Regorafenib adjusted dose for Chilean patients with chemoresistant metastatic colorectal cancer: a case series

José Luis Leal, Juan Briones, Maria Elisa Herrera, Bettina Müller, Bruno Nervi and Sebastián Mondaca

https://ift.tt/2y6GqJn

Effect of Total Flavones from Cuscuta Chinensis on Anti-Abortion via the MAPK Signaling Pathway

For centuries, the Chinese herb Cuscuta chinensis has been applied clinically for abortion prevention in traditional Chinese medicine (TCM). Total flavones extracted from Cuscuta chinensis (TFCC) are one of the active components in the herb and also display anti-abortion effect similar to the unprocessed material. However, how TFCC exerts the anti-abortion effect remains largely unknown. In this study, we aim at characterizing the anti-abortion effects of TFCC and its underlying molecular mechanism in vitro and in vivo using human primary decidua cells and a mifepristone-induced abortion model in rat, respectively. The damage to the decidua caused by mifepristone in vivo was reversed by TFCC treatment in a dosage-dependent manner. High dosage of TFCC significantly upregulated the expression of estrogen receptor (ER), progesterone receptor (PR), and prolactin receptor (PRLR) in decidua tissue but downregulated the expression of p-ERK. Furthermore, we detected higher level of p-ERK and p-p38 in primary decidua cells from spontaneous abortion while treatment by TFCC downregulated their expression. Our results suggest TFCC mediates its anti-abortion effect by interfering with MAPK signaling pathway.

https://ift.tt/2QpJmIK

Lipemia Retinalis, Macular Edema, and Vision Loss in a Diabetic Patient with a History of Type IV Hypertriglyceridemia and Pancreatitis

Background: Lipemia retinalis is a rare but known complication of elevated serum triglycerides. This case describes the clinical course of a diabetic patient who presented with lipemia retinalis and macular edema, which responded to systemic and local treatments. Case Report: A 40-year-old female with a history of type II diabetes mellitus, hypertriglyceridemia, and pancreatitis presented with decreased vision in the left eye. She had peripapillary and macular edema, intraretinal hemorrhages, and prominent exudates in the setting of lipemia retinalis due to type IV hypertriglyceridemia. She was treated with serial intravitreal bevacizumab injections for macular edema and systemic lipid lowering therapy, and her visual acuity improved back to baseline. Conclusions: In the setting of lipemia retinalis and hypertriglyceridemia, the current patient developed macular edema and vision loss. The macular edema was treated with intravitreal injections of bevacizumab, and the patient experienced a rapid recovery of visual acuity.
Case Rep Ophthalmol 2018;9:425–430

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Cancers, Vol. 10, Pages 368: Gap Junction Intercellular Communication Positively Regulates Cisplatin Toxicity by Inducing DNA Damage through Bystander Signaling

Cancers, Vol. 10, Pages 368: Gap Junction Intercellular Communication Positively Regulates Cisplatin Toxicity by Inducing DNA Damage through Bystander Signaling

Cancers doi: 10.3390/cancers10100368

Authors: Sanjeevani Arora Joshua R. Heyza Elaine C. Chalfin Randall J. Ruch Steve M. Patrick

The radiation-induced bystander effect (RIBE) can increase cellular toxicity in a gap junction dependent manner in unirradiated bystander cells. Recent reports have suggested that cisplatin toxicity can also be mediated by functional gap junction intercellular communication (GJIC). In this study using lung and ovarian cancer cell lines, we showed that cisplatin cytotoxicity is mediated by cellular density. This effect is ablated when GJA1 or Connexin 43 (Cx43) is targeted, a gap junction gene and protein, respectively, leading to cisplatin resistance but only at high or gap junction forming density. We also observed that the cisplatin-mediated bystander effect was elicited as DNA Double Strand Breaks (DSBs) with positive H2AX Ser139 phosphorylation (γH2AX) formation, an indicator of DNA DSBs. These DSBs are not observed when gap junction formation is prevented. We next showed that cisplatin is not the “death” signal traversing the gap junctions by utilizing the cisplatin-GG intrastrand adduct specific antibody. Finally, we also showed that cells deficient in the structure-specific DNA endonuclease ERCC1-ERCC4 (ERCC1-XPF), an important mediator of cisplatin resistance, further sensitized when treated with cisplatin in the presence of gap junction forming density. Taken together, these results demonstrate the positive effect of GJIC on increasing cisplatin cytotoxicity.

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CMTR1-ALK: an ALK fusion in a patient with no response to ALK inhibitor crizotinib

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Longitudinal Progression Markers of Parkinson’s Disease: Current View on Structural Imaging

Abstract

Purpose of Review

Advances in neuroimaging techniques pave a rich avenue for in vivo progression biomarkers, which can objectively and noninvasively assess the long-term dynamic alterations in the brain of Parkinson's disease (PD) patients. This article reviews recent progress in structural magnetic resonance imaging (MRI) tools to track disease progression in PD, and discusses specific criteria a neuroimaging tool needs to meet to be a progression biomarker of PD and the potential applications of these techniques in PD based on current evidence.

Recent Findings

Recent longitudinal studies showed that quantitative structural MRI markers derived from T1-weighted, diffusion-weighted, neuromelanin-sensitive, and iron-sensitive imaging have the potential to track disease progression in PD. However, validation of these progression biomarkers is only beginning, and more work is required for multisite validation, the sample size for use in a clinical trial, and drug-responsiveness of most of these biomarkers. At present, the most clinical trial-ready biomarker is free-water diffusion imaging of the substantia nigra and seems well established to be used in disease-modifying studies in PD.

Summary

A variety of structural imaging biomarkers are promising candidates to be progression biomarkers in PD. Further studies are needed to elucidate the sensitivity, reliability, sample size, and effect of confounding factors of these progression biomarkers.

https://ift.tt/2xReeuH

Septic Encephalopathy

Abstract

Purpose of the Review

To discuss the diagnostic approach to patients with septic encephalopathy as well as the need for specific neuro-monitoring and the perspectives on future therapeutic approaches in this setting.

Recent Findings

Most of data-concern experimental studies evaluating the pathophysiology of septic encephalopathy. A combination of neurodegenerative pathways with neurovascular injury is the cornerstone for the development of such complication and the long-term neurological sequelae among survivors.

Summary

Septic encephalopathy is a common complication in septic patients. Clinical presentation may range from mild confusion and disorientation to convulsions and deep coma. The diagnosis of septic encephalopathy is made difficult by the lack of any specific clinical and non-clinical feature, in particular among sedated patients in whom neurological examination is unreliable. In spite of the high mortality rate associated with this condition, there is no prophylactic or targeted therapy to reduce or minimize brain damage in septic patients and clinical management is limited to the treatment of the underlying infection.

https://ift.tt/2NjwbXM