Personalized molecular testing for therapeutic guidance in Taiwan.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22067-e22067
Author(s):  
Kang-Yi Su ◽  
Sung-Liang Yu

e22067 Background: Personalized cancer therapy is based on the precept that detail molecular characterization of tumors as well as tumor microenvironment will enable tailored therapies to improve outcomes and decrease toxicity. The goal of personalized therapy is to target aberrations driving tumor growth and prolongs survival, by administering the right drug combination for the right person. However, several practical and technological challenges including tumor heterogeneity, molecular evolution, costs and morbidity of biopsies as well as technical limitation critical for molecular testing. In addition, development of biomarkers should be considered all aspects of drug development, from discovery through to clinical trials. Methods: In Taiwan, we have established a well-qualified reference laboratory with ISO15189 certification for molecular testing of personalized therapy in clinical practice. Based on our innovation, we utilized DNA mass spectrometry platform to develop high sensitive EGFR mutation identification system. Recently, KRAS, BRAF, HER2 together with EGFR were also combined into multiplex gene testing for biomarker-assessed therapeutic decision. To this end, the National Science Council of Taiwan government had supported this project through NRPB (National Research Program of Biopharmaceutical) at the middle of 2011. This facility performed selected molecular tests for cancer patients from medical centers and regional hospitals. Results: A specific program had also been implemented to anticipate the launch of molecular targeting therapy (MTT) and reduce time-to-assess to MTT drugs and experimental therapies. From Jane 2011 to Dec 2012, more than 2,500 patients with lung cancer in Taiwan benefited from this facility. Conclusions: The Taiwan nationwide initiative for tumor molecular profiling is a tool to fight inequalities in access to molecular testing and target therapy, and demonstrates that molecular stratification of tumor for therapeutic decisions is a cost-effective strategy that can be integrated into the national health-care system.

2017 ◽  
Vol 8 (2-3) ◽  
pp. 31-45 ◽  
Author(s):  
Abir Al Said ◽  
Breda Cushen ◽  
Richard W Costello

The asthma syndrome has many manifestations, termed phenotypes, that arise by specific cellular and molecular mechanisms, termed endotypes. Understanding an individual’s asthma phenotype helps clinicians make rational therapeutic decisions while the understanding of endotypes has led to the development of specific precision medications. Allergic asthma is an example of an asthma phenotype and omalizumab, a monoclonal antibody that neutralizes serum immunoglobulin (Ig)E, is a specific targeted treatment which was developed as a result of an understanding of the endotype of allergic asthma. Omalizumab has been widely used in clinical practice in Europe for over a decade as an add-on therapy to treat patients who have severe refractory allergic asthma. Over this period, many centres have reported their experience with omalizumab as an add-on therapy in patients with severe asthma. These ‘real world’ clinical effectiveness studies have confirmed the benefits, cost-effectiveness and clinical utility of this medication. Combining the outcomes of both sources of research has yielded important insights that may benefit patients with severe asthma, clinicians who treat them, as well as the funding agencies that reimburse the cost of this medication. The purpose of this review is to describe how to identify and evaluate a patient with asthma for whom treatment with omalizumab may be of clinical and cost-effective benefit. The assessment and investigations used to confirm allergic asthma, the objective assessment of adherence to asthma therapy and the expected benefits of add-on omalizumab treatment are described.


2014 ◽  
Vol 138 (12) ◽  
pp. 1611-1628 ◽  
Author(s):  
Kai Zhang ◽  
Hongbin Deng ◽  
Philip T. Cagle

Context Immunohistochemistry has become an indispensable ancillary tool for the accurate classification of pleuropulmonary and mediastinal neoplasms necessary for therapeutic decisions and predicting prognostic outcome in the era of personalized medicine. Diagnostic accuracy has significantly improved because of the continuous discoveries of tumor-associated biomarkers and the development of effective immunohistochemical panels. Objective To increase the accuracy of diagnosis and classify pleuropulmonary neoplasms through immunohistochemistry. Data Sources Literature review, authors' research data, and personal practice experience. Conclusions This review article has shown that appropriately selecting immunohistochemical panels enables pathologists to effectively diagnose most primary pleuropulmonary neoplasms and differentiate primary lung tumors from a variety of metastatic tumors to the lung. The discovery of new mutation-specific antibodies identifying a subset of specific gene-arranged lung tumors provides a promising alternative and cost-effective approach to molecular testing. Knowing the utilities and pitfalls of each tumor-associated biomarker is essential to avoiding potential diagnostic errors.


2018 ◽  
Vol 24 (1) ◽  
pp. 266-294 ◽  
Author(s):  
Amgad Badewi ◽  
Essam Shehab ◽  
Jing Zeng ◽  
Mostafa Mohamad

Purpose The purpose of this paper is to answer two research questions: what are the ERP resources and organizational complementary resources (OCRs) required to achieve each group of benefits? And on the basis of its resources, when should an organization invest more in ERP resources and/or OCRs so that the potential value of its ERP is realised? Design/methodology/approach Studying 12 organizations in different countries and validating the results with 8 consultants. Findings ERP benefits realization capability framework is developed; it shows that each group of benefits requires ERP resources (classified into features, attached technologies and information technology department competences) and OCRs (classified into practices, attitudes, culture, skills and organizational characteristics) and that leaping ahead to gain innovation benefits before being mature enough in realising a firm’s planning and automation capabilities could be a waste of time and effort. Research limitations/implications It is qualitative study. It needs to be backed by quantitative studies to test the results. Practical implications Although the “P” in ERP stands for planning, many academics and practitioners still believe that ERP applies to automation only. This research spotlights that the ability to invest in ERP can increase the innovation and planning capabilities of the organization only if it is extended and grown at the right time and if it is supported by OCRs. It is not cost effective to push an organization to achieve all the benefits at the same time; rather, it is clear that an organization would not be able to enjoy a higher level of benefits until it achieves a significant number of lower-level benefits. Thus, investing in higher-level benefit assets directly after an ERP implementation, when there are no organizational capabilities available to use these assets, could be inefficient. Moreover, it could be stressful to users when they see plenty of new ERP resources without the ability to use them. Although it could be of slight benefit to introduce, for example, business intelligence to employees in the “stabilizing period” (Badewi et al., 2013), from the financial perspective, it is a waste of money since the benefits would not be realised as expected. Therefore, orchestrating ERP assets with the development of organizational capabilities is important for achieving the greatest effectiveness and efficiency of the resources available to the organization. This research can be used as a benchmark for designing the various blueprints required to achieve different groups of benefits from ERP investments. Originality/value This research addresses two novel questions: RQ1: what are the ERP resources and OCRs required to achieve the different kinds of ERP benefits? RQ2: when, and on what basis, should an organization deploy more resources to leverage the ERP business value?


2021 ◽  
pp. 1-36
Author(s):  
Vahideh Angardi ◽  
Ali Ettehadi ◽  
Özgün Yücel

Abstract Effective separation of water and oil dispersions is considered a critical step in the determination of technical and economic success in the petroleum industry over the years. Moreover, a deeper understanding of the emulsification process and different affected parameters is essential for cost-effective oil production, transportation, and downstream processing. Numerous studies conducted on the concept of dispersion characterization indicate the importance of this concept, which deserves attention by the scientific community. Therefore, a comprehensive review study with critical analysis on significant concepts will help readers follow them easily. This study is a comprehensive review of the concept of dispersion characterization and conducted studies recently published. The main purposes of this review are to 1) Highlight flaws, 2) Outline gaps and weaknesses, 3) Address conflicts, 4) Prevent duplication of effort, 5) List factors affecting dispersion. It was found that the separation efficiency and stability of dispersions are affected by different chemical and physical factors. Factors affecting the stability of the emulsions have been studied in detail and will help to look for the right action to ensure stable emulsions. In addition, methods of ensuring stability, especially coalescence are highlighted, and coalescence mathematical explanations of phenomena are presented.


2011 ◽  
Vol 135 (1) ◽  
pp. 67-82 ◽  
Author(s):  
Anne Igbokwe ◽  
Dolores H. Lopez-Terrada

Abstract Context—Molecular testing of solid tumors is steadily becoming a vital component of the contemporary anatomic pathologist's armamentarium. These sensitive and specific ancillary tools are useful for confirming ambiguous diagnoses suspected by light microscopy and for guiding therapeutic decisions, assessing prognosis, and monitoring patients for residual neoplastic disease after therapy. Objective—To review current molecular biomarkers and tumor-specific assays most useful in solid tumor testing, specifically of breast, colon, lung, thyroid, and soft tissue tumors, malignant melanoma, and tumors of unknown origin. A few upcoming molecular diagnostic assays that may become standard of care in the near future will also be discussed. Data Sources—Original research articles, review articles, and the authors' personal practice experience. Conclusions—Molecular testing in anatomic pathology is firmly established and will continue to gain ground as the need for more specific diagnoses and new targeted therapies evolve. Knowledge of the more common and clinically relevant molecular tests available for solid tumor diagnosis and management, and their indications and limitations, is necessary if anatomic pathologists are to optimally use these tests and act as consultants for fellow clinicians directly involved in patient care.


2018 ◽  
Vol 8 (12) ◽  
pp. 2406 ◽  
Author(s):  
Hamed Saghafi ◽  
Mohamad Fotouhi ◽  
Giangiacomo Minak

This paper reviews recent works on the application of nanofibers and nanoparticle reinforcements to enhance the interlaminar fracture toughness, to reduce the impact induced damage and to improve the compression after impact performance of fiber reinforced composites with brittle thermosetting resins. The nanofibers have been mainly used as mats embedded between plies of laminated composites, whereas the nanoparticles have been used in 0D, 1D, 2D, and 3D dimensional patterns to reinforce the matrix and consequently the composite. The reinforcement mechanisms are presented, and a comparison is done between the different papers in the literature. This review shows that in order to have an efficient reinforcement effect, careful consideration is required in the manufacturing, materials selection and reinforcement content and percentage. The selection of the right parameters can provide a tough and impact resistant composite with cost effective reinforcements.


2008 ◽  
Vol 136 (11-12) ◽  
pp. 654-657
Author(s):  
Dragan Sagic ◽  
Zelimir Antonic ◽  
Stevo Duvnjak ◽  
Miodrag Peric ◽  
Branko Petrovic ◽  
...  

INTRODUCTION The sciatic artery represents the earliest embryological blood supply to the lower extremity. It regresses after the 3rd month of embryologic development. The proximal part of the sciatic artery eventually persists as the inferior gluteal artery. Rarely, however, it persists into adulthood when it is frequently associated with numerous possible complications (aneurysm formation, embolism, nerve compression, rupture, thrombosis). CASE OUTLINE In March 1996, a 48-year-old male was admitted for angiography of the blood vessels of the right inferior extremity, before an elective orthopaedic procedure. Arteriography of the right leg was done in a usual manner through the right common femoral artery in order to get an angiogram of the popliteal trifurcation and crural arteries. However, on the first field we noticed a hypoplastic superficial femoral artery, as well as a huge persistent sciatic artery (PSA) originating from the internal iliac artery running distally and overlapping the deep femoral artery. There were no aneurysm and stenotic changes of PSA. CONCLUSION If clinical condition is stable, follow-ups at 12 months intervals should be done by means of ultrasound. The therapeutic decisions also depend on complete or incomplete PSA.


2021 ◽  
Vol 27 ◽  
Author(s):  
Attila Mokánszki ◽  
Emese Sarolta Bádon ◽  
Anikó Mónus ◽  
László Tóth ◽  
Nóra Bittner ◽  
...  

Pathogenic molecular features gained specific significance in therapeutic decisions in lung carcinoma in the past decade. Initial and follow up genetic testing requres appropriate amounts and quality of tumor derived DNA, but tumor sampling, especially for disease monitoring is generally limited. Further to the peripheral blood (PB), samples from pleural fluid, accumulating in diverse lung processes might serve as an alternative source for cell-free DNA (cfDNA) for genetic profiling. In our study, cfDNA isolated from the pleural effusion and from the PB, and genomic DNA (gDNA) obtained from tissue/cellular samples were analyzed and compared from altogether 65 patients with pulmonary disease, including 36 lung adenocarcinomas. The quantity of effusion cfDNA yield appeared to be significantly higher compared to that from simultaneously collected PB plasma (23.2 vs. 4.8 ng/μl, p < 0.05). Gene mutations could be safely demonstrated from the effusion cfDNA fraction obtained from adenocarcinoma patients, 3/36 EGFR, 9/36 KRAS and 1/36 BRAF gene variants were detected. In this series, 9/13 samples showed an effusion+/plasma-mutational status, while only 1/13 samples presented with the opposite findings (effusion-/plasma+). gDNA analysis from sediment cell blocks from the identical effusion sample was surprisingly ineffective for lung adenocarcinoma profiling due to the low DNA yield. In conclusion, the cell free supernatant of pleural effusions appears to concentrate cancer derived cfDNA and seems to be particularly suitable for serial genotyping of pulmonary adenocarcinoma.


Thorax ◽  
2021 ◽  
Vol 76 (3) ◽  
pp. 281-291 ◽  
Author(s):  
Tendai Mugwagwa ◽  
Ibrahim Abubakar ◽  
Peter J White

BackgroundDespite progress in TB control in low-burden countries like England and Wales, there are still diagnostic delays. Molecular testing and/or whole-genome sequencing (WGS) provide more rapid diagnosis but their cost-effectiveness is relatively unexplored in low-burden settings.MethodsAn integrated transmission-dynamic health economic model is used to assess the cost-effectiveness of using WGS to replace culture-based drug-sensitivity testing, versus using molecular testing versus combined use of WGS and molecular testing, for routine TB diagnosis. The model accounts for the effects of faster appropriate treatment in reducing transmission, benefiting health and reducing future treatment costs. Cost-effectiveness is assessed using incremental net benefit (INB) over a 10-year horizon with a quality-adjusted life-year valued at £20 000, and discounting at 3.5% per year.ResultsWGS shortens the time to drug sensitivity testing and treatment modification where necessary, reducing treatment and hospitalisation costs, with an INB of £7.1 million. Molecular testing shortens the time to TB diagnosis and treatment. Initially, this causes an increase in annual costs of treatment, but averting transmissions and future active TB disease subsequently, resulting in cost savings and health benefits to achieve an INB of £8.6 million (GeneXpert MTB/RIF) or £11.1 million (Xpert-Ultra). Combined use of Xpert-Ultra and WGS is the optimal strategy we consider, with an INB of £16.5 million.ConclusionRoutine use of WGS or molecular testing is cost-effective in a low-burden setting, and combined use is the most cost-effective option. Adoption of these technologies can help low-burden countries meet the WHO End TB Strategy milestones, particularly the UK, which still has relatively high TB rates.


2012 ◽  
Vol 136 (12) ◽  
pp. 1585-1592 ◽  
Author(s):  
Alexis B Carter

Laboratory tests performed by molecular methods are increasing in volume and complexity at an unprecedented rate. Molecular tests have a broad set of applications, and most recently have been advocated as the mechanism by which providers can further tailor treatments to the individual patient. As the momentum behind molecular testing continues to increase, pathology practices may find themselves unprepared for the new wave of molecular medicine. This special article has been developed in an effort to provide pathologists who have limited molecular training with a simple and quick algorithm for determining whether a requested molecular test is appropriate for a patient. Additional recommendations for a more intensive and proactive review and management of molecular requests also are included. The principles discussed can easily be applied to requests for any test, including those not using molecular methods, which would be sent to an outside reference laboratory. This special article was developed from a Webinar for the College of American Pathologists targeting education for pathologists about the transformation of pathology practice in the new molecular and digital age.


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