Autoantibodies against p53, MMP-7, and Hsp70 as Potential Biomarkers for Detection of Nonmelanoma Skin Cancers.
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ABSTRACT:
SUBMITTER: Yang SH
PROVIDER: S-EPMC8289574 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Nonmelanoma skin cancer (NMSC) is the most prevalent cancer in light-skinned populations, and includes mainly Basal Cell Carcinomas (BCC), representing around 75% of NMSC and Squamous Cell Carcinomas (SCC). The incidence of these tumors is continuously growing. It was found that the overall number of procedures for NMSC in US rose by 76%, from 1,158,298 in 1992 to 2,048,517 in 2006. Although mortality from NMSC tends to be very low, clearly the morbidity related to these skin cancers is very high. Treatment options for NMSC include both surgical and nonsurgical interventions. Surgery was considered the gold standard therapy, however, advancements in the knowledge of pathogenic mechanisms of NMSCs led to the identification of key targets for drug intervention and to the consequent development of several targeted therapies. These represent the future in treatment of these common forms of cancer ensuring a high cure rate, preservation of the maximal amount of normal surrounding tissue and optimal cosmetic outcome. Here, we will review recent advancements in NMSC targeted therapies focusing on BCC and SCC.
| S-EPMC3757416 | biostudies-other
Project description:This study examined the value of serum p53 autoantibodies (p53-AAb) as detection and prognostic biomarkers in ovarian cancer.p53-AAb were detected by ELISA in sera obtained preoperatively from women undergoing surgery for a pelvic mass. This group included women subsequently diagnosed with invasive serous ovarian cancer (n = 60), nonserous ovarian cancers (n = 30), and women with benign disease (n = 30). Age-matched controls were selected from the general population (n = 120). Receiver operating characteristic curves were constructed to compare the values of p53-AAb, CA 125, and HE4 as a screening biomarker. Kaplan-Meier curves and Cox proportional hazards modeling were used to assess its prognostic value on survival.p53-AAb were detected in 25 of 60 (41.7%) of serous cases, 4 of 30 (13.3%) nonserous cases, 3 of 30 (10%) benign disease cases, and 10 of 120 (8.3%) controls (combined P = 0.0002). p53-AAb did not significantly improve the detection of cases [area under the curve (AUC), 0.69] or the discrimination of benign versus malignant disease (AUC, 0.64) compared with CA 125 (AUC, 0.99) or HE4 (AUC, 0.98). In multivariate analysis among cases, p53-AAb correlated only with a family history of breast cancer (P = 0.01). Detectable p53 antibodies in pretreatment sera were correlated with improved overall survival (P = 0.04; hazard ratio, 0.57; 95% confidence interval, 0.33-0.97) in serous ovarian cancer.Antibodies to p53 are detected in the sera of 42% of patients with advanced serous ovarian cancer.Although their utility as a preoperative diagnostic biomarker, beyond CA 125 and HE4, is limited, p53-AAb are prognostic for improved overall survival.
| S-EPMC2838192 | biostudies-literature
Project description:The incidence of nonmelanoma skin cancer (NMSC) has been increasing worldwide. Most studies have highlighted the importance of cancer-associated fibroblasts (CAFs) in NMSC progression. However much less is known about the communication between normal fibroblasts and epithelia; disruption of this communication affects tumor initiation and the latency period in the emergence of tumors. Delineating the mechanism that mediates this epithelial-mesenchymal communication in NMSC could identify more effective targeted therapies. The nuclear receptor PPARβ/δ in fibroblasts has been shown to modulate adjacent epithelial cell behavior, however, its role in skin tumorigenesis remains unknown. Using chemically induced skin carcinogenesis, we showed that FSPCre-Pparb/dex4 mice, whose Pparb/d gene was selectively deleted in fibroblasts, had delayed emergence and reduced tumor burden compared with control mice (Pparb/dfl/fl). However, FSPCre-Pparb/dex4-derived tumors showed increased proliferation, with no difference in differentiation, suggesting delayed tumor initiation. Network analysis revealed a link between dermal Pparb/d and TGF-β1 with epidermal NRF2 and Nox4. In vitro investigations showed that PPARβ/δ deficiency in fibroblasts increased epidermal Nox4-derived H2O2 production, which triggered an NRF2-mediated antioxidant response. We further showed that H2O2 upregulated NRF2 mRNA via the B-Raf-MEK1/2 pathway. The enhanced NRF2 response altered the activities of PTEN, Src, and AKT. In vivo, we detected the differential phosphorylation profiles of B-Raf, MEK1/2, PTEN, Src, and AKT in the vehicle-treated and chemically treated epidermis of FSPCre-Pparb/dex4 mice compared with that in Pparb/dfl/fl mice, prior to the first appearance of tumors in Pparb/dfl/fl. Our study revealed a role for fibroblast PPARβ/δ in the epithelial-mesenchymal communication involved in cellular redox homeostasis.
| S-EPMC7429869 | biostudies-literature
Project description:Compound 1 is a potent rexinoid that is highly effective in cancer chemoprevention but elevates serum triglycerides. In an effort to separate the lipid toxicity from the anticancer activity of 1, we synthesized four new analogs of rexinoid 1, of which three rexinoids did not elevate serum triglycerides. Rexinoids 3 and 4 are twice as potent as rexinoid 1 in binding to Retinoid X receptor (RXR). All-trans retinoic acid (ATRA) plays a key role in maintaining skin homeostasis, and rexinoids 3-6 are highly effective in upregulating the genes responsible for the biosynthesis of ATRA. Inflammation plays a key role in skin cancer, and rexinoids 3 and 4 are highly effective in diminishing LPS-induced inflammation. Rexinoids 3 and 4 are highly effective in preventing UVB-induced nonmelanoma skin cancer (NMSC) without displaying any overt toxicities. Biophysical studies of rexinoids 3 and 5 bound to hRXRα-ligand binding domain (LBD) reveal important conformational and dynamical differences in the ligand binding domain.
| S-EPMC9942614 | biostudies-literature
Project description:Patients with Parkinson's disease (PD) have an increased risk of melanoma compared with the general population. Considering that Nonmelanoma Skin Cancers (NMSCs) share similar risk factors with melanoma, there is a need to understand a possible connection between PD and NMSCs. The aim of the study was the evaluation of NMSC risk among PD patients via meta-analysis and systematic review. A comprehensive search of PubMed, Scopus, and Web of Science databases was conducted, including studies from January 2000 to April 2020. We identified 16 eligible studies including 140291 PD patients. Upon statistical analysis, a significantly higher risk of developing NMSCs in PD patients was found compared with the control group (odds ratio (OR) = 1.25, 95% CI: 1.17-1.33; p < 0.0001). Among all NMSCs, the risk of developing basal cell carcinoma in PD patients was significantly higher (OR = 1.30, 95% confidence interval (CI): 1.15-1.47; p < 0.0001), contrary to squamous cell carcinoma. Further analysis revealed a significantly higher risk of developing NMSCs in patients with previously diagnosed PD (OR = 1.26, 95% CI: 1.19-1.33; p < 0.0001). Our data suggest the necessity for regular skin examination of PD patients, though further studies are required to explore the mechanisms forming this relationship.
| S-EPMC7913207 | biostudies-literature
Project description:BACKGROUND:Computer-aided diagnosis of skin lesions is a growing area of research, but its application to nonmelanoma skin cancer (NMSC) is relatively under-studied. The purpose of this review is to synthesize the research that has been conducted on automated detection of NMSC using digital images and to assess the quality of evidence for the diagnostic accuracy of these technologies. METHODS:Eight databases (PubMed, Google Scholar, Embase, IEEE Xplore, Web of Science, SpringerLink, ScienceDirect, and the ACM Digital Library) were searched to identify diagnostic studies of NMSC using image-based machine learning models. Two reviewers independently screened eligible articles. The level of evidence of each study was evaluated using a five tier rating system, and the applicability and risk of bias of each study was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. RESULTS:Thirty-nine studies were reviewed. Twenty-four models were designed to detect basal cell carcinoma, two were designed to detect squamous cell carcinoma, and thirteen were designed to detect both. All studies were conducted in silico. The overall diagnostic accuracy of the classifiers, defined as concordance with histopathologic diagnosis, was high, with reported accuracies ranging from 72 to 100% and areas under the receiver operating characteristic curve ranging from 0.832 to 1. Most studies had substantial methodological limitations, but several were robustly designed and presented a high level of evidence. CONCLUSION:Most studies of image-based NMSC classifiers report performance greater than or equal to the reported diagnostic accuracy of the average dermatologist, but relatively few studies have presented a high level of evidence. Clinical studies are needed to assess whether these technologies can feasibly be implemented as a real-time aid for clinical diagnosis of NMSC.
| S-EPMC6394090 | biostudies-literature
Project description:Men continue to develop nonmelanoma skin cancer (NMSC) at higher rates than women, but the epidemiologic pattern of NMSC development is evolving. We present a selective, narrative review of the literature showing that there is a trend toward a development of basal cell carcinomas in women at younger ages, and highlight potential causes of this trend. We review evidence that indoor tanning is associated with the development of NMSC and show that young women use indoor tanning more than any other age-sex group. We discuss societal factors that relate to the tanning behavior of young women. Finally, we argue that facial NMSCs may have more of a negative impact on quality of life in women than in men.
| S-EPMC6374707 | biostudies-literature
Project description:BackgroundCase-control studies have reported that exogenous estrogen use is associated with increased risk of skin cancer. The effects of menopausal hormone therapy on incidence of nonmelanoma skin cancer and melanoma were evaluated in post hoc analyses of the Women's Health Initiative randomized placebo-controlled hormone therapy trials of combined estrogen plus progestin (E + P) and estrogen only (E-alone).MethodsPostmenopausal women aged 50-79 years were randomly assigned to conjugated equine estrogen (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo in the E + P trial if they had an intact uterus (N = 16,608) or to conjugated equine estrogen alone or placebo in the E-alone trial if they had a hysterectomy (N = 10,739); the mean follow-up was 5.6 and 7.1 years, respectively. Incident nonmelanoma skin cancers (n = 980 [E + P trial]; n = 820 [E-alone trial]) and melanomas (n = 57 [E + P trial]; n =38 [E-alone trial]) were ascertained by self-report. Incident cases of cutaneous malignant melanoma were confirmed by physician review of medical records. Incidences of nonmelanoma skin cancer and melanoma were compared between the two randomization groups within each trial using hazard ratios (HRs), with corresponding 95% confidence intervals (CIs) and Wald statistic P values from Cox proportional hazards models. All statistical tests were two-sided.ResultsRates of incident nonmelanoma skin cancer and melanoma were similar between the active hormone (combined analysis of E + P and E-alone) and placebo groups (nonmelanoma skin cancer: HR = 0.98, 95% CI = 0.89 to 1.07; melanoma: HR = 0.92, 95% CI = 0.61 to 1.37). Results were similar for the E + P and E-alone trials when analyzed individually.ConclusionsMenopausal hormone therapy did not affect overall incidence of nonmelanoma skin cancer or melanoma. These findings do not support a role of menopausal estrogen, with or without progestin, in the development of skin cancer in postmenopausal women.
| S-EPMC3186783 | biostudies-literature
Project description:BackgroundMohs micrographic surgery examines all margins of the resected sample and has a 99% cure rate. However, many nonmelanoma skin cancers (NMSCs) are not readily amenable to Mohs micrographic surgery. This defines an unmet clinical need to assess the completeness of non-Mohs micrographic surgery resections during surgery to prevent re-excision/recurrence.ObjectiveWe sought to examine the utility of quenched activity-based probe imaging to discriminate cancerous versus normal-appearing skin tissue.MethodsThe quenched activity-based probe GB119 was applied to NMSC excised from 68 patients. We validated activation of the probe for hematoxylin-eosin-confirmed cancerous tissue versus normal-appearing skin tissue.ResultsTopical application of the probe differentiated basal cell carcinoma and squamous cell carcinoma from normal-appearing skin with overall estimated sensitivity and specificity of 0.989 (95% confidence interval 0.940-1.00) and 0.894 (95% confidence interval 0.769-0.965), respectively. Probe activation accurately defined peripheral margins of NMSC as compared with conventional hematoxylin-eosin-based pathology.LimitationsThis study only examined NMSC debulking excision specimens. The sensitivity and specificity for this approach using final NMSC excision margins will be clinically important.ConclusionsThese findings merit further studies to determine whether quenched activity-based probe technology may enable cost-effective increased cure rates for patients with NMSC by reducing re-excision and recurrence rates with a rapid and easily interpretable technological advance.
| S-EPMC5341746 | biostudies-literature
Project description:Nonmelanoma skin cancers including basal and squamous cell carcinomas (SCC and BCC) represent a significant clinical problem due to their relatively high incidence, imposing an economic burden to healthcare systems around the world. It is accepted that ultraviolet radiation (UVR: λ = 290-400 nm) plays a crucial role in the initiation and promotion of BCC and SCC with UVB (λ = 290-320 nm) having a central role in this process. On the other hand, UVB is required for vitamin D3 (D3) production in the skin, which supplies >90% of the body's requirement for this prohormone. Prolonged exposure to UVB can also generate tachysterol and lumisterol. Vitamin D3 itself and its canonical (1,25(OH)2D3) and noncanonical (CYP11A1-intitated) D3 hydroxyderivatives show photoprotective functions in the skin. These include regulation of keratinocyte proliferation and differentiation, induction of anti-oxidative responses, inhibition of DNA damage and induction of DNA repair mechanisms, and anti-inflammatory activities. Studies in animals have demonstrated that D3 hydroxyderivatives can attenuate UVB or chemically induced epidermal cancerogenesis and inhibit growth of SCC and BCC. Genomic and non-genomic mechanisms of action have been suggested. In addition, vitamin D3 itself inhibits hedgehog signaling pathways which have been implicated in many cancers. Silencing of the vitamin D receptor leads to increased propensity to develop UVB or chemically induced epidermal cancers. Other targets for vitamin D compounds include 1,25D3-MARRS, retinoic orphan receptors α and γ, aryl hydrocarbon receptor, and Wnt signaling. Most recently, photoprotective effects of lumisterol hydroxyderivatives have been identified. Clinical trials demonstrated a beneficial role of vitamin D compounds in the treatment of actinic keratosis. In summary, recent advances in vitamin D biology and pharmacology open new exciting opportunities in chemoprevention and treatment of skin cancers.
| S-EPMC7490773 | biostudies-literature