Characterization of Expression and Function of the Formins FHOD1, INF2, and DAAM1 in HER2-Positive Breast Cancer

Minna Peippo,Maria Gardberg,Pauliina Kronqvist,Olli Carpén,Vanina D. Heuser 한국유방암학회 2023 Journal of breast cancer Vol.26 No.6

Purpose: Human epidermal growth factor receptor 2 (HER2)-targeted therapies, such as trastuzumab, benefit patients with HER2-positive metastatic breast cancer; however, owing to traditional pathway activation or alternative signaling, resistance persists. Given the crucial role of the formin family in shaping the actin cytoskeleton during cancer progression, these proteins may function downstream of the HER2 signaling pathway. Our aim was to uncover the potential correlations between formins and HER2 expression using a combination of public databases, immunohistochemistry, and functional in vitro assays. Methods: Using online databases, we identified a negative prognostic correlation between specific formins mRNA expression in HER2-positive cancers. To validate these findings at the protein level, immunohistochemistry was performed on HER2 subtype breast cancer tumors to establish the links between staining patterns and clinical characteristics. We then knocked down individual or combined formins in MDA-MB-453 and SK-BR-3 cells and investigated their effects on wound healing, transwell migration, and proliferation. Furthermore, we investigated the effects of erb-b2 receptor tyrosine kinase 2 (ERBB2)/HER2 small interfering RNA (siRNA)-mediated knockdown on the PI3K/Akt and MEK/ERK1 pathways as well as on selected formins. Results: Our results revealed that correlations between INF2, FHOD1, and DAAM1 mRNA expression and ERBB2 in HER2-subtype breast cancer were associated with worse outcomes. Using immunohistochemistry, we found that high FHOD1 protein expression was linked to higher histological grades and was negatively correlated with estrogen and progesterone receptor positivity. Upon formins knockdown, we observed effects on wound healing and transwell migration, with a minimal impact on proliferation, which was evident through single and combined knockdowns in both cell lines. Notably, siRNA-mediated knockdown of HER2 affected FHOD1 and INF2 expression, along with the phosphorylated Akt/MAPK states. Conclusion: Our study highlights the roles of FHOD1 and INF2 as downstream effectors of the HER2/Akt and HER2/MAPK pathways, suggesting that they are potential therapeutic targets in HER2-positive breast cancer.

Sulphate Reducing Bacteria and Methanogenic Archaea Driving Corrosion of Steel in Deep Anoxic Ground Water

P. Rajala,M. Raulio,L. Carpén 한국부식방식학회 2019 Corrosion Science and Technology Vol.18 No.6

During the operation, maintenance and decommissioning of nuclear power plant radioactive contaminated waste is produced. This waste is stored in an underground repository 60-100 meters below the surface. The metallic portion of this waste comprises mostly carbon and stainless steel. A long-term field exposure showed high corrosion rates, general corrosion up to 29 μm a-1 and localized corrosion even higher. High corrosion rate is possible if microbes produce corrosive products, or alter the local microenvironment to favor corrosion. The bacterial and archaeal composition of biofilm formed on the surface of carbon steel was studied using 16S rRNA gene targeting sequencing, followed by phylogenetic analyses of the microbial community. The functional potential of the microbial communities in biofilm was studied by functional gene targeting quantitative PCR. The corrosion rate was calculated from weight loss measurements and the deposits on the surfaces were analyzed with SEM/EDS and XRD. Our results demonstrate that microbial diversity on the surface of carbon steel and their functionality is vast. Our results suggest that in these nutrient poor conditions the role of methanogenic archaea in corrosive biofilm, in addition to sulphate reducing bacteria, could be greater than previously suspected.

Unconventional Slow infections of the Central Nervous System

Carp, Richard I 한림대학교 한림과학원 부설 환경ㆍ생명과학연구소 1997 국제학술회의 Vol.1997 No.-

Unconventional slow infections of the central nervous system, also termed transmissible spongiform encephalopathies (TSE) or prion disease, form a unique group of diseases of animals and humans that have received increased attention in recent years. The animal respresentatives of the group include scrapie of sheep and goats (the archetype of the group), transmissible mink encephalopathy, chronic wasting disease of mule deer and elk, bovine spongiform encephalopathy (BSE), and feline spongiform encephalopathy. The human disease that are included in the group are Creutzfeld-Jakob disease (CJD), kuru, Gerstmann-Straussler syndrome(GSS) and fatal familial insomnia. One of the main reasons this group of diseases has evoked such interest recently was the emergence of BSE in the mid 1980's as a scourge upon the bovine population of Great Britain with the possible "spread" of that disease to the human population leading to a form of variant CJD, referred to as vCJD.

The Role of Infectious Agents in the Induction of Aging Changes and in Neurodegenerative Diseases

Carp, Richard I. 한림대학교 환경·생명과학연구소 2002 [일송 국제심포지엄] 노화와 만성퇴행성 신경질환 Vol.- No.4

The role of infectious agents in the induction of neurodegenerative changes and in aging processes is an exciting area of study. In this presentation, we will focus on the two possible origins for these agents, exogenous and endogenous. For exogenous infectious agents, our model will be Transmissible Spongiform Encephalopathies (TSEs), also termed prion diseases. In this presentation, we will emphasize 3points: First, there will be a general discussion of the diseases as a group. Second, we will list and briefly discuss some of the variations in TSE strain characteristics that are seen among the numerous TSE strains. Third, we will describe the 3 theories that attempt to define the nature of the agent and, in this context, we will ask whether it is time to re-examine the prion hypothesis.

실험슬로우 바이러스와 내분비 질환

Carp, Richard I.,김용선,최은경 대한내분비학회 1993 Endocrinology and metabolism Vol.8 No.1

선주권과 세계평화를 위한 국제청년학생컨퍼런스

W-CARP 세계기독교통일신령협회 2003 統一世界 Vol.- No.9

남북통일과 세계평화 및 유엔갱신을 위한 젊은 미래 지도자들의 결의의 장(場), 선(善)주권과 세계평화를 위한 국제청년학생 컨퍼런스' (International Young Leaders'Conference For a Good Governance and Global Peace)가 지난 8월 1일부터 15일까지 선문대학교 아산캠퍼스에서 개최되었다. 참부모님의 특별한 관심과 정성 속에 치러진 이번 행사는 '선(善)주권과 세계평화 실현을 위한 청년의 도전' 이라는 주제로 진행됐으며, 한반도를 둘러싸고 끊임없는 갈등과 대립을 겪어왔고 동시에 남북통일에 중요한 역할을 담당하고 있는 미국, 러시아, 중국, 일본 등의 교수, 대학생 등 900여명이 참석했다.

현진님 세계평화로 가는 유일한 길 제시

World carp 세계기독교통일신령협회 2002 統一世界 Vol.- No.1

강연회의 하이라이트는 두말할 것도 없이 현진님의 주제강연이었다. 첫대회인 예일대학에서는 원고문을 가지고 강연하셨지만, 두 번째 대회부터는 원고문에 의지하지 않는 현진님 특유의 강연을 들을 수 있었다. “Service for Peace: 위기와 희망”의 주제강연을 통해 현진님께서는 9월 11일 테러사건을 위시한 현실문제의 뿌리를 자기중심적 이기주의의 세계적 확대로 진단하고, “위하여 사는 삶”의 정신과 실천만이 유일한 해결방안임을 제시하셨다. 그리고 그 위하는 참사랑의 삶은 가정을 통해서만 배울 수 있고 경험할 수 있기 때문에 하나님을 중심한 참된 가정의 건설이 요구되며, 그런 참가정의 모델을 기반으로 해서 세계가 하나님아래 한가족이라는 의식을 중심삼고 서로 봉사할 때 세계평화의 길은 열릴 것임을 제시하셨다.

스크래피에 감염된 마우스의 뇌 및 간조직에서의 DNA Methylation

최은경,S . Uyeno,T . Ono,R . I . Carp,김용선 대한바이러스학회 1998 Journal of Bacteriology and Virology Vol.28 No.2

DNA methylation degree in the several murine brain and liver genes of different ages and after scrapie infection have been examined by using methylation-sensitive restriction endonuclease digestion. We found that the methylation of c-fos and c-myc in the brain and liver was increased during the late fetal to one month postnatal developmental periods. However, those of the SGP-2, S100j3, APP950, PrP, and APLP1 genes were decreased at the same periods. The comparison of the DNA methylation patterns between scrapie infected brains and controls demonstrated there is no significant difference in methylation degree of scrapie-infected brains. These observations indicate that DNA methylation might be importantly related to the aging process. The scrapie- infected murine brain was not significantly developed more senescent than the same age-controls did.

Seismic Analysis of Absorber Rod in KMRR Reactivity Control Mechanism

조영갑,유봉,김태룡,안규석,Cho, Yeong-Carp,Yoo, Bong,Kim, Tae-Ryong,Ahn, Kyu-Suk Computational Structural Engineering Institute of 1990 전산구조공학 Vol.3 No.3

This study is on a seismic analysis of absorber rod in KMRR Reactivity Control Mechanism. The model being studied is two coaxial tubes(control absorber rod and flow tube) immersed in the water and partially coupled(overlap) by water gap. The hydrodynamic mass effects by the water in each surrounding conditions are considered in the model. The natural frequencies, stresses and displacements of the system due to Safe Shutdown Earthquake are computed in the cases of in-phase modes and out-of-phase modes of two coaxial tubes. The results show that maximum stresses are well below the allowable limit but the maximum displacements at the ends of both tubes are so much that the absorber rod contacts with the flow tube(or surrounding wall). 본 연구에서는 다목적연구로 반응도제어장치의 제어봉에 대한 내진해석을 수행하였다. 해석모델은 물속에 잠겨있는 두개의 관(중성자흡수봉 및 유동관)이 동심축상에 있으며 부분적으로 중첩된 두 관끝단의 유체틈에 의해 서로 동적으로 연결되어 있다. 유체에 의한 동적질량을 고려한 고유진동수를 구하고 안전정지지진에 의해 발생하는 최대응력과 최대변위를 동위상 및 역위상 거동별로 각각 구하였다. 해석결과 최대응력은 허용치보다 작게 나타나 구조적인 건전성은 입증되었으나, 최대변위는 두 개의 관이 서로 부딪히고 중성자흡수봉은 주위의 다른 벽에도 부딪히는 현상을 수발함을 알 수 있었다.

Unconventional Slow Virus에 감염된 마우스에서 비만증 및 인슐린 비의존성 당뇨병 발생연구

김용선,최은경,김홍석,Richard I . Carp 대한바이러스학회 1990 Journal of Bacteriology and Virology Vol.20 No.2

Scrapie is the archetype of the unconventional slow infection diseases. The causative agent has been passaged experimentally in various small animals, including mice, in which the preclinical course is controlled by genetic characteristics of both host and agent. One of the parameters controlled is the development of obesity which is seen in certain scrapie strain mouse strain combination. Body weight, glucose tolerance test (GTT), levels of insulin in serum and levels of proinsulin mRNA in pancreas results were monitored throughout the incubation period in SJL and C57BL mice injected with different scrapie preparations. Increase in weight and aberrant glucose metabolism occurred in the preclinical and clinical phases of disease. Virtually all obese mice showed aberrant GTT results which were manifested by significantly higher blood glucose levels two hours after a glucose overload, however, levels of insulin in serum and levels of proinsulin mRNA in pancreas did not significantly difference. This system has value as a model of obesity/diabetes syndromes in humans.