• 제목/요약/키워드: membrane targeting

검색결과 112건 처리시간 0.024초

The Application of Radiolabeled Targeted Molecular Probes for the Diagnosis and Treatment of Prostate Cancer

  • Luyi Cheng;TianshuoYang;Jun Zhang;Feng Gao;Lingyun Yang;Weijing Tao
    • Korean Journal of Radiology
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    • 제24권6호
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    • pp.574-589
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    • 2023
  • Radiopharmaceuticals targeting prostate-specific membrane antigens (PSMA) are essential for the diagnosis, evaluation, and treatment of prostate cancer (PCa), particularly metastatic castration-resistant PCa, for which conventional treatment is ineffective. These molecular probes include [68Ga]PSMA, [18F]PSMA, [Al18F]PSMA, [99mTc]PSMA, and [89Zr]PSMA, which are widely used for diagnosis, and [177Lu]PSMA and [225Ac]PSMA, which are used for treatment. There are also new types of radiopharmaceuticals. Due to the differentiation and heterogeneity of tumor cells, a subtype of PCa with an extremely poor prognosis, referred to as neuroendocrine prostate cancer (NEPC), has emerged, and its diagnosis and treatment present great challenges. To improve the detection rate of NEPC and prolong patient survival, many researchers have investigated the use of relevant radiopharmaceuticals as targeted molecular probes for the detection and treatment of NEPC lesions, including DOTA-TOC and DOTA-TATE for somatostatin receptors, 4A06 for CUB domain-containing protein 1, and FDG. This review focused on the specific molecular targets and various radionuclides that have been developed for PCa in recent years, including those mentioned above and several others, and aimed to provide valuable up-to-date information and research ideas for future studies.

Differential Behaviour of Selenium Analogs against Anticancer Drug Induced Apoptosis of Lymphocytes in Human Peripheral Blood

  • Elango, Sonaa;Subbiah, Usha;Jain, Jeong
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권5호
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    • pp.2527-2533
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    • 2016
  • Sensitising cancer cells and at the same time desensitizing normal cells is a double task in cancer management. Agents which can combat the debilitating side effects of cancer therapeutics and simultaneously synergize with anticancer agents in specifically targeting cancer cells are needed. Selenium, a proven anticarcinogen, gains due importance in terms of its efficacy to combat the side effects of cancer therapy. This study is a comparative analysis of the chemoprotective effects of selenium compounds, methyl selenol (generated from organic selenomethionine (5mmol/L ; METase 40U/L)) and sodium selenite (inorganic form)($30{\mu}M$) in peripheral blood human lymphocytes exposed to cisplatin and mitomycin. Biochemical alterations occurring in many cells during apoptosis include loss of plasma membrane phospholipid asymmetry, DNA fragmentation, and activation of caspase-3. The present study demonstrated that the selenium metabolite and selenite are efficient in protecting lymphocytes undergoing DNA damage and exerted their activity by reducing caspase 3 expression. Interestingly organic methylselenol (MeSe) was found to offer more protective effects compared to inorganic selenite (SeL), by reducing the induction of apoptosis by the cytotoxic agents. This suggests that MeSe and to a lesser extent selenite might have potential for assessment in clinical trials and could be considered as strong candidates in pharmacogenomics or in the nutriprotective arena.

Decreased Expression of Aquaporin-2 Water Channels in the Kidney in Rats Treated with Reserpine

  • Lee, Jong-Un;Oh, Yoon-Wha;Kim, Sun-Mi;Kim, Soo-Wan
    • The Korean Journal of Physiology and Pharmacology
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    • 제5권4호
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    • pp.307-313
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    • 2001
  • Whether there exists a sympathetic neural mechanism regulating the expression of aquaporin (AQP) water channels in the kidney was investigated. Male Sprague-Dawley rats were treated with reserpine (1 mg/kg, IP), and the expression of AQP1-4 proteins was determined in the kidney one day thereafter. Following the treatment with reserpine, the systolic blood pressure measured in a conscious state was significantly decreased in the experimental group compared with that in the control $(83{\pm}8\;vs\;124{\pm}6\;mmHg;\;n=6\;each,\;P<0.05)$. The expression of AQP2 proteins was decreased in the cortex, outer medulla, and inner medulla. The decrease of AQP2 proteins was in parallel in the membrane and the cytoplasmic fractions, suggesting a preserved AQP2 targeting. No significant changes were observed in the expression of AQP1, AQP3, or AQP4. Neither basal nor AVP-stimulated formation of cAMP was significantly altered. These results suggest that the sympathetic nervous system has a tonic stimulatory effect specifically on the expression of AQP2 water channels in the kidney.

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Gene Targeting of the Acyl-CoA Synthetase Specific to Arachidonate

  • Kang, Man-Jong
    • 한국동물번식학회:학술대회논문집
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    • 한국동물번식학회 2000년도 국제심포지움
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    • pp.3-4
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    • 2000
  • The synthesis of acyl-CoA catalyzed by acyl-CoA synthetase (ACS, EC 6.2.1.3) from fatty acid, ATP, and CoA is a crucial reaction in mammalian fatty acid metabolism. In arachidonate metabolism, acyl-CoA synthetase(ACS) plays a key role in the esterification of free arachidonate into membrane phospholipids. Following its release by the action of calcium dependent phospholipase, free arachidonate is believed to be rapidly converted to arachidonoyl-CoA and reesterified into phospholipids in order to prevent excessive synthesis of eicosanoids. In previous studies, we have characterized five ACSs (designated as ACS1-5) with different tissue distribution. ACS1, ACS2, and ACS5 are similar in structure and fatty acid preference, and completely different from ACS3 and ACS4. The latter are arachidonate-preferring enzymes closely related in structure but expressed in different tissues: ACS3 mRNA is highly expressed in the brain and the mRNA for ACS4 is expressed in steroidogenic tissues including adrenal gland, ovary, and testis. To learn more about the potential function of ACS4 in arachidonate metabolism, we have produced knock-out mice for ACS4 gene. ACS4+/- females become pregnant less frequently and produce small litters with extremely low transmission of the disrupted alleles. Striking morphological changes including extremely enlarged uterine filled with numerous proliferative cysts of various size were detected in ACS4+/- females. Furthermore, marked accumulation of prostaglandins were seen in the uterus of heterozygous females. These results indicate that ACS4 is critical for the uterine arachidonate metabolism and heterozygous disruption of its gene lead to impaired pregnancy.

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일부 군인의 구취관련요인에 따른 구취자각도 (Self-Perception of Halitosis According to Some Soldiers' Halitosis-Related Factors)

  • 이미라;심재숙
    • 보건의료산업학회지
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    • 제7권3호
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    • pp.125-135
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    • 2013
  • The purpose of this study was to enhance soldiers' oral health level and to offer basic data on controlling and preventing halitosis. It surveyed halitosis-related elements and analyzed relationship between subjective self-perception level of halitosis according to it targeting 253 soldiers in their 20s in some areas of Seoul from September 2012 to October. Thus, the following conclusions were obtained. 1. As for subjects' self-perception of halitosis, the perception status of oral health was indicated to be 'very bad' and to be shown most highly in one place. It was indicated to be high in the group of feeling Xerostomia much and the group of often feeling the white membrane of tongue. The statistically significant difference was shown(p<0.01). 2. Subjects' self-perception of halitosis was indicated to be the highest in the group with the largest intake of snacks. It was shown to be the highest in the group of having sinus infection and rhinitis. It was indicated to be the highest in the group of having a habit of oral respiration. Significant difference was shown(p<0.05). 3. Subjects' self-perception of halitosis was indicated to be lower in the group, which ever received oral health education, than the group in opposite case. Significant difference was shown(p<0.05).

Effect of MUC1 siRNA on Drug Resistance of Gastric Cancer Cells to Trastuzumab

  • Deng, Min;Jing, Da-Dao;Meng, Xiang-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권1호
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    • pp.127-131
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    • 2013
  • Trastuzumab is the first molecular targeting drug to increase the overall survival rate in advanced gastric cancer. However, it has also been found that a high intrinsic or primary trastuzumab resistance exists in some proportion of gastric cancer patients. In order to explore the mechanism of resistance to trastuzumab, firstly we investigated the expression of MUC1 (membrane-type mucin 1) in gastric cancer cells and its relationship with drug-resistance. Then using gene-silencing, we transfected a siRNA of MUC1 into drug-resistant cells. The results showed the MKN45 gastric cell line to be resistant to trastuzumab, mRNA and protein expression of MUC1 being significantly upregulated. After transfection of MUC1 siRNA, protein expression of MUC1 in MKN45cells was significantly reduced. Compared with the junk transfection and blank control groups, the sensitivity to trastuzumab under MUC1 siRNA conditions was significantly increased. These results imply that HER2-positive gastric cancer cell MKN45 is resistant to trastuzumab and this resistance can be cancelled by silencing expression of the MUC1 gene.

Zinc in Pancreatic Islet Biology, Insulin Sensitivity, and Diabetes

  • Maret, Wolfgang
    • Preventive Nutrition and Food Science
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    • 제22권1호
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    • pp.1-8
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    • 2017
  • About 20 chemical elements are nutritionally essential for humans with defined molecular functions. Several essential and nonessential biometals are either functional nutrients with antidiabetic actions or can be diabetogenic. A key question remains whether changes in the metabolism of biometals and biominerals are a consequence of diabetes or are involved in its etiology. Exploration of the roles of zinc (Zn) in this regard is most revealing because 80 years of scientific discoveries link zinc and diabetes. In pancreatic ${\beta}$- and ${\alpha}$-cells, zinc has specific functions in the biochemistry of insulin and glucagon. When zinc ions are secreted during vesicular exocytosis, they have autocrine, paracrine, and endocrine roles. The membrane protein ZnT8 transports zinc ions into the insulin and glucagon granules. ZnT8 has a risk allele that predisposes the majority of humans to developing diabetes. In target tissues, increased availability of zinc enhances the insulin response by inhibiting protein tyrosine phosphatase 1B, which controls the phosphorylation state of the insulin receptor and hence downstream signalling. Inherited diseases of zinc metabolism, environmental exposures that interfere with the control of cellular zinc homeostasis, and nutritional or conditioned zinc deficiency influence the pathobiochemistry of diabetes. Accepting the view that zinc is one of the many factors in multiple gene-environment interactions that cause the functional demise of ${\beta}$-cells generates an immense potential for treating and perhaps preventing diabetes. Personalized nutrition, bioactive food, and pharmaceuticals targeting the control of cellular zinc in precision medicine are among the possible interventions.

Small Molecules that Potentiate Neuroectodermal Differentiation of Mouse Embryonic Stem Cells

  • Lee, Jonghwan;Rhee, Ki-Jong;Jung, Dongju
    • 대한의생명과학회지
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    • 제19권1호
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    • pp.32-40
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    • 2013
  • Pluripotent stem cells (PSCs) have enormous potential in the biomedical sciences because they can grow continuously and differentiate into any kind of cell in the body. However, for future application in regenerative medicine, it is still a challenge to control the differentiation of PSCs without using genetic materials. To control the differentiation of PSCs, small molecules might be the best substitute for genetic materials considering the following advantages: small size, which enables penetration of plasma membrane; easy-to-modify structure; and low chance of genetic recombination in treated cells. Herein, we introduce small molecules that induce the neuroectodermal differentiation of mouse embryonic stem cells (ESCs). The small molecules were identified via ESC-based consecutive screenings of small-molecule libraries composed of 324 natural compounds or 93 selected drugs. The natural compounds discovered in the first screening were used to select 93 structurally similar drugs out of 1,200 approved drugs. In the second screening, among the 93 compounds, we found 4 drugs that induced the neuroectodermal differentiation of ESCs. These drugs were progesteroneor corticoid-derivatives. Our results suggest that small molecules targeting the progesterone receptor or glucocorticoid receptor could be used as chemical tools to induce the differentiation of PSCs into a specific germ lineage.

Functions of the Plant Qbc SNARE SNAP25 in Cytokinesis and Biotic and Abiotic Stress Responses

  • Won, Kang-Hee;Kim, Hyeran
    • Molecules and Cells
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    • 제43권4호
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    • pp.313-322
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    • 2020
  • Eukaryotes transport biomolecules between intracellular organelles and between cells and the environment via vesicle trafficking. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE proteins) play pivotal roles in vesicle and membrane trafficking. These proteins are categorized as Qa, Qb, Qc, and R SNAREs and form a complex that induces vesicle fusion for targeting of vesicle cargos. As the core components of the SNARE complex, the SNAP25 Qbc SNAREs perform various functions related to cellular homeostasis. The Arabidopsis thaliana SNAP25 homolog AtSNAP33 interacts with Qa and R SNAREs and plays a key role in cytokinesis and in triggering innate immune responses. However, other Arabidopsis SNAP25 homologs, such as AtSNAP29 and AtSNAP30, are not well studied; this includes their localization, interactions, structures, and functions. Here, we discuss three biological functions of plant SNAP25 orthologs in the context of AtSNAP33 and highlight recent findings on SNAP25 orthologs in various plants. We propose future directions for determining the roles of the less well-characterized AtSNAP29 and AtSNAP30 proteins.

F2 Gel Matrix - a Novel Delivery System for Immune and Gene Vaccinations

  • Tuorkey, Muobarak J
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권7호
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    • pp.3061-3063
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    • 2016
  • Exploiting the immune system to abolish cancer growth via vaccination is a promising strategy but that is limited by many clinical issues. For DNA vaccines, viral vectors as a delivery system mediate a strong immune response due to their protein structure, which could afflect the cellular uptake of the genetic vector or even induce cytotoxic immune responses against transfected cells. Recently, synthetic DNA delivery systems have been developed and recommended as much easier and simple approaches for DNA delivery compared with viral vectors. These are based on the attraction of the positively charged cationic transfection reagents to negatively charged DNA molecules, which augments the cellular DNA uptake. In fact, there are three major cellular barriers which hinder successful DNA delivery systems: low uptake across the plasma membrane; inadequate release of DNA molecules with limited stability; and lack of nuclear targeting. Recently, a polysaccharide polymer produced by microalgae has been synthesized in a form of polymeric fiber material poly-N-acetyl glucosamine (p-GlcNAc). Due its unique properties, the F2 gel matrix was suggested as an effective delivery system for immune and gene vaccinations.