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Medicine Jan 2021To evaluate the efficacy and safety of plasma rich in growth factors (PRGF) in photorefractive keratectomy (PRK) versus Mitomycin C (MMC).This is a comparative,... (Comparative Study)
Comparative Study Observational Study
To evaluate the efficacy and safety of plasma rich in growth factors (PRGF) in photorefractive keratectomy (PRK) versus Mitomycin C (MMC).This is a comparative, longitudinal and retrospective case-control study (MMC vs PRGF), in patients with a spherical correction from -0.25 to -8.00 D and cylinder correction from -0.25 to -3.00. The uncorrected distance visual acuity (UDVA), refractive efficacy and safety indices, and changes in endothelial cell density were evaluated. The predictability was assessed with the postoperative manifest spherical equivalent.Forty-four patients (72 eyes) were treated with MMC and twenty-five patients (45 eyes) with PRGF. The final UDVA (LogMar) in MMC was 0.029 ± 0.065 and in PRGF it was 0.028 ± 0.048 (p = 0.383). The efficacy index for MMC was 0.98 ± 0.10 and 1.10 ± 0.46 for patients treated with PRGF (p = 0.062). The safety index for MMC was 1.03 ± 0.11 and 1.12 ± 0.46 (p = 0.158) for PRGF group. The change percentage of endothelial cell density was 0.9 ± 11.6 for MMC and 4.3 ± 13.1 for PRGF (p = 0.593). The predictability for MMC was 92.1% and for the PRGF was 91.9% (p = 0.976). Hyperemia, eye pain and superficial keratitis were observed in 11.1% of the MMC group; no adverse events were observed with the PRGF.The use of PRGF in PRK surgery is as effective as MMC. The PRGF shows a better safety profile than MMC for its intraoperative use in PRK.
Topics: Adult; Aged; Antibiotics, Antineoplastic; Blood Transfusion, Autologous; Corneal Opacity; Female; Humans; Intercellular Signaling Peptides and Proteins; Longitudinal Studies; Male; Middle Aged; Mitomycin; Ophthalmic Solutions; Photorefractive Keratectomy; Postoperative Complications; Retrospective Studies; Young Adult
PubMed: 33546027
DOI: 10.1097/MD.0000000000024139 -
Cancer Letters Sep 2020The dependency of prostate cancer (PCa) growth on androgen receptor (AR) signaling has been harnessed to develop first-line therapies for high-risk localized and...
The dependency of prostate cancer (PCa) growth on androgen receptor (AR) signaling has been harnessed to develop first-line therapies for high-risk localized and metastatic PCa treatment. However, the occurrence of aberrant expression, mutated or splice variants of AR confers resistance to androgen ablation therapy (ADT), radiotherapy or chemotherapy in AR-positive PCa. Therapeutic strategies that effectively inhibit the expression and/or transcriptional activity of full-length AR, mutated AR and AR splice variants have remained elusive. In this study, we report that mithramycin (MTM), an antineoplastic antibiotic, suppresses cell proliferation and exhibits dual inhibitory effects on expression and transcriptional activity of AR and AR splice variants. MTM blocks AR recruitment to its genomic targets by occupying AR enhancers and causes downregulation of AR target genes, which includes key DNA repair factors in DNA damage repair (DDR). We show that MTM significantly impairs DDR and enhances the effectiveness of ionizing radiation or the radiomimetic agent Bleomycin in PCa. Thus, the combination of MTM treatment with RT or radiomimetic agents, such as bleomycin, may present a novel effective therapeutic strategy for patients with high-risk, clinically localized PCa.
Topics: Antibiotics, Antineoplastic; Cell Line, Tumor; DNA Damage; DNA Repair; Humans; Male; Plicamycin; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen
PubMed: 32485222
DOI: 10.1016/j.canlet.2020.05.027 -
Drug Delivery Dec 2022The traditional systemic chemotherapy through intravenous infusion of doxorubicin (DOX) has many side effects. The aim of this study was to develop a PLGA-based...
The traditional systemic chemotherapy through intravenous infusion of doxorubicin (DOX) has many side effects. The aim of this study was to develop a PLGA-based DOX-loaded implant and to evaluate the efficacy and drug metabolism distribution of the implant in intratumoral chemotherapy for osteosarcoma (OS). In this study, implants containing DOX, poly(d,l-lactide-co-glycolide), and polyethylene glycol 4000 were prepared by melt-molding method. Then, the antitumor activity and systemic drug distribution of the implants were tested in a K7M2 OS bearing mouse model. The scanning electron microscope images showed that DOX was uniformly dispersed in the polymer matrix. Both the and release profiles of implants are characterized by three-phase release. Implantation of DOX-loaded implants into tumors can inhibit tumor growth in a dose-dependent manner. The pharmacokinetic behavior shows that intratumor chemotherapy through implants has a much higher drug concentration in tumors than in normal tissues, which may be the reason for improving antitumor activity and reducing systemic side effects. In summary, the drug release of the implants prepared in this study is sustained and stable, which promotes long-term local accumulation of drugs in tumors, improves the efficacy of chemotherapy and has low toxicity to normal tissues.
Topics: Animals; Animals, Outbred Strains; Antibiotics, Antineoplastic; Bone Neoplasms; Cell Line, Tumor; Doxorubicin; Drug Implants; Drug Liberation; Female; Male; Mice; Mice, Inbred BALB C; Osteosarcoma; Polyethylene Glycols; Polylactic Acid-Polyglycolic Acid Copolymer; Random Allocation; Rats, Sprague-Dawley; Technology, Pharmaceutical; Xenograft Model Antitumor Assays; Rats
PubMed: 35147071
DOI: 10.1080/10717544.2022.2032878 -
ESC Heart Failure Jun 2022Understanding cardiac function after anthracycline administration is very important from the perspective of preventing the onset of heart failure. Although cardiac...
AIMS
Understanding cardiac function after anthracycline administration is very important from the perspective of preventing the onset of heart failure. Although cardiac magnetic resonance and echocardiography are recognized as the 'gold standard' for detecting cardiotoxicity, they have many shortcomings. We aimed to investigate whether cardiac computed tomography (CCT) could replace these techniques, assessing serial changes in cardiac tissue characteristics as determined by CCT after anthracycline administration.
METHODS AND RESULTS
We prospectively investigated 15 consecutive breast cancer patients who were scheduled to receive anthracycline therapy. We performed echocardiography and CCT before and 3, 6, and 12 months after anthracycline treatment. The mean cumulative administered anthracycline dose was 269.9 ± 14.6 mg/m (doxorubicin-converted dose). Of the 15 enrolled patients who received anthracycline treatment for breast cancer, none met the definition of cardiotoxicity. The CCT-derived extracellular volume fraction tended to continue to increase after anthracycline treatment and had relatively similar dynamics to the left ventricular ejection fraction and global longitudinal strain as determined by echocardiography.
CONCLUSIONS
Our findings indicated that CCT could provide adequate information about the characteristics of myocardial tissue after anthracycline administration. CCT may improve the understanding of cardiotoxicity by compensating for the weaknesses of echocardiography. This technique could be useful for understanding cardiac tissue characterization as a 'one-stop shop' evaluation, providing new insight into cardiooncology.
Topics: Anthracyclines; Antibiotics, Antineoplastic; Breast Neoplasms; Cardiotoxicity; Female; Humans; Stroke Volume; Tomography; Ventricular Function, Left
PubMed: 35289088
DOI: 10.1002/ehf2.13867 -
Nanotheranostics 2022Mild hyperthermia (HT) (40-43 °C) has been combined with temperature-sensitive liposomes (TSL), offering on-demand drug release for increased drug bioavailability and...
Mild hyperthermia (HT) (40-43 °C) has been combined with temperature-sensitive liposomes (TSL), offering on-demand drug release for increased drug bioavailability and reduced systemic toxicity. Different HT regimens have been applied to trigger liposome drug release in the blood vessels (intravascular) of heated tumours or following tumour extravasation (interstitial). The present study systematically assessed the doxorubicin (Dox) release and therapeutic efficacy of Dox-loaded TSL with different release profiles. Low temperature-sensitive liposomes (LTSL-Dox), traditional-temperature-sensitive liposomes (TTSL-Dox), and non-temperature-sensitive liposomes (NTSL-Dox) were combined with a single or two HT in different tumour models (murine melanoma B16F10 tumour and human breast MDA-MB-435). The efficacy of each treatment was assessed by monitor tumour growth and mice survival. The level of Dox in tumour tissues was quantified using C-Dox and liquid scintillation while Dox release was assessed using live imaging and confocal laser scanning microscopy. Applying a second HT to release Dox from extravasated TTSL-Dox was not therapeutically superior to single HT application due to Dox clearance from the extravasated TTSL-Dox. Our findings revealed that enhanced blood perfusion in heated tumours during the second water bath HT could be seen as a hurdle for TTSL-Dox's anticancer efficacy, where the systemic toxicity of the redistributed Dox from the tumour tissues could be potentiated.
Topics: Animals; Antibiotics, Antineoplastic; Doxorubicin; Hyperthermia, Induced; Liposomes; Melanoma; Mice; Temperature
PubMed: 35145834
DOI: 10.7150/ntno.61280 -
Trials Dec 2023Alopecia is one of the most common adverse effects of chemotherapy. It reduces the patient's self-esteem and quality of life and the effect of therapy. Scalp cooling is...
BACKGROUND
Alopecia is one of the most common adverse effects of chemotherapy. It reduces the patient's self-esteem and quality of life and the effect of therapy. Scalp cooling is the only verified current method for prevention but success is not guaranteed, particularly after receiving anthracycline-based combinations. Low-level light therapy has been clinically proven to inhibit the progress of androgenic alopecia. A previous study using human subjects shows limited benefits for low-level light therapy for patients who suffer chemotherapy-induced alopecia but an increase in the number of probes and the optimization of light sources may improve the efficacy. This study determines the efficacy of low-level light therapy for the prevention of chemotherapy-induced hair loss for patients with breast cancer using a randomized controlled trial.
METHODS
One hundred six eligible breast cancer patients were randomly distributed into a low-level light therapy group and a control group, after receiving chemotherapy. Subjects in the low-level light therapy group received 12 courses of intervention within 4 weeks. Subjects in the control group received no intervention but were closely monitored. The primary outcome is measured as the difference in the hair count in a target area between the baseline and at the end of week 4, as measured using a phototrichogram (Sentra scalp analyzer). The secondary outcomes include the change in hair count at the end of week 1, week 2, and week 3 and hair width at the end of week 1, week 2, week 3, and week 4, as measured using a phototrichogram, and the change in distress, the quality of life, and self-esteem due to chemotherapy-induced alopecia, at the end of week 4, as measured using a questionnaire.
DISCUSSION
This study improves cancer patients' quality of life and provides clinical evidence.
TRIAL REGISTRATION
Registered at ClinicalTrials.gov- NCT05397457 on 1 June 2022.
Topics: Humans; Female; Low-Level Light Therapy; Quality of Life; Head Protective Devices; Alopecia; Scalp; Antibiotics, Antineoplastic; Breast Neoplasms; Randomized Controlled Trials as Topic
PubMed: 38053197
DOI: 10.1186/s13063-023-07823-x -
Nature Communications Mar 2024Anthracyclines can cause cancer therapy-related cardiac dysfunction (CTRCD) that adversely affects prognosis. Despite guideline recommendations, only half of the...
Anthracyclines can cause cancer therapy-related cardiac dysfunction (CTRCD) that adversely affects prognosis. Despite guideline recommendations, only half of the patients undergo surveillance echocardiograms. An AI model detecting reduced left ventricular ejection fraction from 12-lead electrocardiograms (ECG) (AI-EF model) suggests ECG features reflect left ventricular pathophysiology. We hypothesized that AI could predict CTRCD from baseline ECG, leveraging the AI-EF model's insights, and developed the AI-CTRCD model using transfer learning on the AI-EF model. In 1011 anthracycline-treated patients, 8.7% experienced CTRCD. High AI-CTRCD scores indicated elevated CTRCD risk (hazard ratio (HR), 2.66; 95% CI 1.73-4.10; log-rank p < 0.001). This remained consistent after adjusting for risk factors (adjusted HR, 2.57; 95% CI 1.62-4.10; p < 0.001). AI-CTRCD score enhanced prediction beyond known factors (time-dependent AUC for 2 years: 0.78 with AI-CTRCD score vs. 0.74 without; p = 0.005). In conclusion, the AI model robustly stratified CTRCD risk from baseline ECG.
Topics: Humans; Antineoplastic Agents; Cardiotoxicity; Stroke Volume; Artificial Intelligence; Ventricular Function, Left; Heart Diseases; Antibiotics, Antineoplastic; Ventricular Dysfunction, Left; Anthracyclines; Electrocardiography
PubMed: 38514629
DOI: 10.1038/s41467-024-45733-x -
Molecules (Basel, Switzerland) Jul 2022Different drug classes such as antineoplastic drugs (anthracyclines, cyclophosphamide, 5-fluorouracil, taxanes, tyrosine kinase inhibitors), antiretroviral drugs,... (Review)
Review
Different drug classes such as antineoplastic drugs (anthracyclines, cyclophosphamide, 5-fluorouracil, taxanes, tyrosine kinase inhibitors), antiretroviral drugs, antipsychotic, and immunosuppressant drugs are known to induce cardiotoxic and neurotoxic effects. Recent studies have demonstrated that the impairment of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is a primary event in the pathophysiology of drug-induced cardiotoxicity and neurotoxicity. The Nrf2 pathway regulates the expression of different genes whose products are involved in antioxidant and inflammatory responses and the detoxification of toxic species. Cardiotoxic drugs, such as the anthracycline doxorubicin, or neurotoxic drugs, such as paclitaxel, suppress or impair the Nrf2 pathway, whereas the rescue of this pathway counteracts both the oxidative stress and inflammation that are related to drug-induced cardiotoxicity and neurotoxicity. Therefore Nrf2 represents a novel pharmacological target to develop new antidotes in the field of clinical toxicology. Interestingly, carnosine (β-alanyl-l-histidine), an endogenous dipeptide that is characterized by strong antioxidant, anti-inflammatory, and neuroprotective properties is able to rescue/activate the Nrf2 pathway, as demonstrated by different preclinical studies and preliminary clinical evidence. Starting from these new data, in the present review, we examined the evidence on the therapeutic potential of carnosine as an endogenous antidote that is able to rescue the Nrf2 pathway and then counteract drug-induced cardiotoxicity and neurotoxicity.
Topics: Anthracyclines; Antibiotics, Antineoplastic; Antidotes; Antioxidants; Cardiotoxicity; Carnosine; Humans; NF-E2-Related Factor 2; Neurotoxicity Syndromes; Oxidative Stress
PubMed: 35889325
DOI: 10.3390/molecules27144452 -
Journal of Ethnopharmacology Apr 2021Propolis extracts are widely used in traditional folk medicine and exhibit several properties such as antitumor, anti-inflammatory, and antimicrobial. However, these...
ETHNOPHARMACOLOGICAL RELEVANCE
Propolis extracts are widely used in traditional folk medicine and exhibit several properties such as antitumor, anti-inflammatory, and antimicrobial. However, these products have not been investigated in combination with medicines used in clinical practice.
AIM OF THE STUDY
This study aimed to evaluate the chemical composition of propolis extracts from Apis mellifera scutellata and different Meliponini species and characterize their cytotoxicity against tumor cells, antibacterial effects, and interference with the actions of doxorubicin and gentamicin.
MATERIALS AND METHODS
Chromatographic and spectrometric analyses were performed using ultra-high-performance liquid chromatography (UPLC)-tandem mass spectrometry (MS/MS). Propolis extracts were evaluated for cytotoxicity and synergism using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the antimicrobial activity was examined using the broth microdilution technique and synergism was investigated using checkerboard and time-kill assays.
RESULTS
The chemical characterization revealed the presence of 63 compounds, and the extracts showed selective cytotoxicity against tumor cell lines. Propolis extracts of mandaçaia and mirim exerted selective synergistic cytotoxicity in combination with doxorubicin. Except for the tubuna extract, all evaluated extracts exhibited antibacterial effects on gram-positive strains. Mandaçaia and mirim extracts exerted a synergistic effect with gentamicin; however, only mandaçaia extract exerted a selective effect.
CONCLUSION
Propolis could be a source of antineoplastics and antibiotics. These natural products may reduce the occurrence of doxorubicin and gentamicin related adverse effects, resistance, or both.
Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Bees; Cell Survival; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; HeLa Cells; Hep G2 Cells; Humans; MCF-7 Cells; Propolis; Tandem Mass Spectrometry
PubMed: 33307049
DOI: 10.1016/j.jep.2020.113662 -
BMC Cancer Oct 2023Current treatment of acute leukemia is based on anthracycline chemotherapy. Anthracyclines, despite improving patient survival, have serious cardiotoxicity and therefore... (Observational Study)
Observational Study
BACKGROUND
Current treatment of acute leukemia is based on anthracycline chemotherapy. Anthracyclines, despite improving patient survival, have serious cardiotoxicity and therefore cardiac monitoring should be a priority. The purpose of this study is to explore the possible early predictors of anthracycline-induced subclinical cardiotoxicity(AISC)in acute leukemia patients.
METHODS
We conducted a prospective observational study involving 51 patients with acute leukemia treated with anthracycline. Demographic data, clinical variables, echocardiography variables and biochemical variables were collected at baseline and after 3 cycles of chemotherapy. Patients were divided into the AISC and No-AISC groups according to changes of global longitudinal peak systolic strain. Regression models and receiver operating characteristic curve analysis were used to explore the relationship between the variables and AISC.
RESULT
17 of the patients suffered subclinical cardiotoxicity after 3 cycles of anthracycline treatment. Multiple logistic regression analysis showed a significant association of DBil (OR 0.612, 95% CI 0.409-0.916, p = 0.017), TBil (OR 0.841, 95% CI 0.717-0.986, p = 0.033), PLT (OR 1.012, 95% CI 1.002-1.021, p = 0.016) and Glu (OR 1.873, 95% CI 1.009-3.475, p = 0.047) with the development of AISC. After 3 cycles of chemotherapy, there was a significant difference in PLT between the AISC and NO-AISC groups. Moreover, the dynamic changes in PLT from baseline to after 3 cycles of chemotherapy were each statistically significant in the AISC and NO-AISC groups. The combination of PLT and N-terminal pro-B-type natriuretic peptide (NT-proBNP) had the highest area under curves (AUC) for the diagnosis of AISC than PLT and NT-proBNP alone (AUC = 0.713, 95%CI: 0.56-0.87, P = 0.017).
CONCLUSION
Total bilirubin (TBil), direct bilirubin (DBil), platelets (PLT) and blood glucose (Glu) are independent influencing factors for AISC in acute leukemia patients receiving anthracycline therapy. Bilirubin may be a protective factor and PLT may be a contributing factor for AISC. The combination of baseline PLT and baseline NT-proBNP shows satisfactory predictive ability for AISC in acute leukemia cases treated with 3 cycles of chemotherapy.
Topics: Humans; Acute Disease; Anthracyclines; Antibiotics, Antineoplastic; Bilirubin; Biomarkers; Cardiotoxicity; Leukemia, Myeloid, Acute; Prospective Studies
PubMed: 37833648
DOI: 10.1186/s12885-023-11060-5