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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Melanomas Moles And More

The spectrum of diseases treated by dermatologists is quite wide. Your patients could include a teenager with severe acne vulgaris, a middle-aged woman with dermatomyositis, a sun-burned farmer with malignant melanoma, a young woman suffering from psoriasis, or a baby with contact dermatitis from her diaper. Every year, millions of patients visit a dermatologist for skin-related complaints. Other common problems include impetigo, benign growths, cellulitis,

Exclusion of Nonmalignant Nonmelanoma Lesions of the Skin

In the early 1960s some German dermatologists propagated the opinion that malignant melanomas should be diagnosed by eye and by palpation and that radiation therapy should then follow. This opinion was certainly mistaken and was also dangerous, because it meant that benign nonmalignant lesions were treated with high-dose radiation therapy. Every experienced dermatologist and pathologist is familiar with these melanoma-like lesions, which are When molecular biological methods are used for melanoma staging, detection of tyrosinase activity in the blood is important, as tyrosinase is a precursor enzyme for melanin formation. Detection of tyrosinase-coding mRNA as a marker for melanoma cells can theoretically be usefully attempted in blood and lymph node investigations. mRNA coding tyrosinase released from apoptot-ic or necrotic cancer cells of malignant melanomas can be transported via the lymph stream to the node(s) and give a false-positive reaction. Normal or preneoplastic nevus cells...

Macroscopic Criteria for Malignant Melanoma Development in Preexisting Nevi

Internationally, there have been many campaigns for early detection of malignant melanomas. It is clear that all doctors in all the different medical disciplines must be familiar with the characteristics of this cancer. This is easy to understand, because even specialists responsible for different branches of medicine can detect primaries in their own working fields within the human body. Some striking features are summarized in the so-called ABCD formula Fig. 1. Explosion-like metastasis from malignant melanoma into the lung, which had pigmented and amelanotic metastases Fig. 1. Explosion-like metastasis from malignant melanoma into the lung, which had pigmented and amelanotic metastases

Clinical Staging of Malignant Melanoma Based on Eortc Evaluation

The clinical stages related to the progression of malignant melanomas and the corresponding survival rates are valuable parameters that are helpful in all further diagnostic procedures and adjustments to treatment. The current data published by the EORTC are presented in Table 1. One important method is measurement of the proliferative activity in tumor sections after staining with the antibody MiBI. From our own investigations with this antibody in melanoma research, we know that there is a close correlation between the percentage of MiBI-positive cancer cells and regional metastatic cancer progression, but we cannot exploit this fact in decision making, especially when decisions on SLCC have to be made, because there are many other factors, such as microsatellite instability, that also influence the metastatic potential. Table 1. Basic stage-related data of malignant melanomas presented by EORTC Table 1. Basic stage-related data of malignant melanomas presented by EORTC

Historical Overview of SLN Diagnosis for Melanomas

Despite all that has been said above, Munz et al. (1982) and Wanebo et al. (1985) had already used 99mTc in the 1980s to identify the lymphatic drainage from cutaneous melanomas. Combined techniques using 99mTc and blue dyes are meanwhile excellent after intensive development and are used routinely. It is sufficient to administer 99mTc the day before surgery and inject the blue dye shortly before operation (Silverstein et al. 1994 Pijpers et al. 1995, 1997 Thompson et al. 1996, 1997). This method is also good from the point of view of operating teams and pathologists, the radioactive dose being kept as low as possible. The investigations of Alex et al. (1993, 1996, 1998) were focused on head and neck melanomas and showed that in cases in which SLNs were not recognized regional metastases later developed. Their group confirmed the greater benefit of the lymphoscintigraphic method (96 ) than of blue dye lymphatic mapping (75 ). In recently published animal studies, a contrast agent...

Demonstration of Blue Dye and mTclabeling in Malignant Melanoma Cases

Figure 22 documents a malignant melanoma with the primary located on the back. After peritumoral injection rapid drainage to the right-sided axillary lymph node(s) developed, but very soon drainage to the left-sided axillary nodes also started. Fig. 16. Injection technique before tumor excision in malignant melanoma cases. The same injection technique can be used when the solution(s) is are injected after primary excision Fig. 16. Injection technique before tumor excision in malignant melanoma cases. The same injection technique can be used when the solution(s) is are injected after primary excision Fig. 17 a, b. The four-point injection sites to be used before tumor excision in the case of malignant melanomas on the trunk. Lymphatic drainage can take a one b two or in some cases more directions. In peripheral melanoma localizations (face, legs, hands, etc.) injections need only be given in a semicircle of sites Fig. 17 a, b. The four-point injection sites to be used before tumor...

Treatment of Malignant Melanomas Related to the SLN Status

In malignant melanoma treatment two factors are important for postoperative adjuvant therapy Type of melanoma (superficial spreading or nodal subtype). - It is accepted that in cases with a superficial spreading melanoma in the early stages no search for sentinel nodes is performed. In cases with superficial spreading melanoma with negative sentinels no additional therapy is performed, whereas in nodal cases with or without cancer infiltration of the sentinel node(s) interferon therapy is given after surgical clearance of the basin.

Interferon Alpha and Cytostatics Melanoma Treatment in SLNnegative and in Advanced Cases

As demonstrated in the current literature (Kirkwood et al. 1996 Grob et al. 1998 Pehamberger et al. 1998), INFa significantly inhibits melanoma progression. As adjuvant treatment it delays recurrence and prolongs tumor-free survival, and in some cases it obviously also extends overall survival.

Mcam Muc18 expression in melanomas

MUC-18 is a 113 kDa glycoprotein expressed on the cell surface. The gene MCAM encoding MUC-18 is a member of the immunoglobulin family. The MCAM glycoprotein is an adhesion molecule bearing homology to other cell adhesion molecules such as NCAM and ICAM and also to the DCC gene product (see page 177), as well as to MHC-2 and MHC-1. MCAM is found in some mesenchymal tissues, e.g. smooth muscle cells, endothelial cells and Schwann cells but not in epithelial or haemopoietic cells. MCAM is found consistently in mesenchymal neoplasms of both smooth muscle and endothelial origin and bears obvious relationship to malignancy with the exception that, although it is expressed consistently in neurofibromas and schanno-mas, it is not found in malignant peripheral nerve sheath tumours (Shih et al., 1996). Interestingly, MCAM is expressed in a subset of capillaries and tumour endothelia but it is not found in the endothelia of arteries or large veins (Sers et al., 1994). MCAM is not found in...

Therapy Regimens for Malignant Melanoma

The usual therapy regimen for treatment of malignant melanomas is shown in Table 45. For more information the reader is also referred to Chapter 25. In recent years, the adjuvant therapy regimen using Interferon (IFN)-a2b has been tested in many investigations, its efficacy has been confirmed in some (Agarwala and Kirkwood 2002 Wheatley et al. 2002 Molife and Hancock 2002 Pawlik and Sondak 2003 Mohr et al. 2003). However, the biological profile of melanoma cases in which the therapy is efficient is still not clear, and controversies persist (Sabel and Sondak 2003). In their analysis, Kleeberg et al. (2004) combined the data from EORTC studies and from the DKG-80-1 trial. No advantage of adjuvant melanoma treatment with rIFN-a2 or rIFN-y was found in the treatment of high-risk melanoma patients. Hancock et al. (2004) treated 674 patients with thick melanomas (> 4 mm), some of whom had lo-coregional metastases. Low-dose IFN-a2a (3 mega units) three times per week for 2 years or until...

The Sentinel Node Concept Related to Main Tumor Types and Subtypes Applicability in Daily Routine Work

Malignant Macroscopic Criteria for Malignant Melanoma Development Clinical Staging of Malignant Melanoma Based on EORTC Evaluation . 333 In Transit Metastasis, Double or Multiple Drainage, Bypass and Atypical Morphological Stages of Development of Malignant Melanoma Historical Overview of SLN Diagnosis for Melanomas 339 Malignant Melanomas of the Anal Circle and the Rectum 342 and Early Invasive Malignant of Malignant Melanomas in Cancer-infiltrated Lymph Nodes in Cases Exclusion of Systemic Disease in Malignant Melanoma Cases Melanomas Final Version of the Staging System for Cutaneous Melanomas 360 Therapy Regimens for Malignant

Chromosomal abnormalities in cancer

Chromosomal and DNA ploidy is an important parameter which has served as a marker of prognosis in breast cancer (Hedley et al., 1987 Clark et al., 1989 Ferno et al., 1992 Grant et al., 1992 Wenger et al., 1993), as well as in other forms of cancer such as pancreatic adenocarcinoma (Porschen et al., 1993), melanoma (Karlsson et al., 1993), endometrial cancer (Rosenberg et al., 1989), and gastric leiomyosarcoma (Suzuki and Sugihira, 1993). An image cytometric study carried out in the authors' laboratory on breast cancer aspirate cells has also revealed a highly significant relationship between ploidy and prognosis (see Table 2) (G. V. Sherbet et al., unpublished data). Nevertheless, it should be noted that a dissenting view has been expressed with regard to the significance of aneuploidy as a prognostic indicator (Lanigan et al., 1992 Lipponen et al., 1992). Aneuploidy may be a consequence of cells entering the S-phase of the cell cycle prematurely. This can be inferred from the close...

Early Developments and Continuous Improvements

In the management of skin tumors, such as malignant melanoma or Merkel cell carcinomas, which have a frequent propensity toward regional metastases (Rodrigues et al. 2001), the sentinel node concept is well developed and already widely routinely applied. This means it is assumed that this concept is integrated in treatment protocols for malignant melanomas and Merkel cell cancers (Morton et al. 1992 Reintgen et al. 1994 Slingluff et al. 1994 Albertini et al. 1996 a Alazraki et al. 1997 Kapteijn et al. 1997 a Cascinelli et al. 1998 Glass et al. 1998 Joseph et al. 1998 Leong et al. 1998). In recent years the number of precisely investigated cases has increased markedly in many malignant melanoma treatment centers, so that the statistical significances are now very reliable (Cochran et al. 2000 Gesuelli et al. 2000 M ller et al. 2000 Murray et al. 2000 Temple et al. 2000 Uren et al. 2000 Villa et al. 2000 Wagner et al. 2000 a, b Weiss et al. 2000 Clary et al. 2001 Harlow et al. 2001...

Genetic instability and the generation of metastatic variants

Cifone and Fidler (1981) found that the rates of mutation to ouabain and 6-thiopurine resistance were three to sevenfold greater in cells with high metastatic potential than in cells with low metastatic potential. This study also contained two clones, differing markedly in metastatic ability, derived from the same tumour. The rate of generation of ouabain resistant mutants in the metastatic clone was 4.6-fold greater than in the low metastasis clone, suggesting that the highly metastatic clone was more unstable than the clone with low metastatic ability. These data have been supported by the rates of generation of drug-resistant mutants in Bl6 murine melanoma cell lines with different metastatic potential. The high metastasis variant, F10, has been reported to show a fourfold greater rate of generation of methrotrexate- and PALA-resistant mutations than the low metastasis variant F1 (Cillo et al., 1987). The rate of generation of EMS (ethylmethane sulphonate> induced...

Recessive Traits In Humans

In most ways, people who lack melanin are just like the rest of us. But even though they are highly diverse in terms of a variety of traits, they do have some features in common, such as their unusual coloring and vision problems. The lack of melanin during development of the eyes causes abnormal routing of the optic nerves into the brain and results in inadequate development of the retina. They often use glasses, but their vision often cannot be corrected to 20 20 acuity with either glasses or surgery. They are unusually sensitive to bright light. Some are legally blind, but others see well enough to drive a car when using special lenses. Some are not blind but have vision problems that can't be helped by corrective lenses. In some cases, skin cancer can

DNA repair and repair fidelity in metastatic variants

The recognition and repair of DNA damage occurs before the cells enter the S-phase of the cell cycle and cells are held in the G phase until the repair process is completed. This checkpoint control is exercised by the nuclear phosphoprotein p53 whose levels increase when any damage to the DNA is sustained (see page 28). Defects in DNA damage repair are often encountered, e.g. as seen in the human autosomal recessive disorder xeroderma pigmentosum (XP), which are defective in their ability to repair u.v.-induced DNA damage (Lehmann and Norris, 1989). Ataxia telangiectasia (AT) is another example of an autosomal recessive syndrome comprising progressive cerebellar degeneration, oculocutaneous telangiectasias and immune deficiencies. AT patients show high cancer incidence (Swift et al., 1991). Cell lines isolated from AT patients show hypersensitivity to ionising radiation and to radiomimetic agents this is believed to be due to defective DNA repair (Painter and Young, 1980). All the...

Diagnosis of Lymph Node Metastases

PET offers particular advantages in evaluating lymph nodes. When CT is applied the size of the lymph nodes is a determining factor, although even lymph nodes that are normal in size can be tumor involved, just as lymph nodes can be non-specifically enlarged. In detection of breast cancer and melanoma and in the mediastinal staging of lung cancer, FDG-PET is clearly superior to conventional imaging modalities. In principle, PET permits the recognition of positive lymph nodes regardless of size, but has limited sensitivity in detecting microscopically small tumors. Spatial resolution is an important factor, as existing PET scanners do not have sufficiently high resolution to enable detection of micrometastases. The further development of PET scanners and new imaging processes should, however, improve the spatial resolution in the future.

Genetic recombination in the generation of metastatic variants

Recombination ability of metastatic variants of the B16 melanoma. The pDR plasmid contains a selectable marker (gpt gene) and the neo (neomycin resistance) gene. The latter is present as two truncated, non-tandem but overlapping segments. The plasmid was transfected into the cells and transfectants were selected by growing the cells in XHATM culture medium, indicating gpt function. The transfectant clones were then expanded and subjected to selection for the presence of functional neo gene. Only those transfectants carrying stably integrated plasmid DNA, that have successfully recombined the neo gene fragments into a functional gene, will come through this selection procedure. This procedure allows one to determine the chromosomal recombination events occurring in these cells. Surprisingly, the ability of the low metastasis variant F1 to carry out chromosomal recombination was three orders of magnitude greater than the high metastasis variants BL6 and ML8. Extrachromosomal...

Detection and Radiological Imaging

Node approach is one such theme, challenging medical doctors working in a broad field of cancer diagnosis and treatment its application is currently in the course of being extended from melanoma and breast cancer to head and neck cancers, gastrointestinal cancers, and both male and female urogenital cancers and now involves nearly all surgical disciplines. Initially there was a great deal of enthusiasm for the sentinel node concept, but doctors soon had to realize that good practice is not simple and that there are many aspects needing consideration, while good interdisciplinary cooperation and improvements are necessary before these methods, some of which are quite new, can be successful in all hospitals in which tumor treatment is carried out and which claim to provide optimal quality care (centers of excellence). The objective that the development of a simple, minimally invasive, technique for determining whether regional node metastasis has occurred, was clearly formulated by Krag...

MAGEA3 Marker Function in Breast Cancer Patients Sentinel Node Evaluation

There have been attempts to detect occult cancer cells by RT-PCR, with tyrosinase in malignant melanoma cases and with MAGE-A3 in breast cancer cases. MAGE-A3 mRNA expression in the SLN occurred more frequently with infiltrating lobular carcinomas than with infiltrating ductal carcinomas (P < 0.001). Use of MAGE-A3 mRNA in the development of antigen-specific targeted immu-notherapy has been planned. Basically, it is beset by the same difficulties as tyrosinase RT-PCR evaluations in SLN material from patients with malignant melanomas. It is possible that the tumor marker MAGE-A4 is not derived exclusively from vital melanoma cells, but can also be present in apoptotic or ne-crotic melanoma cells.

Atmospheric Chemistry

Where M is a third body, such as a molecule of N2, which absorbs excess energy from the reaction. The ozone that is formed is very effective in absorbing ultraviolet radiation in the 220- to 330-nm wavelength range, which causes the temperature increase observed in the stratosphere. The ozone serves as a very valuable filter to remove ultraviolet radiation from the sun's rays. If this radiation reached the Earth's surface, it would cause skin cancer and other damage to living organisms.

Baseline CD4 count

Basal-cell carcinoma The most common, and least lethal, form of skin cancer. It usually develops on areas of the skin exposed to sunlight. It commonly appears as a small nodular bump that is raised from the surrounding skin and has a pearly quality. Small basal-cell carcinomas can resemble molluscum c ontagiosum, which is occasionally found in HIV disease. It can also appear as a firm scarlike patch. Basal-cell skin cancer is very slow-growing and seldom fatal. Diagnosis requires the removal of some tissue for a biopsy (a microscopic examination for cancer cells). Frequently, if the cancer is small, the biopsy also removes the cancer. However, if the area is sizable, more tissue may have to be removed until there are clean margins. Treatment depends on the size of the tumor, the type of tumor, and the general health of the patient. Treatment is generally surgery to remove the cancer. The main cause of basal-cell carcinoma of the skin is ultraviolet radiation from the Sun.

P53 cancer progression and prognosis

Cutaneous melanomas show marked p53 immunoreactivity (Bartek et al., 1991 Stretch et al., 1991 Cristofolini et al, 1993 McGregor et al, 1993). Cristofolini et al. (1993) also examined a series of 75 benign skin naevi and described 15 of these specimens as p53-positive. It ought to be pointed out, however, that the criteria for declaring specimens as positive for p53 staining vary considerably. Cristofolini et al. (1993) found less than 1 of cells composing the naevi stained for p53, but the melanomas contained a far higher proportion of p53-staining cells also six out of eight metastatic melanomas were p53-positive with up to 10 of cells staining for the p53 protein. McGregor et al (1993) found malignant melanoma to be highly p53-positive with the majority of tumour cells (> 75 ) staining for p53. These authors regarded tumours with < 10 cells staining for p53 as weakly positive. It seems reasonable therefore to regard the Cristofolini series of benign naevi as weakly staining or...

Subcellular localisation of p53 protein

Be exclusively nuclear or cytoplasmic, or a mixture of both (Faille et al., 1994). Non-Hodgkin's lymphomas show virtually exclusive (90 out of 96 samples) nuclear staining (Pezzella et al., 1993a). Its localisation in breast cancer was described as predominantly cytoplasmic (Horak et al, 1991). Both the nucleus and the cytoplasm may be stained in melanomas (Weiss et al., 1993 Parker et al., 1994a). In the light of the interactions of p53 with cellular proteins (see page 31), it seems likely that the subcellular localisation patterns seen in tumours might be suggestive of the pathways by which wild-type and mutant proteins might be functioning. Moll et al. (1992) carried out sequence analysis of p53 cDNAs from breast cancers showing cytoplasmic staining and found wild-type alleles in six out of seven specimens. In contrast, where nuclear staining of p53 was encountered, missense and nonsense mutations were found. Furthermore, a sample of normal lactating breast tissue also showed...

GADD genes and their regulation by p53

The genes of the S-100 family encode a host of Ca2+ proteins which subserve several important physiological functions. The expression of these proteins is known to be closely associated with cell cycle progression. Several members, e.g. S-100 , calcyclin, etc., are expressed in specific stages of the cell cycle. In common with these other members of the S-100 family, the mouse homologue of 18A2 mtsl gene also shows cell cycle-related expression (Jackson-Grusby et al, 1988). Its expression is also associated with microtubule depolymerisation (Lakshmi et al, 1993). Both Lakshmi et al. (1993) and Parker et al. (1994a) have therefore examined whether the expression of 18A2 mtsl and p53 are related. In these studies, they have demonstrated that an experimental modulation of 18A2 mtsl expression also produces variations in p53 protein expression. The detection of p53 increased or decreased in parallel with increase or decrease in 18A2 mtsl expression. In B16-F10 murine melanoma variant...

Cellular phenotype in primary screening

In collaboration with the American Red Cross, ACI has expanded a bead-based method of screening plasma-derived immunoglobulins for cytotoxic activity against melanoma cell lines. Using this method, thousands of antibodies are isolated and screened daily in an image-based assay that measures both cell number and propidium iodide (PI) fluorescence as an index of antibody-mediated phenotypic change. Fig. 1. Five hundred WM266-4 human melanoma cells were plated to individual wells of a 384-well microculture plate. Beads conjugated with a random library of hexapeptides were incubated with patient plasma immunoglobulins and placed into the melanoma cell cultures at an average density of 30 beads per well. Culture medium included propidium iodide (PI) as an indicator of cell death. Visible and fluorescent red images of each entire well at 40 magnification were taken after 72 h. The percentage ofPI-positive cells is plotted for each well. Two wells were treated with 50 pM etoposide as a...

Dermatology Is Both Medicine And Surgery

In the therapeutic realm, dermatologists are the master surgeons of the skin. One of the most demanding forms of surgery is Mohs micrographic surgery. This advanced treatment for skin cancer involves the removal of cancer from certain areas, such as the face or ears, where skin-sparing excisions are important. It offers the highest potential for recovery. Historically, skin cancers were removed with a standard margin that would ensure the removal of the entire cancer. However, a certain portion of skin removed would be cancer free. Mohs surgeons re

The Doctorpatient Relationship

Although dermatologists have more of a consultative role, they maintain a high level of patient contact. They establish long-term relationships with their many patients whose chronic skin conditions require multiple follow-up appointments over the course of several years. Patients appreciate their dermatologists for their equal emphasis on preventive medicine and immediate treatment of acute skin diseases. While dealing with the current problem at hand, dermatologists also make sure to educate their patients on the importance of skin cancer prevention staying out of the sun, using sunscreen, and watching their own suspicious moles. Many patients do not realize that mole self-checks are just as important as monthly breast self-examinations.

Misperceptions About Dermatology

It also certainly does not help when dermatology gets lampooned in popular culture, such as the episode of Seinfeld, in which a dermatologist is mocked as an aloe pusher and pimple popper, MD. Yet dermatologists are, indeed, true lifesavers when it comes to the treatment of deadly skin cancers. Although most skin diseases treated by dermatologists are benign, cancer of the skin is the most common of all cancers in this country. According to the American Cancer Society, one person dies of melanoma every hour, and among people between the ages of 25-29, melanoma is more common than any non-skin cancer. Dermatologists have the unique position to screen, diagnose, and treat their patients for these life-threatening diseases. If detected early, both basal cell and squamous cell carcinomas have an excellent cure rate. In the medical profession, a common, and playful, dictum explains treatment options for a dermatologist If it is wet, dry it. If it is dry, wet it. Anything else, use...

Response of kiplkip2 genes to antiproliferative signals

Macrophages exposed to mitogenic stimulation by colony stimulating factor 1, show Gj arrest upon cyclic-AMP treatment, and this block of proliferation is associated with an increase in kipl (Kato et al, 1994). Another instance is that of TPA which inhibits the growth of malignant melanoma cells and blocks GrS and G2-M transitions. In this tumour model, Coppock et al (1995) found high levels of wapl cipl and kipl in G, cells and these levels dropped as the cells entered the S-phase. This drop in the level of the cdk inhibitors could be prevented by treating the cells with TPA. Similarly, an increase in the levels of kipl and wafl cipl has been observed in the inhibition of proliferation of MCF-7 breast carcinoma cells (Watts et al, 1995). Interferon, which is a powerful antiproliferative agent causes G arrest of Daudi-Burkitt lymphoma cells, increases kipl expression, but does not appear to affect wafl cipl (Yamada H et al, 1995a). Conversely, cdk inhibitors are inactivated by...

Therapeutic Approaches Involving Regulatory Proteins of Apoptosis

In a human melanoma xenograft model using SCID mice, a marked reduction in tumor growth was noted following treatment with antisense Bcl-2 (58). A phase I clinical trial on non-Hodgkin's lymphoma (NHL) has similarly demonstrated potential for antitumor activity using this method (59). In this particular study, 21 patients with Bcl-2-positive relapsed NHL were treated through subcutaneous infusion with G3139, an 18-mer oligonucleotide complementary to the first 6 codons of the Bcl-2 reading frame. Response assessed by computerized tomography and using standard response criteria demonstrated one complete response, two minor responses, nine cases of stable disease, and nine cases of progressive disease. Another clinical trial using Bcl-2 antisense therapy showed promising outcome on malignant melanoma (60). Bcl-XL, which belongs to the same family of proteins, has also been downregulated in vitro in A549 and HeLa cells using an antisense approach that induced higher levels of...

TNF Receptors and Trail Apo2L

Recombinant human TRAIL (10 mg kg administered once daily for 7 d) (97). One of the most exciting features of TRAIL therapy is the strong positive interaction effect of TRAIL with chemotherapeutic agents or ionizing radiation. TRAIL treatment has been shown to sensitize tumor cells derived from acute leukemia, breast cancer, lung cancer, colon cancer, prostate cancer, and melanoma to chemotherapeutic agents (98-105). In an in vitro setting, TRAIL has been shown to induce apoptosis in normal primary hepatocytes (106). In light of this observation, it remains to be seen whether TRAIL therapy offers a margin of safety in humans, as is seen in mice and monkeys.

A2mtsl protein and HSPs in cell proliferation

Another cellular protein which appears to be associated concomitantly with both cell cycle progression and HSPs, is the 18A2 mtsl protein, a Ca2+-binding protein which is associated with the invasive and metastatic behaviour of cancer cells (see page 191). The cell cycle related expression of the 18A2 mtsl protein is now well documented. A high level of expression of 18A2 mtsl is invariably associated with large S-phase fractions in murine and in human carcinoma cells (Parker et al., 1994a Sherbet et al, 1995). Parker et al. (1994b) have further demonstrated, by means of gene transfer technology, that switching on the exogenous 18A2 mtsl in B16 murine melanoma cells induces them to undergo GrS transition, and it also appears to control the cell cycle traverse. In parallel, these studies have revealed an increase in the detectability of p53 protein (Parker et al, 1994a,b), suggesting that GrS transition may be induced by the sequestration of p53. The concomitant involvement of HSPs in...

Cancers of the Face Nasopharynx and Oral Cavity and of the Salivary Glands

Point 1) Cancers of the skin, predominantly SCC and malignant melanomas, metastasize primarily to the first node related to the different skin regions. Cancer-infiltrated enlarged nodes are often palpable. In many cases the prevalent positions of the SLNs can already be logically derived As in other sites, at least in the early stages of metastatic lymph node involvement the imaging methods have considerable limitations. Jansen et al. (2000) used the labeling methods (99mTc-nano-colloid and blue dye) in investigating 30 cases of melanomas of the head and neck region. In 27 of the 30 cases (90 ) SLNs could be identified, but comparison of the radioactive and blue dye methods showed that only 53 of the sentinel nodes were labeled by both blue dye and 99mTc-nanocol-loid. Tumor positivity was obtained in 8 cases, while false-negative sentinel nodes were found in 2 cases (sensitivity 80 ). The conclusion reached by the authors was that sentinel node biopsy in head and neck cancers...

Dependence of Adjuvant Therapy Regimens in SCCs of the Upper Aerodigestive Tract and the Face on SLN Status

In a retrospective study on a large melanoma database with > 8000 cases of malignant melanomas (American Joint Committee on Cancer), in 39 cases stage I and II melanomas analyses of the pre- or intraparotidean SLNs were carried out (Olilla et al. 1999). The patients had intraoperative lymphatic mapping to identify the SLNs in the parotid gland area.

Special Subtypes of Ductal Salivary Gland Cancers

Shows cytology of an anaplastic small cell salivary gland cancer metastasis of a small cell lung cancer must be excluded. In lymph node lymphoma must also be excluded using T- and B-cell antibodies and melanoma using S100 protein Ab and HMB45 Fig. 18. Shows cytology of an anaplastic small cell salivary gland cancer metastasis of a small cell lung cancer must be excluded. In lymph node lymphoma must also be excluded using T- and B-cell antibodies and melanoma using S100 protein Ab and HMB45 Pre- or intraparotid lymph node involvement or check up of these nodes, for instance in cutaneous malignant melanomas of the face, is rare.

Disease Based Target Identification in a Laboratory

An example of the serendipitous identification of a new gene occurred in the study of adipocyte differentiation melanoma development in our laboratory. Incidence of melanoma is rising at an alarming rate, and on its present course, the lifetime risk will reach 1 in 75 among Caucasians in the United States in the next 10 yr (6). In contrast to most malignancies, melanoma affects a younger population, metastasizes early, and fails to respond to current available therapeutics (7). Despite much clinical and molecular effort directed toward this disease, little is known about the precise genetic lesions leading to melanoma. Normally, spontaneous malignant melanomas are a rare occurrence in rodents. A model system that intrinsically recapitulates a single type of neoplasm will always be a powerful tool for dissecting the molecular events underlying the initiation, promotion, and progression of that neoplasm. Several mouse model systems have been engineered that have proved valuable for the...

Deregulated expression of bcl2 family genes in cancer

Primary tumours and their distant metastases follow similar or comparable kinetics of apoptosis. This may not be the case as shown by Matsuda et al. (1996). Primary and secondary tumours differ markedly in respect of the degree apoptosis. As expected, primary tumours show an inverse relationship between tumour growth and apoptosis but, in contrast, there is an increase of apoptosis in metastatic tumours. This should be taken as a note of caution in order to avoid over-interpretation of the state of expression of bcl-2 genes in tumours as independent predictors of their biological behaviour. Equally, high metastasis variants of the B16 murine melanoma have been reported to be more resistant to apoptosis than variants with low metastatic potential (Glinsky and Glinsky, 1996), and apoptosis index per se may also directly relate to patient survival (Aihara et al., 1995).

Risk of Recurrence and Definitive Risk to Survival

In a multicenter study conducted at the M. D. Anderson Cancer Center in 580 melanoma patients, the SLN status was found to be the most significant prognostic factor with respect to disease-free survival and disease-specific survival according to The locoregional recurrence rate in melanoma patients seems to be important for judgments about the value of the SLN concept. To obtain clear-cut information, Gershenwald et al. (1998) looked for recurrence rates and patterns in 243 stage I and II melanoma cases in which SLNs were negative. The results were 11 with negative SLNs developed local, in-transit, and regional nodal and or distant metastases. In 4 metastases developed in the basin investigated. In 80 of the primarily negative nodes tumor cells were detected in serial sections supported by immunohistochemis-try (see also Chapter 21).

In Transit Metastasis Double or Multiple Drainage Bypass and Atypical Metastasis

In transit melanomas are characterized by an aggressive behavior with recurrence and are associated with a poorer prognosis than other types of metastasis. Intralymphatic trapping of melanoma In parallel with these results, free circulating DNA microsatellites with LOH can be found in melanoma patients. Taback et al. (2001) detected LOH in 32 of 57 patients (56 ) and found a significant correlation between LOH and microsatellite marker D1S228 in the plasma of patients with advanced disease (P 0.0009). The authors suggest that blood testing for circulating tumor genetic markers may provide prognostic information that can be turned to good account in further treatment planning. How in transit metastases in the subcutaneous tissue can be detected in early stages remains an open question. Preliminary data are discussed in some published case reports (Vidal et al. 1998). Multiple drainage pathways have been seen in more than half of the cases in melanoma studies. These results help...

Interval Metastases Definition and Significance

In transit metastases are at least sometimes outgrowths of melanoma cells or cell clusters from lymphatics connecting the primary tumor region with the SLN, with infiltrative growth seen as cancer cell nodule(s) in the skin, while an interval metastasis is a metastasis in a tiny lymph node located as an intermediate station between the primary and the sentinel node. Interval nodes have been described as the forgotten SLNs (Uren et al. 2000). All lymph nodes that receive any of the total lymphatic drainage, regardless of their location, can contain malignant cells, and with these the initial stage of a metastasis. This is also consistent with the knowledge that the main draining lymphatics lead directly to well-defined lymphatic basins. The interval nodes, as transitory lymphatic stations, lie along mostly long lymphatic ways leading to the main basins and can sometimes be seen or detected using the gamma probe in the course of lymphatic mapping for the sentinel node biopsy. When these...

Differential Diagnosis against Pigmented or Nonpigmented Malignant Schwannomas

Pigmented or nonpigmented malignant schwannomas (Fig. 7) must be considered in the differential diagnosis against subcutaneous metastases from malignant melanomas. These tumors can be related to neurofibromatoses (Recklinghausen's disease). Sometimes it is difficult to delineate dysplastic nevi from malignant melanomas. Figure 3 is a macroscopic picture that may give an impression of the changes in pigmentation. Figure 4 shows the main histological features of a superficial spreading melanoma. This subtype is more suitable for preopera-tive labeling to detect sentinel node positions than are extended nodal types. In Figs. 5 and 6 nodal types of malignant melanoma are shown. In such cases sentinel node labeling can be performed before (when the tumor is small) or after excision of the tumor (in extended lesions).

PDGFD Induces Morphological Transformation In Vitro and Tumor Formation In Vivo

The importance of the activation of PDGF-DD was also reported by Furuhashi et al. (28). They have generated PDGF-D-transfected B16 melanoma (B16 PDGF-D) cells that express a low level of ( PDGFR. PDGF-DD was secreted from the B16 PDGF-D cells as a latent product and it did not induce receptor phosphorylation. Accordingly, the proliferation of B16 PDGF-D cells in culture was not different from that of the control B16 cells. Contrary to in vitro observation, in vivo in C57Bl6 mice, compared to B16 tumors, B16 PDGF-D tumors grew significantly faster and caspase-3-mediated apoptosis of B16 PDGF-D cells was significantly decreased. The very low levels of ( PDGFR expression on B16 melanoma cells and the lack of growth stimulatory effect in vitro of B16 PDGF-D cells indicated the presence of a paracrine factor. The authors have reported a paracrine ( PDGFR stimulation of perivascular host cells that was associated with increased tumor growth. Other groups have shown the expression of ( PDGFR...

Routine versus Elective Lymph Node Dissection

Routine lymphadenectomy without exact correlation with localization of the primary, stage, age, etc. did not result in a statistically significant advantage. Therefore, primary lymph node dissection was abandoned by many surgical dermatologists for some time (Tilgen 1995). This has been confirmed in four randomized prospective clinical trials at Sloan Kettering Cancer Center (Hochwald and Coit 1998). However, elective lymph node dissection according to the SLN concept did give improved outcomes for patients aged < 60 years with melanomas 1-2 mm thick, with or without ulceration. Many studies have demonstrated that growth activity can be regarded as a parameter that is valuable in assessment of the risk of regional lymph node metastasis. Studies performed together with Korabiowska et al. (1994) showed that there was a good correlation between the proliferation of oral and skin melanomas and lymph node involvement, whereas there was no significant correlation with local tumor...

Inhibitors of neovascularisation

Angiogenesis has provided a valuable target for developing anti-tumour agents. Earlier, we alluded to the binding of bFGF to heparan sulphate proteoglycans (HSPG) as a mechanism by which bFGF may be localised at the site of its action and protected from degradation. This has inevitably led to the use of heparinoids and related compounds to inhibit the heparin-binding growth factors. The polysulphonated naphthylurea suramin is a moderate inhibitor of these growth factors (Myers et al., 1991 Zugmaier et al., 1992). It appears to inhibit the binding of bFGF to endothelial cells (Takano et al., 1994). Suramin also inhibits VEGF and VEGF-induced chemotaxis of endothelial cells. The inhibition seems to result from inhibition of VEGF-mediated phosphorylation of the VEGF receptors (Waltenberger et al., 1996) possibly a mechanism by which suramin exerts its anti-angiogenic effect could be by interfering with the binding of angiogenic growth factors with their receptors. Braddock et al. (1994)...

Performance in Labeling of SLNs in Cases with Skin Tumors

In injection of blue dye solution and or mTc-na-nocolloid solution the assumed direction of lymph flow is important in the decision on whether injections of the labeling solution should be given in a circular or semicircular formation. For instance, when the malignant melanoma is located on the skin of the trunk a circular arrangement of injections around the malignant melanoma is appropriate in practically all cases, and when the primary Fig. 14. Different localizations of cutaneous malignant melanomas circular and semicircular injection of the labeling solution referred to localization of the primary and possible drainage direction of the lymphatic flow Fig. 14. Different localizations of cutaneous malignant melanomas circular and semicircular injection of the labeling solution referred to localization of the primary and possible drainage direction of the lymphatic flow Fig. 15. For malignant melanomas of the dorsal side of the body the same criteria apply as for ventral melanomas....

Examples of Daily Routine

In this section, results of patent blue labeling techniques obtained in individual cases are shown. Figure 26 illustrates the strategy of patent blue labeling with semicircular injection around a scar with multifocal melanoma recurrence. Fig. 27 shows lym-phangiogram using patent blue injected intrader- Fig. 25. Solid sentinel lymph node metastasis in pelvic site in a case with malignant melanoma of the leg (Skip-metastasis ) Fig. 25. Solid sentinel lymph node metastasis in pelvic site in a case with malignant melanoma of the leg (Skip-metastasis ) Fig. 26. Injection of patent blue solution strongly intrader-mally in a case with extensive acrolenticular malignant melanoma (ALM) of the planta pedis. mally on the dorsum pedis after amputation of the second toe in a case with ALM. Figure 28 shows a patent-blue-labeled SLN in the inguinal basin in a patient with malignant melanoma of the foot. A small, easily portable, gamma probe device and the results of labeling a malignant melanoma on...

Method for Detection of Tyrosinase Transcripts in Blood

Removal of small sentinel nodes from the axilla of a further melanoma patient. a The node is intensely Fig. 34 a, b. Removal of small sentinel nodes from the axilla of a further melanoma patient. a The node is intensely - For the sensitivity check, record corresponding values in RT-PCR blood of a healthy person after infecting it with the ME WO melanoma cell line in dilutions of 106 to 102 cells in 10 ml blood. rived from the melanoma cell line MEWo and as a positive control for tyrosinase RT-PCR.

Nonradioactive Imaging in Followup Control Studies

The follow-up after melanoma operations should include active involvement of the patients in the form of self-inspection and palpation (Kroon and Nieweg 2000). Clinically, high-resolution ultrasound is used for prediction of lymph node metastasis in malignant melanoma cases.

Present Opinions on the Actual Status

Like patients with other tumors, such as breast cancer, a relatively high percentage of melanoma patients do not seem to need extensive lymph node dissection. Glass et al. (1998) recently suggested that complete lymph node resection was avoidable in nearly 85 of SLN-negative cases, whereas sentinel node-positive cases might require adjuvant therapy regimens. In spite of high rates of confirmation of SLN in melanoma cases (98 ), Morton (1984, 1992, 1993, 1997) recently stated that he had come to see lymphatic mapping and selective (sentinel) LND as an investigational procedure with unpro-ven therapeutic utility at first glance this opinion seems disappointing and difficult to understand in view of the recent encouraging data. However, these statements clearly show that we need well-planned long-term multicenter studies and Kaplan-Meier evaluations, with emphasis on the different localizations of the primaries and the quite different biological behaviors of the various malignant...

Vitronectin receptors

The expression of vitronectin, another adhesion-mediating glycoprotein, appears to be associated with glioblastomas but it was not detectable in normal glial cells or low-grade gliomas (Gladson and Cheresh, 1991). The progression of cutaneous melanoma appears to be associated with the emergence of the vitronectin receptor, avj 3 integrin. In MeWo human melanoma cells, retinoic acid has been shown to inhibit cell differentiation, increase melanogenesis and induce morphological changes, together with higher levels of vitronectin receptors (Santos et al., 1994). The emergence of the avj 3 vitronectin receptor in melanoma progression has also been described by Danen et al. (1994). These authors investigated a spectrum of cutaneous tissues including common naevocellular naevi, dysplastic naevi, primary cutaneous melanomas and metastatic melanoma. The vitronectin receptor was found to be associated only with primary melanoma and metastasis, but little is known to date regarding the...

Nstaging of Colorectal Cancers

Lymphatic network and different N-positions. In current surgical strategies the lymphatic chain is removed up to the origin of the arterial supply and the retrorectal nodes are also removed. With enhanced knowledge gained with sentinel node labeling more precise clearance can be achieved. Nodes in the N1-2 positions are now routinely resected en bloc with rectosigmoidal parts. For quantitative resection, these parts can be labeled before operation. Anal cancers (squamous cell cancer, malignant melanoma, cloacogenic basal cell carcinoma) can have inguinal medial sentinel nodes

VCAM1 in cancer invasion

The adhesion of human melanomas to endothelial cells occurs by a preferential recognition of VCAM-1 and is mediated by the integrin a4 , VLA-4 receptor (Rice and Bevilacqua, 1989 Martin-Padura et al., 1991). Invasive breast cancers invariably express ICAM-2 but show no detectable expression of ICAM-3 or VCAM-1 (Fox et al., 1995c). ICAM-1 and MUC18 (a melanoma associated antigen, see page 121) have been found in both benign and malignant cutaneous lesions but VCAM-1 occurs in 79 of benign skin naevi and in 62 of primary melanomas < 1.5 mm in depth compared with this, these ICAMs are expressed in only 6 of thicker melanomas. Also only 14 of lymph nodes metastases expressed VCAM-1 (Denton et al., 1992). These authors have suggested therefore that the loss of ICAM-1 may lead to reduced adhesion and may be conducive to greater metastatic spread of melanomas.

The role ofselectins in cancer dissemination

Them to release factor which may in turn induce the expression of selectins by endothelial cells (Hakamori and Anderson, 1994). This would result in greater interaction and adhesion between tumour cells and the endothelial cells, thus facilitating the invasion of the microvasculature. Antibodies raised against E-selectin inhibit the adhesion of breast cancer cells to TNF-stimulated endothelial cells (Tozeren et al., 1995) and also inhibit invasion of endothelial cell layer in vitro (Okada et al., 1994). Interlukin-1 enhances the formation of lung colonies when A375M human melanoma cells are introduced into nude mice by the intravenous route. This increase in experimental metastasis is inhibited by antibodies to the IL-1 receptor (IL-r) and in vitro the IL-r antibodies have been found to inhibit the induction by IL-1 of E-selectin and VCAM-1 expression on endothelial cells (Chiviri etal, 1993). These findings argue strongly in favour of an important role for adhesion molecule in tumour...

Urokinase in cancer invasion and metastasis

The topographical distribution of PAs in tumours has provided good reasons to believe that they assist the tumour in the invasion of neighbouring tissues. It was demonstrated several years ago that the metastatic potential of B16 murine melanomas can be modulated by altering the uPA activity associated with these cells, and the level of uPA activity of B16 cells was reported to be directly related to their ability to form pulmonary deposits (Hearing et al., 1988). An inhibition of the binding of endogenous PA to the PA receptors on the membrane can result in the inhibition of the invasive ability of tumour cells. Kobayashi et al. (1994) synthesised four Hachiya et al. (1995) have provided some experimental evidence in support of a role for the PAs in cancer invasion. These studies were carried out on the human breast cancer cell lines MCF-7 and MDA-MB-231 cells. The MDA cells produce more PA than the MCF-7 cells and, consistent with this, MDA cells have been found to be more invasive...

Other cellular sensors of viral dsRNA

The RNA-binding activity of RIG-I has been mapped to its helicase domain, which has intrinsic ATPase activity. Critically, the RIG-I helicase domain bound the HCV 5' and 3' nontranslated regions 41 . Thus, the interaction of RIG-I with these highly structured regions of the HCV genome represents an affinity of RIG-I for a natural dsRNA-like viral PAMP. Unstructured single-stranded RNA from HCV was not recognised by RIG-I, confirming the specificity of RIG-I for dsRNA. Melanoma differentiation associated gene-5 (Mda-5), a closely related CARD domain containing DExD H box RNA helicase, similarly enhanced IRF-3 activation in response to

The role ofMMPs and TIMPs in cancer invasion and metastasis

A direct correlation between invasive and metastatic ability and the production of MMPs by cancer cells was documented several years ago. Type IV collagenase was shown to be associated with the degradation of basement membrane collagen and with the invasive and metastastic potential of tumour cells (Liotta et al., 1980 Turpeenniemi-Hujanen et al., 1985 Nakajima et al., 1987 Reich et al., 1988 Murphy et al., 1989). Cell transformation produced by exposure to chemical carcinogens has been known to produce alterations of stromelysin-2 gene transcripts (Matrisian et al., 1986a Ostrowski et al., 1988 Matrisian and Bowden, 1990). Transformation of cells with the H-ras oncogene has similarly been shown to result in the secretion of collagen type IV, together with the gain of metastatic properties (Collier et al., 1988). Oncogenic transformation by ras and myc genes often also generates phenotypes with metastatic ability, but this can be inhibited by the introduction of the E1A gene....

Oncogenes and cancer metastasis

Davies BR et al. (1993) transfected rat mammary epithelial cells with p9Ka gene. The p9Ka-transfected cells produced tumours at a higher frequency, with a reduced latent period, and showed a higher incidence of metastasis than untransfected parental lines. We transfected its murine homologue, the 18A2 mtsl gene, placed under the control of the dexamethasone-inducible mammary tumour virus promoter into B16-F10 murine melanoma cells and demonstrated an increase in lung colonisation by the transfectant cells, when the transfected gene is switched on. In these cells alterations were seen in the cytoskeletal organisation of the cells accompanied by the accumulation of a greater number of cells in the S-phase fraction (Parker et al., 1994b). In both these studies the genes were transfected into either continuous cell lines or into transformed cells and it is suggested that these genes may be capable of altering the biological behaviour of cells only when they have undergone cellular...

Reduced Antigen Presentation by Tumor Cells

Because tumor-specific cytotoxic T lymphocytes (CTL) recognize tumor antigen associated with MHC class I molecules expressed on the tumor surface, any alteration in the tumor antigen processing and presentation will greatly affect CTL immunity. In fact, downregulation or complete loss of MHC I molecules have been demonstrated in a wide array of tumors, particularly prostate, colon, lung, and breast cancers (5-12). Disruption or downregulation of antigen processing components, such as TAP (transporters associated with antigen processing) and LMP (components of the proteasome complex) genes have also been observed in several tumor types, including breast, prostate, and renal cancers (13-15). Another tactic tumors exploit is downregulation or alteration of tumor antigens. Several independent research groups described the loss of melanoma-associated antigen either during treatment by adoptive transfer of ex vivo expanded antigen-specific CTL (16) or during immune therapy by tumor...

Prostate Cancer an Overview30

This cancer type has long been mentally connected with old men's diseases, and the level of commitment to research aimed at the development of new diagnostic and therapeutic approaches to it has therefore been relatively low. Now, however, with increasing survival rates even in older age groups, interest in improving its diagnosis and treatment is growing. With new trends in N-stag-ing (see Wawroschek et al. 1999, 2000) in mind, it will be much more difficult to develop convincing strategies for detection of sentinel lymph node(s) (SLN), and it is also more difficult to dissect them, whether in isolation or together with secondary nodes within the pelvis, in the course of prostate cancer treatment than in the procedures used in breast cancer or malignant melanoma treatment.

The ras oncogene in tumorigenesis

Increased ras expression has been described in several human tumours (Slamon et al., 1984 Spandidos and Agnantis, 1984 Viola et al., 1985,1986). Egan et al. (1987) subsequently showed that ras expression level correlated with metastatic potential in 10T1 2 and NIH-3T3 cells. The relationship between ras gene expression and cell transformation has been studied by several groups. The ras proto-oncogene and also the mutant forms of the gene can produce cellular transformation upon transfection (Egan et al., 1989). There are several other gene transfer experiments with ras (Chambers and Ling, 1984 Spandidos and Wilkie, 1984 Bondy et al., 1985 Pozzati et al., 1986 Collard et al., 1987a Chambers et al., 1990), which have generally supported its role in achieving neoplastic transformation. However, transfection of human melanocytes by ras does not produce the morphological and cytogenetic changes which are known to characterise melanoma in vivo (Albino et al., 1992). More recently Davies BR...

Phase i clinical trials in solid tumors

Recently, results of a phase I trial by Aghajanian et al. have been published. In this study, 43 patients in a variety of neoplasms were treated with single-agent bortezomib in doses ranging from 0.13 to 1.56 mg m2 dose. The tumor types included were non-small-cell lung cancer (NSCLC), colon, head and neck, melanoma, ovary, renal, prostate, bladder, cervix, endometrial, esophagus, gastric, and unknown primary. A total of 89 doses were administered, with an average of 2 cycles per patient. The median number of previous chemotherapeutic regimens was four. Reported DLTs were diarrhea and sensory neurotoxicity. Other side effects seen were fatigue, fever, anorexia, nausea, vomiting, rash, pruritus, and headache. There was no dose-limiting hematological toxicity. One partial response was seen in a patient with NSCLC. The maximum tolerated dose (MTD) was established at 1.56 mg m2. Pharmacodynamics studies showed a dose-related inhibition of 20S proteasome activity with increasing dose of...

Familial And Hereditary Pancreatic Cancer Classification

Classification of familial and hereditary varieties of PC embody certain limitations wherein the diagnostic sine qua non is the presence of a cancer-causing germ line mutation, such as the cationic trypsinogen gene29,30 in hereditary pancreatitis.31,32 When PC segregates in a pattern consistent with an autosomal dominant mode of inheritance transmission, in an extended pedigree, it may become extremely informative to the diagnostician. PC may be associated with a variety of hereditary cancer-prone syndromes, as in Peutz-Jeghers syndrome (PJS) wherein the germ line mutation is STK11 LKB1 (Table 25.2) and in the familial atypical multiple mole melanoma (FAMMM) syndrome with the CDKN2A germ line mutation. Both FAMMM33 and PJS34 also harbor striking phenotypic cutaneous signs that, when coupled with known facts about their germ line mutations of note, will significantly aid in diagnosis and management.

Intraoperative and Postoperative Lymph Node Staging in the Treatment of Prostate Cancer

As in staging procedures used for other cancers see Chapter on Melanoma (Chapter 25) , Okegawa et al. (2000) also performed RT-PCR studies of the dissected lymph nodes for staging prostate cancer by preliminary investigations, to detect early lymph node metastases, and to define the indications for prostatectomy more precisely. Positive results were obtained in 11 of stage pT2a and in 25 of stage pT2b cases.

Cancer And The mTor Pathway

Pathways upstream of mTOR are activated in many human cancers. The dual-function phosphatase that negatively regulates PI3K, PTEN, is mutated, silenced, or deleted in a number of tumor types, including glioblastoma, hepatocellular carcinoma, lung carcinoma, melanoma, endometrial carcinomas, and prostate cancer (95-97). The net effect of loss of function is an upregulation or constitutive activation of AKT and, consequently, mTOR signaling. Mutation and activation of AKT2 or gene amplification occurs frequently. Similarly, mutations in TSC proteins, associated with the tuberous sclerosis syndrome, are associated not only with well-vascularized hamartomas (benign lesions) but also with an increased risk of renal cell carcinoma. Mutations in the LKB1 kinase gene are associated with the Peutz-Jehgers cancer prone syndrome. LKB1 kinase positively regulates AMPK, an activator of TSC2 function. Cancer-related changes in pathways downstream of mTOR are also reported. S6K is overexpressed or...

Selective cox2 inhibitors in clinical trials of cancer therapy

In a clinical pilot study (174), the safety and efficacy of oral metronomic low-dose treo-sulfan chemotherapy in combination with the COX-2 inhibitor rofecoxib as a compound with antiangiogenic potential, a therapeutic regimen optimally targeting endothelial cells instead of tumor cells, were assessed in 12 pretreated advanced melanoma patients. Patients received combined daily treosulfan chemotherapy (500 mg) with rofecoxib (25 mg). Endothelial cells were analyzed for proliferation, apoptosis, and cytotoxicity in response to increasing concentrations of treosulfan, either in the absence or presence of COX-2 inhibitor, to determine whether inhibition of COX-2 enhanced the effect of treosulfan on cell function. Simultaneous inhibition of COX-2 significantly increased the extent to which treosulfan suppressed cell proliferation, without inducing cytotoxicity. Only grade 2 hematologic toxicity was observed. An increase in response rates was observed without prolongation in overall...

Undifferentiated Anaplastic Carcinoma and Metastatic Disease

One of the key entities in the differential diagnosis of undifferentiated carcinoma is a metastasis. Metastatic disease involving the thyroid gland can present as diffuse thyroid enlargement, as multiple nodules, or as a solitary nodule, but it is quite uncommon, being detected in less than 0.1 of all thyroid FNAs. The most frequent metastatic tumors to the thyroid include kidney, colorectal, lung, breast, melanoma, lymphoma, and head and neck squamous cell carcinoma. A majority of patients with thyroid metastases have a prior history of cancer, and FNA is an accurate and reliable method for its detection.

Southern tickassociated rash illness 461

Solar warning index A daily warning index forecasting the ultraviolet light radiation exposure for major cities in the United States designed to help people avoid skin cancer. The index is issued daily to forecast the amount of dangerous ultraviolet light that will reach the Earth's surface at noon the next day. The scale is one to 10 in most areas, rising to one to 15 in regions that receive stronger solar radiation. The higher the number, the greater the danger.

Metastasis suppressor genes

A putative metastasis suppressor gene (nm23) has also been described in murine melanoma (Steeg et al., 1988a,b, 1990), reportedly expressed at low levels in the highly metastatic K-1735 melanoma compared with corresponding cell lines with low metastatic ability. Subsequently, two human homologues of the murine nm23 gene - nm23-Hl (Rosengard et al., 1989) and nm23-H2 (Stahl et al., 1991) - have been cloned. These are located on chromosome 17q21.3. There are several studies in the literature which suggest a high expression of nm23 gene or its product the NDP (nucleoside diphosphate) kinase is consistent with low metastatic potential. There are, however, an equal number of studies which do not bear out the inverse relationship between nm.23 and metastatic potential of cancers. metastatic involvement of the lymph nodes (Bevilacqua G et al., 1989). Hennessy et al. (1991) studied a larger series of 145 tumours and have confirmed the inverse relationship between nm23 expression and lymph...

Differential Diagnosis and Pitfalls

Carcinoma as well as melanoma and colon carcinoma (Figure 11.11). In addition to clinical history, the presence of a well-differentiated component of primary thyroid carcinoma within an aspirate of undifferentiated carcinoma can help exclude metastatic disease. Metastatic carcinomas are identified by morphologic clues, such as the columnar shape of metastatic colon carcinoma or the abundant, vacuolated cytoplasm of metastatic clear cell renal cell carcinoma. However, immunocytochemical stains are often useful in confirming this diagnosis (Table 11.1). In a majority of cases, the patient has a clinical history of a nonthyroid cancer. Metastatic melanoma may present with a pleomorphic, dispersed, single cell pattern similar to undif-ferentiated carcinoma, but can usually be distinguished by clinical history and immunocytochemistry. Metastatic poorly differentiated head and neck squamous cell carcinomas can be difficult to distinguish from undifferentiated carcinomas Melanoma (S-100,...

Ancillary Techniques Immunocytochemistry

An immunocytochemical panel on cell block material can also be useful for metastatic tumors of the thyroid because these tumors are negative for thyroglobulin and most are also negative for TTF-1. Because a majority of patients with metastatic disease have a history of malignancy, a focused immunocytochemical panel can be performed that includes S-100, HMB-45, and MART-1 for aspirates suspicious for malignant melanoma, CK20 for colon carcinoma, RCC and CD10 for renal cell carcinoma, and lymphoid markers for lymphoma.

Characteristics of patients admitted to day care disintegration and loss of self

Social isolation also resulted from the stigmatisation of the patient by others, and the growing sense of alienation that ensued. Patients repeatedly complained that other people had ceased both to see them and to treat them as 'normal', particularly when the progression of their disease (or its treatment) affected their physical appearance. Such a phenomenon is highlighted particularly graphically in anecdotes provided by Anne. Anne's bodily appearance had deteriorated significantly after she became unwell. She originally developed a malignant melanoma, and had brain surgery to remove the tumour, followed by chemotherapy. As a consequence, her hair had become very thin and had not grown back fully where the surgery had been performed. The cancer had also spread to her liver, causing mild jaundice. Due to increasing weakness and lethargy, she had to walk with a stick.

Targeting TLRs with specific ligands

Topical imiquimod therapy is used for the treatment of external genital and perianal warts caused by Papilloma virus infection 17 . The FDA has recently approved imiquimod for the treatment of actinic keratoses, and there is mounting evidence that imiquimod is an effective treatment of certain types of skin cancer 47, 48 . Resiquimod is a more potent analogue of imiquimod, and trials are under way to assess its use in treatment of genital herpes and hepatitis C virus 49 .

Agents targeting Tcells

Studies, there is some evidence of the efficacy of anti-IL-2 in the treatment of psoriasis (Owen and Harrison, 2000 Mrowietz et al., 2000 Krueger et al., 2000). Recently, in a patient with severe chronic atopic dermatitis, the successful use of basiliximab, a chimeric anti-IL-2 receptor monoclonal antibody, has been reported (Kagi & Heyer, 2001). DAB389IL-2 is an IL-2 receptor specific fusion protein in which the receptor-binding domain of the diphtheria toxin has been replaced by human IL-2 and the membrane translocating and cytotoxic domains have been retained. Clinical and laboratory investigations have demonstrated a selective destruction of IL-2 receptor expressing T-lymphocytes and DAB389IL-2 has been successfully used in clinical trials for the treatment of cutaneous T-cell lymphomas and psoriasis. The most common side effects observed were flu-like symptoms with severity increasing at higher doses (Bagel et al., 1998 Martin et al., 2001 Eklund and Kuzel, 2005). Experimental...

Arteriosclerosis arcus senilis

Breast cancer metastatic lesion to angle, metastatic lesion to iris, other metastatic lesions (visible mass, redness), symptoms of metastatic lesions (exophthalmus, hyphema). cancer (see Breast Cancer, Colon Cancer, Leukemia, Lung Cancer, Melanoma). Candida albicans (yeast) swelling of lacrimal gland, lid thrush, conjunctivitis, stringy mucus, keratitis, pseudomembranes.

Arsenic in drinking water

When arsenic contaminates drink at levels like that in the beer once brewed in Manchester (see Chapter 5) it will eventually be discovered and dealt with, because it leads to toxic symptoms in those who consume a lot of it. When arsenic contaminates drinking water at similar levels it may go unnoticed for several years because much less water is drunk at any one time. And therein lies its opportunity to inflict widespread damage. The symptoms which appear are generally skin lesions and skin cancer, although there have been claims that other conditions are linked to it such as bladder cancer, kidney cancer, lung cancer, diseases of the nervous system, high blood pressure, and diabetes. The level of arsenic in drinking water is also high in the Lagunera region of Mexico, the Codoban region of Argentina, Inner Mongolia, Taiwan, Finland, the West Bengal region of India, and Bangladesh. Even in the USA there are regions where the natural level of arsenic in drinking water was once high. In...

Pdgfd Pdgfr a and p Pdgfr Transcript Expression in Human Cancer Cell Lines

The mRNA expression profile of PDGFD in cell lines derived from cancers of multiple origins using real-time quantitative RTQ-PCR has been reported (9). The primer probe set utilized was designed to be PDGFD-specific and, as such, did not detect other known PDGF family members. PDGFD was most highly expressed in lung cancer cell lines such as NCI H596, SW900, HOP62, A549, and NCI-UMC-1. Moderate levels of PDGFD were found in ovarian (RL95-2), renal (Caki-2), and in several central nervous system (CNS)-derived astrocytoma glioblastoma and neuroblastoma cell lines such as U251, SNB-19, SNB-75, SK-N-AS, and SW1783. PDGFD was also expressed to a lesser extent in most melanoma cell lines and it was detected in only 2 of 17 colon carcinoma cell lines tested. Autocrine signaling was suggested for 6 of 11 astrocytoma glioblastoma cell lines and 2 of 4 medulloblastoma neuroblastoma cell lines, ovarian carcinoma cells (OVCAR-8), and lung cancer cells (HOP62) based on coexpression of PDGFD mRNA...

Tracers Most Frequently Used for Detection of SLN

Lized apoptotic or necrotic melanoma cells or fragments of such cells these also contain tyrosinase gene material and are also irrelevant in terms of metastatic spread. c Vital cancer cells containing the tyrosinase gene are those in the red-shaded area, and these are the only ones with potential for growth and further spread Fig. 1 a-c. Schematic illustrating possible scenarios that can yield positive RT-PCR reactions for tyrosinase gene and related products. a Yellow-shaded area contains nonneoplastic nevus cells from random areas of a melanoma these contain the tyrosinase gene but are irrelevant as far as metastasis is concerned. b Green-shaded area contains devita- lized apoptotic or necrotic melanoma cells or fragments of such cells these also contain tyrosinase gene material and are also irrelevant in terms of metastatic spread. c Vital cancer cells containing the tyrosinase gene are those in the red-shaded area, and these are the only ones with potential for growth and further...

Genetic Susceptibilities And Resistance To Toxicants

Another obvious genetic aspect of toxicology has to do with the level in skin of melanin, a pigment that makes skin dark. Melanin levels vary widely with genotype. Melanin confers resistance to the effects of solar ultraviolet radiation, which is absorbed by DNA in skin cells, causing damage that in the worst-case results in deadly melanoma skin cancer. Skin melanin is a chromophore (a

Inhibitors of mTOR Clinical Trials

A Phase 3, Three-Arm, Randomized, Open-Label Study of Interferon Alfa Alone, CCI-779 Alone, and the Combination of Interferon Alfa and CCI-779 in First-Line Poor-Prognosis Subjects With Advanced Renal Cell Carcinoma Phase III Randomized Study of Interferon Alfa Versus CCI-779 Versus Interferon Alfa and CCI-779 in Patients With Poor Prognosis Stage IV or Recurrent Renal Cell Carcinoma Phase II Study of CCI-779 in Patients With Previously Treated Mantle Cell Non-Hodgkin's Lymphoma Phase II Randomized Study of CCI-779 in Patients With Extensive-Stage Small Cell Lung Cancer Phase II Study of CCI-779 in Patients With Metastatic Melanoma Phase I II Study of Sirolimus in Patients With Glioblastoma Multiforme Phase I Study of Sirolimus in Pediatric Patients With Relapsed or Refractory Acute Leukemia or Non-Hodgkin's Lymphoma Stage IV melanoma Recurrent melanoma

Method to Improve Security in Sentinel Node Investigation and Timing in Interdisciplinary Cooperation

In the strategies to detect SLNs in different primaries, such as breast cancer, melanoma, lung and gastrointestinal carcinomas and also neuroendocrine tumors and urogenital cancers, exact timing of the various diagnostic and therapeutic procedures has an important role. As a general rule, it is extremely helpful to have an exact histopatho-logical and or cytopathological diagnosis before sentinel lymphadenectomy is performed. In certain tumor entities, such as melanoma, primary biopsies before radioactive SLN labeling cannot be recommended because the procedure entails a high risk of tumor spread in these. However, in breast cancer, oropharygeal cancer, lung cancer, and gastrointestinal tumors, for example confirmation of the cancer diagnosis is the basis for all further labeling and treatment procedures. In a pilot study we also applied the ultrarapid immunohistochemistry method to lymph nodes in patients with colorectal cancer and melanoma, using anti-pancytokeratin antibodies MNF...

Takeoff

At a certain stage, every health scare provokes a critical response towards which there are a number of contributory factors. The backlash usually starts from representatives of a body of medical or scientific opinion which is sceptical of the basis on which the scare has been launched. The challenge to the role of HIV in Aids from the retrovirologist Peter Duesberg and others, together with criticisms of the official line of exaggerating the risk to heterosexuals, provoked some wider questioning of the Aids panic in the early 1990s. In relation to cot death and malignant melanoma, we have already quoted dissident paediatricians and dermatologists. The scares about the Pill and the MMR vaccine were unusual in that most experts in both fields were bemused by the scares from the outset. In the case of the Pill, most family planning authorities did not believe that the reports of increased risk were clinically significant, and in the case of the MMR vaccine, neither gastroenterologists...

Cancer

Bcl-2 (B-cell lymphoma protein 2) targeting by RNAi is a promising example of how apoptosis can be triggered in tumor cells (106,210,214,218,236). Bcl-2 is an important regulator of programmed cell death, and its overexpression has been implicated in the pathogenesis of some lymphomas. Resistance to chemotherapy, at least in vitro, might also be related to Bcl-2 overexpression. In a comparative study, single siRNAs or combinations of siRNAs were successfully transfected into HeLa cells, lung adenocarcinoma cells, hepatoma cells, ovarian carcinoma cells, and melanoma cells with cationic lipid complexes. Downregulation of other proto-oncogenes and apopotosis inhibitors, such as cdk-2, mdm-2, pkc-alpha, tgf-betal, h-Ras, and vegf, effectively suppressed the proliferation of cancer cells to different extents, leading to the conclusion that chemically synthesized and vector-driven siRNAs can inhibit the growth and proliferation of cancer cells (219). hepatoma cells, ovarian carcinoma...

Survivin

Survivin, a smallest member of the IAP family of proteins with a single BIR domain and carboxyl terminal a-helix, is perhaps one of the most prominent proteins associated with a wide variety of cancers and has attracted significant attention in recent years (148). Sur-vivin expression is cell cycle regulated with peak expression in the G2 M-phase and it localizes to various components of mitotic apparatus (149-151). Immunofluorescence and confocal microscopy techniques demonstrated that survivin localizes to kinetochores and centrosomes (microtubule-organizing centers) during prophase, spindle microtubules during metaphase, central spindle midzone during anaphase, and midbodies during late telophase (149,151-153). One ofthe most exciting and attractive features of survivin is its abnormal overexpression in a vast majority of cancers, but not in normal, terminally differentiated tissues (150,152). Survivin is strongly and broadly expressed in embryonic and fetal tissues...

Search for the SLNs

Compared with patients with cutaneous melanomas, those with anal or rectal melanomas (0.14.6 of all anal malignancies 2-3 of all malignant melanomas) have a worse prognosis (Ben Iz-hak et al. 1997 Helmke et al. 2001). The 5-year survival rate is less than 10 , which is the same as in cutaneous melanoma stage IV (Coit 1993). The reason for this unfavorable biological behavior is not fully understood (unfavorable location different genetically based tumor development and growth activity than in UV-induced cutaneous melanomas ) (Balch et al. 1979 Liw et al. 1996). Only one point seems to be clear in contrast to malignant melanomas located higher in the rectal mucosa, melanomas of the anal circle may invade hemorrhoidal veins early and metasta-size directly into the lungs via the azygos veins. In patients with rectal melanomas, in the search for SLNs the same principles can be applied as in the case of rectal cancer (see Chapter 26, pp. 391393). On the basis of new developments,...

Laminin receptors

There have been several attempts recently to examine the possible correlation between laminin receptor expression and tumour invasion and metastasis. Initial work by Dedhar and Saulnier (1990) on chemically transformed human cells demonstrated that, upon transformation, these cells show a greater than 10-fold enhancement of expression of laminin and collagen receptor integrins < x6fiu a2Pi and a, ,, but fibronectin receptor levels remain unchanged. Some studies with human tumours have reported a direct correlation between laminin receptor positivity and lymph node involvement and the presence of distant metastases in gastric and colorectal cancers (Grigioni et al., 1986 Cioce et al., 1991). In human small cell lung carcinoma the expression of the 67 kDa receptor for laminin was related to tumour cell proliferation (Satoh et al., 1992). In contrast, Marques et al. (1990) found an inverse relationship between laminin receptor levels and relapse-free survival in breast cancer. In node...

Medulla

Melanin The dark, protective pigment of the skin. Exposure to sunlight stimulates melanin production. It can be prepared chemically. melanoma, the most serious type of skin cancer, originates in the cells that produce melanin. melanoma A malignant, darkly pigmented mole or tumor of the skin.

Phosphorylate

Photophoresis A process by which a light-sensitive drug called psoralen is used to treat various autoimmune diseases. The drug is injected into the body after an interval blood containing psoralen is removed from the body and exposed to ultraviolet light, thus activating the drug in white blood cells. Finally, the blood is returned to the body by reinfusion. The whole procedure is usually performed on two consecutive days at monthly intervals and takes about four hours per session. Photophoresis is an approved therapy for a skin cancer called cutaneous t-cell lymphoma. In the test tube, it has been shown to work to inhibit viruses that involve RNA and DNA including HIV.

Prospective Views

Even for some neoplasms, such as breast cancer and malignant melanoma, which have already been the subjects of many studies, there are still open problems and definitive answers to important questions are still lacking. Whereas localization of the sentinel node(s) can be determined in a high proportion of cases, it is still not possible to say definitively on the basis of imaging results whether incipient metastatic involvement is present preop-eratively. Some sophisticated approaches that may be successful in the near future are based on PET, iron oxide nanocolloid application, and the use of labeled monoclonal antibodies or their fragments directed at the surface structures of cancer cells. Another problem is the delineation of the lymphatic stream, especially in head and neck tumors and tumors of different categories draining into the nodes of the inguinal region. These problems arise when the primaries are located in different compartments and organ structures and the lymphatics...

Perspectives

Nonreplicating canarypoxvirus (ALVAC) vector expressing both human carcinoem-bryonic antigen (CEA) and the B7-1 costimulatory molecule was used as cancer vaccine to treat patients with advanced CEA-positive adenocarcinomas in two phase I trials (116, 117). Cancer progressions in three out of six patients were stabilized with increased CEA-specific precursor T-cells in vivo. As discussed earlier, in two other recent phase I trials, combination of CTLA-blocking mAb with GM-CSF treatment or tumor antigen vaccines were tested. Administration of CTLA-4 antibody (MDX-CTLA4) induced moderate antitumor response and led to tumor stabilization in several metastatic melanoma and ovarian carcinoma patients while unfavorably inducing significant autoimmunity (66,67). More complicated combined strategies such as using tumor vaccine transfected with recombinant viral vector expressing multiple costimulatory molecules, given along with immune stimulatory cytokines, are currently under clinical trial.

Closing Remarks

As a rule, the search for the sentinel lymph nodes (SLNs) is easiest to handle in malignant melanoma, and compared with other primaries it is most successful in this condition. In keeping with this, the SLN concept is accepted almost all over the world in melanoma treatment. Uren et al. (2000 a, b) stressed at the conference that in 25 of their cases malignant melanomas drained to unexpected locations (see Uren et al. 1998, 1999a,b). Uren and his group studied 2045 patients within 13 years in 148 of these cases (7.2 ) they found so-called interval nodes (see also Uren et al. 2000 a, b) (nodes between the primaries and the SLNs) micrometastases were found in 14 of these nodes. The authors advise surgical removal of such nodes, together with any additional sentinel nodes in the standard basins. In some patients the interval nodes are the only nodes that contain metastases. Dynamic studies can help to distinguish first-echelon lymph nodes from second-echelon nodes, which need not be...

Metastatic Disease

Sibility of metastatic disease are an admixture of benign-appearing macrofollicles and colloid with the malignant cells and a background tumor diathesis. Although infrequent, two of the most difficult thyroid metastases to diagnosis are renal cell carcinoma and breast carcinoma because they can mimic the cytologic features of a follicular neoplasm. Metastatic melanoma can mimic medullary carcinoma or anaplastic carcinoma, and metastatic papillary lung cancer can be easily misinterpreted as papillary thyroid carcinoma. Immunocyto-chemistry for thyroglobulin on smears or cell block material can be very helpful in evaluating such challenging cases. Keep in mind, however, that when evaluating a thyroid malignancy neither mucin nor keratinization can be taken as definitive evidence of an extrathyroid origin for the malignant cells, as both are known to occur in a subset of primary thyroid tumors.

Surgery Cases

Orthopaedics in the previous NZREX in different combinations. Breast Lump (Cancer Fibro Adenoma Etc) Upper GI Tract Bleeding Lower GI Tract Bleeding Surgical Jaundice Cholelithiasis Acute Abdomen Cancer Colon Rectum Colonic Polyps Cancer Stomach Cancer Esophagus Prostatic Hyperplasia Prostate Cancer Thyroid Nodule Thyroid Cancer Renal Stones Cancer Pancreas Swelling In The Perianal Region Skin Cancer

Oncolytic Viruses

VSV is particularly sensitive against the antiviral effects induced by type I interferon (IFN). Many tumors are defective in their response to IFN and thus are not reacting to the growth inhibitory and apoptotic functions of IFN. Although interferon nonresponsive cancer cells may have acquired a survival advantage over their normal counterparts, they may have simultaneously compromised their antiviral response. Indeed, VSV rapidly replicated in and selectively killed a variety of human tumor cell lines even in the presence of doses of interferon that completely protected normal human primary cell cultures. A single intratumoral injection of VSV was effective in reducing the tumor burden of nude mice bearing subcutaneous human melanoma xenografts (Balachandran and Barber 2000 Stojdl et al. 2000). Thus, treatment of IFN nonresponsive tumors with live rhabdoviruses may be a worthwhile strategy. Oncolytic activity of VSV is effective against tumors exhibiting aberrant p53, Ras, or Myc...

Swimmers itch 485

Even with frequent applications of sunscreen, sunbathers may be at risk for developing melanoma (the most serious form of skin cancer). In fact, skin cells can undergo changes not just by exposure to the sun's ultraviolet-B (UV-B) light (rays between 280 and 320 nanometers) but also light with longer wavelengths, including ultravio-let-A (UV-A) light. In the past scientists had linked melanoma to damaged DNA because those who inherit a defect in their ability to repair DNA are more than 1,000 times more likely than others to get this type of cancer. Because DNA absorbs only UV-B energy, many researchers believed that only this type of light caused the damage. Others suspected UV-A light but lacked hard evidence of a link between the light and cancer. While studying light exposure with fish susceptible to the development of melanoma, scientists at Brookhaven National Laboratory in Upton, New York, found that exposure to a wavelength of 365 nanometers (UV-A used in black lights)...

NTs in CP

In PC, the frequent infiltration of PC cells in pancreatic nerves has been noted for a long time. Perineural invasion extending to the extrapancreatic nerve plexus is a histopathologic characteristic in PC that leads to retropan-creatic tumor extension, precludes curative resection, promotes local recurrence, and finally influences the prognosis of the patients negatively.187-189 However, the mechanisms contributing to the invasion of pancreatic nerves and to the spread of cancer cells along nerves are poorly understood. NGF has been suggested to stimulate tumor growth, cancer cell invasion, and the formation of metastases in neuronal and nonneuronal tumors like lung cancer, prostate cancer, carcinoid tumors, medullary thyroid carcinoma, Wilms tumor, melanoma, and glioblastomas.190-196 Therefore, it has been hypothesized that aberrant expression of the NTs or their receptors may contribute to the malignant phenotype of pancreatic ductal adenocarcinoma through autocrine or paracrine...

Arsenic and cancer

The link between arsenic and cancer was first made in 1888 by Jonathan Hutchinson who noted that patients who were being treated for psoriasis with arsenical mixtures developed cancers of the skin. Prolonged exposure caused chronic dermatitis and he suspected this was what eventually developed into skin cancer. We now know that he was more or less correct and the evidence now points to inorganic arsenic as the villain in other words to the compounds based on arsenite (AsO33-), which is arsenic in oxidation state (III), and arsenate (AsO43-), which is oxidation state (V). There is also epidemiological evidence of links between exposure to inorganic arsenic and bladder, lung, and liver cancer. Research by John Ashby and co-workers at the Central Toxicology Laboratory in Cheshire, England, in 1991 showed that arsenite was capable of causing genetic damage in mice, and thereby possibly triggering cancer, but that orpiment was inactive. when Toby G. Rossman of New York University Medical...