• Title/Summary/Keyword: Targeted

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Intrahepatic cholangiocarcinoma: Evolving role of neoadjuvant and targeted therapy

  • Michael Ghio;Adarsh Vijay
    • Annals of Hepato-Biliary-Pancreatic Surgery
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    • v.27 no.2
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    • pp.123-130
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    • 2023
  • Intrahepatic cholangiocarcinoma is an aggressive, often fatal, malignancy that arises from the bile ducts. As it often presents with metastatic disease, surgery has limited utility. However, in some cases, neoadjuvant chemotherapy has provided the necessary reduction in tumor burden to allow for adequate resection. Consequently, new advances in neoadjuvant chemoradiation and targeted therapy are of interest with numerous case reports and small series published routinely; it is challenging to present a large case series or study given the overall rare frequency with which this malignancy is seen. Herein, we aim to summarize the newest advances in both neoadjuvant chemotherapy and targeted immunotherapy.

Extracranial systemic antitumor response through the abscopal effect induced by brain radiation in a patient with metastatic melanoma

  • D'Andrea, Mark A.;Reddy, G.K.
    • Radiation Oncology Journal
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    • v.37 no.4
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    • pp.302-308
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    • 2019
  • The abscopal effect is a term that has been used to describe the phenomenon in which localized radiation therapy treatment of a tumor lesion triggers a spontaneous regression of metastatic lesion(s) at a non-irradiated distant site(s). Radiation therapy induced abscopal effects are believed to be mediated by activation and stimulation of the immune system. However, due to the brain's distinctive immune microenvironment, extracranial abscopal responses following cranial radiation therapy have rarely been reported. In this report, we describe the case of 42-year-old female patient with metastatic melanoma who experienced an abscopal response following her cranial radiation therapy for her brain metastasis. The patient initially presented with a stage III melanoma of the right upper skin of her back. Approximately 5 years after her diagnosis, the patient developed a large metastatic lesion in her upper right pectoral region of her chest wall and axilla. Since the patient's tumor was positive for BRAF and MEK, targeted therapy with dabrafenib and trametinib was initiated. However, the patient experienced central nervous system (CNS) symptoms of headache and disequilibrium and developed brain metastases prior to the start of targeted therapy. The patient received radiation therapy to a dose of 30 Gy delivered in 15 fractions to her brain lesions while the patient was on dabrafenib and trametinib therapy. The patient's CNS metastases improved significantly within weeks of her therapy. The patient's non-irradiated large extracranial chest mass and axilla mass also shrank substantially demonstrating the abscopal effect during her CNS radiation therapy. Following radiation therapy of her residual chest lesions, the patient was disease free clinically and her CNS lesions had regressed. However, when the radiation therapy ended and the patient continued her targeted therapy alone, recurrence outside of her previously treated fields was noted. The disease recurrence could be due to the possibility of developing BRAF resistance clones to the BRAF targeted therapy. The patient died eventually due to wide spread systemic disease recurrence despite targeted therapy.

Rates and subsequent clinical course of fetal congenital anomalies detected by prenatal targeted ultrasonography of 137 cases over 5 years in a single institute: a retrospective observational study

  • Haewon Choi;Hyo-Shin Kim;Joon Sakong
    • Journal of Yeungnam Medical Science
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    • v.40 no.3
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    • pp.268-275
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    • 2023
  • Background: With the establishment of international guidelines and changes in insurance policies in Korea, the role of targeted ultrasonography has increased. This study aimed to identify the rates and clinical course of anomalies detected using prenatal targeted ultrasonography. Methods: This study was a retrospective analysis of all pregnancies with targeted ultrasonography performed in a single secondary medical center over 5 years. Results: Fetal anomalies were detected by targeted ultrasonography in 137 of the 8,147 cases (1.7%). The rates of anomalies were significantly higher in female fetuses (2.0% vs. 1.3%). In cases of female fetuses, the rate of anomalies was significantly higher in the advanced maternal age group (2.4% vs. 1.2%). In cases of male fetuses, the rate of anomalies was significantly higher in nulliparous (2.4% vs. 1.5%) and twin (5.7% vs. 1.9%) pregnancies. Pulmonary anomalies were significantly more common in the multiparity group (17.6% vs. 5.8%). Among the 137 cases, 17.5% terminated the pregnancy, 16.8% were diagnosed as normal after birth, and 42.3% were diagnosed with anomalies after birth or required follow-up. Conclusion: Through the first study on the rates and clinical course of anomalies detected by targeted ultrasonography at a single secondary center in Korea, we found that artificial abortions were performed at a high rate, even for relatively mild anomalies or anomalies with good prognosis. We suggest the necessity of a nationwide study to establish clinical guidelines based on actual incidences or prognoses.

Targeted chiral lipidomics analysis of bioactive eicosanoid lipids in cellular systems

  • Lee, Seon-Hwa;Blair, Ian A.
    • BMB Reports
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    • v.42 no.7
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    • pp.401-410
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    • 2009
  • We have developed a targeted lipidomics approach that makes it possible to directly analyze chiral eicosanoid lipids generated in cellular systems. The eicosanoids, including prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs) and alcohols (HETEs), have been implicated as potent lipid mediators of various biological processes. Enzymatic formations of eicosanoids are regioselective and enantioselective, whereas reactive oxygen species (ROS)-mediated formation proceeds with no stereo-selectivity. To distinguish between enzymatic and non-enzymatic pathways of eicosanoid formation, it is necessary to resolve enantiomeric forms as well as regioisomers. High sensitivity is also required to analyze the eicosanoid lipids that are usually present as trace amounts (pM level) in biological fluids. A discovery of liquid chromatography-electron capture atmospheric pressure chemical ionization/mass spectrometry (LC-ECAPCI/MS) allows us to couple normal phase chiral chromatography without loss of sensitivity. Analytical specificity was obtained by the use of collision-induced dissociation (CID) and tandem MS (MS/MS). With combination of stable isotope dilution methodology, complex mixtures of regioisomeric and enantiomeric eicosanoids have been resolved and quantified in biological samples with high sensitivity and specificity. Targeted chiral lipidomics profiles of bioactive eicosanoid lipids obtained from various cell systems and their biological implications have been discussed.

Comparative Analysis of the Seriousness of the Adverse Events and Risk of Targeted Therapy for Metastatic Renal Cell Carcinoma Among Medical Professionals (전이성신세포암 표적치료제의 부작용 심각도 및 위해에 대한 전문가그룹별 비교분석)

  • Park, Mi-Hae;Rhee, Jin-Nie;Lee, Eui-Kyung
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.2
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    • pp.100-105
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    • 2011
  • The perception of the 20 adverse events of targeted therapy for metastatic renal cell carcinoma was compared among medical professionals. Thirty-seven oncologists, 167 nurses and 79 pharmacists participated in the survey, and the response rate was 61.9%, 98.2%, 84.9%, respectively. Results showed that the most serious adverse event was GI perforation (8.83 points, 10 being the most serious), whereas the least serious was anemia (5.32 points). There were significant differences among oncologists, nurses and pharmacists especially for the moderately-serious adverse event such as wound-healing complication and lymphopenia. Adverse Events Composite Score (AECS) for each targeted therapy was calculated by multiplying adverse event incidence rate and seriousness score. Sunitinib had the highest score at 6.86 point and bevacizumab had the lowest at 2.1. Among professional groups oncologists showed the lowest AECS, whereas nurses had the highest. The gap on the perception of the adverse events among medical professionals needs to be reduced to get better outcomes of medical therapies for cancer patients.

Rapid Identification of Bifidobacteria in Dairy Products by Gene-targeted Species-specific PCR Technique and DGGE

  • Hong, Wei-Shung;Chen, Ming-Ju
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.12
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    • pp.1887-1894
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    • 2007
  • In this paper, a rapid and reliable gene-targeted species-specific polymerase chain reaction (PCR) technique based on a two-step process was established to identify bifidobacteria in dairy products. The first step was the PCR assay for genus Bifidobacterium with genus specific primers followed by the second step, which identified the species level with species-specific primer mixtures. Ten specific primer pairs, designed from nucleotide sequences of the 16-23S rRNA region, were developed for the Bifidobacterium species including B. angulatum, B. animalis, B. bifidum, B. breve, B. catenulatum, B. infantis, B. longum, B. minimum, B. subtile, and B. thermophilum. This technique was applied to the identification of Bifidobacterium species isolated from 6 probiotic products, and four different Bifidobacterium spp. (B. bifidum, B. longum, B. infantis, and B. breve) were identified. The findings indicated that the 16S-23S rDNA gene-targeted species-specific PCR technique is a simple and reliable method for identification of bifidobacteria in probiotic products. PCR combined with Denaturing Gradient Gel Electrophoresis (DGGE) for identification of the bifidobacteria was also evaluated and compared with the gene-targeted species-specific technique. Results indicated that for fermented milk products consistency was found for both species-specific PCR and PCR-DGGE in detecting species. However, in some lyophilized products, the bands corresponding to these species were not visualized in the DGGE profile but the specific PCR gave a positive result.

Folate-Targeted Nanostructured Lipid Carriers (NLCs) Enhance (Letrozol) Efficacy in MCF-7 Breast Cancer Cells

  • Sabzichi, Mehdi;Mohammadian, Jamal;Khosroushahi, Ahmad Yari;Bazzaz, Roya;Hamishehkar, Hamed
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.12
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    • pp.5185-5188
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    • 2016
  • Objective: Targeted-drug-delivery based lipid nanoparticles has emerged as a new and effective approach in cancer chemotherapy. Here, we investigated the ability of folate-modified nanostructured lipid carriers (NLCs) to enhance letrozol (LTZ) efficacy in MCF-7 breast cancer cells. Methods: New formulations were evaluated regarding to particle size and scanning electron microscope (SEM) features. Anti-proliferative effects of LTZ loaded nanoparticles were examined by MTT assay. To understand molecular mechanisms of apoptosis and cell cycle progression, flow cytometric assays were applied. Results: Optimum size of nanoparticles was obtained in mean average of $98{\pm}7nm$ with a poly dispersity index (PDI) of 0.165. The IC50 value was achieved for LTZ was $2.2{\pm}0.2{\mu}M$. Folate-NLC-LTZ increased the percentage of apoptotic cells from 24.6% to 42.2% compared LTZ alone (p<0.05). Furthermore, LTZ loaded folate targeted NLCs caused marked accumulation of cells in the subG1 phase. Conclusion: Taken together, our results concluded that folate targeted LTZ can be considered as potential delivery system which may overcome limitations of clinical application of LTZ and improve drug efficacy in tumor tissue.

Genetic tests by next-generation sequencing in children with developmental delay and/or intellectual disability

  • Han, Ji Yoon;Lee, In Goo
    • Clinical and Experimental Pediatrics
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    • v.63 no.6
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    • pp.195-202
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    • 2020
  • Developments in next-generation sequencing (NGS) techogies have assisted in clarifying the diagnosis and treatment of developmental delay/intellectual disability (DD/ID) via molecular genetic testing. Advances in DNA sequencing technology have not only allowed the evolution of targeted panels but also, and more currently enabled genome-wide analyses to progress from research era to clinical practice. Broad acceptance of accuracy-guided targeted gene panel, whole-exome sequencing (WES), and whole-genome sequencing (WGS) for DD/ID need prospective analyses of the increasing cost-effectiveness versus conventional genetic testing. Choosing the appropriate sequencing method requires individual planning. Data are required to guide best-practice recommendations for genomic testing, regarding various clinical phenotypes in an etiologic approach. Targeted panel testing may be recommended as a firsttier testing approach for children with DD/ID. Family-based trio testing by WES/WGS can be used as a second test for DD/ID in undiagnosed children who previously tested negative on a targeted panel. The role of NGS in molecular diagnostics, treatment, prediction of prognosis will continue to increase further in the coming years. Given the rapid pace of changes in the past 10 years, all medical providers should be aware of the changes in the transformative genetics field.

TG-SPSR: A Systematic Targeted Password Attacking Model

  • Zhang, Mengli;Zhang, Qihui;Liu, Wenfen;Hu, Xuexian;Wei, Jianghong
    • KSII Transactions on Internet and Information Systems (TIIS)
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    • v.13 no.5
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    • pp.2674-2697
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    • 2019
  • Identity authentication is a crucial line of defense for network security, and passwords are still the mainstream of identity authentication. So far trawling password attacking has been extensively studied, but the research related with personal information is always sporadic. Probabilistic context-free grammar (PCFG) and Markov chain-based models perform greatly well in trawling guessing. In this paper we propose a systematic targeted attacking model based on structure partition and string reorganization by migrating the above two models to targeted attacking, denoted as TG-SPSR. In structure partition phase, besides dividing passwords to basic structure similar to PCFG, we additionally define a trajectory-based keyboard pattern in the basic grammar and introduce index bits to accurately characterize the position of special characters. Moreover, we also construct a BiLSTM recurrent neural network classifier to characterize the behavior of password reuse and modification after defining nine kinds of modification rules. Extensive experimental results indicate that in online attacking, TG-SPSR outperforms traditional trawling attacking algorithms by average about 275%, and respectively outperforms its foremost counterparts, Personal-PCFG, TarGuess-I, by about 70% and 19%; In offline attacking, TG-SPSR outperforms traditional trawling attacking algorithms by average about 90%, outperforms Personal-PCFG and TarGuess-I by 85% and 30%, respectively.

The Inhibition of Melanogenesis Via the PKA and ERK Signaling Pathways by Chlamydomonas reinhardtii Extract in B16F10 Melanoma Cells and Artificial Human Skin Equivalents

  • Lee, Ayeong;Kim, Ji Yea;Heo, Jina;Cho, Dae-Hyun;Kim, Hee-Sik;An, In-Sook;An, Sungkwan;Bae, Seunghee
    • Journal of Microbiology and Biotechnology
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    • v.28 no.12
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    • pp.2121-2132
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    • 2018
  • Abnormal melanin synthesis results in several hyperpigmentary disorders such as freckles, melanoderma, age spots, and other related conditions. In this study, we investigated the anti-melanogenic effects of an extract from the microalgae Chlamydomonas reinhardtii (CE) and potential mechanisms responsible for its inhibitory effect in B16F10, normal human epidermal melanocyte cells, and human skin-equivalent models. The CE extract showed significant dose-dependent inhibitory effects on ${\alpha}$-melanocyte-stimulating, hormone-induced melanin synthesis in cells. Additionally, the CE extract exhibited suppressive effects on the mRNA and protein expression of microphthalmia-associated transcription factor, tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2. The CE extract also inhibited the phosphorylation of protein kinase A and extracellular signal-related kinase, which function as upstream regulators of melanogenesis. Using a three-dimensional, reconstructed pigmented epidermis model, the CE-mediated, anti-pigmentation effects were confirmed by Fontana-Masson staining and melanin content assays. Taken together, CE extract can be used as an anti-pigmentation agent.