Brain Metastasis Growth Kinetics: A Novel Prognosticator for Stereotactic Radiotherapy.

AIMS: The rate of size change in brain metastasis may have clinical implications on tumour biology and prognosis for patients who receive stereotactic radiotherapy (SRT). We analysed the prognostic value of brain metastasis size kinetics and propose a model for patients with brain metastases treated with linac-based SRT in predicting overall survival. MATERIALS AND METHODS: We analysed the patients receiving linac-based SRT between 2010 and 2020. Patient and oncological factors, including the changes in sizes of brain metastasis between the diagnostic and stereotactic magnetic resonance imaging, were collected. The associations between prognostic factors and overall survival were assessed using Cox regression with least absolute selection and shrinkage operator (LASSO) checked by 500 bootstrap replications. Our prognostic score was calculated by evaluating the most statistically significant factors. Patients were grouped and compared according to our proposed score, Score Index for Radiosurgery in Brain Metastases (SIR) and Basic Score for Brain Metastases (BS-BM). RESULTS: In total, 85 patients were included. We developed the prognostic model based on the most important predictors of overall survival: growth kinetics, i.e. percentage change in brain metastasis size per day between the diagnostic and stereotactic magnetic resonance imaging (hazard ratio per 1% increase, 1.32; 95% confidence interval 1.06-1.65), extracranial oligometastatic diseases (≤5 involvements) (hazard ratio 0.28; 95% confidence interval 0.16-0.52) and the presence of neurological symptoms (hazard ratio 2.99; 95% confidence interval 1.54-5.81). Patients with scores 0, 1, 2 and 3 had a median overall survival of 44.4 (95% confidence interval 9.6-not reached), 20.4 (95% confidence interval 15.6-40.8), 12.0 (95% confidence interval 7.2-22.8) and 2.4 (95% confidence interval 1.2-not reached) years, respectively. The optimism-corrected c-indices for our proposed model, SIR and BS-BM were 0.65, 0.58 and 0.54, respectively. CONCLUSIONS: Brain metastasis growth kinetics is a valuable metric for survival outcomes of SRT. Our model is useful in identifying patients with brain metastasis treated with SRT with different overall survival.

Evaluating the Effectiveness of Digital Content Marketing Under Mixed Reality Training Platform on the Online Purchase Intention.

The purpose of this research is to investigate the effectiveness of Digital Content Marketing (DCM) on a Mixed Reality (MR) training platform environment with the consideration of online purchase intention (OPI) through social media. E-commerce today encounters several common issues that cause customers to have reservations to purchase online. With the absence of physical contact points, customers often perceive more risks when making purchase decisions. Furthermore, online retailers often find it hard to engage customers and develop long-term relationships. In this research, a Structural Equation Model (SEM) is proposed to examine the efficacy of DCM from both immediate and long-term OPI. The results examine whether adopting DCM on an MR training platform environment through social media brings positive results in OPI. Empirical research was carried out through online questionnaires collected in 2021 and 2022. A total of 374 questionnaires were qualified for data analysis in this study, conducted with IBM SPSS and AMOS. The results imply that DCM is critical to stimulating both immediate and long-term OPI. The immediate OPI is positively affected by increasing perceived value through MR in DCM. Regarding the long-term OPI, increased customer engagement with DCM under MR environment can cultivate brand trust and significantly affect the long-term OPI.

GC factor 2 represses platelet-derived growth factor A-chain gene transcription and is itself induced by arterial injury.

Platelet-derived growth factor (PDGF) is a mitogen and chemoattractant for a wide variety of cell types. The genes encoding PDGF A chain (PDGF-A) and PDGF B chain (PDGF-B) reside on separate chromosomes and are independently regulated at the level of transcription. Regulatory events underlying inducible PDGF-A expression have been the focus of much investigation. However, mechanisms that inhibit transcription of this gene are not well understood. In this study, we report the capacity of a newly cloned DNA binding factor, GC factor 2 (GCF2), to repress expression driven by the human PDGF-A promoter. 5' Deletion and transient cotransfection analysis in vascular endothelial cells revealed that GCF2 repression is mediated by a nucleotide region located in the proximal region of the PDGF-A promoter. Electrophoretic mobility shift assays demonstrate that GCF2 binds to this region in a specific and dose-dependent manner. Interestingly, the site bound by GCF2 overlaps those for specificity protein-1 (Sp1) and early growth response factor-1 (Egr-1), zinc finger transcription factors that direct basal and inducible expression of the PDGF-A gene. Gel shift experiments revealed that GCF2 competes with these factors for interaction with the PDGF-A promoter. Overexpression of GCF2 suppressed endogenous PDGF-A expression in vascular endothelial cells and smooth muscle cells. GCF2 was induced on mechanical injury of cells in culture as well as after balloon injury of the rat carotid artery wall. Time course studies revealed the sustained induction of GCF2 after injury while PDGF-A levels sharply returned to baseline. Smooth muscle cell proliferation was inhibited by GCF2, an effect reversed by the addition of exogenous PDGF-AA. These findings demonstrate negative regulation of PDGF-A expression by GCF2. This is the first report of the induction of an endogenous transcriptional repressor in the rat vessel wall.

The maximum aerobic power of the Temiars.

A settlement of Temiars, an aboriginal tribe residing in the north-eastern jungles of the Malay Peninsula, was selected for a study of their cardiorespiratory fitness. A step-test was used to elicit the Vo2max, V E max and HR max in a group of 19 boys aged 12 to 18 years and 6 men aged 19 - 40 years. The mean VO2max of the boys was found to be 45.9 +/- 6.9 ml-kg-1-min-1 compared with 45.6 +/- 5.4 ml-kg-1-min-1 for the men. The mean V E max, HR max and blood lactate levels were found to be 65.5 +/- 11.31/min and 69.2 +/- 23.71/min; 194 +/- 8 beats/min and 186 +/- 10 beats/min; and 79.8 +/- 13.4 mg% and 97.7 +/- 33.4 mg% respectively. These results are comparable to those obtained in urban populations as well as those found in other primitive communities. Telemetric monitoring of the routine daily physical activity of the men revealed that these jungle dwellers rarely tax their oxygen transport systems in their daily living and their cardiorespiratory functions were similar to communities who do not specifically train for physical fitness.

Effect of tetrabenazine and alpha-methyl-m-tyrosine on exploratory activity and brain catecholamines in rats.

1. Spontaneous exploratory locomotor activity of Wistar rats was measured in photocell activity cages, and brain noradrenaline (NA) and dopamine (DA) were determined fluorometrically after ion exchange purification.2. Tetrabenazine (TBZ) (10 mg/kg) produced a fall in NA and DA concentrations in rat brain stems which was correlated with the fall in activity in female Wistar rats.3. alpha-Methyl-m-tyrosine (alphaMMT) reduced the concentration of rat brain NA without affecting DA concentration or activity.4. Pretreatment with alphaMMT did not stop TBZ from producing a marked reduction in activity and NA concentration, but partially protected DA from the depleting action of TBZ.5. These results support a role for catecholamines in the control of motor activity, but they do not implicate NA more than DA and they emphasize that the mechanism by which drugs affect the concentrations of catecholamines may be more important than the gross concentrations attained.

Importance of noradrenaline found in a functional pool in maintaining spontaneous locomotor activity in rats.

1. Spontaneous locomotor activity (activity) in male Wistar rats was compared with the concentrations of brain noradrenaline (NA), dopamine (DA) and metaraminol.2. alpha-Methyl-m-tyrosine (alphaMMT) (400 mg/kg) reduced the concentrations of DA as well as NA but activity remained high in the presence of metaraminol formed from the alphaMMT. When tetrabenazine (TBZ) was given after alphaMMT pretreatment there was a fall in the levels of activity and in the concentrations of NA, DA and metaraminol.3. alpha-Methyl-p-tyrosine (alphaMT) produced a fall in activity which was correlated with falls in the concentrations of NA and DA. 5-Hydroxytryptamine (5-HT) did not appear to be affected.4. After depletion of NA and DA by alphaMT and TBZ, administration of L-dopa produced a return in activity which was significantly correlated with the concentration of NA but not DA. When alphaMMT was given to a similar group of pretreated animals there was no recovery of activity despite high concentrations of DA and metaraminol.5. The dopamine beta hydroxylase inhibitor, diethyldithiocarbamate (DDC), suppressed activity as well as the concentrations of NA and DA at high doses (750 mg/kg) but smaller doses (400 mg/kg) plus L-dopa gave high DA concentrations without activity.6. It is concluded that NA and not DA is associated with activity but that it is only part of the total NA which is in the biosynthetic storage granule affected by drugs like alphaMT and TBZ, which controls activity. Drugs that do not affect this pool may lower NA concentrations but not reduce activity.7. The replacement of NA by metaraminol in this functional pool does not restore activity.