Objective:
To review the pharmacokinetics, efficacy, and safety of topical ruxolitinib for treatment of nonsegmental vitiligo.
Data Sources:
Literature published between January 1983 and October 2022 ...was reviewed from MEDLINE and ClinicalTrials.gov.
Study Selection and Data Extraction:
Relevant articles in English and data from clinical trials were included.
Data Synthesis:
In 2 phase II trials, treatment with ruxolitinib cream showed significant improvements in Vitiligo Area Scoring Index (VASI) scores compared with controls. The 1.5% concentration applied twice daily showed the best results after 52 weeks, with 50% VASI improvement in 58% of patients, 75% VASI improvement in 52% of patients, and 90% VASI improvement in 33% of patients. In 2 phase III trials, more patients achieved at least 75% improvement in facial VASI at 24 weeks (primary endpoint; trial 1: 29.9%, trial 2: 29.9%) than controls (trial 1: 7.5% P < 0.0001, trial 2: 12.9% P < 0.01). Common adverse effects were erythema, pruritus, and acne; all events were mild.
Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:
This review summarizes the pharmacokinetics, efficacy, and safety data regarding topical ruxolitinib for vitiligo. Ruxolitinib is associated with significant clinical improvements with low bioavailability and minimal adverse effects compared with conventional topical steroids, calcineurin inhibitors, phototherapy, and depigmentation agents.
Conclusions:
Ruxolitinib cream is the first therapy approved by the Food and Drug Administration for repigmentation of nonsegmental vitiligo. Clinicians should consider these benefits when recommending treatment as conventional therapies may be time-intensive and carry greater risks of adverse effects.
Basal cell carcinoma and squamous cell carcinoma are the two most common types of carcinomas, affecting a total of 5.4 million people each year in the United States. Sun-exposed areas, especially the ...face and nose, are most affected given the strong association between these carcinomas and ultraviolet radiation. Less research has been done surrounding carcinomas of the lip, despite the significant aesthetic and functional importance of this area. Although lip carcinomas tend to follow a classic, unique distribution pattern that favors basal cell carcinoma on the upper lip and squamous cell carcinoma on the lower lip, more cases of lower lip basal cell carcinoma are being reported, warranting further educational awareness to differentiate carcinomas of the lower lip. In this article, we provide an updated overview of the risk factors, presentations, differential diagnoses, metastatic risks, evaluation, management guidelines, and outcomes of lower lip carcinoma. Of note, recent advances in imaging modalities are beginning to show promise as a non-invasive, affordable, and rapid way to detect and stage tumors. We conclude that increased clinical awareness and investigation of lower lip carcinoma is needed to improve early intervention, as a delayed diagnosis can rapidly alter the management and outcomes of lip carcinomas.
Nigella sativa (N. sativa) is a widely used medicinal herb with a rich cultural and religious history in Unani, Ayurveda, Chinese, and Arabic medicine. N. sativa contains many natural bioactive ...agents including alkaloids, saponins, alpha‐hederin, and thymoquinone that contribute to its broad range of benefits as a diuretic, bronchodilator, antihypertensive, antidiabetic, and analgesic. In addition, N. sativa possesses antimicrobial, anti‐inflammatory, and antineoplastic effects, making it an interesting potential therapy for the treatment of dermatological conditions. This article reviews the current literature surrounding the pharmacological effects of N. sativa for the treatment of acne vulgaris, melanoma, vitiligo, atopic dermatitis, plaque psoriasis, and wound healing.
Therapeutic Use of Trace Elements in Dermatology Gade, Anita; Hwang, Jacqueline R; Hoegler, Karl ...
Alternative therapies in health and medicine,
05/2023, Letnik:
29, Številka:
4
Journal Article
Recenzirano
Trace elements (microminerals) play a role in many physiological functions, including hormone production and cellular growth. However, their importance in diagnosing and treating dermatologic disease ...has not been well examined. In this review, we discuss the functions, sources, and recommended requirements of each micromineral. In addition, we analyze the systemic and dermatological manifestations associated with micromineral imbalances. The pathogenesis of genodermatoses, such as Wilson disease, Menkes disease, acrodermatitis enteropathica, and allergic dermatitis, are also discussed. Included are studies examining the potential therapeutic role of zinc, selenium, and copper in inflammatory diseases, skin cancer, and photoaging.
Genomics-driven cancer therapeutics has gained prominence in personalized cancer treatment. However, its utility in indications lacking biomarker-driven treatment strategies remains limited. Here we ...present a "phenotype-driven precision-oncology" approach, based on the notion that biological response to perturbations, chemical or genetic, in ex vivo patient-individualized models can serve as predictive biomarkers for therapeutic response in the clinic. We generated a library of "screenable" patient-derived primary cultures (PDCs) for head and neck squamous cell carcinomas that reproducibly predicted treatment response in matched patient-derived-xenograft models. Importantly, PDCs could guide clinical practice and predict tumour progression in two n = 1 co-clinical trials. Comprehensive "-omics" interrogation of PDCs derived from one of these models revealed YAP1 as a putative biomarker for treatment response and survival in ~24% of oral squamous cell carcinoma. We envision that scaling of the proposed PDC approach could uncover biomarkers for therapeutic stratification and guide real-time therapeutic decisions in the future.Treatment response in patient-derived models may serve as a biomarker for response in the clinic. Here, the authors use paired patient-derived mouse xenografts and patient-derived primary culture models from head and neck squamous cell carcinomas, including metastasis, as models for high-throughput screening of anti-cancer drugs.
Detection of extranodal extension on histopathology in surgically treated head and neck squamous cell carcinoma indicates poor prognosis. However, there is no consensus on the diagnostic criteria, ...interpretation, and reporting of histology detected extranodal extension, which has contributed to conflicting evidence in the literature, and likely clinical inconsistency. The Head and Neck Cancer International Group conducted a three-round modified Delphi process with a group of 19 international pathology experts representing 15 national clinical research groups to generate consensus recommendations for histology detected extranodal extension diagnostic criteria. The expert panel strongly agreed on terminology and diagnostic features for histology detected extranodal extension and soft tissue metastasis. Moreover, the panel reached consensus on reporting of histology detected extranodal extension and on nodal sampling. These consensus recommendations, endorsed by 19 organisations representing 34 countries, are a crucial development towards standardised diagnosis and reporting of histology detected extranodal extension, and more accurate data collection and analysis.
Introduction
Emerging evidence suggests that effective treatment of glioblastoma (GBM), the most common and deadly form of adult primary brain cancer, will likely require concurrent treatment of ...multiple aspects of tumor pathobiology to overcome tumor heterogeneity and the complex tumor-supporting microenvironment. Recent studies in non-central nervous system (CNS) tumor cells have demonstrated that oxaliplatin (OXA) can induce multi-faceted anti-tumor effects, in particular at drug concentrations below those required to induce apoptosis. These findings motivated re-investigation of OXA for the treatment of GBM.
Methods
The effects of OXA on murine KR158 and GL261 glioma cells including cell growth, cell death, inhibition of signal transducer and activator of transcription (STAT) activity,
O
-6-methylguanine-DNA methyltransferase (MGMT) expression, and immunogenic cell death (ICD) initiation, were evaluated by cytotoxicity assays, Western blot analysis, STAT3-luciferase reporter assays, qRT-PCR assays, and flow cytometry. Chemical inhibitors of endoplasmic reticulum (ER) stress were used to investigate the contribution of this cell damage response to the observed OXA effects. The effect of OXA on bone marrow-derived macrophages (BMDM) exposed to glioma conditioned media (GCM) was also analyzed by Western blot analysis.
Results
We identified the OXA concentration threshold for induction of apoptosis and from this determined the drug dose and treatment period for sub-cytotoxic treatments of glioma cells. Under these experimental conditions, OXA reduced STAT3 activity, reduced MGMT levels and increased temozolomide sensitivity. In addition, there was evidence of immunogenic cell death (elevated EIF2α phosphorylation and calreticulin exposure) following prolonged OXA treatment. Notably, inhibition of ER stress reversed the OXA-mediated inhibition of STAT3 activity and MGMT expression in the tumor cells. In BMDMs exposed to GCM, OXA also reduced levels of phosphorylated STAT3 and decreased expression of Arginase 1, an enzyme known to contribute to pro-tumor functions in the tumor-immune environment.
Conclusions
OXA can induce notable multi-faceted biological effects in glioma cells and BMDMs at relatively low drug concentrations. These findings may have significant therapeutic relevance against GBM and warrant further investigation.
Objectives/Hypothesis
Our study aimed to review the impact of preoperative radiotherapy (RT) and other factors on the lymph node count of neck dissection (ND) specimens from patients with head and ...neck cancer (HNC). A retrospective study was conducted on all patients with head and neck cancers who had undergone NDs in Singapore General Hospital between 1992 and 2013.
Study Design
Retrospective study.
Methods
Patients were categorized into two groups: patients treated with RT with or without chemotherapy before ND and patients who had undergone ND surgery without previous history of RT. The primary endpoint for this study would be the lymph node count from ND.
Results
The study cohort consists of 1,024 NDs on 829 patients. There were 597 (58.3%) radical/modified radical NDs involving levels I–V. Within this group, 75 (12.6%) NDs had preoperative RT. Preoperative RT and age were found to significantly reduce nodal yield in both univariate and multivariate analysis in the radical/modified radical ND subgroup. In our multivariate analysis, preoperative RT was shown to decrease the nodal yield by 7.464 (P = .0002, 95% confidence interval CI: −11.35 to −3.58). Advanced age independently decreases nodal yield, even after accounting for the effect of RT (P = .0002, 95% CI: −0.27 to −0.08). In addition, preoperative RT has a more pronounced effect in reducing lymph node count in the older age group.
Conclusions
Preoperative RT and advanced age are independent and synergistic factors that reduce nodal count from NDs in patients with head and neck cancers.
Level of Evidence
4 Laryngoscope, 130: 1947–1953, 2020
Background This article aims to validate and compare the performance of 6 prognostication systems—the World Health Organization 2010 grading criteria, the European Neuroendocrine Tumour Society and ...the American Joint Committee for Cancer staging systems, the Memorial Sloan Kettering Cancer Center staging and grading systems, as well as the Bilimoria criteria in a cohort of patients with pancreatic neuroendocrine neoplasms at a single institution. Methods A retrospective review of 176 patients with histologically proven pancreatic neuroendocrine neoplasm was performed. The prognostic ability of the various prognostication systems for pancreatic neuroendocrine neoplasm was assessed by analyzing the homogeneity, discriminatory ability, monotonicity of gradient, and Akaike information criteria. Results The 5-year overall survival for the 176 patients was 69% and 5-year recurrence-free survival in 119 patients who underwent curative resection was 78%. Comparison between the 6 prognostication systems demonstrated that the World Health Organization 2010 system had the lowest Akaike information criteria score and was hence the best prognostication system in predicting overall survival and recurrence-free survival rates in our cohort of patients. The European Neuroendocrine Tumour Society was superior to the American Joint Committee for Cancer in prognosticating overall survival rates for pancreatic neuroendocrine neoplasms, as there was a statistically significant difference in overall survival across the different stages when stratified by the European Neuroendocrine Tumour Society, while the use of the American Joint Committee for Cancer was limited to distinguishing between patients in stages I and II versus stages III and IV only. Conclusion All 6 prognostication systems were useful in the prognostication of pancreatic neuroendocrine neoplasm. The World Health Organization 2010 grading system was the best prognostication system in predicting both overall survival in our entire cohort of patients and recurrence-free survival in the subset of patients who underwent curative resection.
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