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Heat shock protein (Hsp)-27 is a small-sized, ATP-independent, chaperone molecule that is overexpressed under conditions of cellular stress such as oxidative stress and heat shock, and protects proteins from unfolding, thus facilitating proteostasis and cellular survival. Despite its protective role in normal cell physiology, Hsp27 overexpression in various cancer cell lines is implicated in tumor initiation, progression, and metastasis through various mechanisms, including modulation of the SWH pathway, inhibition of apoptosis, promotion of EMT, adaptation of CSCs in the tumor microenvironment and induction of angiogenesis. Investigation of the role of Hsp27 in the resistance of various cancer cell types against doxorubicin, herceptin/trastuzumab, gemcitabine, 5-FU, temozolomide, and paclitaxel suggested that Hsp27 overexpression promotes cancer cell survival against the above-mentioned chemotherapeutic agents. Conversely, Hsp27 inhibition increased the efficacy of those chemotherapy drugs, both in vitro and in vivo. Although numerous signaling pathways and molecular mechanisms were implicated in that chemotherapy resistance, Hsp27 most commonly contributed to the upregulation of Akt/mTOR signaling cascade and inactivation of p53, thus inhibiting the chemotherapy-mediated induction of apoptosis. Blockage of Hsp27 could enhance the cytotoxic effect of well-established chemotherapeutic drugs, especially in difficult-to-treat cancer types, ultimately improving patients’ outcomes.

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Cancer is a leading cause of death worldwide, with approximately 19 million new cases each year. Lately, several novel chemotherapeutic drugs have been introduced, efficiently inhibiting tumor growth and proliferation. However, developing a new drug is a time- and money-consuming process, requiring around 1 billion dollars and nearly ten years, with only a minority of the initially effective anti-cancer drugs experimentally finally being efficient in human clinical trials. Drug repurposing for cancer treatment is an optimal alternative as the safety of these drugs has been previously tested, and thus, in case of successful preclinical studies, can be introduced faster and with a lower cost into phase 3 clinical trials. Antipsychotic drugs are associated with anti-cancer properties and, lately, there has been an increasing interest in their role in cancer treatment. In the present review, we discussed in detail the in-vitro and in-vivo properties of the most common typical and atypical antipsychotics, along with their mechanism of action.

Aim: Traumatic brain injury (TBI) is a public health issue of increasing incidence. Coagulopathy after TBI is a frequent event, associated with a poor prognosis, and biomarkers that could predict coagulopathy occurrence are needed. The neutrophil-to-lymphocyte ratio (NLR) is useful as a cost-effective biomarker to assess prognosis and the need for cranial computed tomography in patients with mild TBI. As no study has yet evaluated the association of NLR with coagulopathy, we investigated whether the NLR at presentation could predict coagulopathy occurrence after TBI. Materials & methods: A retrospective study was conducted of patients aged >18 years who attended the emergency department (ED) with TBI, over a 3-year period. We included all patients for whom the NLR at presentation was available, and who underwent a brain CT scan. Results: The study included 173 patients (mean age 57.4 ± 21.1 years) with TBI, the most frequent cause of which was a fall. According to the Glasgow Coma Scale, 37 patients had severe TBI, 19 moderate and 117 mild TBI and 40 patients (23.1%) developed coagulopathy. Their mean NLR was 7.5 ± 6.7. Using receiver operating characteristic curve analysis, a cut-off value of 4.2 for NLR had 87.5% sensitivity and 52.9% specificity for predicting coagulopathy occurrence. Conclusion: Coagulopathy occurs frequently after TBI. This study investigated the value of NLR as a biomarker to predict coagulopathy occurrence, and concluded that NLR might be a novel and inexpensive biomarker for decision making in the management of TBI. Combination of NLR with other low-cost biomarkers and the clinical findings might further increase accuracy in the prediction of coagulopathy.

Purpose: The occurrence of coagulopathy in patients with traumatic brain injury (TBI) is related to severe complications. The authors performed the first systematic review to investigate whether biomarkers can predict the occurrence of hypocoagulopathy or progressive hemorrhagic injury in patients with TBI. Methods: The authors included studies that performed a receiver operating characteristics analysis for the biomarker and provided a clear value along with the respective sensitivity and specificity. Additionally, they attempted to classify each biomarker, taking into account its physiological role. Results: Twelve studies were included. All biomarkers were protein molecules, except in one study that examined the prognostic role of glucose. Copeptin had the highest sensitivity, and S100A12 had the highest specificity in predicting coagulopathy, while IL-33 had the highest sensitivity and GALECTIN-3 had the highest specificity in predicting progressive hemorrhagic injury. Conclusion: The study of the role of biomarkers in predicting the occurrence of coagulopathy in patients with TBI remains in its infancy.

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