scholarly journals Multi-Targeting DKK1 and LRP6 Prevents Myeloma-Induced Bone Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1605-1605
Author(s):  
Marija K Simic ◽  
Sindhu T Mohanty ◽  
Ya Xiao ◽  
Tegan L Cheng ◽  
Feng Cong ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Bone Resorption ◽  
Bone Formation ◽  
Combination Treatment ◽  
Bone Volume ◽  
Single Treatment ◽  
Combination Strategy ◽  
Targeted Treatments ◽  
Microct Analysis

Abstract Multiple myeloma (MM) is characterised by an expansion of malignant plasma cells in the bone marrow, systemic bone loss and destructive osteolytic bone lesions. These are mediated by an imbalance in bone remodeling, in which bone resorption is exacerbated and bone formation is suppressed. More than 90% of MM patients present with osteolytic lesions that can lead to pain and increased risk of fracture, significantly impacting their quality of life. Bone-targeted treatments currently used in the clinic can suppress lesion progression and reduce fracture risk, however these agents cannot replace lost bone and patients continue to fracture. Therapeutic strategies aimed at promoting bone formation are therefore required to overcome the loss of skeletal integrity and subsequent fractures in MM patients. Therapeutic agents that target the canonical Wnt signaling pathway, a potent regulator of bone formation, have the potential to address these skeletal complications, where they could rebuild lost bone and improve bone strength in affected individuals. We have demonstrated a novel anti-LRP6 agent, which potentiates Wnt signaling through binding the Wnt receptor LRP6, prevented the development of myeloma-induced bone loss primarily through preventing bone resorption. However, since MM patients present with both increased bone resorption and decreased bone formation, we hypothesised that combining anti-LRP6 with the bone anabolic anti-DKK1 (100mg/kg twice weekly intravenously) would lead to more robust improvements in bone structure than single treatment approaches. MicroCT analysis demonstrated a 74% increase in femoral trabecular bone volume per tissue volume (BV/TV) in naïve, non-tumour bearing mice given the combination treatment compared to control agents (p<0.0001). Mice injected with 5TGM1eGFP murine myeloma cells had a 34% reduction in femoral BV/TV compared to naïve controls (p<0.0001). Combination treatment drastically improved BV/TV in 5TGM1-bearing mice by 111% (p<0.0001), compared to control, and this improvement with the combination treatment strategy was 25% greater than anti-LRP6 single treatment approaches (p<0.001). MicroCT analysis in L4 lumbar vertebrae demonstrated similar bone structural changes in 5TGM1-bearing mice treated with the combination strategy. Consequently, this combination significantly improved resistance to fracture in L4 vertebrae in 5TGM1eGFP-bearing mice compared to their controls (p<0.001), and it provided greater protection against fracture compared to anti-LRP6 single agent treatment. Interestingly, these improvements in bone volume were primarily due to reduced bone resorption, with significant reductions in osteoclast numbers and osteoclast surface per bone surface demonstrated in 5TGM1eGFP-bearing mice treated with the combination strategy (p<0.001) compared to control. Importantly, tumour activity was not altered with either single or combination Wnt-promoting treatment strategies. This study defines a novel therapeutic strategy, which will reduce fractures and improve quality of life in patients with MM when used in combination with tumour-targeted treatments. Figure 1 Figure 1. Disclosures Cong: Novartis Institutes for Biomedical Research: Current Employment. Daley: Novartis Institutes of Biomedical Research: Current Employment.

Low energy amplitude modulated radiofrequency electromagnetic fields in combination with standard treatment or as monotherapy to show improvement in quality of life in patients with advanced hepatocellular carcinoma.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 290-290
Author(s):  
Micelange Carvalho Sousa ◽  
Frederico Costa ◽  
Pablo Diego Lima ◽  
Yone De Camargo Setogute ◽  
Brenda Pires Gumz ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Hepatocellular Carcinoma ◽  
Electromagnetic Fields ◽  
Combination Treatment ◽  
Treatment Modality ◽  
Advanced Hepatocellular Carcinoma ◽  
Single Treatment ◽  
Advanced Hcc ◽  
Radiofrequency Electromagnetic Fields

290 Background: Hepatocellular carcinoma (HCC) is a fatal cancer without curative option for most patients. Hence the importance to improve health related quality of life (HRQoL). Amplitude-modulated radiofrequency electromagnetic fields (EMF), as a novel and non-toxic therapy, has potential for improving HRQoL in advanced HCC patients. Methods: An open-label, single center, prospective clinical protocol was performed in advanced HCC patients as an initial and salvage treatment modality. Systemic exposure to EMF was used in combination with a systemic conventional treatment or as a single treatment. A spoon-shaped antenna placed in the oral cavity delivered EMF over 90 minutes with monthly repetitions until death or consent withdrawal. The effect on HRQoL was the primary objective of this study. Patients answered the EORTC-C30 v3.0 questionnaires prior to every EMF exposure. Clinically meaningful change (CMC) and time to deterioration (TTD) for Global Health (QoL), Role Functioning (RF) and Physical Functioning (PF) were used in the analysis. Results: From March 2018 to April 2020, 55 advanced HCC patients were submitted to 373 EMF exposures. 41/55 (75%) patients had repetitive exposures (mean # 4, ranging from 2-16). 87% were male, median age was 67, 84% were BLCL-C, 16% were Child-Pugh B, 29% had extra-hepatic metastasis, 55% had failed previous treatment and 71% had documented radiological progression. 31(56%) patients received EMF in combination with systemic therapy (28 TKI and 3 anti-PDL1). 24 patients received EMF as a single treatment modality. The mean baseline score was 68.1 for QoL and 77.1 for RF and PF. 61%, 76% and 49% of patients experienced positive change in QoL, RF and PS scores immediately prior to the second exposure, respectively. +CMC was reported in 20%, 17% and 32% of patients, respectively for QoL, RF and PS. The median QoL TTD was not reached. The median RF TTD was 7.2 month and the median PF TTD was 11.9 month. The median RF TTD for patients in combination treatment was 11.4 months and in a single treatment was 13.5 month. The median PF TTD for patients in combination treatment was 12.8 months and in single treatment was 14.5 month. Conclusions: Advanced HCC patients showed positive changes in QoL, RF and PF HRQoL scores after single exposure to EMF. The benefit from EMF in HRQoL was durable both in combination with TKI or as a single modality in advanced HCC patients. These results support future development as a novel palliative treatment modality in advanced HCC patients. Clinical trial information: NCT 01686412.

scholarly journals Long-COVID Syndrome? A Study on the Persistence of Neurological, Psychological and Physiological Symptoms

Healthcare ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 575
Author(s):  
Graziella Orrù ◽  
Davide Bertelloni ◽  
Francesca Diolaiuti ◽  
Federico Mucci ◽  
Mariagrazia Di Giuseppe ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Sleep Disturbances ◽  
Online Survey ◽  
Clinical Presentation ◽  
Demographic Data ◽  
Severity Index ◽  
Long Term Effects ◽  
Targeted Treatments ◽  
Euroqol 5D

Background: Emerging aspects of the Covid-19 clinical presentation are its long-term effects, which are characteristic of the so-called “long COVID”. The aim of the present study was to investigate the prevalence of physical, psychological, and sleep disturbances and the quality of life in the general population during the ongoing pandemic. Methods: This study, based on an online survey, collected demographic data, information related to COVID-19, sleep disturbances, and quality of life data from 507 individuals. The level of sleep disturbances and quality of life was assessed through the Insomnia Severity Index (ISI) and the EuroQol-5D (EQ-5D), respectively. Results: In total, 507 individuals (M = 91 and F = 416 women) completed the online survey. The main symptoms associated with “long COVID” were headache, fatigue, muscle aches/myalgia, articular pains, cognitive impairment, loss of concentration, and loss of smell. Additionally, the subjects showed significant levels of insomnia (p < 0.05) and an overall reduced quality of life (p < 0.05). Conclusions: The results of the study appear in line with recent publications, but uncertainty regarding the definition and specific features of “long COVID” remains. Further studies are needed in order to better define the clinical presentation of the “long COVID” condition and related targeted treatments.

scholarly journals Role of FBXW2 in explant culture of bovine periosteum-derived cells

2020 ◽  
Author(s):  
Mari Akiyma
Keyword(s):  
Quality Of Life ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Bone Fracture ◽  
Tissue Remodeling ◽  
Osteoporosis Treatment ◽  
Explant Culture ◽  
Periosteal Cells

AbstractOsteoporosis and bone fracture decrease quality of life. Bone regeneration is a notable technique for osteoporosis treatment. A previous study reported that F-box and WD-40 domain-containing protein 2 (FBXW2) and osteocalcin have the same shape in the periosteum after 5 weeks. However, the osteoblastic functions of FBXW2 are not clear. In this study, double fluorescent immunostaining revealed a small amount of osteocalcin in the area of FBXW2 aggregation at 1 week, periosteal cells, and osteocalcin pushed toward the edge of periosteum, and, apart from FBXW2 tubes at 2 weeks, multilayered periosteum-derived cells at 3 weeks and sticking of osteocalcin in the periosteum with cells at 4 weeks. At 5 weeks, FBXW2 disappeared at the root of periosteum-derived cells, while osteocalcin and cells remained. Based on these results, it is hypothesized that FBXW2 maintains tissue shapes and prevents escape of inner periosteal cells, and the disappearance of FBXW2 causes migration of periosteum-derived cells out of the periosteum along with osteocalcin. Furthermore, FBXW2 may play a role in dynamic tissue remodeling and bone formation.

scholarly journals 1% ivermectin in combination therapy regimens for rosacea

2020 ◽  
pp. 17-23
Author(s):  
E. A. Khlystova ◽  
A. L. Savastenko
Keyword(s):  
Quality Of Life ◽  
Comparative Analysis ◽  
Combination Therapy ◽  
Combination Treatment ◽  
Clinical Manifestations ◽  
Life Quality ◽  
Clinical Results ◽  
Control Group ◽  
Before And After

Introduction. The article provides latest data on modern methods of treating rosacea. The results of own clinical observations of patients with moderate to severe papulopustular rosacea receiving combination treatment and a comparative analysis of the efficacy of various therapy regimens are presented.Objective of the study. The aim of the study was to conduct a comparative analysis of the therapeutic efficacy of combination therapy using the ivermectin 1% topical drug combined with systemic therapy drugs (doxycycline, minocycline, isotretinoin).Materials and methods. We observed 37 patients with moderate to severe papulo-pustular rosacea subtype. The patients were divided into 4 groups (A, B, C, D). Patients in the control group received monotherapy with 1% ivemectin topical drug, patients in the other groups received combination therapy (1% ivermectin combined with low-dose doxycycline, minocycline and isotretinoin). The efficacy of the therapy was evaluated by measuring rosacea severity on the Scale for Diagnostic Assessment of Rosacea (SDAR), clinical manifestations according to the IGA (Investigator Global Assessment) criteria, and by assessing the patients' quality of life using the DLQI (Dermatology Life Quality Index) questionnaire before and after 3-month treatment.Results. The comparative analysis of changes in severity indicators of the skin process and quality of life in patients with moderate to severe papulopustular rosacea after topical and combination therapy showed that the results of the treatment in patients receiving combination therapy were more significant than those in the group receiving monotherapy.Conclusion. The concomitant use of 1% ivermectin and systemic drugs is most effective in patients with severe papulopustular rosacea subtype. The combination treatment tailored to the clinical forms and severity of rosacea allows to optimize the clinical results of the therapy, which significantly affects the patients' quality of life and opens up potential for an individual approach in the algorithms for the treatment of rosacea.

scholarly journals Effect of Multimodal Intervention Care on Cachexia in Patients with Advanced Cancer Compared To Conventional Management (MIRACLE): An Open-Label, Parallel, Randomized, Phase 2 Trial

2021 ◽  
Author(s):  
Chi Hoon Maeng ◽  
Bo-Hyung Kim ◽  
Jinmann Chon ◽  
Won Sub Kang ◽  
Kyounglan Kang ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Clinical Trial ◽  
Palliative Chemotherapy ◽  
Handgrip Strength ◽  
Complex Interventions ◽  
Omega 3 ◽  
Single Treatment ◽  
Nutritional Counseling ◽  
Multimodal Intervention

Abstract Background: the context and purpose of the studyCancer cachexia (CC) is a multifactorial process characterized by progressive weight loss, muscle mass, and fat tissue wasting, which adversely affects the quality of life and survival of patients with advanced stages of cancer. CC has a complex and multifactorial pathophysiology, and there is no established standard treatment. Therefore, it is often irreversible and a single treatment modality is unlikely to suppress its progression. We are conducting a randomized trial to investigate the efficacy and safety of a multimodal intervention compared to the best supportive care for patients who received palliative chemotherapy.Methods: how the study will be performedPatients with lung or gastrointestinal cancers undergoing palliative chemotherapy are eligible. Patients are randomized into a multimodal intervention care (MIC) arm versus a conventional palliative care (CPC) arm. MIC includes ibuprofen, omega-3-fatty acid, oral nutritional supplement, weekly physical, psychiatric assessment, nutritional counseling, and complementary and alternative medicine. CPC includes basic nutritional counseling and megestrol acetate as needed (i.e., anorexia ≥ grade 2). All interventions are performed for 12 weeks per subject. The co-primary outcomes are median change (kg) in total lean body mass and handgrip strength (kg) from the baseline. A total of 112 patients will be assigned to the two arms (56 in each group). Discussion: a brief summary and potential implicationsThe purpose of this study is to evaluate the effect of MIC in preventing or alleviating CC in patients who underwent palliative chemotherapy. As there is no established single treatment for CC, it is expected that the results of this clinical trial will provide new insights to significantly improve the quality of life of patients with cancer. Considering the complex mechanisms of cachexia, the effect of MIC rather than a single specific drug is more promising. In this study, we did not overly restrict the type of cancer or chemotherapy. Therefore, we attempted to measure the effects of complex interventions while preserving clinical situations. Thus, it is expected that the results of this study can be applied effectively to real-world practice.Trial registration: If your article reports the results of a health care intervention on human participants, it must be registered in an appropriate registry and the registration number and date of registration should be in stated in this section. If it was not registered prospectively (before enrollment of the first participant), you should include the words 'retrospectively registered'. See our editorial policies for more information on trial registration.This clinical trial was registered in the Clinical Research Information Service (KCT0004967), Korean Clinical Trial Registry on April 27, 2020, and ClinicalTrial.gov (NCT 04907864) on June 1, 2021.

Osteonecrosis of the jaw: BRONJ and ARONJ

2014 ◽  
Vol 5 (2) ◽  
pp. 90-93 ◽  
Author(s):  
Salvatore Ruggiero
Keyword(s):  
Quality Of Life ◽  
Bone Resorption ◽  
Osteonecrosis Of The Jaw ◽  
Small Subset ◽  
Antiresorptive Agents ◽  
Osteoclast Function

Bisphosphonates and other more recent antiresorptive agents are potent inhibitors of osteoclast function and osteoclast-mediated bone resorption. As such, they have been effectively utilised to reduce skeletally related events and improve the quality of life of patients with osteoporosis and malignant osteolytic disease. Despite these benefits, osteonecrosis of the jaw continues to be a worrisome complication in a small subset of patients receiving these drugs.

Gingival Medicinal Signaling Cells Conditioned Medium effect on the Osteoclast and Osteoblast number in Lipopolysaccharide-induced Calvaria Bone Resorption in Wistar Rats’ (Rattus novergicus)

2021 ◽  
pp. 5232-5237
Author(s):  
Nastiti Faradilla Ramadhani ◽  
Alexander P. Nugraha ◽  
Igo S. Ihsan ◽  
Yoni A. Agung ◽  
Fedik A. Rantam ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Bone Resorption ◽  
Conditioned Medium ◽  
Wistar Rats ◽  
Potential Effect ◽  
Medium Effect ◽  
Peptide Growth Factor ◽  
Cervical Dislocation ◽  
One Way Anova

The gingival medicinal signaling cells conditioned medium (GMSCs-CM) is a biocompatible material which possessed beneficial cytokine, anti-microbial peptide, growth factor that can be collected after culture. GMSCs- CM may inhibit bone resorption in order to improve the patient’s quality of life. In this study, the potential effect of GMSCs-CM on the number of osteoclasts and osteoblasts in Lipopolysaccharide (LPS)-induced calvaria bone resorption in wistar rats (Rattus novergicus) has been analyzed. Twenty-eight male and healthy wistar rats (R. novergicus) at the age of 1-2 months old with 250-300 grams body weight were divided into 4 groups, namely PBS group: 100μg PBS day 1-7; LPS group: 100μg LPS day 1-7; LPS and GMSCs group: 100μg LPS + 100μg GMSCS-CM day 1 1-7, GMSCs group: 100μg M-GMSCs day 1-7. Escherichia Coli LPS was used to induce the bone resorption on the calvaria with subcutaneous injection. GMSCs-CM was collected after passage 4-5 then injected subcutaneously on the calvaria. All samples were examined on the. 8th day through cervical dislocation. The number of osteoblasts and osteoclasts in calvaria was then observed under 400x magnification. One Way ANOVA and Tukey HSD were conducted to analyze differences between groups (p<0.01). The number of osteoclasts in calvaria decreased significantly in the LPS + GMSCs-CM group compared to LPS group (p<0.01). The number of osteoblasts in calvaria increased significantly in the LPS + GMSCs-CM group compared to LPS group (p<0.01). GMSCs-CM can reduce the amount of osteoclast significantly and increases the production of osteoblast in LPS-induced calvaria bone resorption in wistar rats (R. novergicus).

5 alpha-Dihydrotestosterone partially restores cancellous bone volume in osteopenic ovariectomized rats

1994 ◽  
Vol 267 (6) ◽  
pp. E853-E859 ◽  
Author(s):  
J. H. Tobias ◽  
A. Gallagher ◽  
T. J. Chambers
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Cancellous Bone ◽  
Bone Growth ◽  
Bone Volume ◽  
Ovariectomized Rats ◽  
Trabecular Thickness ◽  
Longitudinal Bone Growth ◽  
Periosteal Bone Formation

Although androgens are thought to be important for skeletal maintenance in females and males, little is known about the mechanisms involved. To investigate this question further, we examined the effects of administering 0.01, 0.1, or 1.0 mg/kg 5 alpha-dihydrotestosterone (DHT) for 60 days on the skeleton of ovariectomized rats. Treatment was delayed until 90 days after ovariectomy to enable bone loss to stabilize. We found that ovariectomy markedly reduced cancellous bone volume of the proximal tibial metaphysis due to a combination of loss and thinning of trabeculae. Cancellous bone volume was partially restored by all doses of DHT, with trabecular thickness, but not number, returning to that of sham-operated animals. DHT also stimulated longitudinal bone growth and endosteal and periosteal bone formation and suppressed histomorphometric indexes of cancellous bone resorption. This suggests that DHT influences skeletal metabolism in osteopenic ovariectomized rats both by stimulating bone formation and suppressing resorption, although it is unclear which, if any, of these actions predominate at cancellous sites.

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