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Experimental Oncology Feb 2024Radiation-induced dermatitis impairs the quality of life of cancer patients and may lead to the need of interrupting radiotherapy. The grade of dermatitis is...
BACKGROUND
Radiation-induced dermatitis impairs the quality of life of cancer patients and may lead to the need of interrupting radiotherapy. The grade of dermatitis is subjectively assessed by the visual examination. There is an urgent need for both objective and quantitative methods for assessing the current grade of dermatitis and predicting its severity at an early stage of radiotherapy.
AIM
The aim of the study was to evaluate the advantages and limitations of infrared thermography for monitoring the current level of radiation-induced dermatitis and predicting its severity by quantitative analysis of the thermal field dynamics in the irradiated zone.
MATERIALS AND METHODS
30 adult patients were examined by infrared thermography during the course of 2D conventional radiotherapy for malignant tumors of various types and localizations. Our approach for quantifying the thermal field caused by dermatitis alone was applied. A statistical (correlation and ROC) analysis was performed.
RESULTS
Dermatitis of varying severity was observed in 100% of the patients studied. The dynamics in the intensity of the anomalous thermal fields in the irradiated zone correlated with the dynamics of dermatitis grades, excluding the case of a radiosensitive tumor (correlation coefficient 0.74÷0.84). It was found that the maximum toxicity (dermatitis grade ≥ 3) develops in patients who how significant hyperthermia in the area of interest (≥ 0.7 °C) at an early stage of radiotherapy. The ROC analysis demonstrated the "good quality" of the prognosis method (AUC = 0.871).
CONCLUSIONS
The non-invasive and cheap infrared thermography is a suitable tool for objective quantitative monitoring the current dermatitis grade during radiotherapy as well as predicting its severity for any tumor location.
Topics: Humans; Adult; Radiodermatitis; Quality of Life; Neoplasms; Prognosis; ROC Curve
PubMed: 38328840
DOI: 10.15407/exp-oncology.2023.04.493 -
Cureus Jan 2024Neuroleptic malignant syndrome (NMS) is characterized by hyperthermia, severe rigidity, and autonomic instability that is life-threatening if not treated promptly by...
Neuroleptic malignant syndrome (NMS) is characterized by hyperthermia, severe rigidity, and autonomic instability that is life-threatening if not treated promptly by intensive supportive care. However, there have been numerous reports of "atypical NMS" where the diagnostic criteria of NMS are only partially satisfied. We present a case of an elderly male who presented with atypical NMS secondary to antidopaminergic drug administration which precipitated acute respiratory failure. Our patient exhibited features of severe rigidity and autonomic instability, without hyperthermia. He developed tachypneic hypoventilation with type 2 hypercapneic respiratory failure which was treated with non-invasive ventilation (NIV). The patient recovered after three days with resolution of rigidity and was transferred to a normal medical ward on oxygen via a facemask, where he gradually improved. This study highlights that non-invasive ventilation may have a role in treating respiratory failure in mild to moderate cases of atypical NMS, avoiding the need for intubation.
PubMed: 38327911
DOI: 10.7759/cureus.51878 -
Biomedical Materials (Bristol, England) Feb 2024Osteosarcoma (OS) is a malignant bone neoplasm plagued by poor prognosis. Major treatment strategies include chemotherapy, radiotherapy, and surgery. Chemotherapy to... (Review)
Review
Osteosarcoma (OS) is a malignant bone neoplasm plagued by poor prognosis. Major treatment strategies include chemotherapy, radiotherapy, and surgery. Chemotherapy to treat OS has severe adverse effects due to systemic toxicity to healthy cells. A possible way to overcome the limitation is to utilize nanotechnology. Nanotherapeutics is an emerging approach in treating OS using nanoparticulate drug delivery systems. Surgical resection of OS leaves a critical bone defect requiring medical intervention. Recently, tissue engineered scaffolds have been reported to provide physical support to bone defects and aid multimodal treatment of OS. These scaffolds loaded with nanoparticulate delivery systems could also actively repress tumor growth and aid new bone formation. The rapid developments in nanotherapeutics and bone tissue engineering have paved the way for improved treatment efficacy for OS-related bone defects. This review focuses on current bifunctional nanomaterials-based tissue engineered (NTE) scaffolds that use novel approaches such as magnetic hyperthermia, photodynamic therapy, photothermal therapy, bioceramic and polymeric nanotherapeutics against OS. With further optimization and screening, NTE scaffolds could meet clinical applications for treating OS patients.
Topics: Humans; Tissue Engineering; Osteosarcoma; Tissue Scaffolds; Bone Neoplasms; Drug Delivery Systems
PubMed: 38324905
DOI: 10.1088/1748-605X/ad270b -
Alternative Therapies in Health and... Jan 2024Deep hyperthermia combined with platinum-based chemotherapy (DHCT) might lead to the development of better therapeutic strategy for patients with malignant tumor. This...
OBJECTIVE
Deep hyperthermia combined with platinum-based chemotherapy (DHCT) might lead to the development of better therapeutic strategy for patients with malignant tumor. This study aimed to analyze the computational medical differences in ovarian cancer patients treated with DHCT compared with platinum-based chemotherapy alone.
METHODS
78 patients with advanced ovarian cancer admitted from November 2017 to November 2021 were randomly selected as subjects. Overall survival analysis and CA125 clinical efficiency evaluation were performed to explore the effect of DHCT on cis-platinum therapy. All patients were informed and consented, and approved by the hospital committee. The data were systematically analyzed by chi-squared test to analyze clinical effect and safety observation, and the Kaplan-Meier method and log-rank test were used for survival analysis.
RESULTS
Survival analysis showed that DHCT was strongly associated with improved overall survival (OS) in the platinum treatment of ovarian cancer patients (Hazard Ratio = 1.57, 95% CI: 0.93-2.44, P = .017). For ovarian cancer patients receiving lobaplatin treatment, DHCT could also elevate their survival (Hazard Ratio = 1.52, 95% CI :1.02-2.25, P = .013). The study also showed a statistically significant difference in clinical outcomes between the two groups (P < .001), and the opposite is true for adverse reactions.
CONCLUSION
Our results suggest that DHCT is expected to be combined with platinum chemotherapy, which is helpful for the molecular classification of ovarian cancer patients. More studies are needed to further verified the clinical significance.
PubMed: 38290437
DOI: No ID Found -
Biofabrication Feb 2024The inflammatory response is one of the general symptoms that accompany tumorigenesis, the pro-inflammatory factors cyclooxygenase-2 (COX-2) and COX-2-derived...
The inflammatory response is one of the general symptoms that accompany tumorigenesis, the pro-inflammatory factors cyclooxygenase-2 (COX-2) and COX-2-derived prostaglandin-2 (PGE-2) in the inflammatory environment surrounding tumors possess promoting tumor development, metastasis and angiogenesis effects. In addition, the hypoxic environment of tumors severely limits the effectiveness of photodynamic therapy (PDT). In this study, a universal extracellular-intracellular 'on-demand' release nanomedicine DOX@PDA-ICG@MnO@GN-CEL was developed for the combined fight against malignant tumors using a spatiotemporal controlled gelatin coated polydopamine (PDA@GN) as the carrier and loaded with the chemotherapeutic drug doxorubicin (DOX), the photosensitizer indocyanine green (ICG), the PDT enhancer MnOand the anti-inflammatory drug celecoxib (CEL) individually. Our results showed that DOX@PDA-ICG@MnO@GN-CEL could release CEL extracellularly by matrix metalloproteinase-2 response and inhibit the COX-2/PGE-2 pathway, reduce chemotherapy resistance and attenuate the concurrent inflammation. After entering the tumor cells, the remaining DOX@PDA-ICG@MnOreleased DOX, ICG and MnOintracellularly through PDA acid response. MnOpromoted the degradation of endogenous HOto generate oxygen under acidic conditions to alleviate the tumor hypoxic environment, enhance PDT triggered by ICG. PDA and ICG exhibited photothermal therapy synergistically, and DOX exerted chemotherapy with reduced chemotherapy resistance. The dual responsive drug release switch enabled the chemotherapeutic, photothermal, photodynamic and anti-inflammatory drugs precisely acted on different sites of tumor tissues and realized a promising multimodal combination therapy.
Topics: Humans; Matrix Metalloproteinase 2; Drug Liberation; Tumor Microenvironment; Cyclooxygenase 2; Manganese Compounds; Hyperthermia, Induced; Oxides; Doxorubicin; Indocyanine Green; Neoplasms; Nanoparticles; Anti-Inflammatory Agents; Cell Line, Tumor
PubMed: 38277678
DOI: 10.1088/1758-5090/ad22ef -
Pharmaceuticals (Basel, Switzerland) Jan 2024Despite efforts in osteosarcoma (OS) research, the role of inductive moderate hyperthermia (IMH) in delivering and enhancing the antitumor effect of liposomal...
Despite efforts in osteosarcoma (OS) research, the role of inductive moderate hyperthermia (IMH) in delivering and enhancing the antitumor effect of liposomal doxorubicin formulations (LDOX) remains unresolved. This study investigated the effect of a combination treatment with LDOX and IMH on Saos-2 human OS cells. We compared cell viability using a trypan blue assay, apoptosis and reactive oxygen species (ROS) measured by flow cytometry and pro-apoptotic Bax protein expression examined by immunocytochemistry in response to IMH (42 MHz frequency, 15 W power for 30 min), LDOX (0.4 μg/mL), and LDOX plus IMH. The lower IC value of LDOX at 72 h indicated increased accumulation of the drug in the OS cells. LDOX plus IMH resulted in a 61% lower cell viability compared to no treatment. Moreover, IMH potentiated the LDOX action on the Saos-2 cells by promoting ROS production at temperatures of <42 °C. There was a 12% increase in cell populations undergoing early apoptosis with a less heterogeneous distribution of Bax after combination treatment compared to those treated with LDOX ( < 0.05). Therefore, we determined that IMH could enhance LDOX delivery and its antitumor effect via altered membrane permeabilization, ROS generation, and a lower level of visualized Bax heterogeneity in the Saos-2 cells, suggesting the potential translation of these findings into in vivo studies.
PubMed: 38276006
DOI: 10.3390/ph17010133 -
Journal of Materials Chemistry. B Feb 2024Colorectal cancer is one of the most common malignant tumors in the world, and its treatment strategies mainly include surgical resection, chemotherapy, adjuvant...
Colorectal cancer is one of the most common malignant tumors in the world, and its treatment strategies mainly include surgical resection, chemotherapy, adjuvant radiotherapy, and immunotherapy. Among them, chemotherapy inevitably produces systemic toxicity due to the lack of tumor targeting properties and drug resistance caused by long-term medication frequently occurs, immensely constraining the efficacy of chemotherapy alone. To solve the above-mentioned problems, rhamnolipid was used to encapsulate the chemotherapeutic drug 5-FU and photothermal agent bismuthene nanosheets (BiNS), chitosan was applied as the shell of the nanoparticle, and BiNS@RHL-CS/5-FU NPs for oral administration was successfully prepared. When transported in the stomach and small intestine, the double protection of rhamnolipid and chitosan shell prevented the early release of BiNS and 5-FU. When transported to the colon, β-glycosidase existing in the microenvironment along with elevated pH degraded the chitosan shell, and the reduction in particle size was beneficial for tumor tissue to uptake nanoparticles, thus greatly improving the tumor targeting ability of 5-FU and reducing the systemic toxicity. Due to the presence of BiNS, 1.0 W cm 808 nm laser irradiation significantly increased the temperature of the tumor site, not only killing tumor cells directly but also promoting cell uptake and penetration of nanoparticles in the tumor tissue, accelerating the release of 5-FU and improving the sensitivity of tumor cells to chemotherapy, eventually solving the shortcomings of traditional chemotherapy alone. Excellent anti-tumor efficacy has been achieved in both and experiments.
Topics: Humans; Chitosan; Nanoparticles; Hyperthermia, Induced; Fluorouracil; Colorectal Neoplasms; Tumor Microenvironment
PubMed: 38270492
DOI: 10.1039/d3tb02393a -
Journal of Molecular Modeling Jan 2024Ryanodine receptors (RyRs) are large intracellular ligand-gated calcium release ion channels. Mutations in human RyR1 in combination with a volatile anesthetic or muscle...
CONTEXT
Ryanodine receptors (RyRs) are large intracellular ligand-gated calcium release ion channels. Mutations in human RyR1 in combination with a volatile anesthetic or muscle relaxant are known to cause leaky RyRs resulting in malignant hyperthermia (MH). This has long been primarily treated with the RyR inhibitory drug dantrolene. Alternatives to dantrolene as a RyR inhibitor may be found through computer-aided drug design. Additionally, molecular dynamics (MD) studies of dantrolene interacting with RyRs may reveal its full mechanism of action. The availability of accurate force field parameters is important for the success of both.
METHODS
In this study, force field parameters for dantrolene were obtained from the CHARMM General Force Field (CGenFF) program and optimized using the force field toolkit (FFTK) and FFParam programs. The obtained parameters were then validated by a comparison between calculated and experimental IR spectra and normal mode analysis, among other techniques.
Topics: Humans; Dantrolene; Ryanodine Receptor Calcium Release Channel; Calcium; Drug Design; Mutation
PubMed: 38261112
DOI: 10.1007/s00894-024-05841-3 -
BioRxiv : the Preprint Server For... Jan 2024As the primary Ca release channel in skeletal muscle sarcoplasmic reticulum (SR), mutations in the type 1 ryanodine receptor (RyR1) or its binding partners underlie a...
As the primary Ca release channel in skeletal muscle sarcoplasmic reticulum (SR), mutations in the type 1 ryanodine receptor (RyR1) or its binding partners underlie a constellation of muscle disorders, including malignant hyperthermia (MH). In patients with MH mutations, exposure to triggering drugs such as the halogenated volatile anesthetics biases RyR1 to an open state, resulting in uncontrolled Ca release, sarcomere tension and heat production. Restoration of Ca into the SR also consumes ATP, generating a further untenable metabolic load. When anesthetizing patients with known MH mutations, the non-triggering intravenous general anesthetic propofol is commonly substituted for triggering anesthetics. Evidence of direct binding of anesthetic agents to RyR1 or its binding partners is scant, and the atomic-level interactions of propofol with RyR1 are entirely unknown. Here, we show that propofol decreases RyR1 opening in heavy SR vesicles and planar lipid bilayers, and that it inhibits activator-induced Ca release from SR in human skeletal muscle. In addition to confirming direct binding, photoaffinity labeling using azipropofol (AziP ) revealed several putative propofol binding sites on RyR1. Prediction of binding affinity by molecular dynamics simulation suggests that propofol binds at least one of these sites at clinical concentrations. These findings invite the hypothesis that in addition to propofol not triggering MH, it may also be protective against MH by inhibiting induced Ca flux through RyR1.
PubMed: 38260485
DOI: 10.1101/2024.01.10.575040 -
African Journal of Paediatric Surgery :... Jan 2024Transanal endorectal pull-through (TERPT) has become one of the preferred treatments for Hirschsprung's disease (HD) in our setting. This report aims to evaluate the...
BACKGROUND
Transanal endorectal pull-through (TERPT) has become one of the preferred treatments for Hirschsprung's disease (HD) in our setting. This report aims to evaluate the current outcome of TERPT in the setting.
MATERIALS AND METHODS
A retrospective review of 71 children who had TERPT for histologically-confirmed HD in 11 years (2006-2017) in Nigeria.
RESULTS
There were 48 boys and 23 girls; aged 3 days-12 years at initial presentation (median = 10 months). Three (4.2%) patients had associated anomalies (duodenal atresia; anorectal malformation and sensorineural deafness with hypopigmented skin patches each). Age at TERPT was 2 months to 15 years (median = 3 years), with surgery waiting time of 1 month-14.9 years (median = 18 months). Sixty-six (93.0%) patients had rectosigmoid, four (5.6%) patients had long segment and one (1.4%) had total colonic disease. Five (7.0%) patients with large megacolon and one (1.4%) with the total colonic disease had assisted abdominal resection of the colon at TERPT. Seventeen (23.9%) patients had post-operative complications, including post-operative enterocolitis 8 (11.3%); anastomotic dehiscence 3 (4.2%); retained aganglionic segment 2 (2.8%); anastomotic stenosis 2 (2.8%), resulting in prolonged hospital stay (P = 0.0001; range = 1-30 days; median = 5 days). The mortality rate was 4.2% (3) from malignant hyperthermia in one patient and in 2 patients, the cause of mortality was unclear. Patients were followed up for 3-6 years (median = 3.5 years). Bowel movement stabilised to 2-4 times daily by 6 weeks after surgery.
CONCLUSION
TERPT is a safe treatment for HD in this setting with good short-term outcomes. Longer follow-up is necessary to further evaluate the long-term bowel movement outcomes.!
Topics: Male; Child; Female; Humans; Hirschsprung Disease; Colonic Diseases; Anastomosis, Surgical; Anorectal Malformations
PubMed: 38259012
DOI: 10.4103/ajps.ajps_93_22