Curcumin-induced HDAC inhibition and attenuation of medulloblastoma growth <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis>

Background  

Medulloblastoma is the most common brain tumor in children, and its prognosis is worse than for many other common pediatric cancers. Survivors undergoing treatment suffer from serious therapy-related side effects. Thus, it is imperative to identify safer, effective treatments for medulloblastoma. In this study we evaluated the anti-cancer potential of curcumin in medulloblastoma by testing its ability to induce apoptosis and inhibit tumor growth in vitro and in vivo using established medulloblastoma models.     

Dexamethasone inhibits the HSV-<Emphasis Type="Italic">tk</Emphasis>/ ganciclovir bystander effect in malignant glioma cells

Background  

HSV-tk/ganciclovir (GCV) gene therapy has been extensively studied in the setting of brain tumors and largely relies on the bystander effect. Large studies have however failed to demonstrate any significant benefit of this strategy in the treatment of human brain tumors. Since dexamethasone is a frequently used symptomatic treatment for malignant gliomas, its interaction with the bystander effect and the overall efficacy of HSV-TK gene therapy ought to be assessed.     

Differential expression of 12 histone deacetylase (<Emphasis Type="Italic">HDAC</Emphasis>) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas

Background  

Glioblastoma is the most lethal primary malignant brain tumor. Although considerable progress has been made in the treatment of this aggressive tumor, the clinical outcome for patients remains poor. Histone deacetylases (HDACs) are recognized as promising targets for cancer treatment. In the past several years, HDAC inhibitors (HDACis) have been used as radiosensitizers in glioblastoma treatment. However, no study has demonstrated the status of global HDAC expression in gliomas and its possible correlation to the use of HDACis. The purpose of this study was to evaluate and compare mRNA and protein levels of class I, II and IV of HDACs in low grade and high grade astrocytomas and normal brain tissue and to correlate the findings with the malignancy in astrocytomas.     

Methylation status of O<Superscript>6</Superscript>-methylguanine-DNA-methyl transferase promoter region in non-small-cell lung cancer patients with brain metastasis

Background  

O6-methylguanine-DNA-methyl transferase (MGMT), a DNA repair gene, is a key enzyme for predicting the response to both radiotherapy and temozolomide in glioma patients. Data on the MGMT promoter methylation status in relation to the time to develop intracranial new metastasis or local relapse at the surgical site after brain surgery followed by radiotherapy is limited in non-smallcell lung cancer (NSCLC) patients with a single brain metastasis.     

Non‐small cell lung cancer brain metastasis screening in the era of positron emission tomography‐CT staging: Current practice and outcomes

Introduction

Several clinical guidelines indicate that brain metastasis screening (BMS) should be guided by disease stage in non‐small cell lung cancer (NSCLC). We estimate that screening is performed more broadly in practice, and patients undergo brain imaging at considerable cost with questionable benefit. Our aim was to quantify the use and detection rate of BMS in a contemporary cohort staged with ¹⁸F‐fluorodeoxyglucose positron emission tomography/computed tomography (PET‐CT).

Methods

We conducted a retrospective review of prospectively collected data from three major lung cancer referral centres in Brisbane between January 2011 and December 2015. Patients included had a new diagnosis of NSCLC and had undergone a PET‐CT to stage extra‐cranial disease. BMS was defined as dedicated brain imaging with contrast‐enhanced computed tomography (CE‐CT) or magnetic resonance (MR), in the absence of clinically apparent neurological deficits.

Results

A total of 1751 eligible cases were identified and of these 718 (41%) underwent BMS. The majority had CE‐CT imaging (n = 703). Asymptomatic brain metastases (BM) were detected in 18 patients (2.5%). Of these patients, 12 had concurrent non‐brain metastases. Only six patients (0.8%) had BM alone. The rate of detection increased with N‐stage (P = 0.02) and overall stage (P < 0.001). It was 0.5%, 1%, 1.6% and 7.3% for stage I, II, III and IV respectively. The overall screening rate increased with T‐stage (P = 0.001), N‐Stage (P < 0.001) and overall stage (P < 0.001).

Conclusions

Non‐small cell lung cancer BMS practices remain at odds with published guidelines. The low number of occult BMs detected supports the existing international recommendations. Rationalising BMS would minimise the burden on patients and the health care system.     

Predicting compliance and survival in palliative whole-brain radiotherapy for brain metastases

Objective  

Brain radiotherapy is the main treatment for patients with brain metastases but its goal is just symptom control. Our aim was to study if different performance tools, used in geriatric practice, could improve patient selection for decision-making in the palliative brain radiotherapy setting.     

Detection of doxorubicin hydrochloride accumulation in the rat brain after morphine treatment by mass spectrometry

Purpose  

The blood–brain barrier discriminates the access of several molecules to the brain. This hampers the use of some drugs, as doxorubicin, potentially active for treatment of brain tumors. We explored the feasibility of active modification of the blood–brain barrier protection, by using morphine pretreatment, to allow doxorubicin accumulation in the brain in an animal model.     

Caffeic acid phenethyl ester decreases acute pneumonitis after irradiation <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis>

Background  

Lung cancer is relatively resistant to radiation treatment and radiation pneumonitis is a major obstacle to increasing the radiation dose. We previously showed that Caffeic acid phenethyl ester (CAPE) induces apoptosis and increases radiosensitivity in lung cancer. To determine whether CAPE, an antioxidant and an inhibitor of NF-kappa B, could be a useful adjuvant agent for lung cancer treatment, we examine the effects of CAPE on irradiated normal lung tissue in this study.     

Plasma and cerebrospinal fluid pharmacokinetics of thalidomide and lenalidomide in nonhuman primates

Purpose  

Thalidomide, originally developed as a sedative, was subsequently identified to have antiangiogenic properties. Lenalidomide is an antiangiogenic and immunomodulatory agent that has been utilized in the treatment of patients with brain tumors. We studied the pharmacokinetics and cerebrospinal fluid (CSF) penetration of thalidomide and lenalidomide in a nonhuman primate model.     

Developmental and oncogenic effects of Insulin-like Growth Factor-I in Ptc1<Superscript>+/-</Superscript> mouse cerebellum

Background  

Medulloblastoma is amongst the most common malignant brain tumors in childhood, arising from neoplastic transformation of granule neuron precursors (GNPs) of the cerebellum via deregulation of pathways involved in cerebellar development. Deregulation of the Sonic hedgehog/Patched1 (Shh/Ptc1) signaling pathway predisposes humans and mice to medulloblastoma. In the brain, insulin-like growth factor (IGF-I) plays a critical role during development as a neurotrophic and neuroprotective factor, and in tumorigenesis, as IGF-I receptor is often activated in medulloblastomas.     

Smoking and risk of glioma: a meta-analysis

Objective  

Although causal relationships between smoking and cancer risk have been established for many sites, most studies of brain cancer have not supported an association. However, two recent cohort studies showed increased risks of glioma among smokers. We quantified the association between smoking and glioma through a meta-analysis of the literature.     

<Emphasis Type="Italic">ERCC2</Emphasis>2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: A preliminary study

Background  

Early relapse in colorectal cancer (CRC) patients is attributed mainly to the higher malignant entity (such as an unfavorable genotype, deeper tumor invasion, lymph node metastasis and advance cancer stage) and poor response to chemotherapy. Several investigations have demonstrated that genetic polymorphisms in drug-targeted genes, metabolizing enzymes, and DNA-repairing enzymes are all strongly correlated with inter-individual differences in the efficacy and toxicity of many treatment regimens. This preliminary study attempts to identify the correlation between genetic polymorphisms and clinicopathological features of CRC, and evaluates the relationship between genetic polymorphisms and chemotherapeutic susceptibility of Taiwanese CRC patients. To our knowledge, this study discusses, for the first time, early cancer relapse and its indication by multiple genes.     

Impact of <Emphasis Type="Italic">UGT2B7</Emphasis><Superscript><Emphasis Type="Italic">His268Tyr</Emphasis></Superscript> polymorphism on the outcome of adjuvant epirubicin treatment in breast cancer

Introduction  

Epirubicin is a common adjuvant treatment for breast cancer. It is mainly eliminated after glucuronidation through uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7). The present study aimed to describe the impact of the UGT2B7 ^His268Tyr polymorphism on invasive disease-free survival in breast cancer patients after epirubicin treatment.     

No influence of the polymorphisms <Emphasis Type="Italic">CYP2C19</Emphasis> and <Emphasis Type="Italic">CYP2D6</Emphasis> on the efficacy of cyclophosphamide,thalidomide, and bortezomib in patients with Multiple Myeloma

Background  

The response to treatment varies among patients with multiple myeloma and markers for prediction of treatment outcome are highly needed. Bioactivation of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is dependent on cytochrome P450 metabolism. We explored the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment.     

Radiosurgery and whole brain therapy in the treatment of brainstem metastases

Purpose  

The incidence of brainstem metastasis (BSM) accounts for 1–3% of brain metastases (BM). They are often associated with multiple BM and produce significant neurological symptoms. We retrospectively analyse the results of treatment with stereotactic radiosurgery (SRS).     

Bioinformatic identification of FGF,p38-MAPK,and calcium signalling pathways associated with carcinoma <Emphasis Type="Italic">in situ</Emphasis>in the urinary bladder

Background  

Carcinoma in situ (CIS) is believed to be a precursor of invasive bladder cancer. Identification of CIS is a valuable prognostic factor since radical treatment strategies can be offered these patients before the disease becomes invasive.     

Targeting tissue factor on tumour cells and angiogenic vascular endothelial cells by factor VII-targeted verteporfin photodynamic therapy for breast cancer <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis>in mice

Background  

The objective of this study was to develop a ligand-targeted photodynamic therapy (tPDT) by conjugating factor VII (fVII) protein with photosensitiser verteporfin in order to overcome the poor selectivity and enhance the effect of non-targeted PDT (ntPDT) for cancer. fVII is a natural ligand for receptor tissue factor (TF) with high affinity and specificity. The reason for targeting receptor TF for the development of tPDT is that TF is a common but specific target on angiogenic tumour vascular endothelial cells (VEC) and many types of tumour cells, including solid tumours and leukaemia.     

The potassium channel Ether à go-go is a novel prognostic factor with functional relevance in acute myeloid leukemia

Background  

The voltage-gated potassium channel hEag1 (K_V10.1) has been related to cancer biology. The physiological expression of the human channel is restricted to the brain but it is frequently and abundantly expressed in many solid tumors, thereby making it a promising target for a specific diagnosis and therapy. Because chronic lymphatic leukemia has been described not to express hEag1, it has been assumed that the channel is not expressed in hematopoietic neoplasms in general.     

The <Emphasis Type="Italic">in vitro</Emphasis>effect of gefitinib ('Iressa') alone and in combination with cytotoxic chemotherapy on human solid tumours

Background  

Activation of the epidermal growth factor receptor (EGFR) triggers downstream signaling pathways that regulate many cellular processes involved in tumour survival and growth. Gefitinib ('Iressa') is an orally active tyrosine kinase inhibitor (TKI) targeted to the ATP-binding domain of EGFR (HER1; erbB1).