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Squamous Cell Carcinoma of the Skin

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81. The burden of cutaneous adnexal carcinomas and the risk of associated squamous cell carcinoma: a population-based study. (PubMed)

The burden of cutaneous adnexal carcinomas and the risk of associated squamous cell carcinoma: a population-based study. Recent studies have shown an increasing incidence of cutaneous adnexal carcinomas (CACs).The aim of our study was to evaluate incidence and survival for cases of CACs and investigate their association with other skin neoplasms.We conducted a population-based study. Data on incident cases of CACs were obtained from the Tuscany Cancer Registry between 1985 and 2010. In order (...) to determine whether the occurrence of squamous cell carcinoma (SCC) among patients with CAC is higher or lower than expected in the general population, the standardized incidence ratio (SIR) was calculated.A total of 242 patients with CAC were observed; the age-standardized incidence rate was 3·8 cases per million person-years. From 1997 to 2010 crude incidence rates increased by 159%. Age-specific incidence was higher in men over 80 years old than in women of the same age and younger individuals

2018 British Journal of Dermatology

82. DNA Damage-Inducible Transcript 4 Is an Innate Guardian for Human Squamous Cell Carcinoma and an Molecular Vector for Anti-carcinoma Effect of 1,25(OH)<sub>2</sub> D<sub>3</sub>. (PubMed)

DNA Damage-Inducible Transcript 4 Is an Innate Guardian for Human Squamous Cell Carcinoma and an Molecular Vector for Anti-carcinoma Effect of 1,25(OH)2 D3. Cutaneous squamous cell carcinoma (SCC) is one of the most common non-melanoma skin cancers worldwide. While its exact tumorigenesis mechanisms is far from well-established and less satisfied therapeutic strategy can be clinically used nowadays. In this study, we intended to investigate the role of DNA damage-inducible (...) transcript 4 (DDIT4) in human SCC. Firstly, we identified DDIT4 is significantly suppressed in human SCC tissue and cultured A431 cell line, and reduced DDIT4 accelerates keratinocytes proliferation but impedes the autophagy flux through mTORC1 pathway by affecting the downstream S6 Kinase1, 4E-BP1, Beclin1 and LC3 II/I. While 1,25(OH)2 D3 enhanced DDIT4 expression and activated autophagy and inhibit mTORC1 to take the effect of anti-proliferation and activating autophagy. Further, formation of direct

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2018 Experimental Dermatology

83. ST2/IL-33 signaling promotes malignant development of experimental squamous cell carcinoma by decreasing NK cells cytotoxicity and modulating the intratumoral cell infiltrate (PubMed)

ST2/IL-33 signaling promotes malignant development of experimental squamous cell carcinoma by decreasing NK cells cytotoxicity and modulating the intratumoral cell infiltrate Squamous cell carcinoma (SCC) is the second most common form of skin cancer and the mechanism(s) involved in the progression of this tumor are unknown. Increases in the expression of IL-33/ST2 axis components have been demonstrated to contribute to neoplastic transformation in several tumor models and interleukin-33 (...) is correlated with poor prognosis of patients with squamous cell carcinoma of the tongue. Based on these observations, we sought to determine the role of the IL-33/ST2 pathway during the development of SCC. Our findings show that ST2-deficiency led to a marked decrease in the severity of skin lesions, suggesting that ST2 signaling contributed to tumor development. An analysis of tumor lesions in wild-type and ST2KO mice revealed that a lack of ST2 was associated with specific and significant reductions

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2018 Oncotarget

84. Topical kinase inhibitors induce regression of cutaneous squamous cell carcinoma. (PubMed)

Topical kinase inhibitors induce regression of cutaneous squamous cell carcinoma. Actinic keratoses (AKs) and squamous cell carcinoma in situ (SCCIS) are precursor lesions for cutaneous squamous cell carcinoma (cSCC), the second most common form of cancer. Current topical therapies for AKs and SCCIS promote skin inflammation to eradicate lesions and do not directly target the biological mechanisms driving growth. We hypothesized that topical small molecule inhibitors targeting kinases promoting (...) indicate that topical small molecule kinase inhibitors targeting drivers of AK/SCCIS/cSCC growth represent a promising therapeutic approach to treat these common skin lesions.© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

2019 Experimental Dermatology

85. The NLRP1 inflammasome pathway is silenced in cutaneous squamous cell carcinoma. (PubMed)

expression is impaired in different types of cancer in humans. In this study, we analyzed inflammasome activation and expression of inflammasome proteins including their downstream cytokines in squamous cell carcinomas (SCCs), a type of non-melanoma skin cancer derived from keratinocytes. We assessed mRNA and protein levels in human primary keratinocytes and skin carcinoma-derived SCC cell lines and detected a strong downregulation of expression of NLRP1 inflammasome components, as well as reduced (...) The NLRP1 inflammasome pathway is silenced in cutaneous squamous cell carcinoma. The inflammasome protein NLRP1 is an important innate immune sensor in human keratinocytes and mediates, together with the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1, the activation and secretion of the pro-inflammatory cytokines IL-1β and IL-18. These cytokines and inflammasomes can have in part opposing roles during tumorigenesis in mice. In contrast, ASC

2019 Journal of Investigative Dermatology

86. Fibulin-3 has anti-tumorigenic activities in cutaneous squamous cell carcinoma. (PubMed)

Fibulin-3 has anti-tumorigenic activities in cutaneous squamous cell carcinoma. Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancers. Several previous studies have shown that Fibulin-3 participates in the occurrence and development of various tumors; however, its role in cSCC remains unknown. In the present study, we observed that the expression of Fibulin-3 was down-regulated in cSCC tissues compared with normal skin tissues, which was due to Fibulin-3 promoter (...) methylation. In vitro, knockdown of Fibulin-3 in cSCC cell lines A431 and SCL-1 cells promoted cell proliferation, protected cells against apoptosis and enhanced the migration and invasion abilities. Conversely, overexpression of Fibulin-3 inhibited cell proliferation by promoting growth arrest during the G1/S phase transition, induced apoptosis, and reduced the migration and invasion abilities. These anticarcinogenic effects of Fibulin-3 were associated with inhibition of the AKT signaling pathway

2019 Journal of Investigative Dermatology

87. Facial distribution of squamous cell carcinoma in Japanese. (PubMed)

Facial distribution of squamous cell carcinoma in Japanese. Squamous cell carcinoma (SCC) is a malignant tumor of the skin. SCC is frequently distributed on highly exposed areas such as the face and dorsal surface of the hands because it is closely related to ultraviolet damage. We retrospectively analyzed 106 cases of SCC treated at Nagoya City University Hospital from April 2004 to October 2015 and examined regional features based on modified facial aesthetic units. SCC occurred more

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2019 Experimental Dermatology

88. Concurrent Selective Lymph Node Radiotherapy and S-1 Plus Cisplatin for Esophageal Squamous Cell Carcinoma: A Phase II Study. (PubMed)

Concurrent Selective Lymph Node Radiotherapy and S-1 Plus Cisplatin for Esophageal Squamous Cell Carcinoma: A Phase II Study. The efficacy, toxicity, and patterns of failure of esophageal squamous cell carcinoma (ESCC) treated with selective lymph node (SLN) conventional fraction radiotherapy (CFRT) and S-1 plus cisplatin (CDDP) were evaluated.67 Patients with clinical stage II-IVa ESCC were enrolled. The total dose of SLN CFRT was 60 Gy in 30 fractions over 6 weeks. The first course (...) chemoradiotherapy underwent two additional cycles of chemotherapy.The objective response rate (ORR) was 82.5%. Grade 3 or 4 toxicities included leukopenia (23.8%), neutropenia (14.3%), thrombocytopenia (14.3%), hemoglobin (4.8%), gastrointestinal (12.7%), skin (1.6%), and esophagus fistula (1.6%). One patient died of severe pneumonia, and two died of late toxicity because of esophagus fistula. With median follow-up of 32 months, the overall survival (OS) and progression-free survival (PFS) at 1 year and 2 years

2019 Annals of Surgical Oncology

89. Chemoradiotherapy could improve overall survival of patients with stage IV cutaneous squamous cell carcinoma: analysis of 34 cases. (PubMed)

Chemoradiotherapy could improve overall survival of patients with stage IV cutaneous squamous cell carcinoma: analysis of 34 cases. Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer, comprising approximately 20% of all skin malignancies1 . The prognoses of patients with unresectable disease, such as locally advanced tumour or distant metastases, are known to be relatively poor due to lack of effective standardized systemic therapies2,3 . When surgery

2019 British Journal of Dermatology

90. ΔNp63 in squamous cell carcinoma: Defining the oncogenic routes affecting epigenetic landscape and tumor microenvironment. (PubMed)

ΔNp63 in squamous cell carcinoma: Defining the oncogenic routes affecting epigenetic landscape and tumor microenvironment. Squamous cell carcinoma (SCC) is a treatment-refractory tumour, which arises from the epithelium of diverse anatomical sites, such as oesophagus, head and neck, lung, and skin. Accumulating evidence has revealed a number of genomic, clinical and molecular features commonly observed in SCC of distinct origins. Some of these genetic events culminate in fostering the activity (...) of ΔNp63, a potent oncogene which exerts its pro-tumorigenic effects by regulating specific transcriptional programs to sustain malignant cell proliferation and survival. In this review, we will describe the genetic and epigenetic determinants underlying ΔNp63 oncogenic activities in SCC, and discuss some relevant transcriptional effectors of ΔNp63, emphasizing their impact in modulating the crosstalk between tumour cells and tumour microenvironment (TME).Molecular Oncology (2019) © 2019 The Authors

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2019 Molecular oncology

91. A patient with squamous cell carcinoma in-situ successfully treated with intralesional 5-Fluorouracil and topical trichloroacetic acid. (PubMed)

A patient with squamous cell carcinoma in-situ successfully treated with intralesional 5-Fluorouracil and topical trichloroacetic acid. The current gold standard and the first line of treatment for non-melanoma skin cancer is surgical excision. Nevertheless, some patients are not good candidates for surgery when wound healing may be impaired.A 96-year-old male presented with 1.2 cm by 1.5 cm tumoral lesion with an ill-infiltrated border and central ulceration located on the mid right lower leg (...) . Biopsy confirmed the diagnosis of squamous cell carcinoma (SCC) in situ. The primary lesion was treated centrally to peripherally with multiple intralesional injections of 1.5 mL 5-Fluorouracil (5-FU) (50 mg/mL). The lesion was also treated with a single layer application of 80% Trichloroacetic acid (topical solution). One additional and final treatment of only 80% TCA was performed after three weeks.There was a complete regression of the SCC three weeks after the second treatment.We demonstrate

2019 Journal of Dermatological Treatment

92. Identification of rigosertib for the treatment of recessive dystrophic epidermolysis bullosa-associated squamous cell carcinoma. (PubMed)

Identification of rigosertib for the treatment of recessive dystrophic epidermolysis bullosa-associated squamous cell carcinoma. Squamous cell carcinoma (SCC) of the skin is the leading cause of death in patients with the severe generalized form of the genetic disease recessive dystrophic epidermolysis bullosa (RDEB). Although emerging data are identifying why patients suffer this fatal complication, therapies for treatment of RDEB SCC are in urgent need.We previously identified polo-like (...) kinase 1 (PLK1) as a therapeutic target in skin SCC, including RDEB SCC. Here, we undertake a screen of 6 compounds originally designated as PLK1 inhibitors, and detail the efficacy of the lead compound, the multi-pathway allosteric inhibitor ON-01910, for targeting RDEB SCC in vitro and in vivo.ON-01910 (or rigosertib) exhibited significant specificity for RDEB SCC: in culture rigosertib induced apoptosis in 10/10 RDEB SCC keratinocyte populations while only slowing the growth of normal primary skin

2019 Clinical Cancer Research

93. Epigenetic regulation of iASPP-p63 feedback loop in cutaneous squamous cell carcinoma. (PubMed)

Epigenetic regulation of iASPP-p63 feedback loop in cutaneous squamous cell carcinoma. Keratinocyte skin cancer, comprising cutaneous squamous (cSCC) and basal cell carcinoma, is the most common malignancy in the UK. P53 is frequently mutated in cSCC. iASPP is a key inhibitor of p53 and NF-kB signalling pathways and has been documented as highly expressed in several types of human cancer. We have previously identified an autoregulatory feedback loop between iASPP and p63, which is critical (...) in epidermal homeostasis. We hypothesised a potential role for dysregulation of this axis in the pathogenesis of keratinocyte malignancies. Immunostaining of 116 cSCC clinical samples revealed increased iASPP and ΔNp63 expression but also highlighted a significant alteration of iASPP cellular localisation, with consequent deregulation of its function. Expression patterns, functionality, gene and microRNA expression analysis were further investigated in 10 cSCC cell lines. Our data suggest that whilst

2019 Journal of Investigative Dermatology

94. Cetuximab as a Component of Multimodality Treatment of High-Risk Cutaneous Squamous Cell Carcinoma: A Retrospective Analysis From a Single Tertiary Academic Medical Center. (PubMed)

Cetuximab as a Component of Multimodality Treatment of High-Risk Cutaneous Squamous Cell Carcinoma: A Retrospective Analysis From a Single Tertiary Academic Medical Center. Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer and has potential for regional or distant metastasis. Despite the standardization of features associated with high-risk cSCC, an advanced subset of cSCC, there is no established consensus regarding proper management of this tumor.To

2019 Dermatologic Surgery

95. Glutathione S-transferase pi 1 variant and squamous cell carcinoma susceptibility: a meta-analysis of 52 case-control studies. (PubMed)

Glutathione S-transferase pi 1 variant and squamous cell carcinoma susceptibility: a meta-analysis of 52 case-control studies. There are several meta-analyses on the genetic relationship between the rs1695 polymorphism within the GSTP1 (glutathione S-transferase pi 1) gene and the risk of different SCC (squamous cell carcinoma) diseases, such as ESCC (oesophageal SCC), HNSCC (head and neck SCC), LSCC (lung SCC), and SSCC (skin SCC). Nevertheless, no unified conclusions have been drawn.Herein

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2019 BMC Medical Genetics

96. Sunbed Use Increases Cutaneous Squamous Cell Carcinoma Risk in Women: A Large-scale, Prospective Study in Sweden. (PubMed)

Sunbed Use Increases Cutaneous Squamous Cell Carcinoma Risk in Women: A Large-scale, Prospective Study in Sweden. The incidence of cutaneous squamous cell carcinoma has increased rapidly in Sweden in the past decades. Here, we present a prospective study of the Melanoma in Southern Sweden (MISS)-cohort, with 29,460 participating women in southern Sweden that investigates the risk factors for cutaneous squamous cell carcinoma. Data on the host and skin cancer risk factors were collected through (...) and the development of cutaneous squamous cell carcinoma. Our findings support the idea of integrating dermatological follow-up examinations for immunosuppressed patients and banning the use of sunbeds in order to prevent cutaneous squamous cell carcinoma.

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2019 Acta Dermato-Venereologica

97. Systemic therapy for advanced cutaneous squamous cell carcinoma. (PubMed)

Systemic therapy for advanced cutaneous squamous cell carcinoma. The incidence of advanced cutaneous squamous cell carcinoma (cSCC) is increasing; of the 1.3 million nonmelanoma skin cancers that arise each year, approximately 20% are cSCC, and between 2-5% of these cases ultimately metastasize. However, there is no established consensus on first-line systemic treatment for those patients who have locally advanced or metastatic disease. Major classes of systemic agents include chemotherapy

2019 Seminars in Cutaneous Medicine and Surgery

98. Somatic mutations in kinetochore gene KNSTRN are associated with basal proliferating actinic keratoses and cutaneous squamous cell carcinoma. (PubMed)

Somatic mutations in kinetochore gene KNSTRN are associated with basal proliferating actinic keratoses and cutaneous squamous cell carcinoma. Mutations in kinetochore gene KNSTRN accelerate the development of cutaneous squamous cell carcinoma (SCC) and may correlate with different histological classifications of actinic keratosis (AKs).To determine KNSTRN gene mutation frequency in healthy skin (HS), actinically damaged skin (ADS), in AKs with different histomorphological gradings, and invasive

2019 Journal of the European Academy of Dermatology and Venereology

99. Oral squamous cell carcinoma arising in a patient with Werner syndrome. (PubMed)

Oral squamous cell carcinoma arising in a patient with Werner syndrome. Werner syndrome (WS) is an autosomal recessive disorder characterized by physical signs and symptoms, including premature aging and scleroderma-like skin changes. The gene responsible for WS is the WRN gene. A significant proportion of WS-related malignant tumours are non-epithelial types, and the incidence of oral squamous cell carcinoma (SCC) is rare. A case of oral SCC of the lower alveolus and gingiva arising in a 63

2019 International Journal of Oral and Maxillofacial Surgery

100. Data independent acquisition proteomic analysis can discriminate between actinic keratosis, Bowen's disease and cutaneous squamous cell carcinoma. (PubMed)

Data independent acquisition proteomic analysis can discriminate between actinic keratosis, Bowen's disease and cutaneous squamous cell carcinoma. Actinic keratosis (AK), Bowen's disease (BD) and cutaneous squamous cell carcinoma (cSCC) are heterogeneous keratinocytic skin lesions (KSL). Biomarkers that can accurately stratify these lesion types are needed to support a new paradigm of personalised, precise management of skin neoplasia. In this paper, we used the data independent acquisition (...) (DIA) proteomics workflow, SWATH-MS, to analyse formalin-fixed paraffin embedded (FFPE) samples of normal skin and KSL including well differentiated (WD), moderately differentiated (MD) and poorly differentiated (PD) cSCC. We quantified 3574 proteins across 93 samples studied. Differential abundance analysis identified 19, five and six protein markers exclusive to AK, BD and cSCC lesions, respectively. Among cSCC lesions of various levels of tumour differentiation, 118, 230 and 17 proteins showed

2019 Journal of Investigative Dermatology

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