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Frontiers in Oral Health 2023Although treatment modalities for head and neck cancer have evolved considerably over the past decades, survival rates have plateaued. The treatment options remained... (Review)
Review
Although treatment modalities for head and neck cancer have evolved considerably over the past decades, survival rates have plateaued. The treatment options remained limited to definitive surgery, surgery followed by fractionated radiotherapy with optional chemotherapy, and a definitive combination of fractionated radiotherapy and chemotherapy. Lately, immunotherapy has been introduced as the fourth modality of treatment, mainly administered as a single checkpoint inhibitor for recurrent or metastatic disease. While other regimens and combinations of immunotherapy and targeted therapy are being tested in clinical trials, adapting the appropriate regimens to patients and predicting their outcomes have yet to reach the clinical setting. Radiotherapy is mainly regarded as a means to target cancer cells while minimizing the unwanted peripheral effect. Radiotherapy regimens and fractionation are designed to serve this purpose, while the systemic effect of radiation on the immune response is rarely considered a factor while designing treatment. To bridge this gap, this review will highlight the effect of radiotherapy on the tumor microenvironment locally, and the immune response systemically. We will review the methodology to identify potential targets for therapy in the tumor microenvironment and the scientific basis for combining targeted therapy and radiotherapy. We will describe a current experience in preclinical models to test these combinations and propose how challenges in this realm may be faced. We will review new players in targeted therapy and their utilization to drive immunogenic response against head and neck cancer. We will outline the factors contributing to head and neck cancer heterogeneity and their effect on the response to radiotherapy. We will review methods to decipher intertumoral and intratumoral heterogeneity and how these algorithms can predict treatment outcomes. We propose that (a) the sequence of surgery, radiotherapy, chemotherapy, and targeted therapy should be designed not only to annul cancer directly, but to prime the immune response. (b) Fractionation of radiotherapy and the extent of the irradiated field should facilitate systemic immunity to develop. (c) New players in targeted therapy should be evaluated in translational studies toward clinical trials. (d) Head and neck cancer treatment should be personalized according to patients and tumor-specific factors.
PubMed: 37496754
DOI: 10.3389/froh.2023.1180869 -
Stress Biology Aug 2023Vesicle trafficking is an essential cellular process upon which many physiological processes of eukaryotic cells rely. It is usually the 'language' of communication... (Review)
Review
Vesicle trafficking is an essential cellular process upon which many physiological processes of eukaryotic cells rely. It is usually the 'language' of communication among the components of the endomembrane system within a cell, between cells and between a cell and its external environment. Generally, cells have the potential to internalize membrane-bound vesicles from external sources by endocytosis. Plants constantly interact with both mutualistic and pathogenic microbes. A large part of this interaction involves the exchange of transport vesicles between the plant cells and the microbes. Usually, in a pathogenic interaction, the pathogen releases vesicles containing bioactive molecules that can modulate the host immunity when absorbed by the host cells. In response to this attack, the host cells similarly mobilize some vesicles containing pathogenesis-related compounds to the pathogen infection site to destroy the pathogen, prevent it from penetrating the host cell or annul its influence. In fact, vesicle trafficking is involved in nearly all the strategies of phytopathogen attack subsequent plant immune responses. However, this field of plant-pathogen interaction is still at its infancy when narrowed down to plant-fungal pathogen interaction in relation to exchange of transport vesicles. Herein, we summarized some recent and novel findings unveiling the involvement of transport vesicles as a crosstalk in plant-fungal phytopathogen interaction, discussed their significance and identified some knowledge gaps to direct future research in the field. The roles of vesicles trafficking in the development of both organisms are also established.
PubMed: 37676627
DOI: 10.1007/s44154-023-00114-0 -
The Journal of Neuroscience : the... Jul 2023Fear learning allows us to identify and anticipate aversive events and adapt our behavior accordingly. This is often thought to rely on associative learning mechanisms...
Fear learning allows us to identify and anticipate aversive events and adapt our behavior accordingly. This is often thought to rely on associative learning mechanisms where an initially neutral conditioned stimulus (CS) is repeatedly paired with an aversive unconditioned stimulus (US), eventually leading to the CS also being perceived as aversive and threatening. Importantly, however, humans also show verbal fear learning. Namely, they have the ability to change their responses to stimuli rapidly through verbal instructions about CS-US pairings. Past research on the link between experience-based and verbal fear learning indicated that verbal instructions about a reversal of CS-US pairings can fully override the effects of previously experienced CS-US pairings, as measured through fear ratings, skin conductance, and fear-potentiated startle. However, it remains an open question whether such instructions can also annul learned CS representations in the brain. Here, we used a fear reversal paradigm (female and male participants) in conjunction with representational similarity analysis of fMRI data to test whether verbal instructions fully override the effects of experienced CS-US pairings in fear-related brain regions or not. Previous research suggests that only the right amygdala should show lingering representations of previously experienced threat ("pavlovian trace"). Unexpectedly, we found evidence for the residual effect of prior CS-US experience to be much more widespread than anticipated, in the amygdala but also cortical regions like the dorsal anterior cingulate or dorsolateral prefrontal cortex. This finding shines a new light on the interaction of different fear learning mechanisms, at times with unexpected consequences. Humans are able to learn about aversive stimuli both from experience (i.e., repeated pairings of conditioned stimulus (CS) and unconditioned stimulus (US; pavlovian conditioning), and from verbal instructions about stimulus pairings. Understanding how experience-based and verbal learning processes interact is key for understanding the cognitive and neural underpinnings of fear learning. We tested whether prior aversive experiences (CS-US pairings) affected subsequent verbal learning, searching for lingering threat signals after verbal instructions reversed a CS from being threatening to being safe. While past research suggested such threat signals can only be found in the amygdala, we found evidence to be much more widespread, including the medial and lateral PFC. This highlights how experience-based and verbal learning processes interact to support adaptive behavior.
Topics: Humans; Male; Female; Conditioning, Classical; Fear; Conditioning, Operant; Brain; Learning
PubMed: 37414559
DOI: 10.1523/JNEUROSCI.0665-22.2023 -
PloS One 2024Height loss is reported to be an independent risk factor for all-cause and cardiovascular mortality. Smoking, which is responsible for a considerable proportion of...
Height loss is reported to be an independent risk factor for all-cause and cardiovascular mortality. Smoking, which is responsible for a considerable proportion of deaths due to any cause, is also associated with lumbar disc degeneration, a major risk factor for height loss. Therefore, smoking could be an independent risk factor for height loss. To clarify the association between smoking status and height loss, a retrospective study with 8,984 (5,518 men and 3,466 women) Japanese workers was conducted. The present study population comprised 9,681 workers aged 40-74 years who participated in annual medical examinations between 2011 and 2017 (baseline). Subjects without a height measurement during 2012-2018 (endpoint) were excluded from the analysis (n = 697). Height loss was defined as being in the highest quartile of annul height decrease (1.48 mm/year for men and 1.79 mm/year for women). Independent of known cardiovascular risk factors, smoking was positively associated with height loss among men but not among women. With never smokers as the referent group, the adjusted odds ratio (95% confidence interval) was 1.15 (0.98, 1.35) for former smokers and 1.24 (1.05, 1.46) for current smokers among men, respectively. Among women, the corresponding values were 0.98 (0.79, 1.21) and 0.90 (0.71, 1.16), respectively. Since height loss and smoking are independent risk factors for all-cause and cardiovascular mortality, these results help clarify the mechanisms underlying the association between height loss and mortality risk.
Topics: Male; Humans; Female; Retrospective Studies; Japan; Smoking; Tobacco Smoking; Risk Factors; Cardiovascular Diseases
PubMed: 38359064
DOI: 10.1371/journal.pone.0298121