Personalized Medicine Universe最新文献

Purpose

Syncope is a common clinical problem characterized by a transient, spontaneously self-terminating loss of consciousness with complete and prompt recovery, the cause of which is insufficiency of cerebral blood flow creating generalized anoxia, most commonly due to a transient fall of systemic arterial pressure to levels below those tolerated by the cerebrovascular autoregulation mechanism. A thorough evaluation of the underlying cause of syncope is warranted in all patients to precisely diagnose the underlying mechanism or cause in order to provide the appropriate treatment of syncope since it is challenging for many reasons. The purpose of this review on syncope is to provide a thorough differential diagnosis as to the underlying cardiac and non-cardiac causes with methods of assessment of the specific causes. Knowledge of the specific cause, especially in the setting of structural heart disease or primary electrical cardiac disease, has an increased incidence of sudden death and overall mortality. It is also important to establish whether or not syncope is due to orthostatic hypotension since it is associated with a twofold increased mortality, whereas those individuals with neurally mediated syncope have an excellent prognosis.

Purpose

Hepatocellular carcinoma (HCC) is one of the most common malignant neoplasms and is associated with a poor survival rate. An increased understanding of the molecular mechanisms underlying HCC carcinogenesis and progression has enabled the identification of many potential HCC biomarkers. In addition to predicting prognosis and recurrence, these markers may guide decisions regarding therapeutic intervention of potential targets and appropriate therapeutic modalities for individual patients. Considering the high recurrence rate associated with HCC resection, improved biomarkers that can be used for early diagnosis, predicting recurrence, and monitoring progression are urgently needed in clinical practice.

Study section and results

This systematic review examines evidence from published studies that have reported emerging prognostic biomarkers, paying particular attention to markers evaluated by histopathological analysis of resected HCC tissues. These markers include molecules involved in cellular proliferation and survival (e.g. cyclins and cyclin dependent kinase inhibitors, mutant p53, and hepatocyte growth factor receptor [c-MET]), aberrantly expressed cell surface proteins (e.g. glypican 3, monocarboxylate transporter 4, and hepatocyte growth factor activator inhibitor type 1), and factors found in altered tumor microenvironments (e.g. angiogenesis factors, regulatory T-cells, tumor-associated macrophages, and hepatic stellate cells).

Conclusion

Identification of novel, effective biomarkers for the diagnosis and prognosis of HCC is critical for the improvement of companion diagnostics in personalized oncology therapies for HCC. The molecules described in this review are attractive candidates for future HCC biomarkers to be used in clinical oncology practice.

Purpose

We synthesized the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) with cyclopropane rings instead of cis-double bonds. Here, we introduce DCP-LA as a novel anti-dementia drug.

Study section and results

DCP-LA selectively and directly activated protein kinase C-ε (PKCε) to enhance the activity of presynaptic α7 acetylcholine (ACh) receptors by promoting receptor translocation to the cell surface and increasing presynaptic glutamate release. This action of DCP-LA caused a long-lasting facilitation of hippocampal synaptic transmission, which improved learning and memory impairments in animal models.

Conclusion

DCP-LA could be developed as a promising anti-dementia drug, offering new hope for treating dementias including Alzheimer disease.

Purpose

Evidence has shown that extracellular adenosine induces apoptosis in variety of cancer cells, mainly through two pathways: an intrinsic pathway relative to adenosine uptake into the cells, and an extrinsic pathway involving the adenosine receptors. We elucidated the mechanisms underlying the adenosine-induced anticancer effects.

Study section and results

Extrinsic pathway analysis showed that extracellular adenosine induces apoptosis in CW2 human colon cancer and RCR-1 rat astrocytoma cells through the A₁ adenosine receptor; in Caco-2 human colon cancer and HepG2 human hepatoma cells through the A_2a adenosine receptor; and through the A₃ adenosine receptor in A549, Lu-65, and SBC-3 human lung cancer cells, RCC4-VHL human renal cancer cells, 5637 human bladder cancer cells, and human malignant pleural mesothelioma cells. In the intrinsic pathways, intracellularly transported adenosine induces apoptosis in GT3-TKB human lung cancer cells, human malignant pleural mesothelioma cells, HuH-7 and HepG2 human hepatoma cells, and MCF-7 human breast cancer cells by a) activating AMPK, b) upregulating p53, c) downregulating c-FLIP expression, d) neutralizing caspase-3 inhibition due to inhibition of apoptosis protein (IAP) in cooperation with DIABLO, e) accumulating AMID in the nucleus, f) regulating apoptosis-related gene transcription, or g) promoting GATA-2-regulated p53 gene transcription.

Conclusions

Adenosine exerts its anticancer action on a wide variety of cancer cell types through diverse signaling pathways. Therefore, adenosine and its signaling cascades can be useful as possible targets in the development of promising anticancer therapies.

With the emergence of molecularly targeted drugs, the phrase “personalized medicine” has recently become frequently used in the medical community. This phrase basically refers to treatments based on the selection of optimum therapies for individual patients but it can also include treatments based on the integration of various new technologies to enhance clinical care. Interest in personalized medicine will likely continue to increase in the future. Given the rapid advances in molecular biology, genetic engineering, biotechnology, and related sciences, personalized medicine is closer to realization but continues to face many issues.

In recent years, the word “strategy” has become an everyday term, especially in phrases such as “management strategy” and “government strategy”. Strategy generally refers to the art or science of coordinated effort and resource management with a long-term perspective and a multifaceted approach in order to reach a specific goal. When translated into the specific context of medical treatment, strategy refers to the methods of preparing, planning, and managing medical treatment from a long-term and overall perspective and would thus seem to be distinct from medical practice, which represents the concrete execution of strategy. Because strategy will likely hold particular importance in the field of personalized medicine, I would like to present an overview of strategy in this field and also draw on my own experience.

Purpose

Emerging evidence has indicated that the sphingolipid sphingosine is involved in cellular differentiation, cell growth, and apoptosis. Here, we elucidated the sphingosine signaling pathways underlying apoptosis and cell growth inhibition.

Study section and results

Sphingosine induced mitochondria-mediated apoptosis in rat hippocampal neurons and astrocytes by activating caspase-3/-9 via the sphingosine-dependent protein kinase (SDK)/14-3-3 protein/Bax/cytochrome c pathway. This may account for the implication of sphingosine/SDK in the pathogenesis of Alzheimer's disease. Additionally, sphingosine induced apoptosis in MKN-28 human gastric cancer cells in an SDK-dependent manner. In the human malignant pleural mesothelioma cell lines, sphingosine suppressed cell growth by arresting the cell cycle at the G₀/G₁ phase, along with inhibiting protein kinase Cδ (PKCδ). This suggests that sphingosine/SDK/PKCδ signaling can be potentially used in treating many types of cancers.

Conclusion

The present review shows that sphingosine induces apoptosis and inhibits the cell cycle by targeting SDK and PKCδ. Our findings represent a fresh insight into sphingosine signaling pathways, and may provide a blueprint for developing drugs for treating Alzheimer's disease and many types of cancers.