Prevention of chemotherapy-induced alopecia in rodent models.
Ontology highlight
ABSTRACT:
SUBMITTER: Jimenez JJ
PROVIDER: S-EPMC2666212 | biostudies-other | 2008
REPOSITORIES: biostudies-other
Similar Datasets
Project description:BackgroundChemotherapy-induced alopecia (CIA) is one of the most dramatic side effects of chemotherapy. Currently no guidelines are available for its prevention and treatment. Several devices and drugs are used, but results are often disappointing.AimsOur aim is to analyze drugs and devices proposed in the literature for prevention and treatment of CIA induced by cytotoxic drugs and to discuss the evidenced-based opinion.Methods and ResultsScalp cooling is the only agent that has been approved by the US Food and Drug Administration for CIA prevention. Minoxidil and bimatoprost should not be used during chemotherapy administration, but they can be used after chemotherapy discontinuation to obtain greater regrowth.ConclusionsTherapy should always be modulated for the patient and no fixed protocol should be used. Trichoscopy and trichogram could be useful tools in supporting this treatment.
| S-EPMC7319796 | biostudies-literature
Project description:Millions of new cancer patients receive chemotherapy each year. In addition to killing cancer cells, chemotherapy is likely to damage rapidly proliferating healthy cells, including the hair follicle keratinocytes. Chemotherapy causes substantial thinning or loss of hair, termed chemotherapy-induced alopecia (CIA), in approximately 65% of patients. CIA is often ranked as one of the most distressing adverse effects of chemotherapy, but interventional options have been limited. To date, only scalp cooling has been cleared by the US Food and Drug Administration (FDA) to prevent CIA. However, several factors, including the high costs not always covered by insurance, preclude its broader use. Here we review the current options for CIA prevention and treatment and discuss new approaches being tested. CIA interventions include scalp cooling systems (both non-portable and portable) and topical agents to prevent hair loss, versus topical and oral minoxidil, photobiomodulation therapy (PBMT), and platelet-rich plasma (PRP) injections, among others, to stimulate hair regrowth after hair loss. Evidence-based studies are needed to develop and validate methods to prevent hair loss and/or accelerate hair regrowth in cancer patients receiving chemotherapy, which could significantly improve cancer patients' quality of life and may help improve compliance and consequently the outcome of cancer treatment.
| S-EPMC10137043 | biostudies-literature
Project description:PurposeChemotherapy-induced alopecia (CIA) negatively affects psychosocial health and quality of life (QoL). Currently, there are no approved pharmacologic agents to prevent CIA. Here, we evaluated the safety, tolerability, and potential signal of efficacy of topical calcitriol (BPM31543) on CIA prevention.Materials and methodsThis Phase 1 trial included 23 female patients with breast cancer, gynecologic cancer, or sarcomas receiving a taxane-based chemotherapy. Patients received a 3 + 3 dose-escalation regimen at 5, 10, 20, 40, 60, and 80 μg/mL, with 3-6 patients per group. Patients applied topical BPM31543 to the scalp twice a day for 2 weeks prior to chemotherapy and continued until chemotherapy treatment was completed. The maximum tolerated dose (MTD) during first 28 day application was determined. Adverse event (AE) monitoring, pharmacokinetics, blinded photographic assessments, and patient self-assessment were evaluated.ResultsOut of 23 patients treated with BPM31543, 8 patients experienced at least 1 treatment-related adverse event (AE). The majority of AEs were mild to moderate in severity. Only 1 patient experienced SAEs (vomiting, nausea, fever, and flank pain) considered treatment related. Alopecia < 50% from baseline was observed in 8 patients at Week 7, and, of which 2 patients had < 50% alopecia maintained at Week 15. There were no detectable effects of topical BPM31543 on serum levels of calcitriol.ConclusionsBPM31543 applied topically twice daily to the scalp is safe and well tolerated in patients receiving taxane-based chemotherapy. No DLT was observed at up to 80 µg/mL, and MTD was not reached. Based on the data from this trial, BPM31543 represents a promising therapy and warrants further investigation in Phase 2/3 trials.
| S-EPMC8388155 | biostudies-literature
Project description:Chemotherapy-induced hair loss (alopecia) (CIA) is one of the most feared side effects of chemotherapy among cancer patients. There is currently no pharmacological approach to minimize CIA, although one strategy that has been proposed involves protecting normal cells from chemotherapy by transiently inducing cell cycle arrest. Proof-of-concept for this approach, known as cyclotherapy, has been demonstrated in cell culture settings.The eukaryotic initiation factor (eIF) 4E is a cap binding protein that stimulates ribosome recruitment to mRNA templates during the initiation phase of translation. Suppression of eIF4E is known to induce cell cycle arrest. Using a novel inducible and reversible transgenic mouse model that enables RNAi-mediated suppression of eIF4E in vivo, we assessed the consequences of temporal eIF4E suppression on CIA.Our results demonstrate that transient inhibition of eIF4E protects against cyclophosphamide-induced alopecia at the organismal level. At the cellular level, this protection is associated with an accumulation of cells in G1, reduced apoptotic indices, and was phenocopied using small molecule inhibitors targeting the process of translation initiation.Our data provide a rationale for exploring suppression of translation initiation as an approach to prevent or minimize cyclophosphamide-induced alopecia.
| S-EPMC4225821 | biostudies-other
Project description:BackgroundCurrent treatments of chemotherapy-induced cardiomyopathy (CCM) are of limited efficacy. We assessed whether repeated intravenous injections of human extracellular vesicles from cardiac progenitor cells (EV-CPC) could represent a new therapeutic option and whether EV manufacturing according to a Good Manufacturing Practices (GMP)-compatible process did not impair their bioactivity.MethodsImmuno-competent mice received intra-peritoneal injections (IP) of doxorubicin (DOX) (4 mg/kg each; cumulative dose: 12 mg/kg) and were then intravenously (IV) injected three times with EV-CPC (total dose: 30 billion). Cardiac function was assessed 9-11 weeks later by cardiac magnetic resonance imaging (CMR) using strain as the primary end point. Then, immuno-competent rats received 5 IP injections of DOX (3 mg/kg each; cumulative dose 15 mg/kg) followed by 3 equal IV injections of GMP-EV (total dose: 100 billion). Cardiac function was assessed by two dimensional-echocardiography.ResultsIn the chronic mouse model of CCM, DOX + placebo-injected hearts incurred a significant decline in basal (global, epi- and endocardial) circumferential strain compared with sham DOX-untreated mice (p = 0.043, p = 0.042, p = 0.048 respectively) while EV-CPC preserved these indices. Global longitudinal strain followed a similar pattern. In the rat model, IV injections of GMP-EV also preserved left ventricular end-systolic and end-diastolic volumes compared with untreated controls.ConclusionsIntravenously-injected extracellular vesicles derived from CPC have cardio-protective effects which may make them an attractive user-friendly option for the treatment of CCM.
| S-EPMC10360184 | biostudies-literature
Project description:Treatment of cancer patients with chemotherapeutics like cyclophosphamide often causes alopecia as a result of premature and aberrant catagen. Because the epidermal growth factor receptor (EGFR) signals anagen hair follicles to enter catagen, we hypothesized that EGFR signaling may be involved in cyclophosphamide-induced alopecia. To test this hypothesis, skin-targeted Egfr mutant mice were generated by crossing floxed Egfr and Keratin 14 promoter-driven Cre recombinase mice. Cyclophosphamide treatment of control mice resulted in alopecia while Egfr mutant skin was resistant to cyclophosphamide-induced alopecia. Egfr mutant skin entered catagen normally, as indicated by dermal papilla condensation and decreased follicular proliferation, but did not progress to telogen as did Egfr wild type follicles. Egfr mutant follicles responded with less proliferation, apoptosis, and fewer p53-positive cells after cyclophosphamide. Treatment of control mice with the EGFR inhibitors erlotinib or gefitinib similarly suppressed alopecia and catagen progression by cyclophosphamide. Secondary analysis of clinical trials utilizing EGFR-targeted therapies and alopecia-inducing chemotherapy also revealed evidence for involvement of EGFR in chemotherapy-induced alopecia. Taken together, our results demonstrated the involvement of EGFR signaling in chemotherapy-induced alopecia, which will help in the design of novel therapeutic regimens to minimize chemotherapy-induced alopecia.
| S-EPMC3716704 | biostudies-literature
Project description:INTRODUCTION: Chemotherapy-induced alopecia is one of the most common adverse events caused by conventional cytotoxic chemotherapy, yet there has been very little progress in the prevention or treatment of this side effect. Although this is not a life-threatening event, alopecia is very psychologically difficult for many women to manage. In order to improve the quality of life for these women, it is important to elucidate the molecular mechanisms of chemotherapy-induced alopecia and develop ways to effectively prevent and/or treat it. To identify the genetic risk factors associated with chemotherapy-induced alopecia, we conducted a genome-wide association study (GWAS) using DNA samples from breast cancer patients who were treated with chemotherapy. METHODS: We performed a case-control association study of 303 individuals who developed grade 2 alopecia, and compared them with 880 breast cancer patients who did not show hair loss after being treated with conventional chemotherapy. In addition, we separately analyzed a subset of patients who received specific combination therapies by GWASs and applied the weighted genetic risk scoring (wGRS) system to investigate the cumulative effects of the associated SNPs. RESULTS: We identified an SNP significantly associated with drug-induced grade 2 alopecia (rs3820706 in CACNB4 (calcium channel voltage-dependent subunit beta 4) on 2q23, P = 8.13 × 10(-9), OR = 3.71) and detected several SNPs that showed some suggestive associations by subgroup analyses. We also classified patients into four groups on the basis of wGRS analysis and found that patients who classified in the highest risk group showed 443 times higher risk of antimicrotubule agents-induced alopecia than the lowest risk group. CONCLUSIONS: Our study suggests several associated genes and should shed some light on the molecular mechanism of alopecia in chemotherapy-treated breast cancer patients and hopefully will contribute to development of interventions that will improve the quality of life (QOL) of cancer patients.
| S-EPMC3978764 | biostudies-literature
Project description:BackgroundChemotherapy-induced alopecia (CIA) is a distressing adverse effect of chemotherapy, with an estimated incidence of 65% and limited treatment options. Cyclophosphamide (CYP) is a common alopecia-inducing chemotherapy agent. Human dental pulp stem cells (DPSCs) secrete several paracrine factors that up-regulate hair growth. Conditioned medium (CM) collected from DPSCs (DPSC-CM) promotes hair growth; culturing mesenchymal stem cells under hypoxic conditions can enhance this effect.MethodsThe effect of DPSC-CM cultured under normoxic (N-) and hypoxic (H-) conditions against CYP-mediated cytotoxicity in keratinocytes was examined using cell viability assay, lactate dehydrogenase (LDH) cytotoxicity assay, and apoptosis detection. The damage-response pathway was determined in a well-established CIA mouse model by analyzing macroscopic effects, histology, and apoptosis. Reverse transcription-quantitative PCR and Caspase-3/7 activity assay were used to investigate the impact of DPSC-CM on the molecular damage-response pathways in CYP-treated mice. The effect of post-CIA DPSC-CM application on post-CIA hair regrowth was analyzed by macroscopic effects and microstructure observation of the hair surface. Furthermore, to investigate the safety of DPSC-CM as a viable treatment option, the effect of DPSC-CM on carcinoma cell lines was examined by cell viability assay and a subcutaneous tumor model.ResultsIn the cell viability assay, DPSC-CM was observed to increase the number of keratinocytes over varying CYP concentrations. Furthermore, it reduced the LDH activity level and suppressed apoptosis in CYP-treated keratinocytes. DPSC-CM exhibited the cytoprotective role in vivo via the dystrophic anagen damage-response pathway. While both N-CM and H-CM downregulated the Caspase-3/7 activity level, H-CM downregulated Caspase-3 mRNA expression. The proportion of post-CIA H-CM-treated mice with > 90% normal hair was nearly twice that of vehicle- or N-CM-treated mice between days 50 and 59 post-depilation, suggesting that post-CIA H-CM application may accelerate hair regrowth and improve hair quality. Furthermore, DPSC-CM suppressed proliferation in vitro in certain carcinoma cell lines and did not promote the squamous cell carcinoma (SCC-VII) tumor growth rate in mice.ConclusionsThe potentiality of DPSC-CM and H-CM as a promising cytoprotective agent and hair regrowth stimulant, respectively, for CIA needs in-depth exploration.
| S-EPMC10949570 | biostudies-literature
Project description:ImportancePersistent chemotherapy-induced alopecia (pCIA) has been recently described in patients with breast cancer and in its most severe form occurs in up to 10% of these patients. Genetic risk factors associated with pCIA have not been adequately explored.ObjectiveTo identify genetic variants associated with pCIA.Design, setting, and participantsIn this genetic association study, 215 women with breast cancer treated with docetaxel-based chemotherapy with a follow-up of 1.5 to 10 years after the end of the treatment were recruited retrospectively through 3 hospital oncology units across Spain between 2005 and 2018. Severe pCIA was defined as lack of scalp hair recovery (Common Terminology Criteria for Adverse Events, version 3.0, grade 2) 18 months or more after the end of treatment. Patients with grade 2 pCIA were selected as cases, and those with no sign of residual alopecia 12 months after the end of docetaxel treatment were selected as controls. A genome-wide association study in a discovery phase was conducted, and logistic regression was used to identify variants associated with the risk to develop this adverse effect. The validity of the association was addressed through a replication phase.ExposuresDocetaxel-based chemotherapy.Main outcomes and measuresGenotypes of single-nucleotide variants associated with pCIA.ResultsIn total, 215 women with breast cancer (median age, 51.6 years; interquartile range, 44-60 years) were recruited (173 patients for the discovery phase and 42 patients for the replication phase). In the discovery phase, ABCB1 genetic variants were associated with risk to develop pCIA. In particular, single-nucleotide variation rs1202179, a regulatory variant located in an enhancer element that interacts with the ABCB1 promoter, was associated with the occurrence of pCIA. This finding was validated in the replication cohort (combined odds ratio, 4.05; 95% CI, 2.46-6.67; P = 3.946 × 10-8). This variant is associated with ABCB1 mRNA expression, and the risk allele was associated with decreased ABCB1 expression levels (P = 1.64 × 10-20).Conclusions and relevanceThis is the first study, to our knowledge, that identifies an association between a regulatory variant in the ABCB1 gene and the occurrence of pCIA in patients with breast cancer who were treated with docetaxel-based therapies. This finding suggests an important insight into the biological mechanisms underlying pCIA and opens the opportunity to explore personalized treatment of these patients.
| S-EPMC7407317 | biostudies-literature
Project description:ImportanceAlopecia induced by classic chemotherapy affects up to 65% of patients and is usually reversible. However, there are increasing reports of persistent chemotherapy-induced alopecia (pCIA), especially for patients treated with taxane-containing chemotherapy regimens.ObjectiveTo analyze the clinicopathologic characteristics and response to treatment of patients with pCIA after chemotherapy for breast cancer.Design, setting, and participantsIn this case series, a retrospective evaluation was performed of patients with a diagnosis of pCIA after chemotherapy for breast cancer in 4 specialist hair clinics from November 1, 2011, to February 29, 2020.Main outcomes and measuresClinical, trichoscopic, and histopathologic characteristics and treatment outcomes were analyzed. For patients who presented with diffuse alopecia or diffuse rarefaction of hair over the midfrontal scalp with widening of the central part line and preservation of the frontal hairline, the Sinclair scale (grades 1-5, where 1 indicates normal hair density and 5 indicates the most severe stage of hair loss, with little or no hair in the centroparietal region) was used to assess severity.ResultsOne hundred patients (99 women [99%]; mean age at presentation, 54.0 years [range, 29.0-74.1 years]) were included. Most patients had diffuse nonscarring alopecia (n = 39), female pattern hair loss (n = 55), or male pattern hair loss (n = 6). Six patients developed cicatricial alopecia. Taxane-containing regimens were used for most patients (92 [92%]) and were associated with more severe alopecia than regimens that did not contain taxanes (median Sinclair grade, 4 [IQR, 3-5] vs 2 [IQR, 2-2.5]; P < .001). A total of 76 of 86 patients (88%) had trichoscopic signs indistinguishable from those of androgenetic alopecia. Of 18 patients who had biopsies, 14 had androgenetic alopecia-like features, 2 had cicatricial alopecia, and 2 had features of both. Both topical and oral minoxidil, sometimes combined with antiandrogen therapy, were associated with an improvement in hair density (median Sinclair grade, 4 [IQR, 3-5] before treatment vs 3 [IQR, 2-4] after treatment; P < .001).Conclusions and relevanceThis case series outlines previously unreported features of pCIA in patients with breast cancer, including a trichoscopic description. Cosmetically significant regrowth was achieved for a significant proportion of patients with topical or systemic treatments, suggesting that pCIA may be at least partly reversible.
| S-EPMC8482302 | biostudies-literature