Malignant Melanoma Healed with Natural Therapies

How To Prevent Skin Cancer

How To Prevent Skin Cancer

Complete Guide to Preventing Skin Cancer. We all know enough to fear the name, just as we do the words tumor and malignant. But apart from that, most of us know very little at all about cancer, especially skin cancer in itself. If I were to ask you to tell me about skin cancer right now, what would you say? Apart from the fact that its a cancer on the skin, that is.

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How I Survived Malignant Melanom

By The Time You've Finished Reading How I Survived Melanoma Skin Cancer Seven Survivors Tell Their Stories. You'll Feel Like A New Person, with A New, More Positive Outlook! You will learn: 1. How do I know if I have melanoma? What are the signs and symptoms? I wanted to know why the doctor was so concerned when she looked at that little mole on my forearm. What was it that looked so sinister? How worried should I be? Was the doctor over-reacting? 2. What tests will the doctor carry out to see if I have melanoma? Will they be able to tell me on the spot if there is a problem? Or will I have to wait for days, fretting about whats going on? 3. How curable is melanoma? If they do tell me its melanoma, what exactly does that mean? Is it a death sentence? Will they tell me You have 12 months to live. Get your life in order and prepare for the worst.? 4. What are the stages of the disease? The reading Id done said that there were different stages of melanoma. What are the symptoms of each stage? What are the survival rates of each stage? If I had a later stage melanoma, wouldnt I know about it? Wouldnt I actually feel like I was sick? 5. How quickly does the disease progress or spread? Should I have gone to the doctor sooner? Id noticed the mole changing over about 3 months. Was this delay critical? 6. How is melanoma normally treated? Would I have to go through chemotherapy and radiation treatment? If so, for how long? What are the odds of curing the disease using these treatments? How extensive is any surgery likely to be? How big will the scars be? 7. What are the common side effects of the treatments? Would I lose my hair? Would I become sterile? What else could I expect? 8. What alternative treatments are available? Id heard of people going on special macro-biotic diets. Id seen lots of herbal remedies on the internet. Which of these are proven and documented, and which ones are snake oil? Is it possible to combine alternative treatments with surgical other western treatments? How do I find a doctor that is open to using both alternative and western treatments? 9. What are the latest treatments being developed, and who is carrying out clinical trials of these new treatments?

How I Survived Malignant Melanom Overview


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Nonmelanoma Skin Cancers

Nonmelanoma skin cancer (NMSC) is the most common cancer diagnosed in the United States. It is estimated that at least 1 million patients are treated for this disease each year. The most common types are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Patients rarely die from these cancers since they rarely metastasize. Most of the morbidity results from local invasion. Treatment frequently includes some form of surgery to remove the tumor with clear margins and thereby prevent recurrence. The significance of nonmelanoma skin cancers has been under appreciated. This is primarily because the mortality rate is very low. In addition, their incidence is not included in most hospital tumor registries. Registries usually record cases of melanoma or metastatic skin cancer. Despite this, there can be significant functional, cosmetic, and financial morbidity. It has been estimated that the annual cost of treating NMSC in the United States alone is 500 million.1 More than 30...

Expression Of Stem Cellassociated And Phenotypespecific Genes By Aggressive Melanoma Cells

Highlights of selected differentially expressed genes from the molecular analyses of more than 30 human cutaneous melanoma cell lines are presented in Tables 1 and 2. Highly aggressive vs poorly aggressive melanoma cells, including genetically matched highly and poorly aggressive cell lines from human cutaneous melanoma patients, were hybridized to cDNA microarrays, as previously described (Bittner et al., 2000). This experimental strategy allowed the expression analysis of 6000 genes, simultaneously. Genes that were differentially expressed 2.1-fold and greater (see Tables 1 and 2) are accompanied by information regarding their putative function. Many of the listed genes have been confirmed by reverse transcriptase polymerase chain reaction measurement, which has shown an excellent concordance with the differential gene expression profile derived by micro- array (Seftor et al., 2002a). The spectrum of genes upregulated and highlighted in Tables 1 and 2 reflects multiple molecular...

Use Of Hsppeptide Complexes As Cancer Vaccines In View Of Existence Of Shared Melanoma Antigens

In that scenario, it would be practically impossible to identify the antigenic epitopes of individual cancer patients. If, however, human tumors are antigenically cross reactive (as outlined in the preceding section), antimelanoma vaccines could be designed simply on the basis of peptide epitopes of known cross reactive melanoma antigens instead of hsp-peptide complexes isolated from individual melanomas. It is the premise of this chapter that hsp-peptide complexes provide a uniquely effective method of vaccination regardless of antigenic individuality or cross reactivity of human tumor antigens. This premise is elaborated as follows. First, the antigenic cross reactivity among human melanomas suggests that once a number of shared melanoma antigens are identified, patients can be immunized with synthetic peptides corresponding to the relevant epitopes and that the vaccinated patients will elicit a CD8+ CTL response. Vaccination with peptides under suitable conditions has...

Malignant Melanoma Melanocytic Nevi

Two main questions concerning nevi or moles When and how should they be removed What is the relationship between nevi and malignant melanomas In the dysplastic nevus syndrome (familial atypical mole-melanoma syndrome), the nevi are more numerous and larger than ordinary (usually 5 to 15 mm in size), have an irregular border, and show a haphazard mixture of tan, brown, pink, and black. There is a propensity for this type of nevus, especially when familial, to develop into malignant melanomas. that histologically has an inflammatory infiltrate usually involutes in several months in contradistinction to the rarer noninflammatory halo nevus. Excision of the halo nevus is usually not indicated unless the central nevus has the appearance of melanoma. COURSE. A child is born with no, or relatively few, nevi, but with increasing age, particularly after puberty, nevi slowly become larger, can remain flat or become elevated, and may become hairy and darker. A change is also seen histologically...

Precursors of Skin Cancer Dysplastic Moles and Actinic Solar Keratoses

Although some skin cancers appear to develop 'de novo'' in normal skin, many others are preceded by proliferations termed atypical or dysplastic. These lesions have already begun to lose normal responsiveness to control mechanisms that determine the order and uniformity typical of normal skin and benign proliferations. ln terms of malignant melanoma, the association of pigmented 'moles' (naevocellular naevi) with malignant melanoma was made over 160 years ago. However, it was not until 1978 that a genuine precursor of melanoma was described in detail. In that year, Clark and colleagues detailed the characteristics of lesions they termed 'BK' mole (a name derived Clinically, BK moles (today more often referred to as dysplastic naevi) are larger than most acquired naevi (often greater than 5 mm across) and may occur as hundreds of lesions on the body surface (Figure 2a, inset). They are flat to slightly raised, often with a 'pebbly' surface. Frequently they form target-like lesions,...

Pregnancy and Melanoma

The role of pregnancy in the clinical course of patients with melanoma has been debated without resolution for years. Melanoma has been reported to enlarge during pregnancy then regress between pregnancies. The possible negative impact of pregnancy on melanoma has left many physicians unsure how to advise their patients who are pregnant or who are thinking of becoming pregnant. Both a decrease in the disease free interval and an increased incidence of nodal metastasis have been reported in melanoma patients who are pregnant. The overall survival has not been shown to be statistically different in pregnant patients versus patients who are not pregnant. The etiology behind these differences has been hypothesized to be hormonal. Estrogen has been most often implicated, although basic science research has not been able to support this hypothesis. Recent reports of the importance of tamoxifen in the Dartmouth Regimen has again raised the issue of effects of female hormones on melanoma...

Malignant Melanoma

Malignant melanoma of the skin can rarely metastasize to the trachea. Even less frequent is a malignant melanoma primary in the trachea, with only about 4 cases reported in the literature so far.57 An additional case of multiple tracheobronchial melanoma has also been published, in which the primary site could have been either the trachea or bronchi.58 Pathology. Grossly, most of these tumors have been polypoid, one of them with a long, narrow stalk (Figure 3-33 Color Plate 5 ).59 Another of the tumors had a flat subepithelial location.60 This flat melanoma had metastasized to the adjacent lymph node. Pulmonary metastasis was present in one case.59 Microscopically, the tumor classically consists of large cells with atypical vesicular nuclei and prominent nucleoli. The cells are arranged in nests and sheets (Figure 3-34 Color Plate 5 ) and contain melanin. If no melanin is seen, one can prove melanocytic differentiation by immunohistochemical or ultrastructural analyses....

Anal Melanoma

The anorectum is the third most common site for melanoma following the skin and eye. Female to male ratio is 2 1 and the disease affects people most commonly in their sixties. Rectal bleeding, anal pain and the presence of a mass in the anal canal are the most common symptoms. The lesion is often advanced at the time of presentation and systemic symptoms are common.

Skin Cancer

Both non-melanoma (NM) and malignant melanoma skin cancer (MMSC) are known to increase following ionizing radiation, with the former being more prevalent than the latter 19,41,47 . Of the two histologic types of NMSC, the risk of basal cell carcinoma is increased following ionizing radiation, while that of squamous cell carcinoma is not increased 26 . To facilitate early detection and the removal of suspicious lesions, patients who have been exposed to ionizing radiation may benefit from an annual skin examination performed by a trained dermatologist.

Measuring MEK1 Kinase Activity

U0126 is a newly discovered potent inhibitor of the dual-specificity kinases MEK1 and MEK2 (26). Like PD98059, U0126 is a noncompetitive inhibitor of MEK1 2. U0126 displays significantly higher affinity for all forms of MEK than PD098059. U0126 inhibits phosphorylation of MEK1 2 and ERK1 2, inhibits the invasion of human A375 melanoma cells, and decreases c-Jun expression, a major component of the transcription factor AP-1 (27). U0126 inhibits T-cell proliferation in response to antigenic stimulation and cross-linked anti-CD3 plus anti-CD28 antibodies. U0126 has an inhibitory concentration (IC50) of 50-70 nmol L, whereas PD098059 has an IC50 of 5 imol L. Ro 09-2210, another inhibitor of MEK-1 and MEK-2, also inhibits other dual-specificity kinases such as MKK-4, MKK-6, and MKK-7, albeit at 4 to 10-fold higher IC50 concentrations compared with its effect on MEK-1 (25).

Clinical Correlations

In contrast to germ-line or inherited mutations, 'sporadic' cancers also can arise when a mutation occurs in a previously normal somatic cell. In this regard, environmental factors are thought to play major roles as mutagens or carcinogenic agents. For example, the relationship between tobacco smoke and lung cancer is well documented (Henderson et al., 1991). Anilines used in rubber tyre production are linked to the development of bladder cancer, while exposure to solar ultraviolet rays can cause melanoma (Case et al., 1993 Armstrong et al., 1997). Hundreds of chemical carcinogens that exist in food and products in daily use can either directly or through the production of secondary metabolites irreversibly alter a normal cell's DNA. So-called 'lifestyle' factors can also play a role. A link has been made between consumption of a diet high in animal fats and prostate cancer (Tzonou

Metastatic Tumors to the Trachea

Secondary involvement of the trachea mostly occurs as direct invasion from adjacent organs, such as the larynx, thyroid (Figures 3-35, 3-36, 3-37 Color Plate 5 ), esophagus, or mediastinal structures, and is rarely due to metastasis (Figure 3-38 Color Plate 5 ). This is in contrast to the bronchial tree, which more commonly receives metastases from distant primaries. All published tracheal metastases consist of carcinomas and melanomas, and no sarcoma has been reported, although the latter has been recognized as a form of bronchial metastasis. Table 3-1 shows the demographic data and types of the 14 published cases of tracheal metastasis.21,22,61-71, Carcinomas of the breast and colon and cutaneous melanoma were the most common

Lee W Thompson Laurence H Brinckerhoff and Craig L Slingluff Jr Scope of the Problem

Melanomas represent a minority of skin cancers (3-5 ), but melanomas cause 65 of the deaths from skin cancer. Although possibly now beginning to plateau, the incidence of melanoma has been increasing faster than any other cancer. Melanoma is a malignancy of melanocytes. Melanocytes originate from neural crest cells therefore, melanoma can occur anywhere neural crest cells migrate in the embryo. Most commonly primary melanoma occurs in the skin. The eye and mucous membranes are less common but well described areas primary melanomas can occur. Risk Factors for the Development of Melanoma

Historical perspective

At the incidence of lung cancer among British doctors. This study established a link between smoking and the development of small cell (oat cell) carcinoma of the lung. Further work undertaken by Doll and Hill has identified that the risk of dying from lung cancer is 32 times higher in heavy smokers compared with non-smokers (Horton-Taylor, 2001). A laboratory experiment, undertaken in 1915, proved for the first time that it was possible to develop cancer as a direct result of exposure to a chemical - coal tar. It was applied directly to the skin of a rabbit, resulting in the development of skin cancer (Yarbro, 2000a). In 1896 a German physicist, Roentgen, identified the use of radiation (X-rays) as a diagnostic tool. Further work looking at the use of radiation resulted in it being used as a new treatment for cancer by the close of the nineteenth century. However, within 7 years of Roentgen discovering the use of X-rays as a diagnostic tool, a causal link between exposure to...

Physical Exam of the Skin

Self-examination of the skin by the educated patient and by routine physician's exam are the best and cheapest way to screen for melanoma. Because melanoma can be successfully treated if recognized at an early stage and because it usually begins in the skin, the appearance of melanoma is very important. The following characteristics aid in the identification of melanomas, and many of them can be remembered with the ABCDE mnemonic 2. Border irregularity Borders that blend, are difficult to see, and nondiscrete are more likely melanoma. Smooth, discrete, uniform borders are more likely benign. 4. Diameter greater than 6 mm a melanoma can be smaller than 6 mm, but lesions larger than 6 mm should be regarded with high suspicion. 5. Elevation The surface of the lesion should be smooth and uniform. Any nodular area, indentation, or nonuniformity in elevation should raise the suspicion of melanoma. Furthermore, ulceration, itching, bleeding, or rapid changes are signs of melanoma. Melanomas...

Selected Readings

Epidemiology of nonmelanoma skin cancer. Clin Plast 2. Grossman D, Leffell DJ. The molecular basis of nonmelanoma skin cancer. Arch Dermatol 1997 133 1263-1270. 4. Skidmore RA, Flowers FP. Nonmelanoma skin cancer. Med Clin N Amer 1998 82 1309-23. 6. Demetrius RW, Randle HW. High-risk nonmelanoma skin cancers. Dermatol Surg 1998 24 1272-1292. 8. Goldberg DP. Assessment and surgical treatment of basal cell skin cancer. Clinics in Plastic Surgery 1997 24 673-686.

Wnt Signaling in Cancer

Taken together, up to 90 of colorectal cancers harbor inactivating mutations in the APC tumor-suppressor gene or activating mutations of the proto-oncogene P-catenin. The tumor-suppressor gene APC is inactivated in the hereditary colorectal cancer syndrome familial adenomatous coli (FAP) (108,109). This inherited autosomal-dominant disease inevitably leads to the rise of hundreds to thousands of colorectal adenomas and if no proctocolec-tomy is performed, to the development of colorectal cancer. Although germline inactivating mutations of APC occur throughout the entire gene, somatic mutations are clustered in exon 15 between codons 1280 and 1500 (110). This results in a frame shift or a premature stop codon and a truncated protein. Mutations close to codon 1300 are mostly associated with allelic loss of the second allele of chromosome 5q, whereas tumors harboring a mutation outside this region tend to have a second truncating mutation (111,112). The APC gene product interacts with...

Disease Associated Transcripts in PBMCs of Patients with Renal Cancer

RCC PBMCs with an unadjusted p value below 0.001 and were expressed in at least 15 of the PBMC samples analyzed. These results are reminiscent of a recent publication that identified profiles in circulating T cells of patients with melanoma that are distinct from those of healthy individuals,33 demonstrating that the transcriptional profiles of circulating CD8+ T cells also appear distinct in the context of melanoma. It will be interesting to determine whether less immunogenic solid tumors bear similar disease-associated signatures.

Other Surrogate Tissue Profiling Studies In Oncology

Pharmacogenomic studies conducted on PBMCs of patients with melanoma receiving interleukin-2 (IL-2) therapy37 demonstrated that treatment with this cytokine results in large gene expression changes in circulating PBMCs. By carefully comparing expression patterns in the circulating mononuclear cells with expression changes identified in the tumor microenvironment, the authors did not find substantial

The Role of NG2HMP in Tumor Stroma Activation 21 Reactive Response to Injury

Cell adhesion and migration on ECM components are promoted by a number of membrane receptors, of which, integrins represent a major class (43). Several lines of evidence indicate that NG2 HMP is also capable of modulating both cell-ECM and cell-cell adhesion. For example, NG2 HMP is localized on microspikes in melanoma cells where it participates in cellular adhesion (44). Furthermore, the human 9.2.27 monoclonal antibody (mAb), which recognizes the NG2 HMP human homolog, HMW-MAA, inhibits melanoma cell migration on ECM proteins (45). The extracellular domain of NG2 can be proteolytically cleaved from the cell surface both in vitro and in vivo (8,42) and is then deposited at the interface between the substrata and the migrating tumor (46), and endothelial cells (47). Although brain CSPGs can promote transient adhesion of neuronal cells, they generally inhibit stable cell adhesion and neurite outgrowth (48). NG2 HMP negatively modulates adhesion of melanoma cells via cluster of...

High Notch Expression in Quiescent Stem Cells

While Notch was shown to be expressed in melanoma cells (Hoek et al. 2004), the Notch signal has not been implicated in MC development. Our analysis on the gene expression profile demonstrated that Notch is expressed at a higher level in qSC. We therefore investigated the role of Notch in MC development as well as the maintenance of qMC by using various strategies. As details of our study are described in Moriyama et al. (in press) paper, we want emphasize that our study demonstrated that the Notch signal is essential for embryonic MC development and may also be important for the maintenance of qMCs.

Hypotaurine Protection On Cell Damage By Singlet Oxygen

Abstract Singlet oxygen (1O2), generated byirradiating methylene blue, is toxic to melanoma cell cultures. Hypotaurine is known to scavenge efficiently singlet oxygen the addition of hypotaurine (800 M) to the medium during irradiation of the dye produces a greater protective effect on cells than taurine added at the same concentration. The assay of some detoxifying enzymatic activities indicate a different mechanism of protection of the two molecules taurine induces an efficient detoxifying enzymatic action with respect to the control hypotaurine exerts its effect greatly by specifically scavenging singlet oxygen.

Thyroid Carcinoma Bronchogenic Carcinoma Other Tumors

Secondary neoplastic invasion of the trachea by direct extension is most often due to carcinomas of the esophagus, thyroid, and lung. Carcinoma of the larynx may also invade the trachea directly or it may recur at the margin of the stoma from lymphatics after laryngectomy. Less commonly, hematogenous metastases involve the trachea or carina. Sites of origin include the breast, melanoma, kidney, and thyroid. Carcinoma metastatic to the mucosa of the trachea from distant primary sites is less common than metastases to the bronchial mucosa, which is in itself an uncommon phenomenon.

Results And Discussion

Carlini melanoma cells were tested for resistance to methylene blue (MB), irradiation, or both (Tables 1 and 2). These cells are resistant to 10 M MB for times as long as 60 min (Table 1) and do not suffer when irradiated in the absence of the dye (data not shown). For protection experiments an incubation time of 10 min was chosen to ensure good viability and negligible toxic effects of that vital dye. The presence of MB during irradiation strongly decreases viability (Table 2). This treatment produces in solution singlet oxygen, one of the most reactive ROS. Viability tests after 24, 48, 72 h confirm the high toxicity of singlet oxygen towards cells. Table 3. Cell viability (evaluated by trypan blue exclusion) in melanoma cells after different treatments dye irradiation was 10 min in all conditions. Hyp hypotaurine Tau taurine MB methylene blue Table 4. Ratios of enzymatic specific activities in cytosolic fractions of cultured melanoma cells 24 h after treatment Table 4. Ratios of...

Cellautonomous Stimulatory Effects Of Tgf8 On Tumour Development

TGF- 3 has been shown to induce epithelial to mes-enchymal transition in culture of normal and transformed breast epithelial cells, squamous carcinoma, ovarian ade-nosarcoma and melanoma cells. The phenotypic changes have been best characterized in NMuMG cells, in which TGF-,3 induces cell shape changes, down-regulates expression of E-cadherin, ZO-1, vinculin and keratin and induces expression of vimentin and N-cadherin, which has been shown to increase cell motility and scattering (Miettinen et al., 1994 Bhowmick et al., 2001). Although the mechanism of TGF- -induced epithelial to mesenchymal differentiation is presumably complex, PI-3-kinase signalling and TGF- -induced Smad and RhoA activation appear to play a role (Bhowmick et al., 2001). In addition, the morphological changes occur rapidly in response to TGF- 3, and are reversible. In vivo, the effect of TGF- 3 on the spindle cell phenotype and invasive behaviour of carcinomas has been well documented for skin carcinomas in mice...

Trks And Metastatic Disease

Neurotrophins also induce the migration of cancer cells by activating Trks and by activating a second receptor, a member of the Fas receptor family, p75NTR. The activation of p75 appears to be important in the invasiveness of melanoma through the upregulation of secreted heparanase and the degradation of extracellular matrix (Herrmann et al., 1993 Innominato et al, 2001 Marchetti et al., 1996 Marchetti et al., 1993 Marchetti and Nicolson, 1997). This activity may be essential for the development of CNS metastatic lesions in melanoma (Menter et al., 1994 Menter et al., 1995).

Assessing methodological quality analysis

May lead to problems for the systematic reviewer, because it is rare that different studies use the same groupings. For example, Buettner et al.20 summarised 14 studies that had examined the prognostic importance of tumour thickness in primary cutaneous melanoma. As shown in Table 13.3, the number of cutpoints varied between two and six. Despite their clear similarities, no two studies had used the same cutpoints. Further, several studies had used the optimised approach that, as noted above, is inherently overoptimistic. Table 13.3 Tumour thickness in primary cutaneous melanoma.20 Cutpoints are shown in clusters around 0.75, 1, 1.5, 2, 3, 4, and > 5 mm. Table 13.3 Tumour thickness in primary cutaneous melanoma.20 Cutpoints are shown in clusters around 0.75, 1, 1.5, 2, 3, 4, and > 5 mm.

On Molecular Pathways

P-CATENIN Integrin P1-positive human kera-tinocytes are also rich in non-cadherin-associated p-catenin, a downstream effector of the Wnt signaling pathway (Zhu and Watt, 1999). Consistent with the inability to form hair follicles in the p1 null mouse genotype, mice ablated of the p-catenin gene also fail to form hair follicles and lose hair follicles when P-catenin is deleted postnatally (Huelsken et al., 2001). Instead, they form intradermal cysts that express markers of keratinocyte differentiation but retain a P1 keratin 15-positive stem cell population in close contact. This indicates that P-catenin is required for stem cell potentiality in the formation of hair follicle structures. That such a conclusion is related to skin cancer development was confirmed by the targeting of a nondegradable mutant form of P-catenin to the skin of transgenic mice (Gat et al., 1998). These mice not only develop a high density of hair follicles, but also develop hair follicle tumors of the...

Hypermethylation of Genes in Cancer

Pl6 was initially identified as a tumour suppressor in melanoma however, its function as a tumour suppressor was questioned early on because many tumours with LOH at this gene locus lacked mutations in the remaining allele. This apparent discrepancy was ultimately explained by the finding that the promoter of the nonmutated allele was often hypermethylated. Promoter region hypermethylation is also frequently the only detectable alteration, suggesting that the two 'hits' required to inactivate a tumour suppressor can both be epigenetic in origin. pl6 promoter methylation also appears to be an early event in carcinogenesis since it is

Oncogenic Tyrosine Kinases

The first report of CD30 (Ki-l)-positive ALCL was published by Stein et al. (1985). This lymphoma was described as a large-cell non-Hodg-kin lymphoma (NHL) with infiltration of the lymph node sinus and anaplastic morphology of the tumour cells. This particular growth pattern and the variable morphology of the ALCL tumour cells has led, historically, to the frequent misdiagnosis of this tumour as carcinoma, melanoma, malignant histiocytosis or other malignancies. ALCL has been found to arise as a primary tumour (primary systemic or primary cutaneous ALCL) or from a preceding condition such as lymphomatoid papulosis (Skinnider et al. 1999).

Genetic Screening Of Cancer

Genes that confer strong susceptibility to other familial cancers are also starting to be screened for in a similar manner. Genetic testing can now be used to confirm diagnosis or to predict disease development in families potentially affected by the many of the better-studied but relatively rare cancer syndromes (e.g. retinoblas-toma, Li-Fraumeni syndrome and Von Hippel-Lindau syndrome) which are caused by single gene defects and have clear patterns of inheritance (Hampel et al., 2004). Screening programmes are being developed and starting to be offered commercially and by some hospitals for other useful genes strongly involved in more general familial cancer syndromes. These include thep16Ink4a gene in familial skin melanoma, and the various tumour-suppressor and DNA-repair genes involved in the familial colon cancer syndromes, such as familial adenomatous polyposis (FAP) and hereditary non-polyposis colon cancer (HNPCC). These genes significantly increase the risk of getting the...

Future Applications Of Cancer Genetics Chemosensitivity And Gene Therapy

Different strategies have been tested in many cancer types, including pancreatic (Halloran et al., 2000), colorectal (Kerr, 2003) and breast cancers (Takahashi et al., 2006). Strategies have included the addition of copies of working tumour suppressor genes or the suppression of oncogenes, protection of bone marrow against chemotherapy by the addition of drug resistance genes, enhancement of the immunological response against a tumour and attempts to enable targeted cell death. A first potential breakthrough for this experimental form of treatment involved removing immune cells from melanoma sufferers and genetically engineering them to better recognize the cancer when reintroduced into the patients (Morgan et al., 2006). Further studies targeting cell death have involved the genetic introduction into the tumour of an enzyme that can convert non-toxic drug precursors into toxic forms that will selectively kill the tumour cells without any side effects. These are a very promising...

Bcgspirulina Combination For Cancer Immune Therapy

In C57BL 6 mouse B-16 melanoma implanting model, preadministration of the B16 melanoma antigenic peptide and BCG-CWS resulted in suppression of tumor growth.33 Specific CTL against B16 melanoma was induced in parallel with tumor regression.33 The CTL induction as well as retardation of tumor growth was completely diminished in MyD88-deficient mice.33 Hence, the mechanism whereby BCG-CWS and tumor antigen contribute to regression of implanted tumor can be explained as follows BCG acts as an adjuvant to activate TLR followed by the MyD88 adapter in antigen-presenting dendritic cells leading to up-regulation of antigen-presenting capacity and the levels of co-stimulators. This was true in in vitro dendritic cell stimulation with BCG-CWS both in mouse33 and human.34

Telomerase Silencing Through RNAi

It has been recently reported that a shRNA, expressed from a lentiviral vector and targeting the sequence encompassing the 11-nt template region of hTR, quickly inhibited the growth of p53-wild type, p53-null HCT116 colon cancer cells and LOX melanoma cells, independently of p53 status or telomere length, and without bulk telomere shortening. By contrast, no effect was detected in the immortalized, telomerase-negative VA13 cell line. Moreover, hTR downregula-tion did not cause telomere uncapping in these experimental models, but induced a modulation of the global gene expression profile, including suppression of specific genes implicated in angiogenesis and metastasis. This finding could be indicative of a novel response pathway distinct from the expression profile changes previously reported by the same authors and induced by telom-ere-uncapping mutant-template telomerase RNAs (83).

Survivin Silencing Through RNAi

Cells were delayed in mitosis and accumulated in prometaphase with misaligned chromosomes. In this model, loss of survivin activated the mitotic checkpoint, which was mediated by induction of p53 and was associated with the increase of its downstream target, p21Waf1. Survivin ablation also caused loss of mitochondrial membrane potential, enhanced caspase-9 proteolytic activation and spontaneous apoptosis (43). More recently, survivin downregulation, accomplished through the use of siRNAs, was seen to reduce clonogenic potential and increase the percentage of multinucleated cells in a panel of human sarcoma cell lines independently of p53 gene status (84). Moreover, survivin knockdown caused radio-sensitization, which was paralleled by an increased activity of caspase-3 and caspase-7, in wild-type-p53 but not in mutant-p53 sarcoma cells (85). An enhanced apoptotic response to APO2L TRAIL treatment was also observed in melanoma and renal carcinoma cell lines transfected with...

Drug Delivery Based on Blood Brain Barrier Disruption

It has been shown that the barrier opening for high molecular weight compounds is of shorter duration than that for small molecules (37). When the degree of barrier opening is measured with methods that are suitable for a regional evaluation (autoradiography in animal studies, positron emission tomography in man), there is a characteristic difference in the degree of barrier opening in the tumor versus normal brain. This opening was consistently found to be more pronounced for the normal BBB (38, 39). While the nonspecific opening of the BBB to plasma proteins has a potential to elicit neuropathologi-cal changes, osmotic disruption has been tested as a strategy for the brain delivery of macromolecular drugs such as monoclonal antibodies, nanopar-ticles, and viruses. Quantitative uptake studies after hyperosmolar BBB opening in animals and humans were performed with radiolabeled monoclonal antibodies and their antigen binding fragments against various tumor antigens (40-42). In normal...

With Differentiation Antigens and Cancer Testis Antigens

The first trials studying the immunogenicity and toxicity of peptide vaccination have been performed in patients with metastatic melanoma (Marchand et al. 1999 Jaeger et al. 1996 Cormier et al. 1996 Rosenberg et al. 1998 Scheiben-bogen et al. 2000 summarized in Table 18.1). In general, objective tumor remissions were only occasionally seen and were usually restricted to melanoma patients with limited disease. For instance, in a MAGE-3 peptide trial reporting a 30 response rate the 7 patients showing an objective tumor remission all had metastatic disease limited to soft tissue or lymph nodes and 14 patients who were not included in the response evaluation had early progressive disease during vaccination (Marchand et al. 1999). Antigens tested in clinical studies were mostly cancer germline antigens or melanocyte differentiation Table 18.1 Clinical studies of peptide vaccination in patients with metastatic melanoma Table 18.1 Clinical studies of peptide vaccination in patients with...

Tumour Classification

Ultrastructural analysis of a tumour was for many years the primary means by which a poorly differentiated tumour was classified. For example, using transmission electron microscopy, malignant nerve sheath tumours could be recognized by their long cytoplasmic processes, primitive cell junctions and fragmented external basal lamina. Rhabdomyosarcomas had 6-nm (actin) and 15-nm (myosin) filaments associated with Z discs. Identification of subcellular structures such as desmosomes (epithelial tumours), neurosecretory granules (neuroendocrine tumours) or melanosomes (malignant melanoma) are also examples of how the electron microscope was applied in diagnostic pathology. Although immunohistochemistry has replaced electron microscopy for many of these applications, it is still useful in some cases and ultrastructural localization of specific antigenic substances may be a powerful tool in the future (Herrera et al, 2000). There is lineage-dependent expression of these proteins that is...

Tumors of Vascular Tissue

2.Granuloma pyogenicum (Fig. -SQ) Also known as proud flesh, this is a rather common end result of an injury to the skin that may or may not have been apparent. Vascular proliferation, with or without infection, produces a small red tumor that bleeds easily. It is to be differentiated from a malignant melanoma. Biopsy and mild electrocoagulation are curative.

Bone Marrow Transplant

Children younger than 10 years at the time of SCT appear to have the greatest risk. Socie reported a 36.6fold excess rate of malignancy in these young children those less than 10 years of age with ALL who receive SCT have an 11 risk of a secondary solid tumor 15 years later 55 . Other studies have reported a 33-fold increased risk, with the incidence ranging from 2.2-6.7 up to 15 years post-transplant 1, 3 . The most common solid tumor following SCT in Bhatia's cohort was malignant melanoma.

Screening And Prevention

Environmental factors are potentially conspiring to produce increasing numbers of skin cancers, such as the progressive depletion of the photoprotective ozone layer by anthropogenic pollutants. Ozone depletion increases the amount of biologically harmful solar UV radiation that reaches the surface of the Earth, leading to an increased incidence of cutaneous neoplasms. Indeed, the incidence of malignant melanoma is increasing at an alarming rate, with an estimate of a 1 in 75 lifetime risk of developing this potentially lethal tumour for individuals born in 2000 (Brown and Nelson, 1999). The Caucasian population in Auckland, New Zealand, has the highest incidence of malignant melanoma in the world (Jones et al., 1999) Kauai, Hawaii, on the other hand has one of the highest melanoma rates recorded in the United States (Chuang et al., 1999). Accordingly, skin cancer prevention has become increasingly focused on public education regarding avoidance of sun exposure and the use of effective...

Tumor Associated Antigens and T cell Epitopes

The first tumor-associated antigens and T cell epitopes were identified by expression cloning of complementary DNA (cDNA) prepared from tumor cells from a melanoma patient into COS cells that had been stably transfected with the genes for an HLA molecule, and probing these double-transfectants with T cells from peripheral blood of the same patient. After repeated sub-cloning, the gene of the tumor-associated antigen was isolated and sequenced for identification (Boon et al. 2006 van der Bruggen et al. 2002). It turned out to be a hitherto unknown protein expressed in tumor cells and testes only, and was dubbed MAGE. It was the first of the extended family of MAGE proteins and the first member of the group cancer-testis antigens. Since testis is an immune-privileged organ, these antigens are relatively tumor-specific and therefore preferred vaccine targets. No function of the tumor testis-associated MAGE proteins has yet been determined. ferent bioinformatic tools. The latter has...

Overview Of Clinical Management

The role of wide excision and lymph node dissection in the setting of vertical growth phase melanoma is potentially problematic. Primary lesions are generally recommended to be excised with a margin that will minimize the likelihood of local recurrence. However, this recommendation is controversial, with some experts arguing that although wider excisions may decrease the incidence of local metastases, they fail to improve survival. This assumption is based on the contention that local metastases of melanoma generally correlate with contemporaneous seeding of distant sites (Ackerman and Scheiner, 1983). In recent years, sentinel lymph node sampling has gained acceptance in the treatment of many vertical growth phase melanomas. In this procedure, a radiographically detectable dye is injected at the site of the primary tumour. This dye is taken up by draining lymphatic vessels and delivered physiologically to regional lymph nodes. The first nodes to be detected by this method are...

Tumor Specific T cell Responses

Several lines of evidence point at the key role of CD8+ cytotoxic T cells in tumor immunity. A large number of lymphocyte depletion or reconstitution experiments in animal tumor models have proved their capacity to identify and kill tumor cells. Similarly, there are a number of in vitro experiments with human tumor and autologous CD8+ T cells that prove the same point. Immunohistochemical analyses have demonstrated the presence of CD8+ T cells in different tumors and, as in the case of melanoma, have correlated high frequencies of these cells in tumor infiltrates with better prognosis (Parmiani 2005 Rosenberg 2005a, b). Consequently, tumor vaccinology has, in contrast to previous efforts in vaccine development, focused on T cell vaccines. Tumor specificity of the T cells may be tested as follows. The receptor specificity can be directly visualized with fluorochrome-labeled tetramer-ized recombinant MHC molecules loaded with the tumor-associated T cell epitopes of interest, and then...

Lessons from Clinical Cancer Vaccination Trials

Toring of the immunological in addition to the clinical effects (Whiteside 2000). Despite the different designs, the outcomes of these trials are often very similar the efficient induction of tumor-specific T cell responses is usually reported. In some patients, 20 and more of all circulating CD8+ T cells were found to be specific for the vaccine antigens (Rosenberg et al. 2005 Trefzer et al. 2004). Several cases of clinical responses were reported. However, objective clinical responses, i.e., regression of the tumors by 50 and more, were the exceptions, and comparisons of the immunological and the clinical responses to therapeutic vaccination in cancer patients failed to demonstrate any correlation (Rosenberg et al. 2005 Trefzer et al. 2004). This conclusion can be illustrated with the results of a clinical trial with hybrid cell vaccines for the treatment of malignant melanoma at advanced stages conducted at the Department of Dermatology of the Charit (Trefzer et al. 2000, 2004,...

Properties of an Ideal Tumour Target

Currently, the growing list of cancer-germ-line genes contains nearly 50 gene families with about 100 individual genes. Particularly prominent among these are the three MAGE (melanoma antigen-encoding gene) families that map to the X chromosome and comprise 21 related genes (MAGE-A1-12, MAGE-B1-6, MAGE-C1-3) (Chomez et al. 2001). The product of each of these genes may provide peptides that can be presented by several different HLA class I and II molecules. For example, MAGE-A1-derived peptides bind to at least 11 types of HLA-A, -B and -C and two types of HLA-DR molecules. The peptides originate from different parts of the MAGE-A1 protein amino acids 161-169 represent the peptide (EADPTGHSY) binding to HLA-A1, while residues 230-238 provide the peptide (SAYGEPRKL) that binds to HLA-Cw3 and -Cw16. A particularly useful feature of HLA class I and II alleles is the fact that the maternal and paternal alleles are co-dominantly expressed, thereby increasing the chances of displaying a...

Human Tumor Antigensindividually Distinct Or Cross Reactive

Tumor antigens of experimental cancers have been historically considered to be antigenically distinct. Early experiments by Prehn and Main (21), Old et al. (22), Globerson and Feldman (15), and Basombrio (16) led to definition of transplantation antigens of methylcholanthrene-induced sarcomas of inbred mice as being antigenically individually distinct, and this became the defining paradigm for cancer immunity. However, recent studies on identification of tumor epitopes recognized by cytotoxic T lymphocytes against human melanomas have begun to challenge this paradigm. So far, at least five cytotoxic T-lymphocytes (CTL) epitopes have been identified, and in four of these, the CTL epitope is derived from a melanocytic differentiation antigen (23-30). Further, in each case, the amino acid sequence of the melanoma CTL epitope is identical to the corresponding sequence in normal melanocytes. Thus, in contrast to the tumor antigens of mutagenized tumors (31-33), no mutations are detected in...

SST Analogs in the Treatment of Nonendocrine Cancers Possible Application of New Analogs and Receptor Targeted

The first report showing antiproliferative activity of SST was published in 1978 by the editor of this book and revealed that SST inhibited the proliferation of normal pituitary cells (the mitogenic action of TRH on the anterior pituitary gland in vitro).11 A few years later, Mascardo and Sherline,12 showed that SST inhibited the centrosomal separation and cell proliferation of some tumor cells (HeLa and gerbil fibroma cells). As a consequence of these two findings an enormous number of data have been published concerning anti-growth effect of SST and its analogs on normal and tumoral tissues. At the end of 1980s, the list of neoplasms whose growth processes were changed via SST analogs was very long and included besides various endocrine tumors, which is the subject of another chapter in this book, also several nonendocrine tumors such as pancreatic cancer, breast cancer, prostatic cancer, colon cancer, hepatocellular cancer, renal cancer, laryngeal cancer, meningioma, lymphoma,...

Peripheral Nerve Metastases

Cancer can affect peripheral nerves either by compression or direct invasion. Direct invasion occurs either from hematogenous spread of tumor to peripheral nerves or dorsal root ganglia or by direct extension to nerve from surrounding structures. Typically, head and neck malignancies, melanoma, lung and breast cancer, and

Applying Cell Based Screening to Telomerase

Vivo, and its activity is modulated by interaction partners such as the chaperone protein hsp90 (Akalin et al. 2001, Forsythe et al. 2001, Holt et al. 1999). It is possible that hsp90 may be required for telomerase stability or for mediating conformational changes allowing the holoenzyme to translocate after synthesis of each individual telomere repeat. Interfering with hsp90 activity using the inhibitors geldanamycin, 17-AAG, and novobiocin inhibits telomerase activity and increases chemosensitivity in melanoma and head and neck cancer cells, providing experimental support for the functional importance of the interaction (Chang et al.

Paraneoplastic Retinal Degeneration or Cancer Associated Retinopathy

The outer retinal layers with relative preservation of the other retinal layers occurs. This syndrome is usually associated with small cell lung cancer but is also observed with other tumors, including melanoma and cervical cancer. The distinctive clinical triad consists of photosensitivity, ring scotomatous visual field loss, and attenuated caliber of retinal arterioles. y

Photosensitivity dermatoses

Pityriasis Rubra Pilaris Face Treatment

Occurring on the lips and ears, these are common and can frighten the patient into thinking that he or she has a melanoma. Capillary Hemangiomas (see Fig 32-17). These are present on the chest and back of almost every elderly person. Malignant Melanoma (see Fig, 32-19). This is an uncommon malignancy, but it can develop from a brownish-black, flat lesion known as a lentigo, which is usually seen on the face and arms. The result is a lentigo maligna melanoma (see Fig 34-3C).

Noninvasive Diagnostic Procedures

Angioplasty For Liver How Its Done

Hepatobiliary calcifications are common. Small, round hepatic parenchymal calcifications can be the result of chronic granulomatous disease such as histoplasmosis or tuberculosis. Irregular, large calcifications in the liver can indicate the location of a benign tumor, such as hemangioma. Metastatic lesions from cancers of the ovary, breast, colon, and stomach can calcify, as can those of melanoma, mesothelioma, carcinoid, and leiomyosarcoma. Primary hepatobiliary tumors typically do not calcify. About 10 to 15 of gallstones develop laminar calcification. Calcification of the gallbladder itself ( Fig. 12-1 ) (porcelain gallbladder) is an indication of chronic cholecystitis and is a risk factor for development of gallbladder cancer.

Methylation Profiling Of Circulating Tumor Dna In Plasma And Serum From Patients With Cancer

Elevated levels of circulating nucleic acids have been shown in patients with cancer.36 DNA concentrations in plasma and serum are especially low in healthy individuals (2 to 30 ng ml) as compared to those in patients with cancer (20 to 1200 ng ml), attributable to the presence of circulating tumor DNA.36-38 In plasma of patients with breast cancer, angiosarcoma, melanoma, or head and neck cancer, the fractional concentration of tumor DNA was determined to range from 3 to 93 (mean 53 ) of the total amount of circulating DNA.38 Tumor DNA may possibly be enriched in plasma by selective DNA release from tumor cells or inhibition of tumor DNA degradation as protected from DNase digestion. MGMT, RAR 2, and or RASSF1A hypermethylation was demonstrated in circulating DNA isolated from preoperative plasma of patients with cutaneous melanoma.21 In serum, the DNA concentration is also much higher among patients with cancer as compared to that among healthy individuals.39 Elevated DNA levels...

Incidence of Somatostatin Receptors in Human Tumors

Using the RT-PCR and immunohistochemical method, demonstrated subtypes sst1, 2 and 3 in both tumoral and nontumoral epithelial cells, whereas sst4 was expressed preferentially in malignant epithelial cells and sst5 was absent. The lung cancers mainly express sst2 (68 of samples examined immunohistochemically). The incidence of other subtypes are scarcer.27 Interestingly, the sst2 expression is not limited to small cell lung cancer (SCLC), which originates from the neuroendocrine cells of bronchial epithelium, but can be revealed also in nonSCLC. Recently, a functional sst2 was found in a nonSCLC cell line, Calu-6.28 Since melanocytes are known to derive from the neural crest, melanoma is also considered as a neuroendocrine cancer. The high incidence of sst receptors was found in these tumors by means of RT-PCR. Ninety-six of samples expressed sst1, 83 sst2, 61 sst3, 57 sst4 whereas only 9 sst5.29 The immunohistochemical findings are roughly similar.30 However, the data on functional...

Preclinical Studies

Several groups designed hammerhead ribozymes targeting the template region of hTERC, resulting in cleavage of hTERC in vitro and telomerase inhibition in extracts of melanoma, endometrial, hepatocellular carcinoma, and breast cancer cells (Folini et al. 2000b, Kanazawa et al. 1996, Yeo et al. 2005, Yokoyama et al. 1998). Growth retardation was shown in breast cancer and melanoma cells stably expressing the ribozymes, and reduced telomere length was observed in breast and endometrial cancer cells but not melanoma cells. Ribozymes directed against the 5' end and T-motif of hTERT mRNA were also reported to reduce hTERT expression and telomerase activity in breast and endometrial cancer cells, with telomere erosion and reduced proliferation shown in breast cancer cells (Ludwig et al. 2001, Yokoyama et al. 2000). It was noted that the T-motif targeted ribozyme synergized with the cytotoxic effect of topoisomerase inhibitors, and high expression induced rapid telomere-length-independent...

Trks And The Regulation Of Cancer Growth

The regulation of cell number during development or in cancer growth reflects a balance of signals that promote proliferation or differentiation and survival or apoptosis. Neurotrophin activation of Trks helps to determine this balance during development and oncogenesis. Thus in cancer Trks can be helpful or hurtful biological modifiers and positive or negative prognostic indicators. Trk activities have been described in diverse cancers arising from many tissues including medullary thyroid carcinoma (McGregor et al., 1999), Wilms' tumor (Donovan et al., 1994 Eggert et al., 2001), glioblastoma multiforme (Singer et al., 1999), lung cancer (Ricci et al., 2001), pancreatic cancer (Schneider et al., 2001), melanoma (Innominato et al., 2001), leukemia (Eguchi et al., 1999), breast cancer (Descamps et al., 1998) and Ewing's sarcoma (Nogueira et al., 1997) (Table 1). A review of well described Trk activities in prostate cancer, medulloblastoma and neuroblastoma serves to demonstrate the...

The Immune System And Cancer

First, cancer patients with tumours infiltrated by many immune cells (e.g. proliferating CD8+ T-lymphocytes, macrophages, NK cells) have a better survival rate than those with few infiltrated immune cells, suggesting that such immune cells are responsible for the improved survival in these patients (Ropponen et al., 1997 Naito et al., 1998 Nakano et al., 2001 Nakayama et al., 2002 Ohno et al., 2002). Second, as described above, the incidence of cancer is higher in older people and in the neonatal period, when immune responses are less efficient. Third, the incidence of cancer is much higher in immunodeficient people (e.g. AIDS patients), than those with a normal immune system. About 40 of HIV infected individuals develop some form of cancer, such as Kaposi's sarcoma, a malignant tumour of the blood vessels in the skin, or lymphoma, a malignant tumour of the lymphatic system (Scadden, 2003). In addition, the incidence of certain types of cancer (e.g. skin cancers, lymphoma) is...

Clinical Manifestations

Another potential late sequelae of treatment is the risk of the development of a secondary skin cancer, usually a basal cell carcinoma 19,56,68 . Basal cell carcinomas are observed in patients with no evidence of chronic skin changes secondary to radiotherapy 19 . The exact risk of a secondary basal cell carcinoma is small in one series the calculated excess risk was 0.31 104 patient-years per Gray 56 . The latency period is usually at least 20 years. There may be no excess risk for a skin surface dose of less than 10 Gy for patients receiving standard fractionations, but this conclusion is controversial. Radiation therapy in childhood has also been implicated in the development of malignant melanoma later in life. In a study utilizing data from five Nordic National Cancer Registries, as well as eight centers in France and Great Britain, between 1960 and 1987, it was found that children receiving greater than 15 Gy had a risk of developing melanoma 13 times as great, compared with...

The Analogs of Somatostatin as Radiopharmaceutics

Depreotide has affinity for the sst2, sst3 and sst5 receptors. This analog labeled with 99mTc binds to sst receptors in NET tumors, melanoma, small cells- and nonsmall cells pulmonary tumors. In addition, it has been shown that sst receptors are also present in the tumor itself and in peritumoral tissue, where angiogenesis takes place.

Epidemiological Studies Evaluating Cancer Causation

When an exposure is fairly common (e.g. smoking, sunlight, poverty, even prevalence of HBV carriers), ecological studies should be able to reveal the effects of these exposures. Thus, following the increase in tobacco consumption, the incidence of lung cancer increased sharply over time skin melanoma is more common in geographic latitudes with more sunshine exposure stomach cancer is generally more common in low-income social strata and the incidence of primary liver cancer is higher in populations with higher prevalence of HBV (Tomatis, 1990). As a corollary, the inability of ecological studies to demonstrate an association between a widespread exposure that has rapidly increased over time (e.g. extremely low-frequency

Intraparenchymal Metastases

Virtually all systemic cancers have the capacity for brain metastasis. The most common sources of metastases to the brain are tumors of the lung, breast, kidney, and gastrointestinal tract (colon and cecum) and malignant melanoma, reflecting the frequent occurrence of these primary malignancies ( T bje 47 2 ). The predilection of melanoma to spread to the brain is emphasized because its histological pattern is different from other metastases. Other sources that are relatively Melanoma Wide variability in the interval between the appearance of the primary cancer and that of the cerebral metastasis is observed. In many instances, the cerebral metastasis represents the first manifestation of a malignant neoplasm, usually of lung or melanoma origin. Slow-growing neoplasms of breast, ovarian, or uterine origin can result in cerebral metastasis up to 15 years after the diagnosis of the primary tumor. The average interval between the diagnosis of the primary...

Classification of Tumors Based on Location

Face seborrheic keratosis, sebaceous gland, hyperplasia, actinic keratosis, lentigo, milium, nevi, basal cell cancer, squamous cell cancer, lentigo maligna melanoma, flat wart, trichoepithelioma, dermatosis papulosa nigra (black females), fibrous papule of the face, colloid milium, dilated pore of Winer, keratoacanthoma, pyogenic granuloma, Spitz nevus, ephelides, hemangioma, adenoma sebaceum, apocrine hidrocystoma, eccrine hidrocystoma, trichilemmoma, trichofolliculoma, Merkel cell carcinoma, angiosarcoma (elderly males), nevus of Ota, warty dyskeratoma, atypical fibroxanthoma, angiolymphoid hyperplasia with eosinophilia, blue nevus. Lip and mouth Fordyce's disease, lentigo, venous lake (varix), mucous retention cyst, leukoplakia, pyogenic granuloma, squamous cell carcinoma, granular cell tumor (tongue), giant cell epulis (gingivae), verrucous carcinoma, white sponge nevus, acral lentiginous melanoma. Chest and back seborrheic keratosis, angioma, nevi, ephelides, actinic keratosis,...

The immune surveillance theory

Have better survival than those with few infiltrated immune cells, suggesting that such immune cells are responsible for the improved survival in these patients (Ropponen et al., 1997 Naito et al., 1998 Nakano et al., 2001 Nakayama et al., 2002 Ohno et al., 2002). Second, as described above, the incidence of cancer is higher in older people and in the neonatal period when immune responses are less efficient. Third, the incidence of cancer is much higher in immunodeficient people (e.g. AIDS patients) than in those with a normal immune system. About 40 of HIV-infected individuals develop some form of cancer such as Kaposi's sarcoma (a malignant tumour of the blood vessels in the skin), or lymphoma (a malignant tumour of the lymphatic system) (Scadden, 2003). In addition, the incidence of certain types of cancer (e.g. skin cancers, lymphoma) is increased by four- to 500-fold in patients who have received organ transplants, whose immune systems have been downregulated with...

CXC Chemokine Receptors 1621 CXCR4

Muller et al. performed a comprehensive examination of chemokine receptor expression on a series of breast cancer and melanoma cell lines (2). Using quantitative RT-PCR and specific probes for CXCR1-5, CCR1-10, CX3CR1, and XCR1, seven breast cancer cell lines expressed mRNA primarily for CXCR4, CXCR2, and CCR7. In comparison with normal mammary epithelial cultures, CXCR4 and CCR7 were consistently elevated in malignant cell lines. Like breast cancer cell lines, melanoma cell lines also expressed high levels of CXCR4 and CCR7, but in addition, these cells expressed high levels of CCR10 compared with normal primary melanocytes. Examination of pleural effusions from breast cancer patients, primary invasive lobular carcinomas, or ductal carcinomas also revealed heightened expression of both CXCR4 and CCR7 mRNA in malignant tissues compared with normal mammary gland. CXCR4 expression in primary tumors, axillary lymph nodes, and pulmonary and hepatic metastases was confirmed by...

About the Lead Authors

Mohammed Kashani-Sabet, Ph.D. is an associate professor of Dermatology and director of the Melanoma Center at the UCSF Cancer Center. His work has focused on the identification of cancer progression genes using ribozyme technology, and on the development of ribozyme gene therapy in patients with cancer, using melanoma as a model.

NG2 at the Tumor Stroma Interface

Glial Cell Differentiation

NG2 shares high-sequence homology with the high-molecular-weight melanoma-associated antigen (HMW-MAA) or human melanoma proteoglycan (HMP) (15-18), where 18 residues of the NG2 amino-terminus are identical to the HMP, identifying it as the human homolog, and shall hereon be denoted NG2 HMP. In contrast, HMP contains three nucleotides in the juxtamembrane domain that are absent from the NG2 sequence (13). The mouse NG2 homolog, designated AN2, has also been identified (19,20) indicating that it is evolutionary conserved. NG2 HMP is a well-established marker for glial progenitor cells in the CNS (21-26). Although differentiation of NG2 HMP-positive progenitors into oligodendrocytes in vivo has been demonstrated, derivation of astrocytes

The Definition Of Cancer

As with lymphatic spread, malignant cells can also infiltrate the vascular system and travel along the vessels until they arrive at an area where they can become lodged, and subsequently replicate to form a secondary (metastatic) deposit. The malignant cells can then migrate via the smaller blood vessels - that is, the capillaries (Walter, 1977). However, there is evidence that only a small percentage of cells entering the vascular system actually survive to give rise to blood-borne metastatic spread (Walter, 1977). Malignancies which are linked to blood-borne spread include melanoma and small cell carcinoma of the lung (Yarbro, Frogge and Goodman, 2005). Liver. The commonest site for blood-borne metastases is the liver. Malignancies originating from the gastrointestine, including the pancreas, commonly metastasize to the liver. Other malignancies which can result in secondary deposits in this organ include breast, melanoma, lung and urological cancers (Wolfe, 1986 Walter, 1977)....

Exploring sources of heterogeneity

That differential recall of past exposures may introduce bias is also evident from a meta-analysis of case-control studies of intermittent sunlight exposure and melanoma69 (Figure 12.4). When combining studies in which some degree of blinding to the study hypothesis was achieved, only a small and statistically non-significant effect (odds ratio 1-17, 95 confidence interval 0-98 to 1-39) was evident. Conversely, in studies without blinding, the effect was considerably greater and statistically significant (odds ratio 1-84, 1-52 to 2-25). The difference between these two estimates is unlikely to be a product of chance (P 0-0004 in our calculation). Figure 12.4 Examples of heterogeneity in published observational meta-analyses saturated fat intake and cancer,66 intermittent sunlight and melanoma,69 and formaldehyde exposure and lung cancer.75 SMR standardised mortality ratio CI confidence interval. Figure 12.4 Examples of heterogeneity in published observational meta-analyses saturated...

Biological Effects and Side Effects of Suncare Products

Although the short-term efficacy of a sunscreen in the prevention of sunburn is undisputed, there is also some evidence that long-term use of sunscreens prevents the appearance of nonmelanotic skin cancer such as solar keratoses 16, 17 and squamous-cell carcinoma but not of basal-cell carcinoma 18 . The results of published epidemiological studies examining sunscreen use and melanoma are extremely controversial. A meta-analysis performed by Bastuji-Garin and Diepgen 9 in 2002 denied a causative association between sunscreen use and melanoma due to discordant results triggered by the low relative risks, the lack of a dose-effect relationship and the numerous biases, especially the uncertainty that the sunscreen preceded melanoma. A further meta-analysis of 11 case-control studies published by Huncharek and Kupelnick 19 in the same year also found no association between sunscreen use and the development of melanoma, concluding that the available data do not support a relationship...

Chemotherapy and Biologic Agents

Interleukin-2 does not have direct antitumor effects. Interleukin-2 directly affects T lymphocytes, causing their proliferation. Because of the importance of T lymphocytes in animal models of melanoma rejection, interleukin-2 is widely used in melanoma research for the proliferation of antimelanoma lymphocytes. The use of IL-2 has spread into human trials, and this cytokine is a part of many ongoing immunotherapy trials. Interleukin-2 therapy alone has a 7 complete response rate that is sustained in 3 4 of patients, but use of interleukin-2 is limited by severe systemic toxicity. Biologic agents such as tumor vaccines and cytokines are now being combined. These clinical trials are ongoing and results are too preliminary to make recommendations for therapy.

Exostosis subungual See Subungual

Folliculitis, perforating, of the nose. A folliculitis of the stiff hairs of the nasal mucocutaneous junction that penetrates deeply through to the external nasal skin. Unless the basic pathology is understood and corrected by plucking the involved stiff hair, the condition cannot be cured. The external papule can simulate a skin cancer.

Sauer notes dos and donts regarding nevi

Do remember that in a child a benign junctional nevus may resemble a malignant melanoma histologically (Spitz nevus). Don't alarm the parents unnecessarily, because these nevi are no threat to life. 5. Don't perform a radical deforming surgical procedure on a possible malignant melanoma until the biopsy report has been returned. Many of these tumors can turn out to be seborrheic keratoses, granuloma pyogenicum, and so on

Normalizing the Stroma Through Targeting NG2HMP 31 mAbDirected Therapy

Antibody-based immunotherapy has been greatly investigated as a therapeutic strategy against NG2 HMP-expressing melanomas. This method utilizes a molecular vehicle, mAb, to selectively deliver radionuclides or toxins to tumor cells (100). Several studies have used various mAbs that recognize the NG2 HMP because the majority of melanomas extensively express it. There is limited intra- and intertumor heterogeneity, where it has been detected on > 90 of melanoma cells (49,101,102). Furthermore, because it is expressed on both tumor cells and the associated vasculature, it offers several advantages over therapies that are strictly tumor-directed. Therapies that target only tumor cells, are limited by both the heterogeneous expression of the NG2 HMP within the tumor, as well as by the high rate of tumor cell mutation (103,104). In contrast, the host activated-stromal vascular cells are relatively homogenous and lack the problems associated with drug resistance (103,105-107). Other than...

Life stages and the skin

Certain physiologic skin changes occur. Perspiration is increased. Hyper-pigmentation of the abdominal midline, nipples, vulva, and face (chloasma) is seen, and, in some brunettes, nevi and freckles also become more prominent and more pigmented. Malignant melanoma is not more common in pregnancy. Hypertrichosis of the scalp may be unnoticed until the excess hair begins to be shed after delivery. Striae of breasts, abdomen, and thighs appear. The skin diseases of pregnancy are herpes gestationis (see Fiig.M 26-11D-E), impetigo herpetiformis, vulvar pruritus (often due to candidal infection), palmar erythema, spider hemangiomas, pyogenic granulomas, rarely erythema multiforme, and pedunculated fibromas. The following dermatoses are usually better, or disappear, during pregnancy psoriasis, acne (can be worse), alopecia areata, and, possibly, systemic scleroderma.

Ultraviolet Radiation

Intermittent unaccustomed sun exposure has the best correlation with melanoma. An example of this is the strong relationship between sunburns and the development of melanoma. Either the people most susceptible to sunburn are also predisposed to melanoma, or the intermittent exposure does not allow the body time to protect itself from the UV light. Direct evidence of the relationship between UV light and melanoma has been difficult to demonstrate in humans however, nonhuman animal models support the contribution of UV light to melanoma. Direct DNA damage, promotion of growth, and suppression of immune systems response to melanoma are three ways UV light has been hypothesized to contribute to melanoma development. Because of the relationship between melanoma and ultraviolet light, it is logical that a typical melanoma patient has a fair complexion (celtic complexion), has a history of sunburning easily, and may be younger than other types of cancer patients (80 of melanoma patients are...

Extracellular Matrix Degradation During Invasion

A large body of literature exists correlating degradative enzyme activity with cancer invasion and metastasis. The most studied proteases include tissue-type plasminogen activator (tPA), plasmin, cathepsin-D, -B, -L and -G, the urokinase plasminogen activator (uPA), metalloproteinases and the heparanases. Urokinase plasminogen activator, a serine protease, has been shown to correlate with a meta-static phenotype of cells. Antibodies against uPA block human HEP-3 cell invasion and murine B16-F10 melanoma cell metastasis after tail vain injection (Ossowski and Reich 1983 Esheicher et al., 1989). Moreover, overexpression of uPA in H-ras transformed cell lines enhance lung metastases (Axelrod et al., 1989). Inhibition of metalloproteinases has been demonstrated to inhibit cell invasion (DeClerck et al., 1991). MMPs can be divided into three general classes (1) interstitial collagenases, (2) stromelysins and (3) gelatinases. Interstitial collagenase degrades type I, II, III and VII...

Mario A Bourdon phd and Richard EB Seftor phd

Microarray analysis of melanoma cell lines suggests that aggressive melanomas have a pluripotent, embryonic-like phenotype, implying the possibility of a stem cell origin for tumor components. Aggressive melanoma cells also form vascular structures and express endothelial-associated genes (including vascular endothelial-cadherin and EphA2) critical for vessel formation, indicating that the tumor cells have the plasticity to generate progeny, which express multiple cellular phenotypes with additional biological potential. This does not occur in poorly aggressive tumors, and, thus, expression of these genes is a predictor of biological behavior of the tumor. The aggressive tumor cells were able to participate in the neovascularization of ischemic tissue and produce factors that influence poorly aggressive tumor cells to assume a vascular phenotype. Understanding the molecular underpinnings of the plasticity of melanoma cells may lead to more effective diagnosis, treatment, and...

Lymph Node Metastases

The management of patients with clinically negative nodes is controversial. In the past, surgeons have either waited until lymph nodes become clinically positive or performed an elective lymph node dissection (ELND) early. Older literature suggests that patients with thin (less than 1 mm thick) or thick (greater than 4 mm thick) melanomas, who do not have clinically positive nodes, are the least likely to benefit from elective lymph node dissections. The patients with intermediate thickness melanomas had been considered the group most likely to benefit. However, three randomized prospective trials failed to show a survival benefit to ELND when Melanoma appears to metastasize over an identifiable route. Cutaneous areas usually drain first to a limited set of lymph nodes known as sentinel lymph nodes. If the sentinel lymph nodes do not have melanoma, then the other lymph nodes are unlikely to be positive. Radionuclide or blue dye can be injected into the area of the primary melanoma,...

Antiproliferative Activity via Signal Transduction Pathways

Calcium and vitamin D3 are well-known differentiating agents that also inhibit carcinogenesis. Calcium induces differentiation in epithelial tissues including rat oesophagus, mouse skin and human mammary gland and colon. Vitamin D3 induces differentiation in human colon, human and mouse myeloid leukaemia cells, mouse skin cells, mouse melanoma cells and other cells. It has been suggested that the effects of the two chemicals on differentiation may be mediated by the same signal transduction pathway, involving the vitamin D3 nuclear receptor with calcium as the messenger.

Liver Metastases Scope of the Problem

A wide variety of cancers will metastasize to the liver. Approximately 50 of patients with colorectal carcinoma or gastric carcinoma will develop liver metastases. Nearly 75 of patients with pancreatic carcinoma will develop liver metastases. Endocrine tumors frequently metastasize to the liver, including carcinoid, gastrinoma, and insulinoma. Patients with breast cancer, melanoma, renal cell carcinoma, and sarcoma may also metastasize to the liver. In the absence of other sites of metastases, the surgeon may consider ablation or resection in select cases.

Normal and Pathological Findings see Tables262 263 and 264

Its breakdown to bilirubin and other pigments. Oxyhemoglobin is red but becomes pink or yellow when diluted. The concentration of oxyhemoglobin is maximal within the first 36 hours and disappears by 14 days. Bilirubin is yellow and is first detected in the CSF 10 hours after subarachnoid bleeding. Its concentration is maximal at 2 days and may persist for up to a month. Other causes for coloration of CSF include an elevated systemic bilirubin from liver disease a brownish or gray coloration in the presence of CNS melanoma and a greenish tinge related to leukemic meningeal infiltration.

How May A Particular Malignant Condition Present

MELANOMA SKIN CANCER Small basal cell and squamous cell carcinomas are fairly straightforward to treat and can usually be surgically removed under local anaesthetic. Any pigmented lesion or mole that changes in appearance should be viewed as suspicious and medical attention should be sought. Signs can include a mole that is getting bigger a change in the shape of the mole, particularly an irregular edge a mole that is itching, bleeding or has become inflamed or crusty a change in colour, especially multi-shaded (research has shown that moles with three or more shades of brown or black are particularly likely to be a melanoma) (Cancer Research UK web site,2002).

Ribozymes Targeting Telomerase

The catalytic sequence described by Kanazawa et al. (64) was exploited in our laboratory to downregulate telomerase activity in intact human tumor cells. Specifically, the JR8 human melanoma cells were transfected with the ribozyme sequence inserted into a mammalian expression vector (67). Ribozyme transfec-tants successfully expressing the ribozyme and characterized by reduced telom-erase activity and a decreased level of telomerase RNA expression compared with mock transfectants were selected. Ribozyme-expressing clones grew more slowly than parental cells and also expressed an altered morphology with a dendritic appearance in monolayer cultures. A small but significant fraction of the cell population also expressed an apoptotic phenotype. However, no telom-ere shortening was observed in these clones even after a prolonged period (50 d) of growth in culture (67).

Staging Of Malignant Disease

The TNM classification system is commonly used throughout the world for solid tumours, but other classification systems do exist. These include the 'Dukes' staging system for colorectal cancer and the 'Clark's' classification for malignant melanoma. For haematological malignancies, the TNM classifications are not appropriate because of the systemic nature of the diseases. Yarbro, Frogge and Goodman (2005) list a number of classification systems for haematological malignancies, including

Separate Versus Comparative Evaluation

In the same vein, decision principles that are hard to apply in isolated evaluation may prove decisive in comparative settings, producing systematic fluctuations in attribute weights. Kahneman and Ritov (1994), for example, asked participants about their willingness to contribute to several environmental programs. One program was geared toward saving dolphins in the Mediterranean Sea another funded free medical checkups for farm workers at risk for skin cancer. When asked which program they would rather support, the vast majority chose the medical checkups for farm workers, presumably following the principle that human lives come before those of animals. However, when asked separately for the largest amount they would be willing to pay for each intervention, respondents, moved by the animals' vivid plight, were willing to pay more for the dolphins than for workers' checkups. In a similar application, potential jurors awarded comparable dollar amounts to plaintiffs who had suffered...

The Natural History Of The Epidemiological Identification Of A Cancer Cause

The formulation of aetiological hypotheses is usually based on the examination of existing data. These data may represent the results of studies in experimental animals, e.g. the occurrence of papillary carcinoma in the bladder of mice after exposure to tobacco tar encouraged investigators to examine whether an association between tobacco smoking and bladder cancer also existed in humans. In other instances, the data may refer to 'unusual' or 'interesting' cases reported in the clinical literature, e.g. the hypothesis linking inorganic trivalent arsenic compounds to skin cancer (IARC, 1980a) and phenacetin-containing analgesics to renal pelvic carcinoma (IARC, 1980b) have been based, to a large extent, on clinical observations and pathophysiological considerations. There have also been situations where hypotheses were developed and subsequently tested on the basis of biological and theoretical arguments. For example, it was hypothesized that passive smoking may cause lung cancer,...

Targeting Downstream Effectors of PCatenin

P-catenin Tcf regulate the expression of multiple genes some of which are known to promote tumor growth, including c-Myc, cyclin D1, c-Jun, VEGF, and COX-2. Therefore, targeting these genes in cancers with deregulated Wnt signaling might be a promising alternative to the previously mentioned concepts. The oncogene c-Myc is overexpressed in a variety of human cancers including leukemia, lymphoma, melanoma, breast cancer, and colorec-tal cancer (189). Being a direct target gene of P-catenin, c-Myc is crucial for the development of cancer and inhibiton of c-Myc is an important step to limit tumor growth. An antisense oligonucleotide targeting c-Myc mRNA was able to significantly reduce the growth and induce apoptosis in prostate cancer cells (15). When tested in a xenograft model, the antisense oligonucleotide caused a dramatic reduction of tumor load. Moreover, antisense oligonu-cleotides against c-Myc have been shown to limit proliferation in leukemia, lymphoma, melanoma, prostate,...

Or Exogenous Reporter Genes

Exogenous Cell Transplantation

Suppresses the malignant behavior of melanoma cells by reversing a block in differentiation and by restoring growth factor-dependent cell survival, activities mediated by serine proteases. Although previous investigations by Coburn et al. (1994) led to the conclusion that DPPIV proteolytic activity was not necessary for immune competence, more recent studies suggest that DPPIV enzymatic activity is essential for certain T-cell activation pathways and is involved in the inactivation of chemokines (Iwata and Morimoto, 1999).

Ribozymes Targeting Survivin

We first demonstrated the possibility to efficiently inhibit survivin expression through the use of ribozymes. Specifically, we designed two hammerhead ribozymes targeting the 3'-end of the CUA110 (RZ7) and the GUC294 (RZ1) triplets in the survivin mRNA and transfected them into the JR8 human melanoma cell line over expressing survivin. Stably transfected clones proven to endogenously express the active ribozyme RZ1 or RZ7 were characterized by a markedly lower survivin protein level than JR8 parental cells, whereas a negligible reduction of survivin expression was observed in cells expressing a mutant ribozyme (which was produced by introducing a mutation in the catalytic core of the active ribozyme RZ1). These cells demonstrated an increased caspase-9-dependent apoptotic response to cisplatin treatment (74). JR8 cells expressing RZ1 also showed a significantly increased sensitivity to the topoisomerase-I inhibitor topotecan (as detected by clonogenic cell survival) as a consequence...

Evidence For The Biological Significance Of Dna Adducts

Ultraviolet (UV) radiation causes DNA damage chiefly by dimerization of adjacent pyridines in the same DNA strand. The biological importance of these lesions is illustrated by the fact that sufferers of xerodema pigmentosum (XP), who have a deficiency in nucleotide excision repair mechanisms that remove pyrimidine dimers from DNA, are prone to sunlight-induced skin cancer. Moreover, mutations in the p53 gene found commonly in such tumours, but rarely in tumours of internal organs, are tandem mutations occurring at pyrimidine pairs (CC TT transitions), highly suggestive that they arose from UV-induced pyrimidine dimers (Dumaz et al., 1993).

Role of Immunological Vaccine Adjuvants

Class I molecules on dendritic cells, which then migrate to the draining lymph nodes where specific T cell activation occurs. Vaccination with TAA-derived peptides alone may be suboptimal to charge and activate dendritic cells, and elicit specific T cell responses it thus requires simultaneous administration of adjuvants. GM-CSF has been used in various vaccine protocols, as it promotes local recruitment and migration of dendritic cells. Enhanced induction of CD8+ peptide-specific T cells and objective tumor responses had initially been reported in three melanoma patients following the addition of GM-CSF to a multipeptide vaccine (Jaeger et al. 1996). In two consecutive small phase I trials performed in tumor-free melanoma patients, no difference in the induction or frequency of peptide-induced T cell responses analyzed by enzyme-linked immunosorbent spot (ELISPOT) assay was observed if tyrosinase peptides were applied alone or in combination with GM-CSF (Scheibenbogen et al. 2003)....

Light therapy phototherapy luminotherapy

The retinal ganglion cells which project to the sup-rachiasmatic nuclei have a peak sensitivity to light of wavelengths 445-475 nm, especially around 460 nm. This bluish light is most effective in shifting circadian rhythms and suppressing melatonin secretion. Ultraviolet light is not required and should be filtered out since it can cause cataracts and skin cancer.

Protective Clothing

The most common site of regularly visible photoaging and nonmelanotic skin cancer is the head and neck therefore, the regular use of hats had been recommended as preventive measurement 2 . Marks 21 noted that the regular wearing of a hat with a 10-cm brim could lower the lifetime skin cancer risk by 40 . However, clothing alone may not provide adequate protection. Typical summer shirt fabrics only offer an SPF of 6.5. Weave tightness is the most important factor in sun protection followed by the fabric type. Darker-colored fabrics provide greater photoprotection than do lighter-colored fabrics 5 . It is also important to note that fabrics are significantly less photoprotective when wet 22 .

Immune Activation By Spirulina

There have been a number of reports relating to the functions of Spirulina in rodents. Zhang et al.16 reported that the hot water extract of Spirulina showed significant hydroxy radical scavenging activity in mice. In another study, the methanolic extract of Spirulina showed weak antioxidant activity in rats.17 Several papers suggested that the relevant substance is phycocyanin in Spirulina.17,18 Using an experimental squamous cell cancer model of hamsters, administration of Spirulina extract has been reported to result in total tumor regression in 30 of animals.19 Intraperitoneal injection of a polysaccharide extract of Spirulina was shown to inhibit proliferation of ascitic hepatoma cells in mice.20 Calcium Spirulan, a polysaccharide isolated from S. platensis, inhibited lung metastasis of mouse B16 melanoma cells by intravenous administration.21 Hence, phycocyanin and water-soluble components, presumably polysaccharides, may be responsible for antioxidant and anticancer effects in...

Other Risk Factors

A few diseases and conditions other than UV light exposure have been associated with increased risk of melanoma Patients with dysplastic nevi (sporadic) have a 10 lifetime risk of developing melanoma, and a 20-fold increased risk over the general population. These melanomas may arise in dysplastic nevi or de novo. Dysplastic nevus syndrome (B-K mole syndrome, or atypical mole syndrome) is often associated with a family history of melanoma, and when that does occur, the patient has approximately a 100 lifetime risk of melanoma. Congenital nevi can be characterized as small (< 1.5 cm), medium (1.5-20 cm), or large (> 20 cm). The large congenital nevi have the strongest correlation with increased risk of melanoma, 5-20 lifetime risk. These nevi have an irregular surface, variation in color especially brown, and hypertrichosis. Malignant transformation of these lesions has been reported during childhood. A familial predisposition is recognized and is thought to be a genetic risk that...

Excision of Primary

The primary melanoma is usually diagnosed with an incisional or excisional biopsy therefore, the original incision made for the biopsy and all remaining tumor must be excised to fascia with a wide margin. The size of the margin required depends on the depth of the primary melanoma. A 0.5 cm margin is recommended for melanoma in situ. Historically melanoma was excised with wide margins that often required split thickness skin grafting. The wide margins caused significant morbidity, so recently trials were performed to address appropriate margin size. A 1 cm margin is appropriate for melanoma that is less than or equal to 1mm thick. A 2 cm margin is considered by most to be adequate for 1 mm to 4 mm thick melanomas and a 2-3 cm margin for melanomas that are greater than 4 mm thick. The site of the primary melanoma, such as on the head and neck, may influence the extent of resection. Attempts should be made to follow the above guidelines while minimizing morbidity.


Metastatic melanoma has remained a deadly disease with no good treatment. Rare patients will develop a complete response on current experimental protocols or after surgical resection. Resection of some metastases is warranted for palliative reasons. In addition, for some patients with isolated pulmonary metastases or subcutaneous recurrences, resection of metastasis has provided prolonged disease-free survival. Surgical excision or gamma-knife irradiation can effectively palliate patients with solitary brain metastases. Other resections of single lesions that will require relatively low risk resections are supported by some groups. Until more effective systemic therapy is available, surgical resection remains a reasonable option for some patients with distant metastases. The risks and benefits must be carefully considered and discussed with each patient, because surgery for metastatic disease in most patients is unlikely to provide survival benefit.

Interferon alpha2b

This drug was approved in 1995 by the FDA for postsurgical adjuvant therapy for high risk patients. A trial by the Eastern Cooperative Oncology Group (ECOG) showed a significant survival benefit with high-dose interferon alfa-2b. However, a repeat study with the same regimen failed to show a survival benefit. The balance of the treatment and control arms of the trial has been criticized. The current regimen requires a full year of high dose therapy, and the toxicity of the regimen is high enough that many patients choose not to take it. Indomethacin may help with some of the side effects, but the fatigue syndrome experienced by many on interferon alfa does not have an effective treatment. Patients with resected stage IV and stage IIB may also be candidates for interferon alpha but clinical trial results are not yet available to demonstrate benefit in these patients. Interferon alpha has theoretical promise in combination with tumor vaccines or defined melanoma antigen vaccines.


The ultraviolet component of sunlight is a major cause of skin cancer. Susceptibility is related to paleness, poor tanning ability, and chronic exposure. Overall incidence of non-melanoma skin cancers in the white U.S. population is about 165 per 100,000. However, the prevalence in Texas is three times that in Iowa. The incidence of melanoma is only about 4 per 100,000, but 65 percent of skin-cancer deaths are caused by this disease. The lesion occurs twice as often on the legs of white women as on those of white men. It occurs nearly twice as frequently on the male trunk than the female trunk. Melanoma is uncommon in blacks, and its location tends to be on palms or soles and within the mouth - less heavily pigmented areas. Melanoma incidence has been increasing everywhere, and mortality has nearly doubled. Whether the increase is attributable to changes in ultraviolet intensity is unknown.