scholarly journals Benefits of combined treatments using antiresorptive agents and cytotoxic drugs

2006 ◽  
Vol 8 (S2) ◽  
Author(s):  
I Holen ◽  
H Neville-Webbe ◽  
RE Coleman
Keyword(s):  
Cytotoxic Drugs ◽  
Combined Treatments ◽  
Antiresorptive Agents

NOXA as Target for the Combination Therapy of Betulinic Acid and Conventional Cytotoxic Drugs

2010 ◽  
Vol 223 (01) ◽  
Author(s):  
I Jeremias ◽  
H Ehrhardt ◽  
I Höfig ◽  
N Terziyska ◽  
P Obexer
Keyword(s):  
Combination Therapy ◽  
Betulinic Acid ◽  
Cytotoxic Drugs

Two drug combinations vs combinations of 3 or more cytotoxic drugs for metastatic breast cancer

2009 ◽  
Author(s):  
Davina Ghersi ◽  
John Simes ◽  
I Craig Henderson ◽  
Russell Basser ◽  
Christine Brunswick ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Drug Combinations ◽  
Cytotoxic Drugs

scholarly journals Combination therapy of anabolic and nonbisphosphonates antiresorptive agents for the treatment of osteoporosis

Medicine ◽  
2017 ◽  
Vol 96 (52) ◽  
pp. e9534 ◽  
Author(s):  
Shenghan Lou ◽  
Lifan Wang ◽  
Yiwen Wang ◽  
Yunduo Jiang ◽  
Jingwei Liu ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Treatment Of Osteoporosis ◽  
Antiresorptive Agents

scholarly journals The Blockade of Tumoral IL1β-Mediated Signaling in Normal Colonic Fibroblasts Sensitizes Tumor Cells to Chemotherapy and Prevents Inflammatory CAF Activation

2021 ◽  
Vol 22 (9) ◽  
pp. 4960
Author(s):  
Natalia Guillén Díaz-Maroto ◽  
Gemma Garcia-Vicién ◽  
Giovanna Polcaro ◽  
María Bañuls ◽  
Nerea Albert ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Cell Types ◽  
Colorectal Tumor ◽  
Cytotoxic Drugs ◽  
Differential Sensitivity ◽  
Paracrine Signaling ◽  
Inflammatory Phenotype ◽  
Heterotypic Interactions ◽  
Carcinoma Associated Fibroblasts

Heterotypic interactions between newly transformed cells and normal surrounding cells define tumor’s fate in incipient carcinomas. Once homeostasis has been lost, normal resident fibroblasts become carcinoma-associated fibroblasts, conferring protumorogenic properties on these normal cells. Here we describe the IL1β-mediated interplay between cancer cells and normal colonic myofibroblasts (NCFs), which bestows differential sensitivity to cytotoxic drugs on tumor cells. We used NCFs, their conditioned media (CM), and cocultures with tumor cells to characterize the IL1β-mediated crosstalk between both cell types. We silenced IL1β in tumor cells to demonstrate that such cells do not exert an influence on NCFs inflammatory phenotype. Our results shows that IL1β is overexpressed in cocultured tumor cells. IL1β enables paracrine signaling in myofibroblasts, converting them into inflammatory-CAFs (iCAF). IL1β-stimulated-NCF-CM induces migration and differential sensitivity to oxaliplatin in colorectal tumor cells. Such chemoprotective effect has not been evidenced for TGFβ1-driven NCFs. IL1β induces the loss of a myofibroblastic phenotype in NCFs and acquisition of iCAF traits. In conclusion, IL1β-secreted by cancer cells modify surrounding normal fibroblasts to confer protumorogenic features on them, particularly tolerance to cytotoxic drugs. The use of IL1β-blocking agents might help to avoid the iCAF traits acquisition and consequently to counteract the protumorogenic actions these cells.

scholarly journals Physical Resilience as a Determinant of Healthspan and Lifespan in Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 829-829
Author(s):  
Nathan LeBrasseur
Keyword(s):  
Middle Ages ◽  
Interest Group ◽  
Later Life ◽  
Cytotoxic Drugs ◽  
Geriatric Syndromes ◽  
Age Related ◽  
Fundamental Biology ◽  
Dynamic Measures ◽  
Biology Of Aging ◽  
Insight Into

Abstract Dynamic measures of physical resilience—the ability to resist and recover from a challenge—may be informative of biological age far prior to overt manifestations such as age-related diseases and geriatric syndromes (i.e., frailty). If true, physical resilience at younger or middle ages may be predictive of future healthspan and lifespan, and provide a unique paradigm in which interventions targeting the fundamental biology of aging can be tested. This seminar will discuss research on the development of clinically-relevant measures of physical resilience in mice, including anesthesia, surgery, and cytotoxic drugs. It will further highlight how these measures compare between young, middle-aged, and older mice, and how mid-life resilience relates to later-life healthspan. Finally, it will provide insight into whether interventions targeting the biology of aging can modify physical resilience in mice. Part of a symposium sponsored by Epidemiology of Aging Interest Group.

scholarly journals Cancer Treatment–Induced Bone Loss (CTIBL): State of the Art and Proper Management in Breast Cancer Patients on Endocrine Therapy

2021 ◽  
Vol 22 (5) ◽  
Author(s):  
Anna Diana ◽  
Francesca Carlino ◽  
Emilio Francesco Giunta ◽  
Elisena Franzese ◽  
Luigi Pio Guerrera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Loss ◽  
Cancer Treatment ◽  
Endocrine Therapy ◽  
Aromatase Inhibitors ◽  
Bone Health ◽  
Optimal Time ◽  
Breast Cancer Patients ◽  
Antiresorptive Agents

Opinion statementAbout 70–80% of early breast cancer (BC) patients receive adjuvant endocrine therapy (ET) for at least 5 years. ET includes in the majority of cases the use of aromatase inhibitors, as upfront or switch strategy, that lead to impaired bone health. Given the high incidence and also the high prevalence of BC, cancer treatment–induced bone loss (CTIBL) represents the most common long-term adverse event experimented by patients with hormone receptor positive tumours. CTIBL is responsible for osteoporosis occurrence and, as a consequence, fragility fractures that may negatively affect quality of life and survival expectancy. As recommended by main international guidelines, BC women on aromatase inhibitors should be carefully assessed for their fracture risk at baseline and periodically reassessed during adjuvant ET in order to early detect significant worsening in terms of bone health. Antiresorptive agents, together with adequate intake of calcium and vitamin D, should be administered in BC patients during all course of ET, especially in those at high risk of osteoporotic fractures, as calculated by tools available for clinicians. Bisphosphonates, such as zoledronate or pamidronate, and anti-RANKL antibody, denosumab, are the two classes of antiresorptive drugs used in clinical practice with similar efficacy in preventing bone loss induced by aromatase inhibitor therapy. The choice between them, in the absence of direct comparison, should be based on patients’ preference and compliance; the different safety profile is mainly related to the route of administration, although both types of drugs are manageable with due care, since most of the adverse events are predictable and preventable. Despite advances in management of CTIBL, several issues such as the optimal time of starting antiresorptive agents and the duration of treatment remain unanswered. Future clinical trials as well as increased awareness of bone health are needed to improve prevention, assessment and treatment of CTIBL in these long-term survivor patients.

scholarly journals On the effect of antiresorptive drugs on the bone remodeling of the mandible after dental implantation: a mathematical model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mehran Ashrafi ◽  
Farzan Ghalichi ◽  
Behnam Mirzakouchaki ◽  
Manuel Doblare
Keyword(s):  
Mathematical Model ◽  
Bone Density ◽  
Bone Remodeling ◽  
Dental Implants ◽  
Implant Design ◽  
Patient Specific ◽  
Dental Implantation ◽  
Antiresorptive Agents ◽  
Antiresorptive Drugs

AbstractBone remodeling identifies the process of permanent bone change with new bone formation and old bone resorption. Understanding this process is essential in many applications, such as optimizing the treatment of diseases like osteoporosis, maintaining bone density in long-term periods of disuse, or assessing the long-term evolution of the bone surrounding prostheses after implantation. A particular case of study is the bone remodeling process after dental implantation. Despite the overall success of this type of implants, the increasing life expectancy in developed countries has boosted the demand for dental implants in patients with osteoporosis. Although several studies demonstrate a high success rate of dental implants in osteoporotic patients, it is also known that the healing time and the failure rate increase, necessitating the adoption of pharmacological measures to improve bone quality in those patients. However, the general efficacy of these antiresorptive drugs for osteoporotic patients is still controversial, requiring more experimental and clinical studies. In this work, we investigate the effect of different doses of several drugs, used nowadays in osteoporotic patients, on the evolution of bone density after dental implantation. With this aim, we use a pharmacokinetic–pharmacodynamic (PK/PD) mathematical model that includes the effect of antiresorptive drugs on the RANK/RANK-L/OPG pathway, as well as the mechano-chemical coupling with external mechanical loads. This mechano-PK/PD model is then used to analyze the evolution of bone in normal and osteoporotic mandibles after dental implantation with different drug dosages. We show that using antiresorptive agents such as bisphosphonates or denosumab increases bone density and the associated mechanical properties, but at the same time, it also increases bone brittleness. We conclude that, despite the many limitations of these very complex models, the one presented here is capable of predicting qualitatively the evolution of some of the main biological and chemical variables associated with the process of bone remodeling in patients receiving drugs for osteoporosis, so it could be used to optimize dental implant design and coating for osteoporotic patients, as well as the drug dosage protocol for patient-specific treatments.

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