Fohotodermatoses and Skin Cancer

Preface Skin cancer is one of the most common types of tumors in Western countries. In the United States only, more than one million people are diagnosed with skin cancer each year. Although the absolute number of skin cancer patients is increasing, the death is inversely decreasing, due to the early detection and treatment. Basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma are three major types of skin cancer. BCC and SCC rarely have metastasis; over 95 percent BCC and SCC patients can be cured. Melanoma only accounts for a small percentage of skin cancer, but it causes 75 percent death of this disease. In this book, we invited a number of experts to present their latest accomplishments on skin cancer research. Although the topics are varied, the authors did great work to help readers better understand skin cancer and learn the knowledge to prevent this disease. There are three sections in this book, starting with etiology. Ultraviolet (UV) light exposure is overwhelmingly believed to be the most frequent cause of skin cancer. In this section, the association between UV and photodermatoses, as well as skin cancer is discussed. Desmosomal cadherins are important molecules in tumor cell adhesion and invasion, and their important roles in BCC are also presented in details. In the diagnosis and treatment section, a few new methodologies are described. As known, the outcome of malignant melanoma greatly depends on the thickness of the tumor at the time of treatment. Accurate determination of melanoma lateral and depth of margins using non-invasive imaging technologies is of importance when making sound decisions for treatment and evaluating a five year survival rate. A novel method named differential scanning calorimetry is capable of predicting metastasis of melanoma patients by monitoring the temperature changes of plasma. Electronic miniature X-ray brachytherapy is introduced as a new technology to treat nonmelanoms skin cancer. Although its potential has not yet been fully realized, chemoprevention, in terms of using chemical agents that naturally occur in foods, or are administered as pharmaceuticals to retard or reverse the process of carcinogenesis and progression of cancer, has been recognized to benefit individuals with precancerous lesions or genetic susceptibilities to cancer. In the prevention section, two chapters summarized the most recognized dietary phytochemicals and their potential application in skin cancer. X Preface This book would not have been possible without the contributions of all authors and the support from the publisher. Especially, I will convey my sincere appreciation to Ms. Tajana Jevtic, who has always been available and supportive of me to accomplish this project. Yaguang Xi, M.D., Ph.D. Assistant Professor of Oncologic Sciences, University of South Alabama, US

Expression of IL-1 family members in human allergic contact dermatitis

The interleukin (IL)-1 family includes 11 members that are important in inflammatory processes. It includes various agonists and two antagonists, IL-1Ra and IL-36Ra. Our aim was to investigate whether the IL-1 family is involved in allergic contact dermatitis (ACD). The expression of IL-1 family members was evaluated by PCR and mmunohistochemistry in the positive patch test reaction site (involved skin), and in the uninvolved skin of ACD patients. We also examined these cytokines in an ex vivo model of ACD. The antagonistic activity of IL-36Ra was evaluated by injecting recombinant IL-36Ra in uninvolved skin biopsies of ACD patients. IL-1Ra and IL-36Ra expression was quantified in mononuclear cells of nickel-sensitized patients challenged in vitro with nickel. IL33-involvement in ACD was investigated by intradermal injection of anti-IL-33 in the uninvolved skin of patients ex vivo. Results showed that IL-1β, IL-1Ra, IL-36α, IL-36β, IL-36γ and IL-33 expression, but not IL-36Ra expression was enhanced in ACD-involved skin. Immunohistochemical analysis and ex vivo skin cultures confirmed these results. Injection of anti-IL-33 in ACD-uninvolved skin inhibited IL-8 expression, whereas IL-36Ra inhibited IL-36α, IL-36β, IL-36γ and IL-8 expression. Nickel induced IL-1Ra expression in lymphocytes of nickel-sensitized patients. In conclusion, various IL-1 agonists and antagonists may be involved in ACD pathogenesis

CARATTERISTICHE CLINICHE E FISIOPATOLOGICHE DEI PAZIENTI CON SINTOMI EXTRAESOFAGEI DI MALATTIA DA REFLUSSO GASTROESOFAGEO: STUDIO CASO CONTROLLO.

INTRODUZIONE: la presenza di sintomi extraesofagei (EERS) correlati a malattia da reflusso gastroesofageo (MRGE) è stimata essere molto presente fra tutti i soggetti che si presentano agli ambulatori di gastroenterologia. I pazienti con EERS sembrano complessivamente avere una minor risposta alla terapia medica e di conseguenza necessitano di un maggior numero di esami per giungere alla diagnosi. SCOPO DELLO STUDIO: Lo scopo del seguente lavoro di tesi è stato quello di valutare le caratteristiche cliniche e fisiopatologiche oltre che la risposta a terapia farmacologica di una popolazione di pazienti con sintomi extra-esofagei di malattia da reflusso gastroesofageo. Per meglio caratterizzare i pazienti essi sono stati suddivisi in base alla presenza/assenza del sintomo pirosi. MATERIALI E METODI: sono stati selezionati pazienti con EERS afferenti agli ambulatori di fisiopatologia con sintomi extraesofagei positivi per MRGE alla valutazione ORL (RSI>13 e RFS>7), in cui fossero stati esclusi disturbi polmonari primitivi e abitudine al fumo. Tutti i pazienti avevano precedentemente eseguito EGDS negativa per lesioni erosive e di conseguenza, su decisione dell’endoscopista una terapia con IPP. Tutti i pazienti sono stati suddivisi sulla base della presentazione del sintomo pirosi. Abbiamo pertanto valutato due gruppi di pazienti: Gruppo H (con pirosi) e Gruppo NH (senza il sintomo pirosi). Tutti i pazienti sono stati sottoposti a esami di fisiopatologia esofagea. Tutti i pazienti sono stati valutati per la loro risposta a terapia con IPP mediante scala validata VAS. RISULTATI: Sono stati arruolati 102 pazienti (M/F 43/59) con età media 50.1±14.3 anni. Il gruppo H era formato da 50 pazienti (M/F 25/25) ed il gruppo NH era formato da 52 pazienti (M/F 18/34). Non sono state evidenziate caratteristiche epidemiologiche (età media e BMI) differenti fra i due gruppi. Dal punto di vista clinico solo la raucedine ha una frequenza superiore nel gruppo NH. Tutti i più frequenti EERS (tosse, globo, raucedine, dolore/bruciore alla gola e necessità di schiarirsi la gola) erano presenti nel 4% del gruppo H e nel 9,6% del gruppo NH. Dal punto di vista pH-impedenziometrico tutti i parametri considerati (AET, AET da supino, numero di reflussi totali e acidi, MNBI e PSPW index) tranne il numero di reflussi debolmente acidi si sono dimostrati più alterati nel gruppo H (p<0.001). Inoltre, dopo trattamento con PPI i responder sono risultati superiori nel gruppo H: la risposta al sintomo pirosi era del 66% e del 52% per EERS. La percentuale di responder agli EERS era dell’11.3% nel gruppo NH. I valori di MNBI e PSPW-index sono risultati più bassi nei responder rispetto ai non-responder. CONCLUSIONI: Sulla base di questi dati è possibile evidenziare che la presenza di pirosi è predittiva di risposta a terapia farmacologica e che la presenza di EERS non è necessariamente correlata a malattia da reflusso ma necessita di essere indagata con esami di fisiopatologia

Fohotodermatoses and Skin Cancer

Preface Skin cancer is one of the most common types of tumors in Western countries. In the United States only, more than one million people are diagnosed with skin cancer each year. Although the absolute number of skin cancer patients is increasing, the death is inversely decreasing, due to the early detection and treatment. Basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma are three major types of skin cancer. BCC and SCC rarely have metastasis; over 95 percent BCC and SCC patients can be cured. Melanoma only accounts for a small percentage of skin cancer, but it causes 75 percent death of this disease. In this book, we invited a number of experts to present their latest accomplishments on skin cancer research. Although the topics are varied, the authors did great work to help readers better understand skin cancer and learn the knowledge to prevent this disease. There are three sections in this book, starting with etiology. Ultraviolet (UV) light exposure is overwhelmingly believed to be the most frequent cause of skin cancer. In this section, the association between UV and photodermatoses, as well as skin cancer is discussed. Desmosomal cadherins are important molecules in tumor cell adhesion and invasion, and their important roles in BCC are also presented in details. In the diagnosis and treatment section, a few new methodologies are described. As known, the outcome of malignant melanoma greatly depends on the thickness of the tumor at the time of treatment. Accurate determination of melanoma lateral and depth of margins using non-invasive imaging technologies is of importance when making sound decisions for treatment and evaluating a five year survival rate. A novel method named differential scanning calorimetry is capable of predicting metastasis of melanoma patients by monitoring the temperature changes of plasma. Electronic miniature X-ray brachytherapy is introduced as a new technology to treat nonmelanoms skin cancer. Although its potential has not yet been fully realized, chemoprevention, in terms of using chemical agents that naturally occur in foods, or are administered as pharmaceuticals to retard or reverse the process of carcinogenesis and progression of cancer, has been recognized to benefit individuals with precancerous lesions or genetic susceptibilities to cancer. In the prevention section, two chapters summarized the most recognized dietary phytochemicals and their potential application in skin cancer. X Preface This book would not have been possible without the contributions of all authors and the support from the publisher. Especially, I will convey my sincere appreciation to Ms. Tajana Jevtic, who has always been available and supportive of me to accomplish this project. Yaguang Xi, M.D., Ph.D. Assistant Professor of Oncologic Sciences, University of South Alabama, US

IL-33 is regulated by TNF-α in normal and psoriatic skin

Interleukin-33 (IL-33) is the most recently discovered IL-1 family member. Considered an endogenous "alarmin" released by necrotic cells in response to tissue injury or damage, IL-33 is constitutively expressed in tissues exposed to the environment, where endothelial and epithelial cells constitute its major sources. Several findings reported that pro-inflammatory stimuli, such as IFN-γ and TNF-α, as well as IL-17, can induce IL-33 expression in normal human epidermal keratinocytes. In the present study, we deeply investigated the relation between IL-33 and TNF-α, by employing the whole skin as study model. TNF-α dose- and time-dependently induced IL-33 gene expression in ex vivo healthy skin organ culture. Similarly, TNF-α significantly increased IL-33 mRNA expression in normal human epidermal sheets. Moreover, IL-33 was enhanced in psoriatic skin and anti-TNF-α therapy was able to significantly reduce it. The biology of IL-33 is gaining in complexity, and this molecule is now known to have additional roles beyond its original description. In particular, we can assess that IL-33 is regulated by TNF-α in normal and psoriatic ski

IL-33 is regulated by TNF-α in normal and psoriatic skin

Interleukin-33 (IL-33) is the most recently discovered IL-1 family member. Considered an endogenous "alarmin" released by necrotic cells in response to tissue injury or damage, IL-33 is constitutively expressed in tissues exposed to the environment, where endothelial and epithelial cells constitute its major sources. Several findings reported that pro-inflammatory stimuli, such as IFN-γ and TNF-α, as well as IL-17, can induce IL-33 expression in normal human epidermal keratinocytes. In the present study, we deeply investigated the relation between IL-33 and TNF-α, by employing the whole skin as study model. TNF-α dose- and time-dependently induced IL-33 gene expression in ex vivo healthy skin organ culture. Similarly, TNF-α significantly increased IL-33 mRNA expression in normal human epidermal sheets. Moreover, IL-33 was enhanced in psoriatic skin and anti-TNF-α therapy was able to significantly reduce it. The biology of IL-33 is gaining in complexity, and this molecule is now known to have additional roles beyond its original description. In particular, we can assess that IL-33 is regulated by TNF-α in normal and psoriatic skin

IL-33 is regulated by TNF-α in normal and psoriatic skin

Interleukin-33 (IL-33) is the most recently discovered IL-1 family member. Considered an endogenous "alarmin" released by necrotic cells in response to tissue injury or damage, IL-33 is constitutively expressed in tissues exposed to the environment, where endothelial and epithelial cells constitute its major sources. Several findings reported that pro-inflammatory stimuli, such as IFN-γ and TNF-α, as well as IL-17, can induce IL-33 expression in normal human epidermal keratinocytes. In the present study, we deeply investigated the relation between IL-33 and TNF-α, by employing the whole skin as study model. TNF-α dose- and time-dependently induced IL-33 gene expression in ex vivo healthy skin organ culture. Similarly, TNF-α significantly increased IL-33 mRNA expression in normal human epidermal sheets. Moreover, IL-33 was enhanced in psoriatic skin and anti-TNF-α therapy was able to significantly reduce it. The biology of IL-33 is gaining in complexity, and this molecule is now known to have additional roles beyond its original description. In particular, we can assess that IL-33 is regulated by TNF-α in normal and psoriatic skin