• Title/Summary/Keyword: breast cancer

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Gadobutrol-dendrimer effects on metastatic and apoptotic gene expression

  • Kebriaezadeh, Abbas;Ashrafi, Sepehr;Rasouli, Rahimeh;Ebrahimi, Seyed Esmaeil Sadat;Hamedani, Morteza Pirali;Assadi, Artin;Saffari, Mostafa;Ardestani, Mehdi Shafiee
    • Advances in nano research
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    • v.4 no.2
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    • pp.145-156
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    • 2016
  • Dendrimers are one of the most appropriate nanocaries for imaging moieties in imaging applications.The purpose of this study was the evalution of cytotoxicity and inducing apoptosis of dendrimers. This study was conducted in order to investigate the metastasis suppression effect of dendrimer in human breast MCF-7 cell line and finding the nanoparticle protein corona in biological enviromental. Dendrimer cytotoxicity effect was assessed by MTT assay. The mRNA experession level of KAI1 as a metastasis suppressor gene, Bax as Pro- apoptotic gene, Bcl-2 as an anti-apoptotic gene and GAPDH as a housekepping gene were determined by real-time PCR assays.concentration-dependent nanoparticle cytotoxicity effect was proofed at range of 1-2 mg/mL in 24 hours, significant upregulation of mRNA expression of Bax, was observed whereas expression of anti-apoptotic Bcl-2 was down-regulated, also expression of metastasis suppressor gene KAI1 was up-regulated. So far a few studies confirmed apoptosis enhancement effect of dendrimers in MCF-7 cell line via bax/bcl-2 pathways. dendrimer nanoparticles was able to act as metastase inhibitor via upregulation of KAI1 gene.

Review of Herbs Used as Treatment for Menopausal Patients in Alternative Medicine (대체의학에서 갱년기 증후군에 사용되는 약물에 대한 고찰)

  • Kim, Seung-Hyun;Lee, Jin-Moo;Lee, Chang-Hoon;Cho, Jung-Hoon;Jang, Jun-Bock;Lee, Kyung-Sub
    • The Journal of Korean Obstetrics and Gynecology
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    • v.21 no.3
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    • pp.90-98
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    • 2008
  • Purpose: Menopausal syndrome is caused by urgent changes of sex hormone in women. The hormonal therapy can soothe the problems of menopausal patients, but it can increase the probability of another disease, such as breast cancer, heart attack, etc. So the demand of alternative herb therapy is increasing in Western countries. In Korea, herbal medicine is imported and used by Western doctors. To know and use the alternative herbal medicine, Korean Medical doctors should know their efficacy and safety. Methods: We researched the Medline(Pubmed) with the key word such as 'CAM', 'herb' and 'menopause'. We selected the herbs known as treating the menopausal syndrome and researched the similar or same herbs that are used in Korean medicine by the scientific name and efficient ingredients. To evaluate the efficacy of the herbs, we compared the herbs that were differently defined in alternative and Korean medicine Results: Balm, black cohosh, chaste berry, dong quai. evening primrose oil. ginkgo, St. John's wort, valerian root, and sarsaparilla were chosen as prevalent herbs used in alternative medicine. The pharmacologic effect of Black cohosh, licorice root, St. John's wort were recognized. But these three herbs are not usually prescripted for menopausal patients in Korean medicine. So we could apply these three herbs as one of Korean medical treatments. The efficacy of other herbs cannot be surely prescripted for menopausal patients. Conclusion: The efficacy and safety of alternative medicine is not proved yet. But to diversify the treatmental methods of Korean medicine, we need to prove and use these medicine as one of Korean medical treatment.

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Kinetics, Isotherm and Adsorption Mechanism Studies of Letrozole Loaded Modified and Biosynthesized Silver Nanoparticles as a Drug Delivery System: Comparison of Nonlinear and Linear Analysis

  • PourShaban, Mahsa;Moniri, Elham;Safaeijavan, Raheleh;Panahi, Homayon Ahmad
    • Korean Chemical Engineering Research
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    • v.59 no.4
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    • pp.493-502
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    • 2021
  • We prepared and investigated a biosynthesized nanoparticulate system with high adsorption and release capacity of letrozole. Silver nanoparticles (AgNPs) were biosynthesized using olive leaf extract. Cysteine was capped AgNPs to increase the adsorption capacity and suitable interaction between nanoparticles and drug. Morphology and size of nanoparticles were confirmed using transmission electron microscopy (TEM). Nanoparticles were spherical with an average diameter of less than 100 nm. Cysteine capping was successfully confirmed by Fourier transform infrared resonance (FTIR) spectroscopy and elemental analysis (CHN). Also, the factors of letrozole adsorption were optimized and the linear and non-linear forms of isotherms and kinetics were studied. Confirmation of the adsorption data of letrozole by cysteine capped nanoparticles in the Langmuir isotherm model indicated the homogeneous binding site of modified nanoparticles surface. Furthermore, the adsorption rate was kinetically adjusted to the pseudo-second-order model, and a high adsorption rate was observed, indicating that cysteine coated nanoparticles are a promising adsorbent for letrozole delivery. Finally, the kinetic release profile of letrozole loaded modified nanoparticles in simulated gastric and intestinal buffers was studied. Nearly 40% of letrozole was released in simulated gastric fluid with pH 1.2, in 30 min and the rest of it (60%) was released in simulated intestinal fluid with pH 7.4 in 10 h. These results indicate the efficiency of the cysteine capped AgNPs for adsorption and release of drug letrozole for breast cancer therapy.

Genetic alterations in Wnt family of genes and their putative association with head and neck squamous cell carcinoma

  • Aditya, Jain;Smiline Girija, A.S.;Paramasivam, A.;Priyadharsini, J. Vijayashree
    • Genomics & Informatics
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    • v.19 no.1
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    • pp.5.1-5.11
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    • 2021
  • Head and neck squamous cell carcinoma (HNSCC) is the most frequent type of head and neck cancer that usually arises from the mucosal surfaces of several organs including nasal cavity, paranasal sinuses, oral cavity, tongue, pharynx, and larynx. The Wnt signaling pathway is a crucial mechanism for cellular maintenance and development. It regulates cell cycle progression, apoptosis, proliferation, migration, and differentiation. Dysregulation of this pathway correlates with oncogenesis in various tissues including breast, colon, pancreatic as well as head and neck cancers. The present study aims to assess the gene alterations in the Wnt family of genes so as to derive an association with HNSCC. Computational approaches have been utilized for the identification of gene alterations in the Wnt family of genes. Several databases such as cBioportal, STRING, and UALCAN were used for the purpose. The frequency of alteration was high in case of Wnt family member 11 (5%). Gene amplification, deep deletions, missense and truncating mutations were observed in HNSCC patients. There was a marked difference in the gene expression profile of WNT11 between grades as well as normal samples. The survival probability measured using the Kaplan-Meier curve also presented with a significant difference among male and female subjects experiencing a low/medium level expression. The female patients showed less survival probability when compared to the male subjects. This provides the prognostic significance of the WNT11 gene in HNSCC. Taken together, the present study provides clues on the possible association of WNT11 gene alterations with HNSCC, which has to be further validated using experimental approaches.

Synthesis and evaluation of 64Cu-labeled avidin for lymph node imaging

  • Kang, Choong Mo;Kim, Hyunjung;Lee, Yong Jin;Choe, Yearn Seong
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.5 no.1
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    • pp.54-60
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    • 2019
  • Sentinel lymph node (SLN) imaging plays an important role in surgery of patients with breast cancer and melanoma. In this study, avidin (Av), a tetrameric protein glycosylated with mannose and N-acetylglucosamine molecules, was labeled with $^{64}Cu$ and then evaluated for LN imaging. $^{64}Cu$-Labeled $NeutrAvidin^{TM}$ (NAv), a non-glycosylated form of Av, was used for comparison. 1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-conjugated Av and NAv were prepared from the corresponding proteins and DOTA-NHS ester, which were then labeled with copper-64 and purified using PD-10 columns. The numbers of DOTA molecules conjugated to Av and NAv were 4.9 and 3.3, respectively. [$^{64}Cu$]Cu-DOTA-conjugated Av and NAv were prepared in 93% and 73% radiochemical yields, respectively. In vitro serum stability study showed that copper-64 remained stable on all radiotracers for 24 h (>97%). MicroPET/CT images showed that high radioactivity was accumulated in LNs within 15 min after footpad-injection of radiotracers. Tissue distribution data of mice demonstrated significantly higher uptake in the popliteal (PO) LN than lumbar (LU) LN for $^{64}Cu$-labeled Av (relative % ID/g excluding the injection sites: 66.2% and 26.0%, respectively) compared with those of $^{64}Cu$-labeled NAv (43.0% and 49.2%, respectively). The results of this study suggest that mannose molecules on Av enabled the radiotracer to retain in the first LN after mouse footpad-injection.

Co-Expression of a Chimeric Protease Inhibitor Secreted by a Tumor-Targeted Salmonella Protects Therapeutic Proteins from Proteolytic Degradation

  • Quintero, David;Carrafa, Jamie;Vincent, Lena;Kim, Hee Jong;Wohlschlegel, James;Bermudes, David
    • Journal of Microbiology and Biotechnology
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    • v.28 no.12
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    • pp.2079-2094
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    • 2018
  • Sunflower trypsin inhibitor (SFTI) is a 14-amino-acid bicyclic peptide that contains a single internal disulfide bond. We initially constructed chimeras of SFTI with N-terminal secretion signals from the Escherichia coli OmpA and Pseudomonas aeruginosa ToxA, but only detected small amounts of protease inhibition resulting from these constructs. A substantially higher degree of protease inhibition was detected from a C-terminal SFTI fusion with E. coli YebF, which radiated more than a centimeter from an individual colony of E. coli using a culture-based inhibitor assay. Inhibitory activity was further improved in YebF-SFTI fusions by the addition of a trypsin cleavage signal immediately upstream of SFTI, and resulted in production of a 14-amino-acid, disulfide-bonded SFTI free in the culture supernatant. To assess the potential of the secreted SFTI to protect the ability of a cytotoxic protein to kill tumor cells, we utilized a tumor-selective form of the Pseudomonas ToxA (OTG-PE38K) alone and expressed as a polycistronic construct with YebF-SFTI in the tumor-targeted Salmonella VNP20009. When we assessed the ability of toxin-containing culture supernatants to kill MDA-MB-468 breast cancer cells, the untreated OTG-PE38K was able to eliminate all detectable tumor cells, while pretreatment with trypsin resulted in the complete loss of anticancer cytotoxicity. However, when OTG-PE38K was co-expressed with YebF-SFTI, cytotoxicity was completely retained in the presence of trypsin. These data demonstrate SFTI chimeras are secreted in a functional form and that co-expression of protease inhibitors with therapeutic proteins by tumor-targeted bacteria has the potential to enhance the activity of therapeutic proteins by suppressing their degradation within a proteolytic environment.

Geometric Evaluation of Patient-Specific 3D Bolus from 3D Printed Mold and Casting Method for Radiation Therapy

  • An, Hyun Joon;Kim, Myeong Soo;Kim, Jiseong;Son, Jaeman;Choi, Chang Heon;Park, Jong Min;Kim, Jung-in
    • Progress in Medical Physics
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    • v.30 no.1
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    • pp.32-38
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    • 2019
  • Purpose: The objective of this study is to evaluate the geometrical accuracy of a patient-specific bolus based on a three-dimensional (3D) printed mold and casting method. Materials and Methods: Three breast cancer patients undergoing treatment for a superficial region were scanned using computed tomography (CT) and a designed bolus structure through a treatment planning system (TPS). For the fabrication of patient-specific bolus, we cast harmless certified silicone into 3D printed molds. The produced bolus was also imaged using CT under the same conditions as the patient CT to acquire its geometrical shape. We compared the shapes of the produced bolus with the planned bolus structure from the TPS by measuring the average distance between two structures after a surface registration. Results and Conclusions: The result of the average difference in distance was within 1 mm and, as the worst case, the absolute difference did not exceed ${\pm}2mm$. The result of the geometric difference in the cross-section profile of each bolus was approximately 1 mm, which is a similar property of the average difference in distance. This discrepancy was negligible in affecting the dose reduction. The proposed fabrication of patient-specific bolus is useful for radiation therapy in the treatment of superficial regions, particularly those with an irregular shape.

A Review of the Domestic Study Trends on Obstetrics & Gynecological Diseases with Pharmacopuncture Therapy (한방 여성의학 영역에서 활용된 약침요법에 대한 국내 연구 동향 분석)

  • Hwang, Su-In;Park, Kyung-Dug;Park, Jang-Kyung;Yoon, Young-Jin
    • The Journal of Korean Obstetrics and Gynecology
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    • v.32 no.3
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    • pp.192-213
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    • 2019
  • Objectives: The purpose of this study is to analyze the domestic study trends of pharmacopuncture therapy on obstetrics and gynecological diseases in Korean literature, through reviewing the clinical and experimental studies. Methods: We searched for clinical and experimental studies using pharmacopuncture therapy on obstetrics and gynecological diseases, published from January 2000 to May 2019, through 5 Korean databases. The study design, target disease, type of pharmacopuncture, method of intervention, and study results were analyzed. Results: 36 experimental studies and 15 clinical studies were finally included according to inclusion and exclusion criteria. In experimental studies, there were 12 studies about postmenopausal osteoporosis, 9 studies about obesity, 4 studies about endometriosis, 3 studies about hemostatic effects and analgesic anticoagulative effects, 2 studies about ovarian function, and analgesic antiphlogistic anticoagulative effects, and 1 study about menopausal symptoms. In clinical studies, there were 3 studies about obesity, postpartum disorders, dysmenorrhea, and women's urologic disease, and 1 study about menopausal symptoms, atypical squamous cells of undetermined significance (ASCUS) and breast cancer. Various types of pharmacopuncture have been proved to have a therapeutic effect in each of those obstetrics and gynecological diseases. Conclusions: This study indicates that pharmacopuncture therapy could be a good treatment for obstetrics and gynecological diseases. However, more well-designed and high-quality clinical researches are needed in further studies, to prove the effectiveness and safety of pharmacopuncture therapy.

A Nationwide Study of Surgery in a Newly Diagnosed Spine Metastasis Population

  • Sohn, Seil;Chung, Chun Kee;Han, Kyung Do;Jung, Jin Hyung;Hyeun, Joung Ho;Kim, Jinhee;Chang, Ung-Kyu;Sohn, Moon Jun;Kim, Sung Hwan
    • Journal of Korean Neurosurgical Society
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    • v.62 no.1
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    • pp.46-52
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    • 2019
  • Objective : The aim of this nationwide study was to analyze the current state of patients with newly diagnosed metastatic spine tumors according to surgical methods. Methods : Data was extracted from the Korean Health Insurance Review and Assessment Service database. Surgery was categorized into three methods : fusion, decompression, and vertebroplasty. Data included patient age, sex, health insurance type, and co-morbidities. Survival rates of metastatic spine tumor patients according to each surgical method were evaluated. Results : Among 1677 patients who had an operation, 823 patients were treated by fusion, 141 patients underwent decompression, and 713 patients were treated by vertebroplasty. The three most prevalent primary tumor sites were the lung, breast, and liver & biliary. On the other hand, the three most prevalent primary tumor sites of patients who underwent surgery were the lung, liver & biliary, and the prostate. The median survival periods for each surgical method in the metastatic spine tumor patients were 228 days for those who underwent surgery, 249 days for decompression, and 154 days for vertebroplasty. Age, sex, and comorbidities significantly affected survival rate. Conclusion : For every primary tumor site, decompression was the least common surgical method during the study period. Although the three surgical methods did not significantly affect the survival period, patients with a poor prognosis tended to undergo vertebroplasty.

Propranolol Inhibits the Proliferation of Human Glioblastoma Cell Lines through Notch1 and Hes1 Signaling System

  • Kim, Hyun Sik;Park, Young Han;Lee, Heui Seung;Kwon, Mi Jung;Song, Joon Ho;Chang, In Bok
    • Journal of Korean Neurosurgical Society
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    • v.64 no.5
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    • pp.716-725
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    • 2021
  • Objective : The anti-tumor effect of the beta-adrenergic receptor antagonist propranolol in breast cancer is well known; however, its activity in glioblastoma is not well-evaluated. The Notch-Hes pathway is known to regulate cell differentiation, proliferation, and apoptosis. We investigated the effect of propranolol to human glioblastoma cell lines, and the role of Notch and Hes signaling in this process. Methods : We performed immunohistochemical staining on 31 surgically resected primary human glioblastoma tissues. We also used glioblastoma cell lines of U87-MG, LN229, and neuroblastoma cell line of SH-SY5Y in this study. The effect of propranolol and isoproterenol on cell proliferation was evaluated using the MTT assay (absorbance 570 nm). The impact of propranolol on gene expression (Notch and Hes) was evaluated using real-time polymerase chain reaction (RT-PCR, whereas protein levels of Notch1 and Hes1 were measured using Western blotting (WB), simultaneously. Small interfering RNA (siRNA) was used to suppress the Notch gene to investigate its role in the proliferation of glioblastoma. Results : Propranolol and isoproterenol caused a dose-dependent decrease in cell proliferation (MTT assay). RT-PCR showed an increase in Notch1 and Hes1 expression by propranolol, whereas WB demonstrated increase in Notch1 protein, but a decrease in Hes1 by propranolol. The proliferation of U87-MG and LN229 was not significantly suppressed after transfection with Notch siRNA. Conclusion : These results demonstrated that propranolol suppressed the proliferation of glioblastoma cell lines and neuroblastoma cell line, and Hes1 was more closely involved than Notch1 was in glioblastoma proliferation.