Κυριακή 21 Μαρτίου 2021

Therapeutic challenges in radiation-induced salivary gland cancers

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imagePurpose of review To give an overview of recent advances in therapeutic approaches of radiation-induced salivary gland cancers (ri-SGCs). Recent findings Reirradiation with protons and carbon ions demonstrated to be feasible, safe and to offer good local control rates, with the possibility of overcoming radioresistance and dosimetric issues in previously irradiated cancer patients. Chromosomal rearrangements, gene fusions and expression profiles are important to identify specific cancer subtypes and can guide tailored systemic therapy. Summary Ri-SGCs are rare and heterogeneous. Patients are often heavily pretreated and at risk of toxicities, and their management remain challenging. A multidisciplinary approach in referral centers is mandatory. Knowledge about SGCs cellular and molecular mechanisms is constantly evolving. In the last years, novel advances in therapeutic approaches, such as carbon ion radiotherapy, are emerging as safe and effective options in active treatment, but further efforts are needed to offer tailored personalized treatments and to improve survival.
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A roadmap of six different pathways to improve survival in laryngeal cancer patients

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imagePurpose of review Laryngeal cancer continues to require improvement in earlier stage diagnosis and better imaging delineation of disease, and hence 'more evidence-based' selection of treatment, as recent evidence suggests that related mortality, in the last decades, has not significantly decreased worldwide. Even though the reasons are not fully understood, there persists an urgency for a review and development of future strategies to embrace such clinical and diagnostic challenges from a political, societal, as well as scientific and clinical points of view. Recent findings This review of the published literature suggests that survival improvement in laryngeal cancer may be achieved by fuelling and combining at least some or all of six targeted agendas: documentation of disease global incidence and national burden monitoring; development and implementation of high-quality cancer registries; education on risk factors and hazardous habits associated with laryngeal cancer for the general population; active modification of proven at-risk population lifestyles; centralization of treatment; and use of machine learning of gathered 'big data' and their integration into approaches for the optimization of prevention and treatments strategies. Summary Laryngeal cancer should be tackled on several fronts, commencing with disease monitoring and prevention, up to treatment optimisation. Available modern resources offer the possibility to generate significant advances in laryngeal cancer management. However, each nation needs to develop a comprehensive approach, which is an essential prerequisite to obtain meaningful improvement on results.
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Oral potentially malignant disorders: new insights for future treatment

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imagePurpose of review The purpose of this review is to define the issues regarding oral potentially malignant disorders (OPMDs) and provide an overview of currently available treatments and ongoing clinical trials for future opportunities. Recent findings Nowadays, the treatment of choice of OPMD is surgery, whose role in preventing malignant transformation is however limited because of the high rate of recurrence and field cancerization. There have been several attempts of combining systemic therapies with surgery to reduce risk of malignant transformation. The identification of biomarkers that could predict malignant transformation is crucial in better tailoring the risk profile and possible therapeutic approaches. Summary Loss of heterozygosity remains the most predictive marker of malignant transformation; however, role of specific microRNA and OPMD immune infiltration are emerging as potential biomarkers. Given the failure of previous trials with various chemopreventive strategies, new strategies should be defined to address the issue of systemic prevention of malignant transformation. Recent updates about immune infiltration and the immune-equilibrium concept for OPMD could shed light into new preventive approaches.
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Precision head and neck surgery: robotics and surgical vision technology

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imagePurpose of review As the molecular basis of head and neck cancer becomes more clearly defined, precision medicine has gradually refined the multidisciplinary treatment paradigm for patients with oropharyngeal cancer. Although precision medicine is often thought to refer to new molecular diagnostics or unique medical therapy, the recent adoption of robotic surgery has ushered in the era of 'precision' head and neck surgery. Recent findings Surgeons now routinely utilize a virtual reality environment to reduce the morbidity of head and neck surgical care and improve oncologic and functional outcomes. The development and subsequent FDA approval of the da Vinci SP system, a single-arm system with a flexible camera, has allowed for improved visualization and access to the deep oropharynx and larynx. Groups investigating anti-EGFR antibodies tagged with fluorescent dye as well as inherent autofluorescence differences between normal and cancerous mucosal tissues show promise for improving positive surgical margin rates. Summary The evolution of robotics and visualization for oropharyngeal cancer represents a novel and innovative utilization of new technology to improve care. Further advancements in techniques, from refinement of the robotic platform itself, to novel real-time tumour imaging options will be critical to further advance precision care for these patients.
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Πέμπτη 18 Μαρτίου 2021

Modulation of the ERK1/2-MMP-2 pathway in the sclera of guinea pigs following induction of myopia by flickering light

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Exp Ther Med. 2021 Apr;21(4):371. doi: 10.3892/etm.2021.9802. Epub 2021 Feb 19.

ABSTRACT

It has been shown that flickering light can affect the development of eyeballs. However, the exact mechanism remains unclear. The ERK1/2-MMP-2 pathway is a classic pathway involved in the modulation of the extracellular matrix (ECM) in cancer tissues. However, to the best of our knowledge, the role of this pathway in modulating the scleral ECM in myopia has not been previously examined. The present study aimed to determine the effects of the ERK1/2-MMP-2 pathway on the formation of flickering light-induced myopia (FLM). Guinea pigs were raised under illumination at a flash rate of 0.5 Hz for 6 weeks to induce FLM. Peribulbar injections of dimethylsulfoxide or PD98059 (an inhibitor of phospho-ERK1/2) were administered starting at the third week of FLM modeling. Refraction was measured prior to and following treatments. The thickness of the posterior sclera (PS) was measured under a light microscope following H&E staining. The mRNA levels of MMP-2 were detected by the reverse transcription-quantitative PCR assay. The expression levels of MMP-2 and ERK1/2 were assayed by western blot and immunohistochemical analyses. Following 6 weeks of treatment, the refraction of the FLM group became more myopic compared with that of the control group, while PD98059 treatment inhibited the changes noted in the refraction. A marked reduction in the thickness of PS was observed in the FLM group, while PD98059 inhibited the remodeling of PS. In addition, the expression levels of MMP-2 and protein levels of phospho-ERK1/2 were increased in the FLM group, while PD98059 significantly inhibited MMP-2 mRNA and protein levels. These results indicated that ERK1/2-MMP-2 may be involved in the formation of FLM in guinea pigs by regulating the remodeling of PS.

PMID:33732344 | PMC:PMC7903414 | DOI:10.3892/etm.2021.9802

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Effects of neutron radiation on Nrf2-regulated antioxidant defense systems in rat lens

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Exp Ther Med. 2021 Apr;21(4):334. doi: 10.3892/etm.2021.9765. Epub 2021 Feb 8.

ABSTRACT

Accumulating evidence suggests that ionizing radiation (IR)-induced cataract may be associated with oxidative stress. Nuclear factor erythroid 2-related factor 2 (Nrf2) serves as a master regulator of the antioxidant defense system against oxidative stress. The present study aimed to investigate the effects of different doses of neutron radiation on the Nrf2-reegulated antioxidant defense system in rat lens and assess the status of oxidative stress. A total of 24 SD rats were randomly divided into the following four groups: i) Control group; iis) 0.4 Sv group; iii) 1.2 Sv group; and iv) 3.6 Sv group. The rats were sacrificed 7 days after radiation and lenses were dissected for histological, biochemical (malondialdehyde, glutathione and superoxide dismutase) and western blot (Nrf2, glutamate-cysteine ligase catalytic subunit and heme oxygenase 1) ana lyses. The morphological features of the lenses remained intact in the 0.4 Sv, 1.2 Sv and control groups, whilst the lenses in the 3.6 Sv group exhibited injuries. Results from the TUNEL assay demonstrated apparent apoptosis in lens epithelial cells following 3.6 Sv neutron radiation whereas sparse apoptosis was observed following 0.4 Sv and 1.2 Sv radiation. Malondialdehyde levels were reduced in the 0.4 Sv and 1.2 Sv groups but increased in the 3.6 Sv group, compared with those in the control group. Conversely, glutathione expression and the activity of superoxide dismutase were higher in the 0.4 Sv and 1.2 Sv groups, but lower in the 3.6 Sv group, compared with those in the control group. In addition, the total and nuclear protein levels of Nrf2 were increased following neutron radiation compared with those in the control group, though the Nrf2 protein levels decreased in the 3.6 Sv group compared with those in the 1.2 Sv group. The levels of glutamate-cysteine ligase catalytic s ubunit and heme oxygenase 1, downstream antioxidant enzymes of Nrf2, demonstrated the same profile as that in Nrf2. Taken together, the results of the present study suggest that neutron radiation affects Nrf2-regulated antioxidant systems in a two-stage process. Namely, the induction phase for low-dose radiation and regression phase for high-dose radiation. Therefore, it was hypothesized that activation and enhancement of the Nrf2-regulated antioxidant system may be useful in preventing or delaying IR-induced cataract, which may be extended even for other diseases associated with oxidative stress.

PMID:33732307 | PMC:PMC7903385 | DOI:10.3892/etm.2021.9765

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Downregulation of DEC1 inhibits proliferation, migration and invasion, and induces apoptosis in ovarian cancer cells via regulation of Wnt/β-catenin signaling pathway

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Exp Ther Med. 2021 Apr;21(4):372. doi: 10.3892/etm.2021.9803. Epub 2021 Feb 19.

ABSTRACT

DEC1 has been reported to regulate the expression of multiple target genes, participate in cell differentiation, apoptosis, aging and the development and progression of numerous tumors, but the detailed effects and possible mechanisms of DEC1 in ovarian cancer (OC) remain unknown. The present study aimed to investigate the expression and mechanism of function of DEC1 in OC. The present results demonstrated that DEC1 was highly expressed in OC tissues and cell lines using reverse transcription-quantitative PCR, western blotting and immunohistochemistry, and high expression of DEC1 was negatively associated with the prognosis of patients with OC. In addition, knockdown of DEC1 significantly inhibited proliferation in SKOV3 and OVCAR3 cells compared with control. DEC1 knockdown also induced apoptosis and increased the expression of apoptosis-related p roteins in OC cells. The results suggested that knockdown of DEC1 inhibited OC cell migration and invasion via regulation of epithelial-mesenchymal transition-related protein. It was also found that DEC1 knockdown significantly inhibited the Wnt/β-catenin pathway. Collectively, the current results indicated that knockdown of DEC1 inhibited proliferation, migration and invasion, and induced apoptosis in OC cells via modulating the Wnt/β-catenin signaling pathway. Thus, DEC1 may participate in malignant progression of OC, and may be a target for treatment and diagnosis of OC.

PMID:33732345 | PMC:PMC7903451 | DOI:10.3892/etm.2021.9803

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