KR20120096169A - Inhibiting the growth of cancer cells with the application of endorphine - Google Patents
Inhibiting the growth of cancer cells with the application of endorphine Download PDFInfo
- Publication number
- KR20120096169A KR20120096169A KR1020110015419A KR20110015419A KR20120096169A KR 20120096169 A KR20120096169 A KR 20120096169A KR 1020110015419 A KR1020110015419 A KR 1020110015419A KR 20110015419 A KR20110015419 A KR 20110015419A KR 20120096169 A KR20120096169 A KR 20120096169A
- Authority
- KR
- South Korea
- Prior art keywords
- endorphin
- cancer
- opioid
- growth
- cell
- Prior art date
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Gastroenterology & Hepatology (AREA)
- Endocrinology (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Toxicology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
Abstract
Description
본 발명은 엔돌핀을 처리하였을 시, 뇌신경교모세포종의 성장과 생육능력이 저하된다는 점을 발견하여 이 방법을 이용하여 암세포 성장을 억제하거나 조절할 수 있을 것이라고 사료된다.When the endorphins are treated, the present invention finds that the growth and growth capacity of the neuroglioblastomas are reduced, and it is considered that the method can inhibit or control the growth of cancer cells.
현대사회에서 암은 주된 사망 요인 중 하나이며, 항암제나 방사선 치료를 사용하기도 하나 항암제에 의한 면역력 약화, 방사선에 의한 신경조직손상등 한계가 있다.In modern society, cancer is one of the major causes of death, and chemotherapy or radiation therapy is used, but there are limitations such as weakening of immunity caused by anticancer drugs and nerve tissue damage caused by radiation.
인간의 뇌암 중 다형성 교모세포종 (glioblastoma multiforme)은 가장 흔한 악성 종양으로, 5년 생존율이 5％ 도 안된다(Berger et al, 1999; Maher et al, 2001; Lacroix et al, 2001). 악성교세포종은 WHO의기준 Grade IV로서 50세 이후에 가장 흔한 뇌암으로 일반적인 화학요법에 반응을 잘 안하는 것으로 알려져 있다(Kleihus et al, 2007). 이러한 뇌암조직에서 유래한 세포 U87MG 또는 U251MG의 명칭을 가진 세포주는 항암제의 암세포의 성장 및 억제에 미치는 영향을 알기위해 오래전부터 세포모델로 이용되어 왔다 (Wolff et al, 1999; Wang et al, 2005; Yoshida et al, 206; Nomura et al, 2007; Lin et al, 2007 a, b).Among human brain cancers, glioblastoma multiforme is the most common malignant tumor with a 5-year survival of less than 5% (Berger et al, 1999; Maher et al, 2001; Lacroix et al, 2001). Malignant glioma is a grade IV of the WHO and is the most common brain cancer after age 50. It is known that malignant glioblastoma does not respond well to general chemotherapy (Kleihus et al, 2007). Cell lines derived from these brain cancer tissues, U87MG or U251MG, have been used as cell models for a long time to understand the effects of anticancer drugs on the growth and inhibition of cancer cells (Wolff et al, 1999; Wang et al, 2005; Yoshida et al, 206; Nomura et al, 2007; Lin et al, 2007 a, b).
뇌종양을 기존의 수술, 항암제 또는 방사선 치료이외에 좀 더 치료 효과를 높이기 위하여 뇌신경 종양세포의 생장이나 분열에 영향을 줄 수 있는 물질이나 자극을 병행하면 효율성이 높아진다. 특히 인간의 신경계에 흔히 존재하고 있는 물질을 이용하여 뇌종양세포에 처리, 암세포의 성장을 조절하는 물질을 탐색하고 분석하고자 하였다.In addition to conventional surgery, chemotherapy, or radiation therapy, brain tumors have increased efficiency when combined with substances or stimuli that can affect the growth or division of brain tumor cells. In particular, the aim of this study was to search for and analyze substances that are treated in brain tumor cells and regulate the growth of cancer cells using substances that are commonly present in the human nervous system.
특히 엔돌핀의 경우는 뇌에서 분비되는 몰핀과 유사한 성분으로 스트레스 해소, 면역력 증강 등과의 관련성이 보고되어 있다. 스트레스와 뇌에서의 엔돌핀 생성은 이미 오래전부터 잘 알려진 사실이며 (Bronstein et al, 1991; Merenlender-Wagner et al, 2009), 이러한 endorphin은 opioid receptor를 통해 작용을 한다 Tseng et al, 2001; Narita et al, 1998).Endorphins, in particular, have been reported to be related to morphine-like components secreted by the brain to relieve stress and enhance immunity. Stress and the production of endorphins in the brain have long been well known (Bronstein et al, 1991; Merenlender-Wagner et al, 2009), and these endorphins act through opioid receptors Tseng et al, 2001; Narita et al, 1998).
대부분의 신경계에 관련된 opioid-endorphin 계통의 연구는 감각기능과의 관련, 통증에 대한 기전에 대해 보고가 되어 있다 (Garland, 1995). Rat을 이용한 연구에서 사지에 stress를 가할 경우, 면역기능이 저하되며, 악성종양에 대한 저항성을 떨어뜨린다고 보고가 되었으며, 이는 아마도 opioid계열에서의 조절기능과 관련성이 있을 것으로 추측하였다 (Shavit et al, 1985). 뇌종양주위에 엔돌핀의 존재에 대해 보고가 된 바가 있으나, 엔돌핀과 뇌종양의 증식과 연관된 연구결과는 드믈다. Tug McGraw Research Center의 보고로 뇌종양을 앓고 있는 환자군에 정신적인 stress의 정도가 높으며 (Keir et al, 2007), 반면, 프랑스 
따라서 본 연구에서는 신경계에 자연적으로 존대하고 있는 엔돌핀이 뇌종양세포를 포함한 암의 성장에 미치는 영향을 확인하고자 하고자, 뇌암세포배양 모델을 이용하여 분석하였다.Therefore, in this study, to determine the effect of endorphins naturally present in the nervous system on cancer growth, including brain tumor cells, the brain cancer cell culture model was analyzed.
스트레스감소와 즐거운 상태에서 엔돌핀이 분비되며, 면역기능강화 및 암치료가능이 알려져 있으나, 과학적인 증명이 이루어진 경우는 없다. 본 연구에서는 베타 엔돌핀을 종양세포증식에 사용하는 방법을 개발하는데 그 목적이 있다.Endorphins are secreted under reduced stress and a pleasant state, and it is known to enhance immune function and treat cancer, but there is no scientific proof. The purpose of this study is to develop a method of using beta endorphin in tumor cell proliferation.
엔돌핀 처리Endorphin treatment
엔돌핀은 synthetic beta endorphin을 구입하여 (Sigma, MO) 사용하였다.Endorphins were obtained by using synthetic beta endorphin (Sigma, MO).
사용 농도는 아래 기존의 문헌에서 사용된 농도를 기준으로 하여 0.1μM?10μM의 범위에서 사용하였다. Cell counting시에는 1μM, 5μM, 10μM의 농도에서 측정을 하였으며, WST-1 assay 에서는 0.1μM, 1μM, 10μM에서 측정을 하였다. 각각의 대조군도 역시 같은 조건하에서 배양하였다.The concentration used was in the range of 0.1 μM-10 μM based on the concentration used in the following literature. Cell counting was performed at concentrations of 1 μM, 5 μM and 10 μM, and WST-1 assay at 0.1 μM, 1 μM and 10 μM. Each control was also incubated under the same conditions.
Cell농도에 대한 이미지 분석Image analysis for cell concentration
세포배양하는 culture plate 를 현미경위에 올려놓은 뒤 컴퓨터와 연결하여 컴퓨터 화상을 찍는다. 특히, 배경 색깔은 초록색으로 하고, 배율은 100배로 하며, 사진 preview 상의 초점이 맞도록 유의한다. 사진 촬영 시, 처리물질의 농도, 경과 시간, 날짜, 배율 등의 라벨링을 명확히 한다. 시간 간격은 24h, 48h 로 이틀에 걸쳐 촬영한다.Place the culture plate on the microscope onto the microscope and connect to a computer to take a computer image. In particular, the background color is green, the magnification is 100 times, and care is taken to ensure that the focus is on the photo preview. When photographing, labeling of the concentration, elapsed time, date, magnification, etc. of the treatment material should be clarified. The time interval is 24h, 48h to shoot over two days.
Cell CountingCell counting
Cell 수를 counting하기 전에 먼저 cell plate 에 붙어있는 cell 을 분리해서, 일정 량 취한 후 세포수를 분석해야한다.Before counting the number of cells, first remove the cells attached to the cell plate, take a certain amount and analyze the cell number.
Cell counting도구로 Hemocytometer(Marienfeld) 5x5 격자를 사용하였다. Cell plate에 남아 있는 DMEM media를 제거한 후 PBS로 배지를 한번 더 세척후, Tris-EDTA buffer로 DMEM을 제거한 cell plate에 넣은 후 37도 incubator에 수분 간 보관한다. 이후 0.5％ TE buffer을 각각 1ml씩 처리한다. 수용액을 처리한 용액의 1㎖를 균일하게 희석한 후 10㎕를 취한다. Hemocytometer(Marienfeld)를 이용하여 cell count를 한다. 하나의 square의 부피는 0.1 mm3(1 mm×1 mm×0.1 mm), 즉 104 ml 이므로 세포 현탁액의 농도는 세포수 x 104/ml 가 된다. 5x5격자에 있는 cell을 센다.Hemocytometer (Marienfeld) 5x5 grid was used as a cell counting tool. After removing the remaining DMEM media on the cell plate, wash the medium once more with PBS, put it in the cell plate from which DMEM was removed with Tris-EDTA buffer, and store it in a 37-degree incubator for a few minutes. Thereafter, 1 ml of 0.5% TE buffer is treated. After uniformly diluting 1 ml of the solution treated with the aqueous solution, take 10 μl. Perform a cell count using a hemocytometer (Marienfeld). The volume of one square is 0.1 mm3 (1 mm x 1 mm x 0.1 mm), or 10 4 ml, so that the concentration of the cell suspension is the number of cells x 10 4 / ml. Count the cells in the 5x5 grid.
Cell proliferation Reagent WST-1Cell proliferation Reagent WST-1
WST-1 Cell Proliferation Assay System은 세포 증식능력이나 세포생존 능력을 정량하는 기법의 하나로 세포내의 미토콘드리아 탈수소효소에 의해 Tetrazolium salt (WST-1) 이 formazan색소로 변환 것을 기본으로 하여 색의 진한 정도에 따라 spectrophotometry로 세포수를 추정할 수 있게 되어있는 방법이다. 96well plate를 사용하였고, 각 well당 100μl/well의 부피에 배양되어 있는 well에 10 μl/well Cell Proliferation Reagent WST-1를 첨가하여 사용한다 (1:10 final dilution)WST-1 Cell Proliferation Assay System is a technique to quantify cell proliferation ability or cell viability. Based on the intensity of color based on the conversion of Tetrazolium salt (WST-1) to formazan pigment by intracellular mitochondrial dehydrogenase It is a method to estimate the number of cells by spectrophotometry. A 96 well plate was used, and 10 μl / well Cell Proliferation Reagent WST-1 was added to the well incubated at a volume of 100 μl / well per well (1:10 final dilution).
Statistical analysisStatistical analysis
관찰된 data에 대해 box-plot을 이용하여 평균과 data의 분포가 양군간 t-test로 비교검정하는데 지장이 없는지 확인하였으며, 동시에 box-plot을 이용 도식화하였다. 양군간의 검정은 Student t-test를 이용, p-value 0.05를 유의수준으로 하였다. 평균 및 분산 구하는 C언어 프로그램, t 검정을 위한 두 자료의 Sp 값, box plotting을 위한 program을 자체 개발, 사용하였다. (별첨 1, 2)The box-plot was used to confirm that the distribution of the mean and data was not interfered with the t-test between the two groups, and the box-plot was plotted. For the test between the two groups, the Student t-test was used as the p-value of 0.05. A C-language program for average and variance, Sp values for two tests, and a program for box plotting were developed and used. (
결론적으로, 우리의 연구는 glioblastoma 뇌암세포 배양모델을 이용하여 beta-endorphin으로 증식억제가능성에 대해 검증하였으며, 암세포 종류와 농도에 따른 반응이 존재함을 확인하였다. 엔돌핀은 membrane domain에 6곳의 opioid binding receptor site를 통해 작용을 할 것으로 예측된다.In conclusion, our study verified the possibility of proliferation inhibition with beta-endorphin using glioblastoma brain cancer cell culture model and confirmed that there was a response according to cancer cell type and concentration. Endorphins are expected to act through six opioid binding receptor sites in the membrane domain.
[도1] 혈중 호르몬 농도에 관한 표
[도2] U87 뇌신경교모세포종의 엔돌핀 농도 증가에 따른 암세포 성장 억제 곡선 (평균 WST-1 흡광도)
[도3] U251 뇌신경교모세포종의 엔돌핀 농도 증가에 따른 암세포 성장 억제 곡선 (평균 WST-1 흡광도)
[도4] 엔돌핀 처리군의 대조군에 대한 세포 수 감소 비율(％), 초록색은 10％ 이상 감소한 것으로 매우 유의하게 감소된 것을 나타냄.1 Table for blood hormone concentration
[Figure 2] Growth inhibition curve of cancer cells with increasing endorphin concentration of U87 cerebral neuroglioma (mean WST-1 absorbance)
[Figure 3] Growth inhibition curves of cancer cells with increasing endorphin concentrations of U251 glioblastoma (average WST-1 absorbance)
Fig. 4 The percentage of cell number reduction for the control group of the endorphin treatment group, green, showed a significant decrease of 10% or more.
본 연구는 뇌신경내에 자연적으로 존재하며, 통증기전을 조절하고 면역능력의 향상에 도움을 줄 수 있다고 알려진 엔돌핀이, 뇌암성장의 억제효과가 존재하는지 실질적인 증명을 위해 뇌교모세포종 뇌암실험모델과 합성 엔돌핀을 이용하여 실험관내에서 분석하였다. Cell count와 WST-1 assay상 약간의 차이는 있으나, 전반적으로 뇌교모세포암종세포의 증식을 억제하는 경향으로 나타났으며, 일부 조건에서는 세포에서는 증식이 유도가 되는 biphasic한 현상도 아울러 존재한다는 결과을 확인하였다.This study was carried out with a brain glioblastoma brain cancer model and synthetic endorphins to prove whether endorphins, which are naturally present in the cranial nerve, can control pain mechanisms and improve immunity. It was analyzed in vitro. Although there was a slight difference in cell count and WST-1 assay, there was a general tendency to inhibit the proliferation of glioblastoma carcinoma cells, and in some conditions, there was also a biphasic phenomenon in which proliferation was induced. It was.
오피오이드는 여러가지 화학적물질들의 복합체이며, 그 작용은 G protein-coupled receptor로 opioid receptor를 통해 역할을 한다. 여기에는 k, u, m 등의 여러개의 아형이 존재하며 heptahelical 모형의 단백질로 말초조직은 물론 중추신경계에도 발현이 되어 있다. 즉 이들은 내부의 opioid, enkephalins, endorphins, 및 dynorphins과 결합하는 것으로 알려져 있으며, 본연구에서는 beta-endorphin을 연구분석의대상으로 하였다 (Tegeder et al, 2004; Trescot et al, 2008)Opioids are complexes of various chemicals, and their action is via the opioid receptors as G protein-coupled receptors. There are a number of subtypes such as k, u, and m. Heptahelical proteins are expressed in peripheral tissues as well as the central nervous system. In other words, they are known to bind internal opioids, enkephalins, endorphins, and dynorphins. In this study, beta-endorphin was the subject of study analysis (Tegeder et al, 2004; Trescot et al, 2008).
임상적으로는 opioid계열은 이미 진통제의 역할로 알려져 있으며, 암으로 인한 만성통증을 조절하기위해 사용되기도 한다. 기타 중추 또는 말초조직에서 여러 가지로 신경조절에 중요한 역할을 한다. 예를 들면 호흡, 면역, 행동, 장운동 등에 영향을 준다. 그렇지만 통증에 대한 영향뿐만 아니라 세포성장에 영향을 줄 수 있으며, 특히 암치료를 받는 경우 opioid사용에 있어서 암세포의 증식을 촉진하거나 저해하는 지의 경우를 같이 파악, 주의를 해야 될 부분이다 (Tegeder et al, 2004). 이와관련 vascular endothelial growth factor receptor의 활성화를 자극하여 암이 악화되는 현상이 보고가 되기도 하였다 (Gupta et al, 2002; Singleton et al, 2006). 따라서 본 실험의 주된 목적은 뇌종양세포, 특히 이 두가지 type의 glioblastoma cell에 대해 내부적으로 생성될 수 있는 opioid가 암성장억제 또는 촉진여부를 간접적으로 알 수 있고, 이러한 환경이 암치료에 도움이 될 수 있는지 증명하는 기본적인 data가 되었다.Clinically, the opioid family is already known for its role as an analgesic and may be used to control chronic pain caused by cancer. In other central or peripheral tissues it plays an important role in neuromodulation in many ways. For example, it affects breathing, immunity, behavior and bowel movements. However, it may affect not only the effect of pain but also cell growth. In particular, if the patient is treated with cancer, it should be noted that the use of opioid promotes or inhibits the proliferation of cancer cells (Tegeder et al.). , 2004). It has been reported that cancer is worsened by stimulating the activation of vascular endothelial growth factor receptor (Gupta et al, 2002; Singleton et al, 2006). Therefore, the main purpose of this experiment is to know indirectly whether opioid, which can be generated internally for brain tumor cells, especially these two types of glioblastoma cells, can indirectly inhibit or promote cancer growth. This is the basic data that proves it is there.
본 연구결과에 의하면, 0.1 uM의 level에서는 효과가 미약하거나 (U87), 오히려 암세포가 증가되는 (U251) 현상을 관찰할 수 있었으며, 농도가 증가됨에 따라 점차 세포의 증식을 억제하는 현상을 관찰할 수 있었다. Lazarczyka et al (2010) 연구에선 morphine이 glioblastoma T98G 뇌암세포를 증식시키는 것을 확인하였고 (20, 40 uM의 농도에서도), 반면 morhpine보다 통증효과가 1000배가량 강한 Biphalin의 경우에는 암세포증식을 감소시키는 효과를 보고하였다.According to the results of this study, we could observe the effect that the effect is weak (U87) or rather increased (U251) at the level of 0.1 uM, and gradually suppress the proliferation of the cells as the concentration is increased. Could. Lazarczyka et al (2010) have found that morphine proliferates glioblastoma T98G brain cancer cells (at concentrations of 20 and 40 uM), whereas biphalin, which is 1000 times more pain-prone than morhpine, reduces cancer cell proliferation. Reported.
임상적으로는 opioid계열은 이미 진통제의 역할로 알려져 있으며, 암으로 인한 만성통증을 조절하기위해 사용되기도 한다. 기타 중추 또는 말초조직에서 여러가지로 신경조절에 중요한 역할을 한다. 예를 들면 호흡, 면역, 행동, 장운동 등에 영향을 준다. 그렇지만 통증에 대한 영향뿐만 아니라 세포성장에 영향을 줄 수 있으며, 특히 암치료를 받는 경우 opioid사용에 있어서 암세포의 증식을 촉진하거나 저해하는 지의 경우를 같이 파악, 주의를 해야 될 부분이다 (Tegeder et al, 2004). 이와관련 vascular endothelial growth factor receptor의 활성화를 자극하여 암이 악화되는 현상이 보고가 되기도 하였다 (Gupta et al, 2002; Singleton et al, 2006). 따라서 본 실험의 주된 목적은 뇌종양세포, 특히 이 두가지 type의 glioblastoma cell에 대해 내부적으로 생성될 수 있는 opioid가 암성장억제 또는 촉진여부를 간접적으로 알 수 있고, 이러한 환경이 암치료에 도움이 될 수 있는지 증명하는 기본적인 data가 되었다.Clinically, the opioid family is already known for its role as an analgesic and may be used to control chronic pain caused by cancer. In other central or peripheral tissues it plays an important role in neuromodulation in many ways. For example, it affects breathing, immunity, behavior and bowel movements. However, it may affect not only the effect of pain but also cell growth. In particular, if the patient is treated with cancer, it should be noted that the use of opioid promotes or inhibits the proliferation of cancer cells (Tegeder et al.). , 2004). It has been reported that cancer is worsened by stimulating the activation of vascular endothelial growth factor receptor (Gupta et al, 2002; Singleton et al, 2006). Therefore, the main purpose of this experiment is to know indirectly whether opioid, which can be generated internally for brain tumor cells, especially these two types of glioblastoma cells, can indirectly inhibit or promote cancer growth. This is the basic data that proves it is there.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020110015419A KR20120096169A (en) | 2011-02-22 | 2011-02-22 | Inhibiting the growth of cancer cells with the application of endorphine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020110015419A KR20120096169A (en) | 2011-02-22 | 2011-02-22 | Inhibiting the growth of cancer cells with the application of endorphine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20120096169A true KR20120096169A (en) | 2012-08-30 |
Family
ID=46886235
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020110015419A KR20120096169A (en) | 2011-02-22 | 2011-02-22 | Inhibiting the growth of cancer cells with the application of endorphine |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR20120096169A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20170000856U (en) | 2015-08-27 | 2017-03-08 | 박성훈 | Medical device for inserting medical niddle |
-
2011
- 2011-02-22 KR KR1020110015419A patent/KR20120096169A/en not_active Application Discontinuation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20170000856U (en) | 2015-08-27 | 2017-03-08 | 박성훈 | Medical device for inserting medical niddle |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Galletti et al. | Pathophysiological basis of migraine prophylaxis | |
| Guiard et al. | Functional interactions between dopamine, serotonin and norepinephrine neurons: an in-vivo electrophysiological study in rats with monoaminergic lesions | |
| Rocha et al. | Histamine: a new immunomodulatory player in the neuron-glia crosstalk | |
| Jin et al. | The neuroprotective effects of cordycepin inhibit glutamate-induced oxidative and ER stress-associated apoptosis in hippocampal HT22 cells | |
| Liu et al. | Dysfunction in serotonergic and noradrenergic systems and somatic symptoms in psychiatric disorders | |
| Li et al. | Vincristine-induced peripheral neuropathy: a mini-review | |
| Lomonaco et al. | The induction of autophagy by γ‐radiation contributes to the radioresistance of glioma stem cells | |
| Hu et al. | Salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells | |
| Chen et al. | Inhibition of NF‐κB and metastasis in irinotecan (CPT‐11)‐resistant LoVo colon cancer cells by thymoquinone via JNK and p38 | |
| Hong et al. | Chronic stress effects on tumor: pathway and mechanism | |
| Mirshekar et al. | Neuroprotective effects of gallic acid in a rat model of traumatic brain injury: behavioral, electrophysiological, and molecular studies | |
| Urueña et al. | Gallotannin-rich Caesalpinia spinosa fraction decreases the primary tumor and factors associated with poor prognosis in a murine breast cancer model | |
| Shirazi et al. | Involvement of central TRPV1 receptors in pentylenetetrazole and amygdala-induced kindling in male rats | |
| Das et al. | An overview on chemotherapy-induced cognitive impairment and potential role of antidepressants | |
| Li et al. | Autophagy inhibitor regulates apoptosis and proliferation of synovial fibroblasts through the inhibition of PI3K/AKT pathway in collagen-induced arthritis rat model | |
| Wang et al. | Echinacoside suppresses pancreatic adenocarcinoma cell growth by inducing apoptosis via the mitogen‑activated protein kinase pathway | |
| Freitas et al. | Lectin from Abelmoschus esculentus reduces zymosan-induced temporomandibular joint inflammatory hypernociception in rats via heme oxygenase-1 pathway integrity and tnf-α and il-1β suppression | |
| Nelson et al. | Manganese toxicity is targeting an early step in the dopamine signal transduction pathway that controls lateral cilia activity in the bivalve mollusc Crassostrea virginica | |
| Calabrese et al. | Hormesis and neural stem cells | |
| Xu et al. | Roburic acid targets TNF to inhibit the NF-κB signaling pathway and suppress human colorectal cancer cell growth | |
| Timeus et al. | In vitro antiproliferative and antimigratory activity of dasatinib in neuroblastoma and Ewing sarcoma cell lines | |
| KR20120096169A (en) | Inhibiting the growth of cancer cells with the application of endorphine | |
| Erin et al. | Vagus nerve regulates breast cancer metastasis to the adrenal gland | |
| CN105307682B (en) | Antitumor agent | |
| Shen et al. | Roles of nicotinic acetylcholine receptors in stem cell survival/apoptosis, proliferation and differentiation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| E601 | Decision to refuse application |