Feature extraction of segmented skin lesions is a pivotal step for implementing accurate decision support systems. Existing feature sets combine many ad-hoc calculations and are unable to easily provide intuitive diagnostic reasoning. This thesis presents the design and evaluation of a set of features for objectively detecting melanoma in an intuitive and accurate manner. We call these "high-level intuitive features" (HLIFs). The current clinical standard for detecting melanoma, the deadliest form of skin cancer, is visual inspection of the skin's surface. A widely adopted rule for detecting melanoma is the "ABCD" rule, whereby the doctor identifies the presence of Asymmetry, Border irregularity, Colour patterns, and Diameter. The adoption of specialized medical devices for this cause is extremely slow due to the added temporal and financial burden. Therefore, recent research efforts have focused on detection support systems that analyse images acquired with standard consumer-grade camera images of skin lesions. The central benefit of these systems is the provision of technology with low barriers to adoption. Recently proposed skin lesion feature sets have been large sets of low-level features attempting to model the widely adopted ABCD criteria of melanoma. These result in high-dimensional feature spaces, which are computationally expensive and sparse due to the lack of available clinical data. It is difficult to convey diagnostic rationale using these feature sets due to their inherent ad-hoc mathematical nature. This thesis presents and applies a generic framework for designing HLIFs for decision support systems relying on intuitive observations. By definition, a HLIF is designed explicitly to model a human-observable characteristic such that the feature score can be intuited by the user. Thus, along with the classification label, visual rationale can be provided to further support the prediction. This thesis applies the HLIF framework to design 10 HLIFs for skin cancer detection, following the ABCD rule. That is, HLIFs modeling asymmetry, border irregularity, and colour patterns are presented. This thesis evaluates the effectiveness of HLIFs in a standard classification setting. Using publicly-available images obtained in unconstrained environments, the set of HLIFs is compared with and against a recently published low-level feature set. Since the focus is on evaluating the features, illumination correction and manually-defined segmentations are used, along with a linear classification scheme. The promising results indicate that HLIFs capture more relevant information than low-level features, and that concatenating the HLIFs to the low-level feature set results in improved accuracy metrics. Visual intuitive information is provided to indicate the ability of providing intuitive diagnostic reasoning to the user.

DE LA TESIS:Se trata de un estudio observacional no controlado, de 120 pacientes afectos de melanoma uveal, tratados todos ellos con braquiterapia con semillas de Yodo-125, a los que se les ha efectuado un seguimiento desde el punto de vista oftalmológico, durante al menos un año. El objetivo principal de la tesis fue determinar los factores que influyen en la evolución de la agudeza visual tras la aplicación de dicho tratamiento, y la descripción de un modelo matemático que pueda explicar la evolución de dicha variable clínica oftalmológica.Tras la finalización del estudio, se observó que la pérdida de agudeza visual de forma significativa está en relación con las variables: dosis administrada en la mácula, dosis administrada en el cristalino y tiempo de seguimiento tras el tratamiento. Esta relación se concreta en la fórmula siguiente:AV final= Av basal+Tiempo+Dosis Mácula+Dosis mácula*Tiempo

No description available.

Melanoma is a cancer of the pigment producing cells, melanocytes, and is the most serious type of skin cancer. Cancer is a condition in which one type of cell grows without limit in a disorganized fashion, disrupting and replacing normal tissues and their functions. Normal melanocytes reside in the outer layer of the skin and produce a brown pigment called melanin, which is responsible for skin color. Melanoma occurs when melanocytes become cancerous, grow, and invade other tissues. Pro-opiomelanocortin (POMC) is a precursor polypeptide of 241 amino acids and the prohormone of various neuropeptide, including corticotropin (ACTH), £\-melanocyte-stimulating hormone (£\-MSH), and £]-endorphin (£]-EP). Recently, we demonstrated that systemic POMC overexpression potently suppresses the growth and metastasis of B16-F10 melanoma in vitro and in vivo. However, despite potent inhibition of tumor proliferation and angiogenesis, B16-F10 melanoma still managed to survive after POMC gene therapy. The underlying survival mechanism of B16-F10 melanoma remains unclear. Microphthalmia-associated transcription factor (MITF) is a basic helix-loop-helix transcription factor that plays a key role not only in melanin synthesis, but also in melanocyte development and survival. Besides, MITF binds to the hypoxia-inducible factor-1£\ (HIF-1£\) promoter to stimulate its transcriptional activity. In this study, we investigate the influence of POMC gene delivery on the pro-survival MITF/HIF-1£\ pathway in B16-F10 melanoma cells. Quantitative RT-PCR and western blot analysis revealed that POMC gene delivery increased the MITF mRNA and protein level in B16-F10 melanoma cells. Besides, POMC gene delivery significantly enhanced the HIF-1£\-driven luciferase activities in melanoma cells. By transfection and puromycin selection, we generated and characterized a MITF-knockdown B16-F10 melanoma cells (MITF KD) stably expressing short hairpin RNA against MITF. The growth, invasion, and colonies formation of MITF-KD were similar to those of vector control. However, implantation of MITF-KD cells led to melanoma with significantly reduced tumor size compared with those in mice implanted with vector control cells. Histological analysis revealed a significant reduction of CD31-positive blood vessels in implantation of MITF-KD cells-treated tumors, which was accompanied with a decrease in Ki-67-positive proliferating cells and an increase in TUNEL-positive apoptotic cells. Moreover, POMC-mediated upregulation of MITF and HIF-1 £\ was significantly attenuated in MITF KD-B16-F10 cells. Acetylsalicylic acid (aspirin; ASA) is widely used as an analgesic/antipyretic drug. ASA exhibits a wide range of biological effects, including preventative effects against heart attack, stroke, and the development of some types of cancer. In our study, we found ASA enhanced cell proliferation. However, in invasion test, ASA had no effect on cell migration. POMC gene delivery elevated the mRNA and protein level of hemeoxygenase-1 (HO-1), a downstream effector of HIF-1£\ pathway and an enzyme catalyzing the converting reaction of heme to carbon monoxide, ion and biliverdine. Inhibition of HO-1 activities augmented the inhibitory effect of POMC gene delivery on proliferation, migration and anchorage-independent growth of B16-F10 melanoma cells. These studies indicated that activation of MITF/HIF-1£\/HO-1 indeed contributes to melanoma survival after POMC gene delivery.

An experienced dermatopathologist can reliably diagnose most cutaneous malignant melanomas based on well-established morphologic characteristics. However, in a minority of cases, traditional histopathologic evaluation and immunohistochemistry (IHC) are inadequate to confidently distinguish melanoma from benign melanocytic lesions such as Spitz nevi and dysplastic nevi. The advent of high-throughput gene expression array technology has resulted in the identification of hundreds of potential molecular diagnostic biomarkers, but no single chromosomal, DNA, RNA or protein marker has yet been shown to differentiate melanoma from nevus with sensitivity and specificity approaching 100%. We selected the protein products of 11 genesATP1B1, CYCLIN D1, DLX-1, HOXB13, LIF, MEIS2, MITF, MYC, PHACTR1, PTPRF and TWISTup-regulated in melanoma cell-culture and tissue-based expression arrays as candidate diagnostic biomarkers for preliminary investigation. Based on the results of our pilot studies, we proposed that increased expression of Phactr1 protein, as measured by IHC, could be used to differentiate malignant melanomas from nevi. We applied Phactr1 monoclonal antibody to a 480-core tissue microarray that included samples from 28 nevi and 62 primary melanomas. A simple scoring algorithm derived from this data distinguished primary melanoma from nevus in the training set with 92% sensitivity and 100% specificity. These data suggest that Phactr1 immunohistochemical staining is a potentially useful aid in the clinical diagnosis of primary cutaneous melanoma.

Thesis (Ph. D.)--University of Missouri-Columbia, 1998. / Typescript. Vita. Includes bibliographical references (leaves 153-156). Also available on the Internet.

Thesis (M.S. in Applied Physics)--Naval Postgraduate School, December 2009. / Thesis Advisor(s): Karunasiri, Gamani. Second Reader: Smith, Craig. "December 2009." Description based on title screen as viewed on January 28, 2010. Author(s) subject terms: Zinc Selenide, photodetectors, ultraviolet, Schottky, responsivity, current-voltage, depletion region, bandgap, melanoma, dark current, forward biased, reverse biased. Includes bibliographical references (p. 39-40). Also available in print.

Thesis (Ph. D.)--University of Missouri-Columbia, 1998. / Typescript. Vita. Includes bibliographical references (leaves 153-156). Also available on the Internet.

Thesis (Ph. D.)--West Virginia University, 2003. / Title from document title page. Document formatted into pages; contains xv, 146 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 117-129).

Recent evidence suggests that leflunomide, a dihydroorotate dehydrogenase (DHODH) inhibitor, disrupts neural crest development and melanoma pathogenesis via inhibiting transcription elongation. DHODH is an enzyme in the pyrimidine biosynthetic pathway and inhibition of this enzyme by leflunomide triggers a low nucleotide state. Leflunomide effectively ablates the neural crest lineage in embryonic zebrafish, preventing the formation of mature melanocytes, among other neural crest lineages. This drug also effectively suppresses melanoma and is in a clinical trial, administered in combination with the BRAF inhibitor vemurafenib, for metastatic melanoma. Despite knowing that leflunomide targets transcription elongation, the mechanism by which low nucleotides directly regulates transcription is unknown.