Personalized Medicine Universe最新文献

Purpose

Drug development has often occurred serendipitously, rather than by using rational approaches. Drug repositioning is an approach that can exploit serendipitous features of a licensed drug.

Study selection and results

Drug repositioning has mainly been used to develop anti-tumor drugs. There are two approaches, drug-based and non-drug-based. The drug-based method develops new drugs using information related to drug function, cohort studies, or side effects. This approach identified anti-tumor drugs, including alpha-1 blockers, HIV-1 protease inhibitors, and metformin. On the other hand, the non-drug-based approach aims to identify drugs using drug libraries and an appropriate assay for each disease. This approach is similar to traditional drug development methods.

Discussions and conclusions

Drug repositioning approaches have enabled our group and others to identify novel anti-tumor drugs. Therefore, drug repositioning can be useful in the development of promising anticancer therapies.

Purpose

Hypoxia inducible factor-1α (HIF-1α) and NF-E2-related factor-2 (Nrf2) play central roles in intracellular defense against hypoxia and oxidative stress, respectively. The two stresses are common factors in a variety of disorders, including cardiovascular disease and cancer. In addition, the two stresses occur in succession under ischemia-reperfusion in the context of ischemic cardiovascular disease or organ transplantation. Elucidation of the crosstalk between hypoxic response and oxidative stress response will be beneficial for the treatment of these diseases.

Study selection and results

This review focuses on the molecular crosstalk between the two stress responses, and introduces our findings about the protein factors and chemical compounds that regulate HIF-1α and Nrf2. Cellular stress response (CSR) and small Maf protein G (MafG), both of which act in response to oxidative stress, were found to contribute to the stabilization of HIF-1α. Furthermore, Nrf2 was suppressed under hypoxia in a manner independent of Keap1, which is a primary regulatory pathway for Nrf2, and seven in absentia homolog 2 (Siah2) was identified as a new regulator of Nrf2. Siah2 is a ubiquitin ligase of the prolyl hydroxylase domain containing protein (PHD), which contributes to the degradation of HIF-1α, suggesting that Siah2 regulates both hypoxic and oxidative stress responses. This review also introduces the regulation of HIF-1α and Nrf2 by phenolic compound, bisphenol A (BPA).

Conclusions

Hypoxic and oxidative stress responses are regulated by common factors and are closely linked to each other.

Next-generation sequencing has revealed the genomic landscapes of human cancers and has strengthened the claim that TP53 is the most frequently mutated gene in human cancers. In this review, we intend to clarify the molecular mechanisms underlying the tumor suppressive functions of p53 and understand the involvement of the p53 signaling pathway in tumorigenesis. One of the major goals of this review is to guide the development of more effective approaches for reducing cancer prevalence and fatality.

Objective

This paper presents an innovative idea of applying a hybrid ensemble technique i.e. ensemble of ensemble methods for improving the predictive performance of Artificial intelligence based system for screening of cervical cancer by characterization and classification of Pap smear images.

Methodology

Papanicolaou smear (also referred to as Pap smear) is a microscopic examination of samples of human cells scraped from the lower, narrow part of the uterus, called the cervix. A sample of cells after being stained by using Papanicolaou method is analyzed under microscope for the presence of any unusual developments indicating any precancerous and potentially precancerous changes. Abnormal findings, if observed are subjected to further precise diagnostic subroutines. Examining the cell images for abnormalities in the cervix provides grounds for provision of prompt action and thus reducing incidence and deaths from cervical cancer. It is the most popular technique used for screening of cervical cancer. Pap smear test, if done with a regular screening programs and proper follow-up, can reduce cervical cancer mortality by up to 80% [1]. The contribution of this paper is that we have pioneered to apply hybrid ensemble technique to screen cervical cancer by classification of Pap smear data. The hybrid ensemble designed in this work has also presented an idea to use an ensemble of ensemble techniques. Using such a technique, the classification potentials of individual algorithms are fused together to gain greater classification accuracy. In addition to this we have also presented a comparative analysis of various artificial intelligence based algorithms for screening of cervical cancer.

Results

The results indicate that hybrid ensemble technique is an efficient method for classification of Pap smear images and hence can be effectively used for diagnosis of cervical cancer. Among all the algorithms implemented, the hybrid ensemble approach outperformed & expressed an efficiency of about 96% for 2-class problem and about 78% for 7-class problem. The results when compared with the all the standalone classifiers were significantly better for both 2-class and 7-class problems.

Background

Psychotropic medications are widely used to treat a variety of mental disorders, but a unifying explanation of their modes of action remains obscure.

Objective

To examine the limitations of existing models of psychotropic drug action, and to propose an integrative, patient-oriented model that explains the wide spectrum of actions of psychotropic medications.

Method

The traditional “disease-centered” model of psychotropic action, and its most logical contemporary alternative, the “drug-centered” model – are critically analysed, and their limitations identified. An alternate model, which acknowledges the importance of patient-related factors in determining drug effects is outlined. The two processes involved in this model, and the evidence in its support, are explained at length with reference to specific psychiatric disorders.

Conclusion

The patient-centered model proposed in this paper, though provisional, provides a broad-based, unified framework for understanding the actions of psychotropic drugs, and can enhance clinical practice and research.

Aims

Jidabokuippo (JDI) is a traditional Japanese medicine used for alleviating contusion-induced swelling and pain. Usually, nonsteroidal anti-inflammatory drugs (NSAIDs) are used for the treatment of swelling and pain associated with fractures of the extremities. However, one disadvantage of NSAIDs use is their potential to cause gastrointestinal problems, even in patients concomitantly treated with anti-ulcer drugs. In this study, we assessed the effectiveness of JDI in patients with fractures of the extremities.

Methods

Fifty patients (15 men and 35 women) with fractures of the extremities were recruited into the study. All participants were treated using non-invasive methods and administered JDI alone within 3 days of injury. The effectiveness of JDI was assessed following administration by evaluating the need for NSAIDs or other medication. In addition, adverse reactions were monitored.

Results

Comorbidities were present in 42% of the study participants. The mean duration of treatment was 9.9 ± 6.7 days (range 1–35 days). Forty-four patients did not require any medication other than JDI, testifying to its effectiveness. Five participants had their medication switched to NSAIDs, and one patient had eppikajutsuto added to the JDI treatment. In summary, 90% of the patients were effectively treated with traditional Japanese medicines. No adverse reactions were observed.

Conclusion

This study suggests that JDI can be used more widely for fractures of the extremities.

Personalized medicine is that branch of medicine whereby a patient's treatment and prognosis are based on his genes. Recent genetic research explains the variations and similarities between humans, their diseases, and their responses to various treatments. Because governments and universities have not set strict standards, there are numerous tests and kits available to detect genetic problems. But are these kits accurate? The validity of some biomarkers is suspect.

The ethics of personalized medicine became an issue when some laboratory tests resulted in women incorrectly having been told that they have a high risk of breast or ovarian cancer when they did not. Ethical issues are not confined to the utilization of genetic information, but can be raised with the acquisition of human material for the advancement of knowledge. Whose genes are these? Who owns your DNA?

In the US, patients are given prenatal genetic advice upon which they can decide for themselves how to proceed. But in Russia, patients have no choice. The state makes most decisions. Selective breeding would be unacceptable in western countries.