Current Challenges and Opportunities of Photodynamic Therapy against Cancer

BACKGROUND: Photodynamic therapy (PDT) is an established, minimally invasive treatment for specific types of cancer. During PDT, reactive oxygen species (ROS) are generated that ultimately induce cell death and disruption of the tumor area. Moreover, PDT can result in damage to the tumor vasculature and induce the release and/or exposure of damage-associated molecular patterns (DAMPs) that may initiate an antitumor immune response. However, there are currently several challenges of PDT that limit its widespread application for certain indications in the clinic. METHODS: A literature study was conducted to comprehensively discuss these challenges and to identify opportunities for improvement. RESULTS: The most notable challenges of PDT and opportunities to improve them have been identified and discussed. CONCLUSIONS: The recent efforts to improve the current challenges of PDT are promising, most notably those that focus on enhancing immune responses initiated by the treatment. The application of these improvements has the potential to enhance the antitumor efficacy of PDT, thereby broadening its potential application in the clinic

Current Challenges and Opportunities of Photodynamic Therapy against Cancer

BACKGROUND: Photodynamic therapy (PDT) is an established, minimally invasive treatment for specific types of cancer. During PDT, reactive oxygen species (ROS) are generated that ultimately induce cell death and disruption of the tumor area. Moreover, PDT can result in damage to the tumor vasculature and induce the release and/or exposure of damage-associated molecular patterns (DAMPs) that may initiate an antitumor immune response. However, there are currently several challenges of PDT that limit its widespread application for certain indications in the clinic. METHODS: A literature study was conducted to comprehensively discuss these challenges and to identify opportunities for improvement. RESULTS: The most notable challenges of PDT and opportunities to improve them have been identified and discussed. CONCLUSIONS: The recent efforts to improve the current challenges of PDT are promising, most notably those that focus on enhancing immune responses initiated by the treatment. The application of these improvements has the potential to enhance the antitumor efficacy of PDT, thereby broadening its potential application in the clinic

Distinct Platelet Ribonucleic Acid Signatures in Patients with Pulmonary Hypertension

Rationale: Pulmonary hypertension encompasses progressive disorders leading to right ventricular dysfunction and early death. Late detection is an important cause of poor clinical outcomes. However, biomarkers that accurately predict the presence of pulmonary hypertension are currently lacking. Objectives: In this study, we provide evidence that blood platelets contain a distinctive ribonucleic acid (RNA) profile that may be exploited for the detection of pulmonary hypertension. Methods: Blood platelet RNA was isolated prospectively from 177 prevalent patients with different subtypes of pulmonary hypertension as well as 195 control subjects clinically not suspected of pulmonary hypertension. Sequencing libraries were created using SMARTer (Switching Mechanism at 5' end of RNA Template) copy desoxyribonucleic acid amplification and sequenced on the Illumina High Throughput Sequencing platform. RNA-sequencing reads were mapped to the human reference genome, and intron-spanning spliced RNA reads were selected. Differential spliced RNA panels were calculated by analysis of variance statistics. A particle swarm optimization-enhanced classification algorithm was built employing a development (n = 213 samples) and independent validation series (n = 159 samples). Results: We detected a total of 4,014 different RNAs in blood platelets from patients with pulmonary hypertension (n = 177) and asymptomatic control subjects (n = 195). Gene ontology analysis revealed enhanced RNA concentrations for genes related to RNA processing, translation, and mitochondrial function. A particle swarm optimization-selected RNA panel of 408 distinctive differentially spliced RNAs mediated detection of pulmonary hypertension with 93% sensitivity, 62% specificity, 77% accuracy, 0.89 (95% confidence interval, 0.83-0.93) area under the curve, and a negative predictive value of 91% in the independent validation series. The prediction score was independent of age, sex, smoking, pulmonary hypertension subtype, and the use of pulmonary hypertension-specific medication or anticoagulants. Conclusions: A platelet RNA panel may accurately discriminate patients with pulmonary hypertension from asymptomatic control subjects. In the light of current diagnostic delays, this study is the starting point for further development and evaluation of a platelet RNA-based blood test to ultimately improve early diagnosis and clinical outcomes in patients with pulmonary hypertension

Personality traits predict brain activation and connectivity when witnessing a violent conflict

As observers we excel in decoding the emotional signals telling us that a social interaction is turning violent. The neural substrate and its modulation by personality traits remain ill understood. We performed an fMRI experiment in which participants watched videos displaying a violent conflict between two people. Observers' attention was directed to either the aggressor or the victim. Focusing on the aggressor (vs. focusing on the victim) activated the superior temporal sulcus (STS), extra-striate body area (EBA), occipital poles and centro-medial amygdala (CMA). Stronger instantaneous connectivity occurred between these and the EBA, insula, and the red nucleus. When focusing on the victim, basolateral amygdala (BLA) activation was related to trait empathy and showed increased connectivity with the insula and red nucleus. STS activation was associated with trait aggression and increased connectivity with the hypothalamus. The findings reveal that focusing on the aggressor of a violent conflict triggers more activation in categorical (EBA) and emotion (CMA, STS) areas. This is associated with increased instantaneous connectivity among emotion areas (CMA-insula) and between categorical and emotion (EBA-STS) areas. When the focus is on the victim, personality traits (aggression/empathy) modulate activity in emotion areas (respectively STS and postcentral gyrus/ BLA), along with connectivity in the emotional diencephalon (hypothalamus) and early visual areas (occipital pole)