A Natural Skin Cancer Cure

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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Use in patients with metastatic melanoma

In an analysis of data from 270 patients with metastatic melanoma in eight clinical trials, high-dose aldesleukin (8.4-9.8 MU kg during each cycle) produced an overall objective response rate of 16 , with 17 complete responses and 26 partial responses (12). Although the response rate was low, there was a durable response for at least 24 months in 10 of 17 complete responders. Adverse effects were primarily the same as those previously described in patients with metastatic renal cell carcinoma, and severe hypotension (64 ) was the most frequent. Six patients died from bacterial sepsis, but none was taking prophylactic antibiotics. In a randomized trial, 102 patients with metastatic melanoma had more frequent treatment-related adverse effects, particularly hematological suppression in patients

R Could fertility treatments cause malignant melanoma

Concern that the drug treatment of female infertility might predispose the user to malignant melanoma was first engendered by a US study published in 1995 (2C). Among women who had used clomiphene citrate for infertility the incidence of melanoma was higher (RR 1.8 95 CI 0.8, 3.5) than among American women in general. However, in a case-cohort study of nearly 4000 infertile women there was a similar increase in the incidence of melanoma among those who had been treated with human chorionic gonadotrophin compared with the rest there was no association with the use of clomiphene. Quite apart from the inherent discrepancy in these findings, several pieces of evidence have confused the debate. In the first place, the cohort of melanoma cases was small barely a handful. In the second place, some earlier papers had suggested that infertility in women might of itself have an association with melanoma. The same impression came from various studies, in which the incidences of cancers in...

Organs and Systems Cardiovascular

The cardiopulmonary toxicity of high-dose intravenous bolus aldesleukin has been analysed in 199 metastatic melanoma or renal cell carcinoma patients without underlying cardiac disease (24). Cardiovascular events occurred within hours after starting infusion, persisted throughout aldesleukin therapy, and normalized within 1-3 days after treatment withdrawal. Hypotension was the most frequent adverse effect (53 of treatment courses) and resolved promptly with vasopressor treatment. Unexpectedly, the response to treatment was significantly better in patients with melanoma who had hypotension. There were cardiac dysrhythmias in 9 of patients they mostly consisted of easily manageable atrial fibrillation or supraventricular tachycardia. Further courses of aldesleu-kin in 11 of these patients produced recurrent dysrhyth-mias in only two, and long-term treatment of dysrhythmias was never required. High-degree atrioven-tricular block and repetitive episodes of ventricular

Psychological psychiatric

The short-term occurrence of depressive symptoms has been investigated by using the Montgomery and Asberg Depression Rating Scale (MADRS) before and after 3 and 5 days of treatment in 48 patients without a previous psychiatric history and treated for renal cell carcinoma or melanoma with aldesleukin alone (n 20), aldesleukin plus interferon alfa-2b (n 6), or interferon alfa-2b alone (n 22) (44). On day 5, patients in the aldesleukin groups had significantly higher MADRS scores, whereas there were no significant changes in the patients who received interferon alfa-2b alone. Eight of 26 patients given aldesleukin and only three of 22 given interferon alfa-2b alone had severe depressive symptoms. Depressive symptoms occurred as early as the second day of aldesleukin treatment and were more severe in the patients who received both cytokines. Early detection of mood changes can be useful in pinpointing patients at risk of subsequent severe neuropsychiatric complications.

Long Term Effects Tumorigenicity

Isolated case reports have described relapses of acute myeloid leukemia or the proliferation of leukemic blasts cells with phenotypic changes in a patient with acute myelocytic leukemia a high percentage of blasts expressed the CD25 antigen in both reports (121,122). A reversible increase in peripheral monoclonal B cell lymphocyte count in a patient with B cell lymphocytic lymphoma and Hodgkin's disease in a woman receiving aldesleukin for metastatic melanoma were also documented in single reports.

Physical description It is an

Pharmaceutical interest Analysis of Sarcandra glabra (Thunb.) Nak. and its medicinal preparations by capillary electrophoresis has been reported by Zheng et a ., 2003. The plant is interesting because it accumulates betulinic acid which might hold potential for the treatment of melanoma, Human Immunodeficiency Virus and bacterial infection. Twenty-six cases of idiopathic thrombo-cytopenic purpura were clinically treated with Sarcandra glabra (Zhang JZ, 1981). Are pentacyclic triterpenes involved in the medicinal uses mentioned above

Family Cucurbitaceae A L de Jussieu 1789 nom conserv the Cucumber family

And melanoma, and are therefore worth exploring further. Cucurbitacin E (ela-terin), the active principle of Ecballium elaterium (L.) A. Rich., annihilates efficiently the survival of prostate carcinoma cells cultured in vitro (IC50 7 nM-50 nM in 2-to 6-day exposures). The cytotoxicity of cucurbitacins is related to their ability to disrupt the F-actin cytoskeleton and thereby the division of cells. Note that Cucurbitaceae are also interesting for the proteins they contain in their roots and seeds. These proteins are abortifacient, antitumoral, ribosome inactivating, anti-HIV and immunomodulatory. It will be interesting to learn whether more intensive future research on Cucurbitaceae will disclose any molecules of chemotherapeutic interest. About 50 Cucurbitaceae plant species are medicinal in the Asia-Pacific, mostly on account of their steroidal and triterpenes contents. The fruits are mainly used to promote urination, soothe inflamed parts, check hemorrhages, counteract poisoning,...

Pharmaceutical interest

Platelet aggregation, B16-F10 melanoma cell adhesion to extracellular matrix and B16-F10 melanoma cell invasion, and inhibits pulmonary metastasis and tumor growth by blocking integrin receptor (Fig. 138) (Kang HY et al, 2001) Integrin receptors are transmembrane protein receptors which monitor platelet adhesion within the vasculature during clotting, apop-tosis, proliferation, migration, spreading, and adhesion of tumor cells.

Overexpression of Protein Kinases

Expression of EGFR and its associated primary ligands epidermal growth factor (EGF) and transforming growth factor a (TGF-a) has been studied in several human malignancies with coexpression of EGFR and EGF observed to have both prognostic significance and a possible role in the pathogenesis of several human cancers. Specifically, overexpression of EGFR and EGF in several tumor types significantly reduces patient prognosis. For example, members of the EGFR kinase family (EGFR, ErbB-2, HER2 neu, ErbB-3, and ErbB-4) are known to be overexpressed in some types of breast tumors. The HER2 neu RTK has been found to be amplified up to 100 times in the tumor cells of approximately 30 of cancer patients with invasive breast disease, and its presence is also associated with poor prognosis. Similarly, overexpression of PDGF and PDGFR has been reported in meningioma, melanoma, and neuroendocrine cancers as well as tumors of the ovary, pancreas, stomach, lung, and prostate. Elevated levels of SRC...

General Information

Malignant diseases hairy cell leukemia, chronic myelogenous leukemia, cutaneous T cell lymphoma, follicular lymphoma, multiple myeloma, Kaposi's sarcoma, diffuse melanoma, renal cell carcinoma, carcinoid tumors Viral diseases condylomata acuminata, chronic active hepatitis B and C

Organs and Systems Hematologic

Single cases of agranulocytosis and Coombs' negative hemolytic anemia have been attributed to twice-weekly interleukin-12 in 28 patients with renal cell cancer or melanoma (2). The patients responded only to cyclophosphamide and or glucocorticoids, and the causative role of interleukin-12 was therefore inconclusive.

General adverse effects

When levodopa is given alone, severe gastrointestinal upsets are very common during the first year of treatment they are much less common when a decarboxylase inhibitor is also given. Postural hypertension is not uncommon. Dyskinesias occur in some patients only after starting therapy. Some mental changes are seen in a high proportion of cases. Psychological dependence occurs in a small subset of patients (1). Effects on the liver, renal function, and hema-tological parameters are usually slight. Individual prescribers and clinics tend to develop their own approaches to obtaining the best balance between effects and adverse reactions a ''drug holiday'' (for example 2 days week) has long been recommended by some workers to reduce the incidence of adverse effects (2), but others have described a neuroleptic malignant syndrome when the administration of the drug was temporarily discontinued (SEDA-17, 147) (3). Allergic type reactions do not seem to occur, but carbidopa has been reported...

Examples of Vaccines in Development

There are too many experimental cancer vaccines in early-stage clinical trials to discuss here in detail. Instead, some examples are listed below to provide insight into the range of clinical studies presently underway. It is important to note that, for vaccines, the promise observed in early-stage clinical trials, which often enroll only a small number of patients, is not always sustained in larger trials. For example, in one recent trial of a melanoma vaccine, the early findings suggested that the vaccine might help prevent melanoma from recurring in patients at high risk from this. However, in a subsequent larger trial that include approximately 750 patients who were at high risk for melanoma recurrence, high-dose interferon proved superior to the vaccine in preventing return of the disease.

Current and Future Trends

It is evident from the number of new cases of skin cancer that there is a need for new sunscreens with better protection. However, the cost and time required for introducing new sunscreen agents through an NDA is prohibitive. Therefore, a large portion of the current research in the field focuses on novel drug delivery systems to prolong the duration of the sunscreening effect, enhance the water resistance (substantivity) of the products, enhance their SPF, or decrease their irritation potential. Another important area is improving the aesthetics of sunscreen products, particularly physical sunscreens. Alternative approaches for photodamage repair and protection is an emerging trend in sun protection. Antioxidants (particularly vitamin E) are common ingredients in commercially available sunscreens. It has been previously shown that topical application of vitamin E inhibits UVR-induced cellular damage, edema, and erythema (317). In the past few years, there has been rising interest in...

Susceptibility Factors

Relative contraindications to PUVA therapy include a history of arsenic intake, previous ionizing radiation, long-term use of cytostatic drugs, skin cancer, cataracts, and severe cardiovascular disease. In patients with photosensitive dermatoses and in patients who are using systemic photosensitizing drugs, PUVA should be administered with caution. The possible long-term adverse effects should be taken into consideration, especially when young patients are candidates for photoche-motherapy. Uncontrolled use of psoralens may lead to life-threatening burns (27).

Miscellaneous Compounds

Rossing MA, Daling JR, Weis NS, Moore DE, Self SG. Risk of cutaneous melanoma in a cohort of infertile women. Melanoma Res 1995 5 123-7. 7. Young P, Purdle D, Jackman L, Molloy D, Green A. A study of infertility treatment and melanoma. Melanoma Res 2001 11 535-41. 10. Glass AG and Hoover RN. The emerging epidemic of melanoma and squamous cell skin cancer. J Am Med Assoc 1989 262 2097-100.

General Aspects of Animal Tumor Models for Pharmacology

Orthotopic models are designed to implant the tumor within the tissues where the primary tumor is located in humans, and unlike most subcutaneous tumor implantation models, metastases frequently arise (28,33-36). Orthotopic tumor implantation places tumor cells in an environment better mimicking the location from which they arose. For example, placing human breast tumor cell lines into the mammary fat pad of nu nu mice consistently improves tumor growth as compared with subcutaneous injection, which did not occur with human colon, renal, and melanoma cells injected in the same location (37). Orthotopic growth of the tumors often results in differential sensitivity of the tumors to chemotherapy, at least with conventional agents. Human small-cell lung cancer growing in the lungs of nude mice is susceptible to cisplatin, but not to mitomycin C (the reverse of the situation with subcutaneously growing tumor), better reflecting the clinical situation (38). Although primary orthotopic...

Improving Plasmid Dnamediated Gene Transfer By Electroporation

Membrane allowing molecules, which otherwise do not gain access inside the cell, to enter cells. A variety of genetic materials were inserted into the cells in vitro by electroporation (62-64). Electrochemotherapy, a cell elec-tropermeabilization approach that facilitates the cellular entry of hydrophilic anticancer agents such as bleomycin, was used to obtain drastically improved antitumor effect (65) in malignant melanoma. The electroporation-mediated in vivo gene transfer had been successfully used for hepatic parenchyma (70, 71), hepatocellular carcinoma (72), skin (73, 74), skeletal muscle (69, 75,761, mouse testes (77), melanoma (65), human primary myoblast (78), glomeruli (79), brain (80), human primary hematopoietic stem cells (81), human esophageal tumor (82), and rat skeletal muscle for correcting anemia of renal failure (83).

Drug administration route

The most interesting and encouraging experience has been obtained using hyperthermic isolated limb perfusion (HILP) of tumor necrosis factor alfa combined with cytostatic drugs (for example melphalan) in melanoma and sarcoma (18). Although systemic toxicity was moderate in this setting, there was still a risk of severe hemodynamic changes, with clinical features of septic shock and a direct nephrotoxic effect of tumor necrosis factor alfa (19,20). A mild neuropathy, marked by transient paresthesia, is also frequent (21). Other rare adverse effects included lung infiltrates, fever, neutropenia, thrombocytopenia, coagulation disorders, transient rise in transaminases and bilirubin, and an increased risk of more severe rhab-domyolysis (SED-13, 1111) (22).

Organs and Systems Nervous system

The effect of clioquinol-metal chelates has been tested on neural crest-derived melanoma cells (6). The effect of clioquinol chelates on cells was further studied by electron microscopy and by a mitochondrial potential-sensitive fluorescent dye. Of the ions tested, only clioquinol-zinc chelate was cytotoxic. This cytotoxicity was extremely rapid, suggesting that its primary effect was on the mitochondria, and electron microscopic analysis showed that the chelate caused mitochondrial damage. This was further confirmed by the observation that the chelate reduced the mitochondrial membrane potential. The phenomenon of clioquinol-mediated toxicity appeared to be specific to zinc and was not seen with other metals tested. Since clioquinol causes increased systemic absorption of zinc, it is likely that clioquinol-zinc chelate was present in appreciable concentrations in patients with SMON and may have been the causative toxin.

PDGF in Malignant Disease

Whereas expression of PDGF ligands is frequently detected in epithelial tumor cells, PDGF receptors are mainly found on mesenchymal cells of the tumor stroma (141,142). The vascular PDGF P-receptor staining pattern observed in human tumors has been attributed to pericytes, as well as to endothe-lial cells (143-145). However, PDGF P-receptor expression was found to co-localize with the pericyte antigen antigen (HMW-MAA), and not with the endothelial cell antigen on Willebrand factor (vWF) (146). In experimental fibrosarcoma, PDGF-B was expressed in endothelial cells whereas vessel-associated mural cells expressed the PDGF P-receptor (147). Pro-angiogenic effects of PDGF-BB, and to some extent of PDGF-AA and -AB, have been demonstrated in the chick chorioallantoic membrane assay (148,149). Interestingly, neovessels induced by PDGF-BB showed extensive branching and recruitment of smooth muscle a-actin expressing mural cells, in contrast to the brush-like vascular formations induced by...

Cumulative index of special reviews Annuals 1625

Polystyrene sulfonates, 25.271 Polyvinylpyrrolidone, storage disease, 22.522 Propolis, allergy, 17.181 Proton pump inhibitors, tumors, 23.383 PUVA, malignant melanoma, 22.166 beta-carotene, 25.454 carotenoids, 25.454 fertility drugs, 24.474 growth hormone, 23.468 omeprazole, 16.423 proton pump inhibitors, 23.383 PUVA, malignant melanoma, 22.166 sex hormones, 22.465 vitamin K, 23.424 Use in pregnancy

Hedera rhombea Miq Bean

Pharmaceutical interest The plant contains the monodesmosidic triter-penoid, saponin a-hederin, which is widespread in the genus Hedera. This saponin protects lymphocytes cultured in vitro against mutation caused by doxorubicin, as well as inhibits the growth of mouse B16 melanoma cells and noncancer mouse 3T3 fibroblasts cultured in vitro (Amara-Mokabe YA et al., 1996 Danloy S et al., 1994). It also modifies the cellular contents and cell membrane of Candida albicans after 24 hours of exposure (Moulin-Traffort J et al., 1998).

Structure Activity Relationships

In vitro cytotoxicity studies with LI210 mouse leukemia cells were then extended to other cell lines, and subnanomolar potencies were also established against P388 mouse leukemia, A549 lung cancer, HT29 colon cancer, MEL-28 melanoma cells, and human tumors explanted from patients. In vivo activity was then evaluated in mouse tumor models and a variety of human tumors xenografted in nude mice. Complete regressions were observed in MEXF989 melanoma, MX-1 breast carcinoma, LXFL529 non-small cell lung carcinoma, and HOC22 ovarian carcinoma xenografts, and partial regressions were seen in renal MRIH121 and PC2 prostate carcinoma xenografts. Interestingly, changes in the C-subunit were seen to modulate the biological activity of both Et 736 and its N-12 demethylated analog Et 722, relative to Et 743, suggesting that this part of the molecule plays an important role in cytotoxicity. For example, Et 722 and Et 736 displayed a higher level of activity in vivo against P388 leukemia in mice,...

Mechanisms of Action of Sunscreens

Little is known regarding the quantitative ability of sunscreens to prevent UVR-induced adverse effects other than sunburn. For example, there is no information on the threshold or dose-response for UVR-induced immunosuppression and DNA damage (237), but there is strong evidence that regular use of Sunscreens reduces the incidence of precancerous lesions. A large population study in Australia proved the effectiveness of sunscreens in reducing the incidence of solar keratosis (291). Solar keratosis is a known precursor for squa-mous cell carcinoma and an established risk factor for basal cell carcinoma and melanoma. 8.2.4 Sun Protection Factor. Sunscreens were originally developed to prevent sunburn and minimize erythema (224). The efficacy of sunscreen products is rated by their sun protection factor (SPF), which is defined as the ratio of UV energy required to produce a minimal erythemal dose (MED) on protected skin to the UV energy required to produce MED on unprotected skin. It is...

Mammalian Target of Rapamycin mTOR Inhibitors

Preclinical studies have demonstrated efficacy of rapamycin analogs and the parent compound in multiple tumor types. In the National Cancer Institute (NCI) 60 tumor cell line panel, both rapamycin (NSC 226080) and CCI-779 (NSC 683864) demonstrated growth inhibitory activity against a broad spectrum of tumors with a subset of leukemia, lung, brain, prostate, breast, as well as renal and melanoma tumor cell lines being inhibited at low nanomolar concentrations (http dtp.nci.nih.gov ). Early animal studies at the NCI and at Ayerst Research Laboratories demonstrated modest growth inhibitory properties of rapamycin in murine tumor models of B16 melanoma, P388 lymphocytic leukemia, EM ependymo-blastoma, CD8F1 breast carcinoma, Colon 38, CX-1, and 11 A colon cancer models (Eng et al. 1984). Subsequently published studies have documented significant tumor growth inhibition with rapamycin or CCI-779 treatment of DAOY medulloblastoma, U251 or SF295 glioma, PC-3, DU-145, LAPC4, or LAPC9 prostate...

Anticancer Drugs Acting On Apoptotic Signalling Pathways

Cancer Drugs Pathways

Ultimate sensitivity or resistance of cells to a number of apoptotic stimuli (hypoxia, radiation, oxidants, Ca2+ overload, ceramide, and growth factor neurotrophin deprivation). BCL-2 proteins are over-expressed in a large number of cancers, including 90-100 of hormone-refractory prostate cancers, 90 of malignant melanomas, 80-90 of estrogen-positive breast cancer, and 50 of non-Hodgkin's lymphoma, among others. Antisense oligonucleotides that reduce the excpression of anti-apoptotic BCL-2 genes are currently undergoing clinical trials.12 Thus, oblimersen sodium is an 18-mer oligonucleotide that, in combination with dacarbazine, has been shown to lead to stabilized or improved disease in 57 malignant melanoma patients, while the standard malignant melanoma therapy leads only to 1-20 positive response.128 Other anti-cancer drugs have been associated with oblimersen for a number of other indications, including chronic lymphocytic leukaemia and acute myelogenous leukaemia. Some...

Chronic Effects of UVR

Skin cancer is the most serious adverse effect of UVR. There are three common types of skin cancer melanoma, basal cell carcinoma (BSC), and squamous cell carcinoma (SCC). BSC and SCC are known collectively as non-melanoma skin cancer (NMSC). BSC is the most common skin cancer, but it has the lowest mortality rate (269). Malignant melanoma is the most serious type of skin cancer. Although the link between skin cancer and exposure to sunlight is very strong, the susceptibility of individuals to the carcinogenic effect of UV radiation varies depending on several factors including skin pigmentation, age, sex, and phenotype. Particularly, factors such as fair skin, blue eyes, red or fair hair, and inability to tan have been linked to increased risk of NMSC in several studies (270-276). Both chronic human studies and animal studies proved the causal relationship between cumulative UVR exposure and skin cancer (277), particularly non-melanoma skin cancer (NMSC). The...

Topoisomerase Inhibition Enhances Radiation In Vivo and In Vitro

Preclinical data show that both Topo-I and Topo-II inhibitory agents can act as radiosensitizers (Kim et al. 1992 Kirichenko et al. 1997 Takahashi et al. 2003). Topo-I inhibition has enhanced radiosensitity through in vitro experiments with camptothecin derivatives in V-79 Chinese hamster cells (Marples et al. 1996), MCF-7 breast cancer cells (Chen et al. 1997), and human U1-Mel melanoma cells (Boothman et al. 1992). This effect has been seen in further in vivo experiments in murine MCa-4 mammary tumors (Kirichenko et al. 1997) and fibrosarcoma (Kim et al. 1992). Topo-II inhibition has been seen to enhance radiosensitivity in vitro in V-79 fibroblasts (Giocanti et al. 1993 Haddock et al. 1995 Marples et al. 1996) and human breast cancer cells (Iwata and Kanematsu 1999). Human clinical studies followed these encouraging preclinical results.

Controlled Release Microparticles

Importantly, tumor cells express proteins that are foreign to the host because of their genetic mutations. Thus, they are vulnerable to an immune response of the human body. That is why efforts have been made to delivery immune response stimulating substances locally and in a controlled manner to brain tumors. For instance, interleukin-2 (IL-2)-loaded, gelatin- and chondroitin-6-sulfate-based microparticles have been proposed by Hanes et al. (71). Bioactive IL-2 was found to be released over at least 2 weeks in vitro in vivo significant concentrations could be detected up to 3 weeks. The efficiency of these microparticles to protect mice challenged intracranially with B16-F10 melanoma cells is illustrated in Figure 15A (the melanoma cell challenge and microparticle injection were simultaneous). Clearly, the IL-2-loaded microparticles were able to protect the mice, whereas placebo systems were not. Interestingly, even autologous B16-F10 cells engineered to secrete IL-2 were not as...

Cellular studies with DACA

In subcutaneous colon 38 adenocarcinomas in BDFl mice, DACA had activity comparable to that of 5-fluorouracil and superior to that of doxorubicin, cyclophosphamide, and asulacrine. Mitoxantrone, amsacrine, etoposide, teniposide, and daunorubicin showed minimal activity in this assay. DACA also showed significant activity against NZM3 human melanoma cell xenografts in athymic mice 69 . Studies with 3H-labeled DACA showed that the kinetics of both uptake and efflux were very rapid, with equilibrium being reached within seconds of drug addition to cultures of Lewis lung carcinoma, P388 leukemia, and multidrug resistant P DACT cells. DACA had an uptake ratio of 550 in Lewis lung cells. It was proposed that DACA's known high affinity for membranes contributes to the rapid uptake and efflux that allows it to overcome transport-mediated multidrug resistance 70 . DACA and a series of acridine-substituted analogs showed broadly equivalent potencies in a wild-type human Jurkat leukemia line and...

Spectral Characteristics Of Sunlight And Artificial Light Sources

Therefore, it has been suggested that the interval from 290 to 320 nm be adopted as a practical definition of the UVB (Frederick, 1993), but this has not received official sanction. The purine and pyrimidine bases of DNA and the aromatic amino acids are the major cellular absorbers of UVB. Although the intensity of UVB in the solar UVR reaching the Earth's surface is relatively small (Thorington, 1985), it is abundantly clear that UVB is the most important band because it causes sunburn, skin cancer, and other biological effects and is responsible for the direct photoreac-tion of many chemicals in natural sunlight (Epstein, 1989). The UVB intensity at a particular latitude varies greatly with time of day and the season of the year, as the variation of the solar azimuthal angle varies the path length of the Sun's rays through the stratospheric ozone layer.

Cytotoxic drugs

In a phase III trial in 190 patients with metastatic melanoma, sequential chemotherapy with dacarbazine, cisplatin, and vinblastine plus interferon alfa and alde-sleukin modestly increased the response rates and produced considerably more frequent and severe adverse effects than chemotherapy alone (128). In particular, severe episodes of anemia and thrombocytopenia that required blood or platelet transfusions were 2-6 times more frequent in the chemotherapy group.

Phototherapy

Carcinogenicity The PUVA Follow up Study has prospectively evaluated 1380 patients who started using PUVA for psoriasis in 1975 and 1976. They recently reported an increased risk of melanoma in PUVA-treated patients (n 822), beginning 15 years after first exposure (65C). Incidence rates during 1996-9 were 10-fold higher than those expected from incidence data in the general population (data available only for 1992-6). There was an nonsignificant trend towards a higher incidence of melanoma in patients who had received more courses of PUVA (over 200). This risk should be weighed against the substantial efficacy of PUVA therapy in severe psoriasis.

Selenium

Effects Selenium detoxifies heavy metals (such as arsenic, cadmium, lead, and mercury), alcohol, peroxidized fats, and some drugs reportedly slows down some of the aging processes, and inhibits the oxidation that leads to hardening of the tissues, keeping them more elastic. One study found that 200 micrograms day can protect against lung, colon, and prostate cancer, but appears to have no effect on skin cancer, though it may help eradicate moles and brown spots. Other studies have correlated high levels of selenium with a low incidence of leukemia and cancers of the rectum, pancreas, breast, ovary, bladder, skin, stomach, esophagus, liver, and gastrointestinal tract. Studies have shown that, when given in doses around 220 micrograms day, it improves moods and thinking, even in those who are not deficient, indicating most people do not get enough.

Anticancer Effects

Menon et al. reported curcumin-induced inhibition of B16F10 melanoma lung metastasis in mice 62 . Oral administration of curcumin at concentrations of 200nmol kg body weight reduced the number of lung tumor nodules by 80 . The life span of the animals treated with curcumin was increased by 143.85 62 . Curcumin treatment (10 g ml) significantly inhibited the invasion of B16F10 melanoma cells by inhibition of matrix metalloproteinases (MMP), thereby inhibiting lung metastasis. Odot et al. showed that curcumin was cytotoxic to B16-R melanoma cells resistant to doxorubicin 66 . Treatment with a prophylactic immune preparation of soluble proteins from B16-R cells, in combination with curcumin, resulted in substantial inhibition of growth of B16-R melanoma and a significant increase in the median survival time of the animals.

Tyrosine

Because it might increase blood pressure in a small percentage of susceptible individuals, those with high blood pressure should take it only under the guidance of a physician. Those taking MAO-inhibiting antidepressants should not take tyrosine supplements, as they can have adverse effects on blood pressure, as well as other serious consequences. Tyrosine should not be taken by anyone with melanoma. It could also trigger headaches in those already susceptible.

Modern uses

Production, regulation of interactions between tumor and stromal cells, modulation of tumor immunity, modulation of adhesion molecules, and inhibition of cyclooxygenase type 2 (7,8). The malignancies in which thalidomide has been used include multiple myeloma, glioblastoma multiforme, renal cell carcinoma, and malignant melanoma.

Direct injection

Of gene delivery by DNA-liposomes was also analyzed in pigs and rabbits in vivo. There were no clinically significant immunopathol-ogy in major organs such as the brain, heart, lung, liver, kidney, spleen, and skeletal muscles. To induce local tumor immunity in patients with stage IV melanoma, Nabel et al. (187) injected pDNA encoding MHC class I antigen complexed with cationic lipid directly into the cutaneous tumor nodules. Treated lesions exhibited presence of T-cells, followed by an enhanced reactivity of tumor infiltrating lymphocytes. As a result, local inhibition of tumor followed by complete diminution of tumor was observed in some of the treated patients. Mohr et al. (188) have shown that direct liposome-pDNA complex injection to intrahepatic hepatocellular carcinoma produced by human HCC cells seemed far superior to systemic administration for gene therapy for localized intrahepatic tumors, because the direct administration to tumors left the surrounding normal hepatic cells...

Sunscreens

Most people are at least occasionally exposed to the sun for extended periods of time, either as a result of their lifestyle and recreational activities or as a normal part of their jobs. The main adverse effects to exposure to the sun-' light are sunburn, photoaging, and skin cancer. Skin cancer is the most common type of cancer, accounting for almost 40 of all malignancies (221).According to the American Cancer Society, overl.3 million people will be diagnosed with nonmelanoma skin cancer in the United States each year, and 53,600 people will be diagnosed with skin melanoma (221, 222). Approximately 9600 people will die from various types of skin cancer, with the majority dying from malignant melanoma. Unprotected long-term exposure to sunlight is blamed for about 90 of skin cancer cases. Ultraviolet radiation (UVR) is believed to be responsible for most of the harmful effects of sunlight. The UVB band, which ranges from 290 to 320 nm, is the most potent radiation in producing...

Phenylalanine

Precautions It should not be taken by those with pigmented malignant melanoma cancer, phenylketonuria (or PKU, a genetic metabolic disorder), psychosis, or Wilson's disease (otherwise known as hepatolenticular degeneration, a rare hereditary disease chiefly characterized by a toxic buildup of copper in the organs and tissues of the body). Likewise, those taking MAO-inhibitor drugs should avoid phenylalanine, as should pregnant or lactating women. Early studies seem to indicate that phenylalanine and tyrosine encourage the growth of melanomas (or skin cancers, one of the deadliest forms of cancer), and doctors usually have patients restrict their intake of these amino acids. Those with high blood pressure should only take it under the guidance of a health professional.

Chemicals

Occupation-associated cancer is not just a feature of recent times. In 1775, Sir Percival Pott noted the high frequency of scrotal skin cancer in young chimney sweeps. Poor hygiene in this population meant that tarry deposits from coal fires were in contact with the sensitive skin of the scrotum for long periods of time. More recently, vinyl chloride (Structure 1.1) used by workers in the plastics industry has been associated with angiosarcoma of the liver, and furniture industry workers have been prone to nasopharyngeal malignancies induced by the inhalation of small particles carrying organic compounds that arise from leather and wood polishing processes. Many of these organic carcinogens exert their effects by covalently modifying DNA (either before or after metabolism).

Triazenes

Dacarbazine (DTIC) is employed in combination therapy for the treatment of metastatic malignant melanoma and Hodgkin's disease. This compound was initially designed as an antimetabolite since it is an analog of 5-aminoimidazole-4-carbox-amide, an intermediate in purine biosynthesis. However, its cytotoxic activity is due to the generation during its metabolism of methyldiazonium, which methylates DNA.53 Methyldiazonium has a half-life of about 0.4 s in aqueous solution, which is sufficient to allow it to reach its target. A mechanism for this process is summarized in Fig. 5.29, where activation of dacarbazine by metabolic oxidative demethylation to 5.46 MTIC) was proved by the isolation of labeled formaldehyde and 5-aminoimidazole-4-carboxamide (AIC) when dacar-bazine was labeled with 14C at one of the methyl groups. Intermediate 5.46 is then transformed by tautomerism into 5.47, a diazonium precursor. The major methyla-tion reaction takes place at the guanine N-7 atom, and is...

Begonia species

Pharmaceutical interest The counter-irritant property of the Begonia species is attributed to the crystals of oxalic acid which abound in the plant. Crystals of oxalic acid are sharp and irritate the mucosa and the epidermis. Begonia species have attracted a great deal of interest on account of cucur-bitacins (see p.). An extract of Begonia plejeba displays a characteristic pattern of differential cytotoxicity profile predominantly toward renal and brain tumors and melanoma in the NCI human disease-oriented screening panel. Furtherfractionations resulted in the characterization of cucur-bitacin B (Fuller RW etal., 1994).

Cytotoxic Agents

In vitro studies using human cancer cell lines reveal that tetrahydrocannabinol does not potentiate or antagonise the cytotoxic actions of actinomycin D, adriamycin, methotrexate, cisplatin, nitrogen mustard or velban (Harbell and DiBella, 1982). The cancer cell lines used were for human breast, uterus, ovary and melanoma.