it is shown that cineole improves the olfactory sensitivity of nematodes.
本実施例では、シネオールが線虫の嗅覚の感受性を向上させることを示す。 Example 1: Evaluation of chemotaxis behavior by nematodes smelled with cineole In this example, it is shown that cineole improves the olfactory sensitivity of nematodes.
線虫の野生株にシネオールとして1,8-シネオールを嗅がせ、その後、ベンズアルデヒド(BZ)またはイソアミルアルコール(IAA)に対する線虫の走性行動を評価した。
具体的には、1,8-シネオールを10万倍に希釈し、培養容器の蓋の内側に付着させた。付着後、線虫の培養培地に線虫の卵を載せて、成虫になるまで成長させた。線虫を回収し、常法に従ってBZまたはIAAに対する走性を観察した。 A nematode wild strain was sniffed with 1,8-cineole as cineol, and then the chemotactic behavior of worms against benzaldehyde (BZ) or isoamyl alcohol (IAA) was evaluated.
Specifically, 1,8-cineole was diluted 100,000 times and adhered to the inside of the lid of the culture vessel. After attachment, the nematode eggs were placed on the nematode culture medium and grown until they became adults. Nematodes were collected and chemotaxis to BZ or IAA was observed according to a conventional method.
具体的には、1,8-シネオールを10万倍に希釈し、培養容器の蓋の内側に付着させた。付着後、線虫の培養培地に線虫の卵を載せて、成虫になるまで成長させた。線虫を回収し、常法に従ってBZまたはIAAに対する走性を観察した。 A nematode wild strain was sniffed with 1,8-cineole as cineol, and then the chemotactic behavior of worms against benzaldehyde (BZ) or isoamyl alcohol (IAA) was evaluated.
Specifically, 1,8-cineole was diluted 100,000 times and adhered to the inside of the lid of the culture vessel. After attachment, the nematode eggs were placed on the nematode culture medium and grown until they became adults. Nematodes were collected and chemotaxis to BZ or IAA was observed according to a conventional method.
実施例で用いたプレートを図1に示す。図1における、プレートのサンプル配置部位5の箇所に上記匂い物質を塗布し、プレートの線虫配置部位3に線虫を配置して、その後23℃において線虫の行動観察を行った。線虫を配置した30分後に領域2および領域4に存在する線虫数をカウントし、以下式により走性インデックスを求めた。
(走性インデックス)={N(2)-N(4)}/{N(2)+N(4)}
{式中、N(2)は、図1の領域2に分布した線虫の数であり、N(4)は、図1の領域4に分布した線虫の数である。} The plates used in the examples are shown in FIG. In FIG. 1, the odorant was applied to thesample placement site 5 of the plate, the nematode was placed on the nematode placement site 3 of the plate, and then the behavior of the nematode was observed at 23 ° C. Thirty minutes after the nematode was placed, the number of nematodes present in region 2 and region 4 was counted, and the chemotaxis index was determined by the following equation.
(Taxis) = {N (2) −N (4)} / {N (2) + N (4)}
{Where N (2) is the number of nematodes distributed inregion 2 in FIG. 1, and N (4) is the number of nematodes distributed in region 4 in FIG. }
(走性インデックス)={N(2)-N(4)}/{N(2)+N(4)}
{式中、N(2)は、図1の領域2に分布した線虫の数であり、N(4)は、図1の領域4に分布した線虫の数である。} The plates used in the examples are shown in FIG. In FIG. 1, the odorant was applied to the
(Taxis) = {N (2) −N (4)} / {N (2) + N (4)}
{Where N (2) is the number of nematodes distributed in
走性インデックスは、1に近いほど線虫の誘引行動が強く表われたことを意味する。結果は、図2Aに示される通りであった。
The chemotaxis index means that the closer to 1, the stronger the attracting behavior of nematodes. The result was as shown in FIG. 2A.
図2Aに示されるように、1,8-シネオール存在下で培養した線虫は、上記走性インデックスが、BZに対しては約0.2から約0.75へと飛躍的に増加し、IAAに対しては、約0.3から約0.75へと飛躍的に増加した。全く異なる種類の匂い物質の両方に対して嗅覚感度が向上したものであり、1,8-シネオールは、線虫の嗅覚の高感度化を起こすこと、線虫の走性行動(誘引行動)の感受性を向上させることが明らかになった。
As shown in FIG. 2A, nematodes cultured in the presence of 1,8-cineole showed a dramatic increase in the chemotaxis index from about 0.2 to about 0.75 for BZ, For IAA, it increased dramatically from about 0.3 to about 0.75. The olfactory sensitivity is improved for both completely different types of odorants, and 1,8-cineole increases the olfactory sensitivity of nematodes and the chemotaxis behavior (attraction behavior) of nematodes. It has been shown to improve sensitivity.
次に、シネオールとして、1,4-シネオールを用いて同様の実験を行った。具体的には、1,4-シネオールを10万倍に希釈し、培養容器の蓋の内側に付着させた。付着後、線虫の培養培地に線虫の卵を載せて、成虫になるまで成長させた。線虫を回収し、常法に従ってIAAおよび2-ノナノンに対する走性を観察した。実験は2回行った。
その結果、図2Bに示されるように、1,4-シネオール存在下で培養した線虫は、誘引物質であるIAAに対しては、走性インデックスが向上させたのに対して、忌避物質である2-ノナノンに対する走性インデックスを変化させることは無かった。このことから、1,4-シネオールは、1,8-シネオールと同様に、線虫の嗅覚の高感度化を起こすこと、走性行動(誘引行動)の感受性を向上させることが明らかになった。 Next, the same experiment was conducted using 1,4-cineole as cineole. Specifically, 1,4-cineole was diluted 100,000 times and adhered to the inside of the lid of the culture vessel. After attachment, the nematode eggs were placed on the nematode culture medium and grown until they became adults. Nematodes were collected and chemotaxis to IAA and 2-nonanone was observed according to a conventional method. The experiment was performed twice.
As a result, as shown in FIG. 2B, nematodes cultured in the presence of 1,4-cineole improved the chemotaxis index against the attracting agent IAA, whereas the nematode was repellent. There was no change in the chemotaxis index for a certain 2-nonanone. From this, it was clarified that 1,4-cineole, like 1,8-cineole, raises the sensitivity of nematode olfactory and improves the sensitivity of chemotaxis behavior (attraction behavior). .
その結果、図2Bに示されるように、1,4-シネオール存在下で培養した線虫は、誘引物質であるIAAに対しては、走性インデックスが向上させたのに対して、忌避物質である2-ノナノンに対する走性インデックスを変化させることは無かった。このことから、1,4-シネオールは、1,8-シネオールと同様に、線虫の嗅覚の高感度化を起こすこと、走性行動(誘引行動)の感受性を向上させることが明らかになった。 Next, the same experiment was conducted using 1,4-cineole as cineole. Specifically, 1,4-cineole was diluted 100,000 times and adhered to the inside of the lid of the culture vessel. After attachment, the nematode eggs were placed on the nematode culture medium and grown until they became adults. Nematodes were collected and chemotaxis to IAA and 2-nonanone was observed according to a conventional method. The experiment was performed twice.
As a result, as shown in FIG. 2B, nematodes cultured in the presence of 1,4-cineole improved the chemotaxis index against the attracting agent IAA, whereas the nematode was repellent. There was no change in the chemotaxis index for a certain 2-nonanone. From this, it was clarified that 1,4-cineole, like 1,8-cineole, raises the sensitivity of nematode olfactory and improves the sensitivity of chemotaxis behavior (attraction behavior). .
なお、酢酸ボルニル、D-カンファー、カンフェン、リナロール、酢酸リナリル、グラニオール、フェニルエチルアルコール、シトロネロール、ピネン、リモネン、酢酸ベンジル、バニリン、オイゲノール、およびミルセンそれぞれについて、同様に線虫の走性行動に与える影響を調べたが、これらについては有意な効果は観察されなかった。
In addition, bornyl acetate, D-camphor, camphene, linalool, linalyl acetate, graniol, phenylethyl alcohol, citronellol, pinene, limonene, benzyl acetate, vanillin, eugenol, and myrcene are similarly given to the behavior of nematodes. Although the effects were examined, no significant effects were observed for these.
実施例2:odr-3変異体を用いた分析
上記実施例で観察された匂い物質に対する応答性が、嗅覚に基づくことを確かめるため、誘引行動に関わる嗅覚神経であるAWC神経に異常があるodr-3変異体の走性行動に対するシネオールの効果を確認した。 Example 2: Analysis using odr-3 mutant In order to confirm that the responsiveness to the odorant observed in the above example is based on olfaction, there is an abnormality in the AWC nerve, which is the olfactory nerve involved in the attraction behavior The effect of cineol on the chemotaxis behavior of the -3 mutant was confirmed.
上記実施例で観察された匂い物質に対する応答性が、嗅覚に基づくことを確かめるため、誘引行動に関わる嗅覚神経であるAWC神経に異常があるodr-3変異体の走性行動に対するシネオールの効果を確認した。 Example 2: Analysis using odr-3 mutant In order to confirm that the responsiveness to the odorant observed in the above example is based on olfaction, there is an abnormality in the AWC nerve, which is the olfactory nerve involved in the attraction behavior The effect of cineol on the chemotaxis behavior of the -3 mutant was confirmed.
線虫は、餌が存在する箇所の塩濃度(NaCl)を学習し、その塩濃度の箇所対して走性を示す。線虫に対して塩濃度(濃度50 mM)を1,8-シネオール存在下若しくは非存在下で学習させ、または学習させずに繁殖させた。
The nematode learns the salt concentration (NaCl) of the place where the food is present and shows chemotaxis to the salt concentration part. Nematodes were allowed to learn salt concentration (concentration 50 mM) in the presence or absence of 1,8-cineole, or propagated without learning.
その後に、常法に基づいて塩濃度(100 mM)に対する塩走性を評価した。結果は図3Aおよび3Bに示される通りであった。
Thereafter, salt chemotaxis against salt concentration (100 mM) was evaluated based on a conventional method. The results were as shown in FIGS. 3A and 3B.
図3Aに示されるように、塩走性は、シネオールによって塩走性の走性インデックスがより大きく低下することが明らかになった。一方で、図3Bに示されるように、塩走性に関する走性インデックスは、odr-3変異体では変化がなかった。従って、シネオールは、嗅覚に基づいて線虫の走性行動を変化させるモデュレータ-であることが明らかとなった。
As shown in FIG. 3A, salt chemotaxis was found to be greatly reduced by cineol. On the other hand, as shown in FIG. 3B, the chemotaxis index related to salt chemotaxis was unchanged in the odr-3 mutant. Therefore, it became clear that cineole is a modulator that changes the chemotaxis behavior of nematodes based on the sense of smell.
Claims (6)
- シネオールを含む、線虫の嗅覚の感受性を増強させることに用いるための組成物。 A composition for use in enhancing the olfactory sensitivity of nematodes, including cineole.
- シネオールを含む、線虫の嗅覚に基づく走性行動を増強させることに用いるための組成物。 A composition for enhancing chemotaxis behavior based on the sense of smell of nematodes, including cineole.
- 走性行動が、遊走行動および/または忌避行動である、請求項2に記載の組成物。 The composition according to claim 2, wherein the chemotaxis behavior is idle movement and / or repelling behavior.
- 線虫の嗅覚の感受性を増強させる方法であって、
シネオールまたはシネオールを含む組成物と線虫とを接触させることを含む、方法。 A method of increasing the olfactory sensitivity of a nematode,
Contacting a nematode with cineole or a composition comprising cineole. - 線虫の嗅覚に基づく走性行動を増強させる方法であって、
シネオールまたはシネオールを含む組成物と線虫とを接触させることを含む、方法。 A method for enhancing chemotaxis behavior based on the sense of smell of nematodes,
Contacting a nematode with cineole or a composition comprising cineole. - 走性行動が、遊走行動および/または忌避行動である、請求項5に記載の方法。 The method according to claim 5, wherein the running behavior is a free running behavior and / or a repelling behavior.
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