investigating-alterations-caecum-microbiota-after-traumatic-brain

Investigating Alterations in Caecum Microbiota After Traumatic Brain Injury in Mice

Increasing evidence shows that the microbiota-gut-brain axis plays an important role in the pathogenesis of brain diseases. Several studies also ...

Zhejiang University

Chemotherapy is the only choice for most of the advanced hepatocellular carcinoma (HCC) patients, while few agents were available, making it an urgent need to develop new chemotherapy strategies. A phase II clinical trial suggested that the efficacy of irinotecan in HCC was limited due to dose-dependent toxicities. Here, we found that gefitinib exhibited synergistic activity in combination with SN-38, an active metabolite of irinotecan, in HCC cell lines. And the enhanced apoptosis induced by gefitinib plus SN-38 was a result from caspase pathway activation. Mechanistically, gefitinib dramatically promoted the ubiquitin-proteasome-dependent degradation of Rad51 protein, suppressed the DNA repair, gave rise to more DNA damages, and ultimately resulted in the synergism of these two agents. In addition, the increased antitumor efficacy of gefitinib combined with irinotecan was further validated in a HepG2 xenograft mice model. Taken together, our data demonstrated for the first time that the combination of irinotecan and gefitinib showed potential benefit in HCC, which suggests that Rad51 is a promising target and provides a rationale for clinical trials investigating the efficacy of the combination of topoisomerase I inhibitors and gefitinib in HCC. 

Gefitinib Synergizes with Irinotecan to Suppress Hepatocellular Carcinoma via Antagonizing Rad51-Mediated DNA-Repair.

Capecitabine, as the first-line treatment for multiple tumor types, has a serious drawback of hand-foot-syndrome (HFS) that limits its clinical use. However, the pathophysiology and mechanism of capecitabine-induced HFS is rarely known. Here we built the experimental mouse model of HFS induced by capecitabine at first and it was shown that 3 of 6 mice appeared HFS in the 5th day and 5 mice occurred HFS in the 30th day. The corneous layer was reduced in capecitabine-induced HFS in vivo. Moreover, we found that capecitabine could significantly induce keratinocytes cells death in vitro through activated apoptosis pathway and decreased mitochondrial membrane potential. In conclusion, these results suggested that HFS of capecitabine may be developed from reduction of corneous layer through stimulation of intracellular mitochondrial dysfunction following activation of caspase-dependent apoptosis pathway.

The contribution of keratinocytes in capecitabine-stimulated hand-foot-syndrome.

Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumour and has poor prognosis. Currently, systematic chemotherapy is the only approach to prolong survival. Thus the development of new treatment regimens is urgently needed to improve the therapeutic efficacy. Our study intended to assess the combination of dasatinib and irinotecan against HCC and made an effort to develop a potential medical choice for advanced HCC patients.

Dasatinib synergises with irinotecan to suppress hepatocellular carcinoma via inhibiting the protein synthesis of PLK1.

Chronic subdural hematoma (CSDH) is a common disease in neurosurgical practice with substantial recurrence rate. We aimed to estimate recurrence rate of CSDH and to identify risk factors for CSDH recurrence.

Prevalence of and risk factors for recurrence of chronic subdural hematoma.

Hyperbaric oxygen therapy (HBOT) is an efficient therapeutic option to improve progress of lots of diseases especially hypoxia-related injuries, and has been clinically established as a wide-used therapy for patients with carbon monoxide poisoning, decompression sickness, arterial gas embolism, problematic wound, and so on. In the liver, most studies positively evaluated HBOT as a potential therapeutic option for liver transplantation, acute liver injury, nonalcoholic steatohepatitis, fibrosis and cancer, especially for hepatic artery thrombosis. This might mainly attribute to the anti-oxidation and anti-inflammation of HBOT. However, some controversies are existed, possibly due to hyperbaric oxygen toxicity. This review summarizes the current understandings of the role of HBOT in liver diseases and hepatic regeneration. Future understanding of HBOT in clinical trials and its in-depth mechanisms may contribute to the development of this novel adjuvant strategy for clinical therapy of liver diseases.

Hyperbaric Oxygen Therapy in Liver Diseases.

Hypopituitarism is a common but potentially undiagnosed complication in patients who suffer traumatic brain injury (TBI). The identification of risk factors of hypopituitarism after TBI is vital to establish a rational testing approach for these patients.

Article	Year
Gefitinib Synergizes with Irinotecan to Suppress Hepatocellular Carcinoma via Antagonizing Rad51-Mediated DNA-Repair. PloS one\| PubMed ID: 26752698	2016
The contribution of keratinocytes in capecitabine-stimulated hand-foot-syndrome. Environmental toxicology and pharmacology\| PubMed ID: 27951409	2017
Dasatinib synergises with irinotecan to suppress hepatocellular carcinoma via inhibiting the protein synthesis of PLK1. British journal of cancer\| PubMed ID: 28267710	2017
Prevalence of and risk factors for recurrence of chronic subdural hematoma. Acta neurochirurgica\| PubMed ID: 29532258	2018
Hyperbaric Oxygen Therapy in Liver Diseases. International journal of medical sciences\| PubMed ID: 30008587	2018
Risk Factors for Anterior Hypopituitarism in Patients With Traumatic Brain Injury. The Journal of craniofacial surgery\| PubMed ID: 30950947	2019

Yuanrun Zhu

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