Basal Cell Cancer Research Articles

Low-Dose Methotrexate for the Prevention of Atherosclerotic Events

BackgroundInflammation is causally related to atherothrombosis. Treatment with canakinumab, a monoclonal antibody that inhibits inflammation by neutralizing interleukin-1β, resulted in a lower rate of cardiovascular events than placebo in a previous randomized trial. We sought to determine whether an alternative approach to inflammation inhibition with low-dose methotrexate might provide similar benefit.MethodsWe conducted a randomized, double-blind trial of low-dose methotrexate (at a target dose of 15 to 20 mg weekly) or matching placebo in 4786 patients with previous myocardial infarction or multivessel coronary disease who additionally had either type 2 diabetes or the metabolic syndrome. All participants received 1 mg of folate daily. The primary end point at the onset of the trial was a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Near the conclusion of the trial, but before unblinding, hospitalization for unstable angina that led to urgent revascularization was added to the primary end point.ResultsThe trial was stopped after a median follow-up of 2.3 years. Methotrexate did not result in lower interleukin-1β, interleukin-6, or C-reactive protein levels than placebo. The final primary end point occurred in 201 patients in the methotrexate group and in 207 in the placebo group (incidence rate, 4.13 vs. 4.31 per 100 person-years; hazard ratio, 0.96; 95% confidence interval [CI], 0.79 to 1.16). The original primary end point occurred in 170 patients in the methotrexate group and in 167 in the placebo group (incidence rate, 3.46 vs. 3.43 per 100 person-years; hazard ratio, 1.01; 95% CI, 0.82 to 1.25). Methotrexate was associated with elevations in liver-enzyme levels, reductions in leukocyte counts and hematocrit levels, and a higher incidence of non–basal-cell skin cancers than placebo.ConclusionsAmong patients with stable atherosclerosis, low-dose methotrexate did not reduce levels of interleukin-1β, interleukin-6, or C-reactive protein and did not result in fewer cardiovascular events than placebo. (Funded by the National Heart, Lung, and Blood Institute; CIRT ClinicalTrials.gov number, NCT01594333.)

Psychosocial and Cultural Determinants of Interest and Uptake of Skin Cancer Genetic Testing in Diverse Primary Care

Background: Translational research in genomics has limited reach and requires efforts to broaden access and utility in diverse populations. Skin cancer is common and rates are rising, including among Hispanics. Germline variants in the melanocortin-1 receptor (MC1R) gene are common in the population and confer moderate risk for melanoma and basal cell cancers across skin types. Feedback about MC1R risk status may promote skin cancer risk awareness and risk reduction. Aims: We examined the level of interest in pursuing MC1R testing, and patterns of interest across skin cancer perceived threat and control attitudes, cultural beliefs (family influence on health, health system distrust, cancer fatalism, skin cancer misconceptions), and health literacy. Methods: We used a study website to inform primary care patients in Albuquerque, NM about the benefits and drawbacks of MC1R testing. Website logon, request of a saliva test kit, and return of the test kit (yes vs. no) were primary assessments of study interest and uptake. Results: Of 499 participants provided with a test offer, 33% requested and returned the test. Lower family influence on participants’ health was an important factor both overall and within ethnicity subgroups, and may indicate that primary care patients interested in skin cancer genetic testing see themselves as proactive health seekers, independent from family encouragement. Lower self-efficacy for skin cancer prevention was also an important characteristic of those who tested. Conclusion: As evidence for common genetic markers for skin cancer accumulates, these findings suggest characteristics of those most likely to pursue genetic testing for skin cancer risk.

Demographic-specific Validity of the Cancer Prevention Study-3 Sedentary Time Survey.

This study examined the 1-yr test-retest reliability and criterion validity of sedentary time survey items in a subset of participants from a large, nationwide prospective cohort. Participants included 423 women and 290 men age 31 to 72 yr in the Cancer Prevention Study-3. Reliability was assessed by computing Spearman correlation coefficients between responses from prestudy and poststudy surveys. Validity was assessed by comparing survey-estimated sedentary time with a latent variable representing true sedentary time estimated from the 7-d diaries, accelerometry, and surveys through the method of triads. Sensitivity analyses were restricted to 566 participants with an average of 14+ h of diary and accelerometer data per day for 7 d per quarter. Reliability estimates for total sitting time were moderate or strong across all demographic strata (Spearman ρ ≥ 0.6), with significant differences by race (P = 0.01). Reliability estimates were strongest for the TV-related sedentary time item (Spearman ρ, 0.74; 95% confidence interval, 0.70-0.77). The overall validity coefficient (VC) for survey-assessed total sedentary time was 0.62 (95% confidence interval, 0.55-0.69), although VC varied by age group and activity level (P < 0.05). However, VC were similar across groups (P < 0.05) when restricting to highly compliant participants in a sensitivity analysis. The Cancer Prevention Study-3 sedentary behavior questionnaire has acceptable reliability and validity for ranking or categorizing participants according to sedentary time. Acceptable reliability and validity estimates persist across various demographic subgroups.

Treatment of basal cell cancer in the periorbital area using a pulsed copper vapour laser

An increase in life expectancy in developed countries is inevitably accompanied by an increase in the number of nonmelanoma skin diseases, which are primarily represented by basal cell cancer (BCC) occurring in elderly and old-age patients. The pathogenesis of such diseases is associated both with impaired proliferation and differentiation of the keratinocytes of the epidermal basal layer, as well as with the transformation of the vasculature in the papillary dermis in the vicinity of BCC. In recent years, such conditions have been increasingly treated using CO2 , neodymium, diode and pulsed-dye lasers. In many cases, these devices allow malignant BCC cells to be successfully eliminated. However, the use of near-infrared lasers in the periorbital area is limited due to a higher risk of damaging the organs of the visual system. Therefore, a search for new laser surgery methods that can be used for treating malignant skin tumours seems to be a prospective research direction.Methods. 3 male and 9 female patients diagnosed with primary BCC were treated using a copper vapour laser (Yakhroma-Med). The age of the patients varied from 34 to 77 years. Laser treatment was carried out in one session under the following irradiation parameters: the wavelength of 511 and 578 nm, the average power of up to 3 W and a series of 15 ns pulses. The pause between the pulses was 60 μs, with the exposure time ranging from 200 to 600 ms. The light spot diameter on the skin surface was 1 mm. The follow-up monitoring duration was 24 months.Results. In all the BCC patients, one session of copper vapour laser treatment allowed malignant cells in the disease area to be completely eliminated without relapses during 2 years after the therapy. The duration of skin healing in the irradiated area was 2 weeks in patients under the age of 40 years, compared to 3–4 weeks in elderly patients. After the treatment, short-term side effects, such as a slight edema, erythema and peeling, were observed.

Ultrasonographic features of superficial and nodular basal cell carcinoma.

To describe the ultrasonographic findings of surface and nodular basal cell skin cancer (BCC) using high frequencyultrasonography. We examined 60 primary BCCs in different locations with the High FrequencyUltrasound (HFU) system DUB Skin Scanner using 75 MHz and 30 MHz probes. Epidermis, dermis, and depth of tumorsspread in the region of interest (ROI) were measured. Visually unchanged, contralateral skin areas were examined as the control.Results: The surface BCC most often had elongated contours, clear margins and hypoechoic structure, while the nodularBCC had round or oval outlines and diffusely hypo-heterogeneous structure with clear margins. Sclerodermiform BCCs werevisualized as hypoechoic areas of irregular shape penetrating in the dermis, with wavy fuzzy margins. The average thickness ofthe surface BCC in the US examination was 556.28±136.95 μ, the nodular BCC thickness was 2439.71±865.92 μ and the sclerodermiformthickness was 1500±325.33 μ. A statistically significant increase in the average thickness of tumors of the nodularand scleroderma forms was observed in comparison with the surface clinical variant (p<0.05). Hyperechoic inclusions wereobserved in 11% of the surface BCC's and in the 100% of the nodular BCC's. Their average number was 2±0.57 and 4±4.8,with the average area of 0.03±0.02 mm2 and 0.04±0.03 mm2 (p>0.05), respectively. In the surface BCC, they were mainlylocated along the periphery of the hypoechoic zones. In nodular BCC, the inclusions had a peripheral and combined (centerand peripheral) distribution. Ultrasound allows differentiating BCC as diffuse-heterogeneous, hypoechoic, formationsin the dermis with distinct contours. Depending on the clinical picture, they differ in form, depth of bedding, as wellas in the quantitative ratio and distribution of the point hyperechoic structures in them.

CD4+ T-Cell Lymphopenia in Frequent Platelet Donors Who Have Ceased Platelet Donation for at Least 1 Year

IntroductionWe recently discovered that a number of frequent apheresis platelet donors at our donor center had CD4+ T-lymphocyte counts below 200 cells/µL. The cause appears to be repeated extraction of these cells by the Trima Accel Automated Blood Collection System's leukoreduction system chamber. Plateletpheresis at our donor center has been conducted exclusively with this instrument since 2006. How long CD4+ T-cell lymphopenia persists after stopping plateletpheresis is unknown. Whether there are infectious or other complications that could relate to CD4+ T-cell lymphopenia in former donors is also unknown. We therefore investigated the blood counts (including CD4+ T-lymphocyte counts) and medical histories of former platelet donors who had a history of frequent platelet donation but had stopped donating platelets for at least 12 months.MethodsWe mailed a questionnaire to former frequent apheresis platelet donors who had not donated platelets at our donor center for at least 12 months. Donors who replied to the questionnaire were contacted by phone to schedule a study visit. Frequent platelet donation was defined as 20-24 plateletpheresis sessions in at least one 365-day period starting in 2011. Donors who consented to participate in the study confirmed that they had not donated platelets in the prior 12 months, provided a blood sample for analysis, and completed a health questionnaire that included questions about opportunistic infections and malignancies. Medical records of these donors were also reviewed, where available. Approval for the study was obtained from the Partners HealthCare Institutional Review Board (2017P002880) and all participants provided written informed consent.ResultsOf 52 former frequent platelet donors identified as eligible to receive a questionnaire, one was known to have died of a myocardial infarction and another had requested not to receive communications from the donor center. Therefore, 50 potential study candidates were mailed a questionnaire. Twelve questionnaires were returned as undeliverable. Five potential study candidates returned the questionnaire but either declined to participate in the study or did not respond when contacted to schedule a study visit. Fourteen former frequent platelet donors elected to participate in the study after receiving the first mailing of the questionnaire. Of these 14 study participants, 6 were female and all were Caucasian. The median age was 65. The most common reason for ceasing platelet donation was a positive HLA antibody test (5 participants) followed by “low white blood cells,” “heart trouble,” and “inconvenience” (2 participants each). All former donors had tested negative for HIV while donating platelets. There were 2 participants with CD4+ T-lymphocyte counts below 200 cells/µL (Figure 1); one of these participants had prior CD4+ T-lymphocyte counts available for review. These showed that the CD4+ T-lymphocyte count in this former donor had improved slightly since ceasing donation one year earlier (Figure 2). Three study participants had a CD4+ T-lymphocyte count between 200 and 300 cells/µL. A review of prescription medications and medical problems did not identify an etiology for the low CD4+ T-lymphocyte counts. Responses to the health questionnaire showed that no study participant had ever had a severe infection, an infection with an unusual pathogen (“bug”), or thrush. Two former frequent platelet donors had a history of shingles, both of whom had CD4+ T-lymphocyte counts slightly below the normal range (441-2156 cells/µL) at the time of participation in the study. Five former donors had a history of cancer: Two episodes of squamous cell skin cancer (1 participant), papillary thyroid carcinoma (1 participant), glioblastoma (1 participant), basal cell skin cancer (1 participant), and squamous cell skin cancer as well as melanoma in situ (1 participant).ConclusionIn our small cohort, there is no evidence that CD4+ T-cell lymphopenia predisposes to opportunistic infections or to malignancies classically associated with immune dysregulation. Plateletpheresis-associated CD4+ T-cell lymphopenia has improved slightly in one former frequent platelet donor a year after ceasing plateletpheresis but the count remains below 200 cells/µL. Frequent plateletpheresis involving a leukoreduction system chamber should be considered in the differential diagnosis of idiopathic CD4+ lymphopenia. [Display omitted] DisclosuresGansner:Novimmune SA: Research Funding; UpToDate: Patents & Royalties.

Cells to Surgery Quiz: December 2018

Cells to Surgery Quiz: December 2018

UV-radiation as a Risk Factor for Non-melanoma Skin Cancer. Genetic Determinants of Carcinogenesis

The review presents modern data on the role of ultraviolet (UV) radiation in the pathogenesis of non-melanoma skin cancer (NMSC), the problem of THE risk of developing NMSC, in particular, squamous cell and basal cell skin cancer both in the population and in long-term repeated irradiation of phototherapy (PUVA therapy, UVB therapy, UVB-311 therapy) in patients with psoriasis. The paper considers the mechanisms of UV-induced cell damage by different spectral ranges (UVA, UVB) including the formation of photoproducts, damage to genomic DNA and other cellular structures, violation of the regulation of signaling pathways, the development of chronic inflammation, secondary immunosuppression. The review summarizes the results of large epidemiological studies discussing the role of gene polymorphisms in the homologous DNA repair XRCC3, gene telomerase TERT-CLPTMI, cytokine IL10 gene, MTHFR gene, encoding the folate synthesis, genes involved in pigmentirovanie MC1R, EXOC2, UBAC2 in the modulation of risk of carcinogenic effect of UV radiation. According to the authors’ opinion, the most vital and significant is data on the role of vitamin D receptor (VDR) gene polymorphisms as possible predictors of the risk of NMSC development. The further prospects of academic research on the cumulative role of the genome and environmental factors in the risk assessment of NMSC are revealed.

Karcinomi kože uzrokovani solarnim zračenjem kao profesionalna bolest

SUMMARY: The aim of this review article is to point out to the danger for workers who, by the nature of their occupation, spend most of their working hours outdoor and are exposed to sunlight that increases their risk of skin cancer. Exposure to sunlight during outdoor work increases the average annual dose of UV radiation for 4-5 times compared to people who do not work in the sun, which in outdoor workers significantly increases the risk for the occurrence of actinic keratosis, basal-cell skin cancer and squamous-cell skin cancer. It is considered that the risk for the occurrence of these disorders is doubled if the total lifetime UV radiation dose for persons occupationally non exposed to sun (130 SED annually) is exceeded by 40%. In the EU countries, including Croatia, the introduction of UV radiation personal dosimetry for outdoors workers is in progress. In order to prevent skin cancer caused by occupational UV exposure, it is necessary to implement preventive measures for outdoor workers. Minimum standards for prevention at the EU level include the application of personal protection measures (sunglasses, headgear, clothing, creams with sun protective factor) and health and safety educational programs implemented in the curricula of secondary high schools, and provided to workers at risky workplaces. Skin cancers or multiple actinic keratosis can be recognized as an occupational disease if: 1) diagnosis of squamous-cell skin cancer or basal-cell skin cancer or multiple actinic keratosis (minimum 6 changes) is histologically confirmed; 2) the changes are expressed in occupationally exposed areas of the skin; 3) the history of the disease reveals sufficient occupational exposure to UV radiation.

Overexpression of Desmoglein 2 in a Mouse Model of Gorlin Syndrome Enhances Spontaneous Basal Cell Carcinoma Formation through STAT3-Mediated Gli1 Expression

Activation of the hedgehog pathway is causative of virtually all sporadic and Gorlin syndrome-related basal cell carcinomas (BCCs), with loss of function of Ptc1 being the most common genomic lesion. Sporadic BCCs also overexpress Dsg2, a desmosomal cadherin normally found in the basal layer. Using a mouse model of Gorlin syndrome (Ptc1+/lacZ mice), we found that overexpressing Dsg2 in the basal layer (K14-Dsg2/Ptc1+/lacZ mice) or the superficial epidermis (Inv-Dsg2/Ptc1+/lacZ mice) resulted in increased spontaneous BCC formation at 3 and 6 months, respectively. The tumors did not show loss of heterozygosity of Ptc1, despite high levels of Gli1 and phosphorylated Stat3. A panel of sporadic human BCCs showed increased staining of both Dsg2 and phosphorylated Stat3 in all nine samples. Overexpression of Dsg2 in ASZ001 cells, a Ptc1-/- BCC cell line, induced Stat3 phosphorylation and further increased Gli1 levels, in both an autocrine and paracrine manner. Three different Stat3 inhibitors reduced viability and Gli1 expression in ASZ001 cells but not in HaCaT cells. Conversely, stimulation of Stat3 in ASZ001 cells with IL-6 increased Gli1 expression. Our results indicate that Dsg2 enhances canonical hedgehog signaling downstream of Ptc1 to promote BCC development through the activation of phosphorylated Stat3 and regulation of Gli1 expression.

Basal cell carcinoma arising at tattoo site of radiotherapy field marking in a patient with multiple malignancies

Basal cell cancer is one of the commonest human malignancies It has also been reported as a part of various genetic syndromes There are scarce reports of basal cell carcinoma arising at tattoo sites with roughly ten cases reported in literature on cosmetic tattoos postulated to be due to the trauma of procedure and carcinogenic effect of dyes in tattoo ink Therapeutic ionizing radiation causing DNA damage is an independent risk factor Herein we report a patient with history of Non Hodgkins lymphoma adenocarcinoma stomach colon and prostate treated with radiotherapy and chemotherapy which developed Basal cell carcinoma at the site of therapeutic tattoo used for radiotherapy skin marking

Rare clinical cases of “combined” skin carcinomas in cadaver renal allograft recipients

The most prevalent skin cancer in the transplant organ recipients is squamous cell cancer, followed by basal cell cancer. The skin cancer incidence and related mortality in the transplant organ recipient are significantly higher than those in the general population, which is to be linked with prolonged pharmaceutical immunosuppression. Multiple tumors are also typical for this patient group. The article describes two rare combinations of skin carcinomas with different histological characteristics in patients with cadaver renal allograft (CRA). Clinical case 1: A 43-year old female patient. In 2011, she was transplanted with a CRA due to end-stage renal failure caused by congenital cystic dysplasia (multicystic kidney disease), with subsequent removal of the allograft at 1.5 months after the transplantation. In 2014, she had her second CRA transplanted and until now is on immunosuppressive therapy. In 2013, the patient noticed two slowly growing masses in her right and left supraclavicular areas; they were clinically assessed as basal cell cancer and surgically resected. Histological examination of the resected skin fragments showed squamous cell carcinoma focuses in situ (Bowen's disease), with alternating superficial basalioma focuses; proliferating keratinizing squamous cell cancer with polymorphous structure, with prevailing acantholytic type, morphoeic basal cell carcinoma and basal squamous cell carcinoma were found throughout the dermal layer, up to the subcutaneous tissue. Clinical case 2: A 63-year old male patient was transplanted with CRA in 2007, due to end-stage renal failure caused by nephrolithiasis and chronic pyelonephritis. During the examination performed in 2013, a mushroom-like tumor (with a 3 cm diameter and a stipe of 1 cm in diameter, with erythematous tuberous surface) was found on the anterior neck surface, near the suprasternal notch. The tumor was surgically resected within the normal skin. Histological and immunochemical examinations showed that the mass consisted of two different tumors closely adjacent one to the other and separated by a narrow dermal layer, namely, neuroendocrine Merkel cell skin carcinoma and porocarcinoma with some signs of squamous cell and sebaceous cell differentiation.Conclusion: The descriptions of the rare cases confirm that transplantation-related skin cancers are highly relevant. Due to continuous renewal of the tissue components that is intrinsic to this organ, and due to deterioration of the immune control over proliferation and differentiation, they are characterized by a multiplicity of histological types and an unfavorable prognosis.

Current Basal and Squamous Cell Skin Cancer Management.

After studying this article, the participant should be able to: 1. Characterize basal and squamous cell carcinomas as low or high risk based on size, location, histology, and clinical features. 2. Understand appropriate surgical margins in low- and high-risk lesions, and other management options, including Mohs micrographic surgery, electrodissection and curettage, topical agents, cryotherapy, photodynamic therapy, and radiation therapy. 3. Discuss adjuvant therapies for locally advanced and metastatic disease, including radiation therapy, chemotherapy, and targeted therapies such as hedgehog pathway inhibitors. 4. Educate patients on preventive measures such as skin examinations, sun protection, oral retinoids, and oral nicotinamide (vitamin B3). 5. Devise a reconstructive plan once clear oncologic margins are obtained. With the growing incidence of basal and squamous cell carcinoma, there is an increasing demand for appropriate oncologic management and aesthetic reconstruction. The goal of this CME article is to provide a foundation of knowledge to accurately diagnose, stage, and treat nonmelanoma skin cancers. In addition, it provides the practicing plastic surgeon alternate tools for managing these skin lesions, including topical agents, destructive therapies, and radiation therapy. Lastly, reconstructive plans for selected soft-tissue defects are discussed.

Frequent basal cell cancer development is a clinical marker for inherited cancer susceptibility.

Innate DNA repair mechanisms play a critical role in protecting skin keratinocytes from UV mutagenesis and skin cancer development. We hypothesized that individuals who develop frequent skin cancers may harbor germline defects in DNA repair genes and have increased predisposition to internal malignancies. We enrolled 61 patients with unusually frequent basal cell carcinoma (BCC) development, seen at Stanford Hospital and Clinics from January 2005 until December 2015, for germline analysis of 29 DNA repair genes. In parallel, a case-control retrospective review was performed to interrogate the association of malignancies with frequent BCC development in a large US medical insurance claims database (Truven), which included 13,264 individuals with 6 or more BCCs from 2007 to 2011. 19.7% of the frequent BCC cohort harbored pathogenic mutations in DNA repair genes: APC, BARD1, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, NBN, and PALB2. Individuals with 6 or more BCCs had an increased risk of other malignancies, with a 3.5-fold increase in the frequent BCC cohort and a 3.2-fold increase in the Truven database. Individuals who developed frequent BCCs have an increased prevalence of germline mutations in DNA repair genes and increased malignancy risk. Our data implicate frequent BCC development as an external marker of inherited cancer risk.

Accuracy of Raman spectroscopy for differentiating skin cancer from normal tissue.

Background:Raman spectroscopy could be applied to distinguish tumor from normal tissues. This meta-analysis assessed the accuracy of Raman spectroscopy in differentiating skin cancer from normal tissue.Methods:PubMed, Embase, Cochrane Library, and CNKI were searched to identify suitable studies before Februray 4th, 2018. We estimated the pooled sensitivity, specificity, positive, and negative likelihood ratios, diagnostic odds ratio, and constructed summary receiver-operating characteristics curves to identify the accuracy of Raman spectroscopy in differentiating skin cancer from normal tissue.Results:A total of 12 studies with 2461 spectra were included. For basal cell skin cancer (BCC) ex vivo detection, the pooled sensitivity and specificity were 0.99 (95% confidence interval [CI] 0.97–0.99) and 0.96 (95% CI 0.95–0.97), respectively. The area under the curve (AUC) was 0.9837. For BCC in vivo detection, the pooled sensitivity and specificity were 0.69 (95% CI 0.61–0.76) and 0.85 (95% CI 0.82–0.87), respectively. The AUC was 0.9213. For melanoma (MM) ex vivo detection, the pooled sensitivity and specificity were 1.00 (95% CI 0.91–1.00) and 0.98 (95% CI 0.95–1.00), respectively. The AUC was 0.9914. For MM in vivo detection, the sensitivity (0.93) and the specificity (0.96) balanced relatively well. For squamous cell skin cancer (SCC) ex vivo detection, the pooled sensitivity and specificity were 0.96 (95% CI 0.81–1.00) and 1.00 (95% CI 0.92–1.00), respectively. For SCC in vivo detection, the sensitivity was 0.81 (95% CI 0.70–0.90) and the specificity was 0.89 (95% CI 0.86–0.91).Conclusion:This meta-analysis suggested that Raman spectroscopy could be an effective and accurate tool for differentiating BCC, MM, SCC from normal tissue, which would assist us in the diagnosis and treatment of skin cancer.

YAP-TEAD signaling promotes basal cell carcinoma development via a c-JUN/AP1 axis.

The mammalian Hippo signaling pathway, through its effectors YAP and TAZ, coerces epithelial progenitor cell expansion for appropriate tissue development or regeneration upon damage. Its ability to drive rapid tissue growth explains why many oncogenic events frequently exploit this pathway to promote cancer phenotypes. Indeed, several tumor types including basal cell carcinoma (BCC) show genetic aberrations in the Hippo (or YAP/TAZ) regulators. Here, we uncover that while YAP is dispensable for homeostatic epidermal regeneration, it is required for BCC development. Our clonal analyses further demonstrate that the few emerging Yap-null dysplasia have lower fitness and thus are diminished as they progress to invasive BCC Mechanistically, YAP depletion in BCC tumors leads to effective impairment of the JNK-JUN signaling, a well-established tumor-driving cascade. Importantly, inthis context, YAP does not influence canonical Wnt or Hedgehog signaling. Overall, we reveal Hippo signaling as an independent promoter of BCCpathogenesis and thereby a viable target for drug-resistant BCC.

Basal cell cancer treatment. Therapeutic experience with vismodegib therapy

Most patients with basal cell cancer (BCC) can be cured if timely diagnosed. However approximately 1,3% of BCCs may develop into locally-advanced and sometimes even metastatic disease when local treatment options are limited and systemic therapy is warranted. Vismodegib was the first drug which demonstrated efficacy for the treatment of locally-advanced and metastatic BCC, inhibiting pathologically active Sonic Hedgehog (SHh) signaling pathway in tumor cells and preventing their uncontrolled proliferation.

Design of a label-free photonic crystal refractive index sensor for biomedical applications

Two photonic crystal optical refractive index sensors have been proposed in this paper. These sensors can be used for detection of basal cell cancer. A rod-type square lattice of GaAs is used for this purpose. The sensor topologies are based on a photonic crystal ring-shaped resonator coupled to two and waveguides respectively. Instead of using ultra-high quality factor cavities for improving the sensitivity, the resonance profile is localized and concentrated on the analyte to achieve good distinction. A 13 nm cavity resonance frequency shift for normal and cancer cells is obtained for detection of basal cell carcinoma. Finite difference time domain method and plane wave expansion methods are used to simulate and analyze the structures. The proposed biosensors have a sensitivity equal to 720 and 638 nm/RIU. The simplicity of the design and its high sensitivity make it a suitable choice for bio-sensing applications.

Prevalence of PDL1 Amplification and Preliminary Response to Immune Checkpoint Blockade in Solid Tumors

Copy number alterations in programmed cell death ligand 1 (PDL1 or CD274), programmed cell death 1 ligand 2 (PDCD1LG2 or PDL2), and Janus kinase 2 (JAK2) genes (chromosome 9p24.1) characterize Hodgkin lymphoma, resulting in high response rates to programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) blockade. The prevalence and utility of PDL1 amplification as a response biomarker to PD-1/PD-L1 blockade are unknown in other tumors. To examine the prevalence of PDL1 amplification and its utility as a response biomarker to PD-1/PD-L1 blockade in solid tumors. This retrospective study (October 1, 2012, to October 1, 2017) used a deidentified tumor database from a commercial company and annotated clinical records from a subset of patients treated at a university tertiary referral center. The study analyzed 118 187 tumors from the deidentified database, including a clinically annotated subgroup of 2039 malignant tumors. Comprehensive genomic profiling was performed on all samples to determine PDL1 amplification, microsatellite instability, and tumor mutational burden (TMB). A subset of patients was treated with PD-1/PD-L1 blockade. The prevalence of PDL1 amplification was determined among 118 187 patient samples that underwent next-generation sequencing. Solid tumors treated with checkpoint blockade were evaluated for response and progression-free survival (PFS). Of the 118 187 deidentified tumor samples, PDL1 amplifications were identified in 843 (0.7%), including more than 100 types of solid tumors. Most PDL1-amplified tumors (84.8%) had a low to intermediate TMB. PDL1 amplification did not always correlate with high-positive PD-L1 expression by immunohistochemical analysis. Six of 9 patients (66.7%) from 1 center with PDL1-amplified solid tumors had objective responses after checkpoint blockade administration. The median PFS among all treated patients was 15.2 months. Responders included 1 patient with glioblastoma (PFS, ≥5.2 months), 2 patients with head and neck squamous cell cancer (PFS, ≥9 and 15.2 months), 2 patients with metastatic basal cell cancer (PFS, 3.8 and ≥24.1 months), and 1 patient with urothelial cancer (PFS, ≥17.8 months). The results of this study suggest that PDL1 amplification occurs in a small subset of malignant tumors. Additional large-scale, prospective studies of PDL1-amplified cancers are warranted to confirm the responses to checkpoint blockade described herein, even in the absence of microsatellite instability, high PD-L1 expression, and a high TMB.

Characterizing the tissue dielectric constant of skin basal cell cancer lesions

Measuring tissue dielectric constant (TDC) of cancer tissues to distinguish them from normal or non-cancerous tissues has been an active area of research that has targeted several different cancer types usually using in vitro specimens. The goal of this study was to determine if and to what extent TDC values measured in vivo at 300MHz using a simple hand-held measuring device might differentiate between skin cancer lesions and non-cancerous skin. Triplicate TDC measurements were made in 32 patients who were subsequently diagnosed with skin basal cell carcinoma (BCC) and in 14 patients subsequently diagnosed as having non-cancerous lesions. Lesion TDC values were compared to contralateral unaffected skin and between lesion types. A significantly lower TDC value (mean±SD) of BCC lesions (TDCL ) vs TDC values of contralateral non-affected skin (TDCC ) was found (22.4±16.2 vs 38.1±15.2, P<.00001). A similar pattern was found for non-cancerous lesions with lesion TDC values less than non-affected skin (14.5±9.0 vs 29.1±9.0, P<.0001). However, TDC values were not statistically different between BCC lesions and non-cancerous lesions (22.4±16.2 vs 14.5±9.0, P=.096) and calculated TDCL /TDCC ratios between BCC lesions and non-cancerous lesions also were not significantly different (0.596±0.345 vs 0.501±0.261, P=.364). (1) Main results do not support using TDC measurements to differentiate in vivo skin cancer lesions from non-cancerous lesions. (2) TDC values strongly suggest reduced water content of both cancerous and non-cancerous lesions. (3) Lesion TDC measurements provide reference values for future studies.