Natural Cures For Prostate Cancer

The 21 Day Prostate Fix

21 Day Prostate Fix written by Radu Belasco is a healthier alternative to drugs and invasive medical procedures. Radu Belasco is an early prostate problem sufferer, with a family history of prostate pain, problems and cancer. Using a unique system of natural remedies, he fixed his prostate problems and wrote them in his smash hit eBook The 21 Day Prostate Fix. It is about miraculous herbs and fruits from all over the world. These unique foods have the power to cure your prostates inflammation in record time and shrink it to a healthier size. Also, you will learn how to concoct the miracle elixir that will not just cleanse your prostate, but also burn body fat. Aside from these, youll get topnotch information on nutrition, so you can keep your prostate healthy and your sex drive at its peak. Plus, youll learn other health conditions that might be contributing to your prostate issues, so you can also remedy them and get your body in its best shape ever.

The 21 Day Prostate Fix Overview

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Prostate Cancer In Western Countries

The incidence of prostate cancer in the U.S. and certain Western countries has risen sharply during the past decade. In U.S. men, between 1987 and 1992, prostate cancer incidence rate increased 85 , followed by a decline of 29 between 1992 and 1995, and then increasing again by 2.3 per year beginning in 1995. Recent prostate cancer incidence increased by 3.0 per year among white men and by 2.3 per year among black men.96 Prostate cancer mortality in the U.S. stopped increasing in 1991, and decreased an average of 4.4 annually from 1994 through 1997.97 Declines in prostate cancer mortality might reflect improvements in treatment and longer survival due to prostate specific antigen (PSA)-related early detection.98

Example of Prostate Cancer Screening

The American Cancer Society estimated that, in 2004, 230,110 men would be diagnosed with prostate cancer 29,900 men would die of this disease.20 The age-adjusted prostate cancer incidence in nine Surveillance, Epidemiology, and End Results (SEER) registries between 1996 and 2000 was about 173 per 100,000 men.21 The mortality during that period was about 33 per 100,000 men. The probability at birth of being diagnosed with prostate cancer by age 80 is about 14 the probability at birth of dying of this disease by age 80 is about 1.26 .22 The difference between prostate cancer incidence and mortality is one of largest for any cancer this difference increased greatly after PSA screening became widespread. This is a strong indication that at least some prostate cancers now detected by screening would never become clinically important. The incidence of prostate cancer increased dramatically after the beginning of PSA screening in the late 1980s and then stabilized in the later 1990s....

Prostate Specific Membrane Antigen

Although prostate cancer has received much attention because of the success of diagnostic biomarkers, the success of RIT for the disease has lagged behind. Studies of 131I -murine CC49 did not show objective response (87) in patients with prostate cancer. Subsequent attempts to increase antigen expression using interferon pretreatment also did not result in objective treatment responses (88). Fourteen patients received seven doses of interferon, followed by 2775 MBq m2 (75 mCi m2) 131I-CC49 treatment. Although antigen (TAG-72) expression seemed to be upregulated, evidenced by increased tumor localization, no significant response was achieved. The immunogenicity of the murine protein remained a problem. Prostate-specific membrane antigen (PSMA) is a nonsecreted internalizing antigen, and therefore an excellent target for RIT. Humanized mAb J591 targets the external domain of PSMA (89). Phase 1 studies of 90Y and 177Lu labeled humanized J591 have been completed, and have shown an...

Prostate Cancer Screening

Prostate cancer is a challenge in clinical care because 1 in every 6 men will be diagnosed with it in his lifetime but only 1 in 29 will die of it.11 Therefore, prostate cancer will not affect the life expectancy of many men diagnosed with the disease, even if they were never screened. Because it is impossible for an individual to know the effect of the diagnosis on his life expectancy, many men diagnosed with prostate cancer overestimate the benefit they gain from screening.1,142 A smaller proportion (48 ) of men who went untreated for prostate cancer were satisfied with their therapy compared with men treated with androgen (63 ), radiation (70 ), or radical prostatectomy (59 ).143 Although individuals may be satisfied with therapy, its effect has implications for morbidity and quality of life for those who are told they have the disease.1,144 In 2004, an estimated 230,110 new cases of prostate cancer were diagnosed in the United States and 29,900 men will have died of the...

Staphylococcus Saprophytics In Prostate

Bacterial cystitis is common in women, promoted by a relatively short urethra, use of a diaphragm, and sexual intercourse. Middle-aged men are prone to infection because enlargement of the prostate gland partially obstructs their urethra. Placement of a bladder catheter commonly results in infection

Case Study V Finasteride and Prostate Cancer

The Prostate Cancer Prevention Trial (PCPT) is a doubleblind chemoprevention trial of prostate cancer in 18,882 non-symptomatic, healthy men who were randomized to 5 mg day of finasteride or placebo for 7 years.79 Finasteride is an inhibitor of ( 90 of) 5-a-reductase, an enzyme involved in hormone metabolism of testosterone to dihydrotestosterone (DHT), the most active androgen in the prostate. Intraprosta-tic DHT is thought to be a major stimulus for prostate cancer cell growth, as evidenced by in vitro and in vivo studies.80,81 Thus, reducing DHT by inhibiting 5-a-reductase activity is a plausible strategy for preventing prostate cancer development. There was significant preclinical and clinical experience with finasteride before the initiation of the PCPT. Numerous animal model studies suggested finasteride had prostate cancer preventive activity in several rats,82 and finasteride had been approved and was in wide clinical use as treatment for benign prostatic hyperplasia.83 The...

Evolving Technologies In Imaging Of The Prostate Gland

The emergence of disease-targeted ablative therapies, such as cryosurgery, bra-chytherapy, high-intensity focused ultrasound, and intensity-modulated radiation therapy, has necessitated accurate pretreatment tumor localization and staging. These techniques also require a means by which to assess posttreatment tumor response. Although standard endorectal coil MRI provides excellent anatomic detail of the prostate, it is limited by decreased specificity with regards to tumor detection and localization. As has been seen, a large number of false-positive diagnoses can occur due to hemorrhage, prostatitis, and therapeutic effects, causing low signal intensity on T2-weighted imaging (116,120). A number of emerging approaches have shown promise in improving upon these limitations in MRI specificity. Magnetic resonance spectroscopy (MRS) provides metabolic information from multiple contiguous voxels within the prostate and has been shown to improve tumor localization (121), prediction of...

Mr Imaging Of Prostate Cancer Technique

MRI evaluation of the prostate requires optimal technique using phased array pelvic surface coils. Endo-rectal coils (ERCs) used either alone or in combination with pelvic phased array coils have been shown to improve staging accuracy by better depiction of pseudocapsular penetration. ERCs have the drawbacks of causing patient discomfort and therefore possible movement artifact, and producing near field artifact although the latest scanners have software to overcome this problem. Thin section T2-weighted turbo spin echo sequences are essential for differentiating normal internal zonal prostatic anatomy and pathology. The prostate and seminal vesicles must be covered in their entirety. Off-axis imaging, parallel to the prostate, can be helpful in evaluating extra-prostatic extension. Magnetic resonance spectroscopy is currently under evaluation in prostate cancer. Initial findings indicate that there is increase in the ratio of choline plus creatine to citrate in prostate tumour...

Prostate

The prostate is a pyramidal structure approximately 3.0-4.5 cm long composed of glandular and fibromuscular tissue. It is enclosed by a 2.0-3.0mm band of concentrically orientated fibromuscular stromal tissue, inseparable from the prostate gland that forms a false capsule. This is deficient at the apex allowing a route of extracapsular tumour spread. A fibrous prostatic sheath that is continuous with the puboprostatic ligaments surrounds the capsule. Between the prostatic capsule and sheath is the prostatic venous plexus. The prostate is broader superiorly with a base closely related to bladder neck. Inferiorly, the apex rests on the urogenital diaphragm in contact with fascia of the urethral sphincter and deep perineal muscles. Its anterior surface is separated from the symphysis pubis by loose areolar tissue in the retropubic space, which contains the puboprostatic ligament and part of the prostatic venous plexus. Infero-laterally the prostate rests on the levator ani muscles....

Prostate Cancer

Specifically, in prostate cancer contrast-enhanced CT and conventional MRI have a low sensitivity (40 ), which is improved to 100 on a patient level and to 90 on a nodal level (Harisinghani et al., 2003). When using ferumoxtran-10-enhanced MRI, patients may be reliably selected for prostatectomy or radiotherapy without the need for invasive and costly procedures, such as open and

Prostate Cancers

Rubin, Chinnaiyan, and colleagues at the University of Michigan have published extensive studies of molecular profiles of prostate cancer (Dhanasekaran et al., 2001). Using methods similar to those of Alizadeh et al., they classified carefully dissected prostate tissue specimens into normal adjacent tissue, benign prostatic hypertrophy, localized prostate cancer, and metastatic prostate cancer. Two control or comparison groups were utilized first ,a commercial pool of normal prostates from men with no cancers, and second, normal adjacent prostate from men with prostate cancers. Each type of specimen was differentiated by the microarray clustering method, combined with arrays of prostate tissue from many patients. Many of the genes with substantial up- or downregulation fell into well-recognized categories of functions, including transcription factors, cell adhesion, p rotease an ti-protease, phosphatase kinase, free radical scavenger, and inflammation immunity genes (and protein...

Prostate Carcinoma

Prostate cancer is second only to lung cancer as the leading cause of cancer-related deaths in men. Histological evidence of prostate cancer is directly related to increasing age. The incidence of occult disease has been shown to be as high as 30 in patients over the age of 50 years and over 70 in patients over the age of 80 years. The presence or absence of metastases primarily determines the prognosis of prostate cancer. The highest incidence of prostate metastases is found in bone, and lesions in the spine are felt to precede those in other areas of the body, such as the lung or liver. Kuban et al. found that spinal cord compression occurs in approximately 7 of all men with prostate cancer. Many argue for a backward venous spread of tumor to the spine. This is felt to account for the gradual decrease in spine involvement from the lumbar to the cervical spine (from 97 to 38 ). New onset of back pain in elderly men should be carefully evaluated for evidence of metastatic prostate...

Prostate Problems

Prostate problems include inflammation, enlargement, or cancer of the prostate gland which surrounds the urethra, the tube through which urine flows. An inflammation of the gland is called pros-titis resulting in pain during urination and ejaculation, frequent urination and possibly low back pain. The causes include infection, too much or too little ejaculation, jarring exercises such as horseback and bicycle riding, and food irritants like caffeine, alcohol, tobacco, and red pepper. Drinking plenty of water is important in keeping a flow of urine and in preventing dehydration, which can be in effect even though not thirsty, and is a condition that is very stressful for the prostate. Enlargement of the prostate, called benign prostatic hyperplasia (BPH), usually occurs in men over 50 and causes difficulty in urination because enlargement squeezes the urethra it surrounds and interferes with urine flow. BPH is due to an excess of testosterone in the gland. Symptoms are night and...

Evidence Linking Diet To Cancer

Chapter 1 describes the worldwide epidemiology of cancer. The estimated incidence rates for various cancers worldwide in 2002 found lung, colon rectum, and stomach to be the most common cancers in both men and women, as well as prostate and liver cancer in men, and breast and cervical cancer in women.3 The pattern of cancer distribution based on incidence and mortality rates varies geographically. In general, the predominant cancers in economically developing countries contrast to those in the industrially developed world. For Asia, Africa, and Latin America, there is a relatively high rate of cancer of the upper aerodi-gestive tract, stomach, liver, and cervix, whereas in Europe and North America there is a relatively high rate of cancer of the colon rectum, breast, and prostate. These Western cancers have a strong environmental component, with diet and lifestyle factors particularly important, while in developing countries, infections with such agents as viral hepatitis and...

Pathogenesis Of Cancer Acquired Capabilities

Research over the past 25 years has produced a deeper understanding of the molecular, biochemical, and cellular changes that occur as cells are transformed from normal cells to malignant cancers. The multiple genetic defects leading to cancer cell production can result from exposure to environmental, dietary, and lifestyle factors, as well as infectious agents. The multistep, multistage process of gradual carcinogenetic changes in the biological behavior of a clonogenic population of cells is illustrated schematically in Figure 2.1.20As indicated, this progression of cellular changes may span years or decades.21 Among the epithelial cancers, such as colorectal, breast, prostate, lung, pancreas, and others, a diffuse genomic instability after exposure to damaging agents (inflammation, toxins, etc.), and increased epithelial hyperplasia is the initiating act. A single basal cell may develop one or more mutations of a number of critical oncogenic or tumor suppressor genes, allowing...

Enhancement of Apoptosis

Tumor growth is thought to require activation of telomerase, making it a target for chemoprevention.39 Retinoids induce senescence in malignant and pre-malignant human and rat breast carcinoma cells, in vitro and in vivo.40 Retinoids also synergize with vitamin D in inhibiting telomerase. The combination of vitamin D3 and 9-cis-retinoic acid inhibited telomerase activity through direct interaction of the heterodimer of the vitamin D3 receptor and retinoid X receptor (RXR) in prostate cancer cells.41 Other nutritional factors, including EGCG and curcumin, also regulate telomerase activity. In nude mice models bearing both telomerase-dependent and -independent xenograft tumors cloned from a single human cancer progeny, only the telomerase-dependent tumors responded to prolonged oral administration of EGCG.42 Furthermore, curcumin inhibits telomerase activity in MCF-7 breast cancer cells via downregulation of hTERT expression.43

Inhibition of Tissue Invasion and Metastasis

As outlined above, green tea and EGCG are effective antiangiogenic agents. They also are found to inhibit genes related to adhesion, invasion, and metastasis, including urokinase, MMP-2, and MMP-9.4748 Interestingly, when black tea and a soy phytochemical concentrate were combined in a mouse model of orthotopic androgen-sensitive human prostate cancer, the combination resulted in a syner-gistic interaction to inhibit prostate tumorigenicity, final tumor weight, and metastases to lymph nodes in vivo.49

Increased Antioxidant Capacity and Genomic Stability

Prostaglandins and other members of the eicosanoid pathway are thought to induce carcinogenesis through action on nuclear transcription sites and downstream gene products important in the control of cell proliferation. Eicosanoids are locally acting hormone-like compounds derived predominantly from arachi-donic acid in tissue cells and tumor-infiltrating leukocytes.56 The most well-known eicosanoids, prostaglandins, are produced by the action of the cyclooxygenases (COX), but the lipoxygenase group of enzymes produce the leukotrienes and hydroperoxyeicosatetraenoic acids, which also have important proinflammatory effects.57 Substantial evidence from animal studies and human epidemiological and clinical trials show that nonsteroidal anti-inflammatory drugs (NSAIDs), which are inhibitors of COX, are associated with reduced risk of a number of cancers, including those of the colon-rectum, esophagus, stomach, pancreas, breast, lung, prostate, bladder, brain, and cervix.57

Nutrients Vitamin D In Colon Cancer

Vitamin D is an example of a nutrient that exhibits many of the mechanisms described above in inhibiting cancer development, particularly in inhibition of proliferation, induction of differentiation, activation of apoptosis, and blocking initiation. Vitamin D and its analogs have been investigated for some time for their anticancer properties in a number of cancers, including colorectal, prostate, breast, and leukemia.9 The classical role of the most bioactive form of vitamin D, 1a,25-dihydroxyvitamin D3 (1a,25(OH)2D3), is to regulate calcium absorption in the intestine, maintain mineral homeostasis in the kidney, and regulate bone remodeling. This function can lead to toxic hypercalcemia when exogenous 1a,25(OH)2D3 is administered in therapeutic doses therefore, a number of pharmaceutical analogs have been developed that retain their anticancer properties with minimal effects on circulating calcium.71 Many tissues other than those involved with mineral metabolism have specific...

Mechanism Of Vitamin A Action

Despite the expectation of exquisite specificity fostered by the various discrete combinations of RAR and RXR isoforms, these receptors exhibit a great deal of apparent functional redundancy and or ability to compensate for loss of another. In gene knockout experiments, more than one receptor can perform the same function in vivo, although this may represent an artifact of the knockouts and demonstrate what can happen, not necessarily what does occur.11 Nevertheless, receptor ablation has provided enormous insight into receptor function. Deletion of the RARa gene results in postnatal lethality within 24 h RARa-null mice represent only 3 of the population by 1 to 2 months of age. Of these, 60 have webbed digits on both fore and hind limbs. A few mice survive 4 to 5 months, but no males are fertile, and all have severe degeneration of the testis germinal epithelium. RARP-null mice have locomotor defects, reminiscent of Parkinson's disease, but are fertile with normal longevity....

Vitamin D And The Cancer Connection

The role of vitamin D in cancer prevention perhaps has been known for more than 50 years. Although excessive sun exposure has been documented to increase the risk of skin cancer, research conducted starting as early as 1936 has proved this population of patients with skin cancer to be at a lower risk for other types of cancer. Sun exposure has been correlated with decreased incidence of certain types of cancer such as cancers of the prostate, breast, and colon. Individuals residing in the U.S., which lies in the northern latitudes, have a risk for cancer incidence which is two to three times higher than the risk of cancer incidence of people living in sunnier, equatorial parts of the world.40 This intriguing observation by Apperly40 was followed by several epidemiological studies that demonstrated an inverse relationship between 25-(OH)D3 levels and cancer risk and

Epidemiological Studies

Lower selenium levels were found in serum collected from American subjects 1 to 5 years prior to diagnosis of cancer as compared to those who remained cancer free during this time.20 This association was strongest for gastrointestinal and prostatic cancers. Evidence that low serum selenium is a prediagnostic indicator of higher cancer risk was subsequently shown in studies conducted in Finland21 and Japan.22 In further case-control studies, low serum or plasma selenium were found to be associated with increased risk of thyroid cancer,23 malignant oral cavity lesions,24 prostate cancer,25 esophageal and gastric cancers,26 cervical cancer mortality rates,27 and colorectal adenomas.28 A decade-long prospective study of selenium status and cancer incidences indicated that initial plasma selenium concentration was inversely related to subsequent risks of both nonmelanoma skin cancer and colonic adenomatous polyps.29 Patients with plasma selenium levels less than 128 ng ml (the average...

Cancer And Phytoestrogens

Phytoestrogens have been considered to have a preventive effect against various cancers. The consumption of phytoestrogen-rich foods such as soy, a source of isoflavones, and whole grain products, which contain lignans, is thought to play a role in the prevention of breast, prostate, and colon cancer. Other cancers also may be influenced by the presence of dietary phytoestrogens, but the studies in humans are comparatively few. 15.3.2 Prostate Cancer Two studies have been carried out to examine the effect of soy consumption with and without high levels of isoflavones to determine whether over a period of months prostate specific antigen (PSA) levels could be reduced. 31,32 No effect was observed in serum PSA levels either in the men with high starting levels of PSA or in those with low levels.33 More hopeful data were obtained by Kumar et al.33 They assessed the effect of a soy beverage containing 60 mg genistein vs. the control in 12-week studies in 76 men with prostate cancer and...

Cyclooxygenase Activity And Expression

Protein kinase D (PKD) is a family of three isozymes, PKD1-3, that have in common with PKC a conserved DAG TPA binding-site. However, PKD is not activated by DAG TPA, and is instead activated downstream of PKC by phosphorylation at activation-loop residues serine 744 748. PKD is involved in the transmission of PKC-dependent cell proliferative and survival signals.46 Interestingly, cell survival signaling by PKD may involve suppression of the JNK signaling pathway through PKD-JNK complex formation.47 A comparison of the inhibitory effects of resveratrol against purified PKD-1 (formerly called PKC j) vs. the PKC isozymes analyzed in Reference 45 determined that the polyphenol is somewhat more potent against PKD-1, and markedly so with respect to the kinase autophosphorylation reaction.48 This suggested that resveratrol inhibition of PKC might be reinforced in cells by coordinate inhibition of the PKC effector PKD. A recent analysis of growth-suppressive effects of resveratrol in the...

Inhibitory Mechanisms Of Cla On The Stages Of Carcinogenesis

CLA has been shown to modulate the protein kinase C (PKC) abundance activity in membranes from prostate cancer cells (LNCaP) to produce an apoptotic profile with increased PKC-8, -a, and -Z and a decreased PKC-i,73 but Ip and colleagues60 did not observe any changes in the isoforms in mammary tissue for rats in the study. On the other hand, CLA downregulated ErbB3 signaling, the phosphoinositide 3-kinase, and the Akt pathway in human colon cell line,71 and inhibited the expression of extracellular-mitogen-activated protein kinase phosphatase-1 protein in a rodent model of forestomach neoplasia.74 These

Cla Modulation Of Lipid Metabolism And Gene Expression

CLA may modulate lipid metabolism in part by a third mechanism dependent on the activation of the nuclear hormone receptors, peroxisome proliferator-activated receptors (PPARs).1 It has been shown that CLA moderates affinity for binding to and activating PPARy,8687 and modulates transcription of genes responsive to PPARy in adipose tissue in vivo15 and in vitro.85 PPARy is found in extrahepatic tissues such as adipose, prostate, colon, and mammary gland, and is a required factor in adipose tissue differentiation.88 In addition to evidence showing that CLA may induce PPARy-responsive genes in vivo, CLA may increase the level of PPARy itself.89 Because activators of PPARy are protective against cancers arising in the mammary gland, colon, and prostate,18 90 it is possible that some of the molecular mechanisms of action of CLA on carcino-genesis are mediated by PPARy. The ability of PPARy to mediate effects of CLA is through increased levels of PPARy protein89 or through activation of...

Mechanisms Of Cancer Prevention By Exogenous Sphingolipids

In Min mice that were fed the control AIN 76A diet alone and developed a large number of intestinal tumors, we found a high expression of cytosolic P-catenin in intestinal sections as determined by fluorescence immunohisto-chemistry. Min mice that were fed sphingolipid supplements and that had developed only a small number of tumors displayed mostly membrane-associated P-catenin. This is the localization found in the genetic background mice, suggesting a reversal of aberrant P-catenin expression by sphingolipids.72 The same effect of exogenous sphingolipids could be seen in vitro in human colon cancer cell lines that also carry an APC mutation, and stably overexpress cytosolic P-catenin. Both sphingosine and ceramides in nontoxic concentrations reduced cytosolic and nuclear P-catenin.72 This is a critical step in cancer prevention because removal of cytosolic and nuclear P-catenin has been shown to reverse the transformed properties of cells92 and suggests that the reversal of...

Prevalence Of Overweight And Obesity

26.4.5 Prostate Cancer The evidence of a link between prostate cancer incidence and obesity is insufficient 13 cohort studies reported a small or modest positive association37,43,44,154-163 and 12 other cohort studies, 6 of which were included in the three reviews, did not.33-35,41,46,69,164-166 For case-control studies, only 4 studies observed a modest increase in prostate cancer risk associated with BMI47,167-169 and others found no association with BMI 33-35 one study found an inverse association with BMI.170 Among the studies reporting a positive association with obesity, the association is stronger for, or restricted to, fatal or more aggressive tumors or is stronger with mortality than with incidence.156-158,160,162 One meta-analysis of 6 studies of incident cases produced a modest relative risk of 1.01 (95 confidence interval 1.00 to 1.02) per unit of increase in BMI.35 Two studies suggested that the larger effect found in men aged 50 to 59 years than in other age groups154 and...

A25OH2D3 Analogs In The Treatment Of Cancer

There is extensive literature available on the use of deltanoids as anticancer agents. With VDR being expressed in more than 30 nonclassical target tissues and many cancer-related cells, the deltanoids have been shown to inhibit cell proliferation in many tumor cell types in culture. Initial findings using hemato-poietic-derived tumor cells showed inhibition of cell proliferation. Further evidence indicated the versatile use of deltanoids across several nonhematopoietic malignancies including transformed breast, prostate, skin, lung, colon, ovary, pancreas cells, as well as neuroblastoma and melanoma cells.6675-7980 Although much of the mechanistic data gathered in vitro point toward cell cycle arrest, differentiation, and induction of apoptosis, the proposed mechanism of action of deltanoids is likely to differ based on the type of tumor model examined. No unified hypothesis has emerged so far on the basis for the anticancer effects of 1a,25-(OH)2D3and its analogs. In addition, as...

Increased Response to Antigrowth Signals and Induction of Differentiation

Of specific phenotypic traits characteristic of the mature cell type. As cells move toward the differentiated state, the rate of proliferation slows, so that fully differentiated cells do not proliferate, or at least do so at a very slow rate. Cancer cells are poorly differentiated yet retain the potential to differentiate into more mature cells. Thus, induction of differentiation (or redifferentiation) is a cancer prevention and treatment strategy, although its effectiveness is lower for relatively slow-growing cancers like breast or prostate than for faster ones such as leukemia. Several nuclear acting nutrients, including vitamins D and A, have been the most comprehensively studied as differentiation-promoting agents, although a number of other compounds have been shown to induce cellular markers of differentiation in vitro, including a variety of flavonoids, the n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and resveratrol.36

Molecular Mechanisms Of Action Of Isoflavones

Nuclear factor-KB (NF-kB) pathway plays important roles in the control of cell growth, differentiation, apoptosis, inflammation, stress response, and many other physiological processes in cellular signaling. Because of its importance in cancer development and progression, NF-kB has been described as a major culprit and a therapeutic target in cancer.84-88 To investigate whether genistein regulates cell growth and apoptosis through NF-kB pathway, our laboratory examined NF-kB DNA-binding activity in genistein treated PC3 and LNCaP prostate cancer cells by electrophoretic mobility shift assay (EMSA).89 The results showed that genistein significantly inhibited NF-kB DNA-binding activity in both cell lines and abrogated the induction of NF-kB DNA-binding activity stimulated by either H2O2 or TNF-a. These results demonstrated that genistein inhibits NF-kB DNA-binding activity in both nonstimulated and stimulated conditions.89 Similar results have been reported by other investigators,...

Mechanisms Of Cancer Reduction By Selenium

The findings that antitumorigenic amounts of selenium (1.5 mg kg or above) reduced tissue lipid peroxidation potential only slightly93 or not at all94 suggest that those effects are independent of the function of the GPXs. Therefore, at present it is probable that antitumorigenic effects of high levels of selenium involve mechanisms unrelated to the activities of GPXs. The 15 kDa (sep 15) selenoprotein has been suggested to be involved in the reduction of tumors. The sep 15 selenoprotein is localized on chromosome 1p31, a genetic locus commonly mutated or deleted in human cancers.95 96 The sep 15 selenoprotein genes are manifested at highest levels in prostate, liver, kidney, testis, and brain in humans and mice these levels of this selenoprotein are reduced substantially in malignant prostate cell line and in hepatocarcinoma. Because there is loss of heterozygosity at the sep 15 locus in certain human tumor types, it was suggested that this selenoprotein may be involved in cancer...

Resveratrolinduced Cancer Cell Apoptosis

Resveratrol induces apoptosis of diverse leukemia and epithelial cancer cell lines. Leukemia cells subject to resveratrol-induced apoptosis include early myeloid (K562, KCL22, HL60), monocytic (U937, THP1), B-lymphoid (WSU-CLL), and T-lymphoid (Jurkat).141920 Human carcinoma cell lines that apoptose in response to resveratrol span human breast cancer (MCF-7), prostate cancer (LNCaP, DU145), colorectal cancer (SW480), pancreatic cancer (PANC-1, AsPC-1), and esophageal cancer (Bic-1, Seg-1, HCE7).1421-25 Resveratrol induces apoptosis of MCF-7 cells by a p53-dependent mechanism. Induction of MCF-7 cell apoptosis by resveratrol was accompanied by induction of p53 phosphorylation and acetylation, post-translational modifications implicated in stabilization of p53 and consequent increased p53 abundance. Pifithrin-a, a selective p53 inhibitor, blocked resveratrol-induced p53 post-trans-lational modification and apoptosis of the MCF-7 cells.24 MCF-7 cells express wild-type p53.26 Resveratrol...

Selenium Metabolism In Tissue Culture Models

In other research, selenium was shown to significantly downregulate the expression of prostate-specific antigen transcript and protein within hours in the androgen-responsive cells.81 Selenium also suppressed the binding of androgen receptor to the androgen responsive element site, as shown by electrophoretic mobility shift assay of the androgen receptor-androgen responsive element complex. In further work from this laboratory, exposure to sub-apoptotic concentration of methylseleninic acid specifically inhibited prostate specific antigen expression in the androgen-responsive LNCaP prostate cancer cell model.82 Interestingly, selenite and Semet lacked this inhibitory effect. Work from another laboratory indicated that the use of the recombinant enzyme methioninase, methylselenol-generating chemiluminescence by superoxide was shown to be catalytically produced from Semet, selenoethionine but not from methionine or SeMYCS. It was concluded that methylselenol can be produced from other...

Introduction Cancer Epidemiology

On the other hand, cancer may be characterized at the same time by a high incidence rate and a quite long natural history, having a large prevalence in the population under consideration (e.g., prostate cancer). In defining the relationship between incidence rate and prevalence of a disease of interest, many factors, not only the disease mean duration, should be taken into account, since, in the same population, subgroups of individuals might deeply differ in terms of measures of disease occurrence on the basis of parameters such as gender, age, ethnicity, education, income, social class, disability, geographic location.1

Vitamin A And Cancer In Experimental Animals

Lasnitski28 developed organ culture of mouse prostate and demonstrated with it that RA and synthetic retinoids could inhibit or reverse MC-induced neoplastic changes. This, of course, generated a great deal of interest in the potential use of retinoids to prevent and or treat prostate cancer. A subsequent study demonstrated that fenretinide, a retinoid active against carcinogen-induced breast cancer, caused a 76 decrease in prostate cancer in rats treated with the carcinogen MNU and testosterone.29 In addition, RA and other retinoids at higher doses inhibited the growth of established prostate cancer cell lines and induced apoptosis.30 Perhaps not surprisingly, given previous experience with retinoids and with established cell lines, retinoid effects on cultured prostate cancer cells are retinoid-and cell line-dependent. RA, for example, is effective with LNCaP cells, WPEI-NB11, and WEI-NB14 cells, but not with DU-145 or PC-3 cells. Fenretinide, however, was more effective than RA in...

Demographic Factors

Prostate cancer is a disease that typically strikes older men. It is usually diagnosed in very few people aged younger than 50 years (< 0.1 of all patients). The mean age of patients with this disorder is 72 to 74 years, and about 85 of patients are diagnosed after age 65.99 There are striking international differences, as much as 90-fold, in prostate cancer incidence and mortality rates between highly developed countries and less-developed countries. The lowest rates are found in Asia, especially among Chinese men in Tianjin, China (1.9 per 100,000 per year), and the highest are in North America and Scandinavia, especially in African American men in the U.S. (137 per 100,000 per year).100 Results of migrant studies appear to show some real shift in incidence toward the new host country, providing evidence that these international and racial differences in prostate cancer incidence are not based entirely on genetic predisposition or differences in health care and cancer...

Endocrine Factors

Human prostate carcinomas are often androgen sensitive and react to hormonal therapy by temporary remission, followed by relapse to an androgen-insensitive state. These well-established features of prostate cancer strongly suggest that steroid hormones, particularly androgens, play a major role in human prostatic carcinogenesis, but the precise mechanisms by which androgens affect this process are unknown. In addition, the possible involvement of estrogenic hormones is not entirely clear.107 Estrogens induce mitosis of both normal and malignant prostatic epithelial cells in many species, including humans.108,109 An important metabolic pathway of the estrogens is the formation of hydroxylated estrogens. Muti et al.,110 in a case-control study on urinary estrogen metabolites and prostate cancer risk, showed a protective effect of the metabolic pathway favoring 2-hydroxylation over 16-hydroxylation on risk of prostate cancer. Two distinct lines of epidemiologic and basic science research...

Conclusion

There is accumulating evidence that the vitamin D3 VDR axis is important in multiple cancers. Epidemiological studies on the association of the occurrence and outcome of cancers with serum 1a,25-(OH)2D3 levels or vitamin D3 status are consistent with vitamin D insufficiency being a factor in the development of certain malignancies, primarily prostate, breast, and colon cancer. Given the direct link between 1a,25-(OH)2D3 and its nutritional precursor vitamin D3, new frontiers in current research include investigating the physiological role of extrarenal 1-hydroxylases in cells prone to cancer. There is also current emphasis on manipulating 1a,25-(OH)2D3 levels in patients with cancer as an alternative means of exploiting the anticancer properties of 1a,25-(OH)2D3. Clinical trials95-97 are under way examining the safety and efficacy of weekly high dose of 1a,25-(OH)2D3 in the presence or absence of docetaxel, carboplatin, or dexamethasone in patients with androgen-independent prostate...

Days of Treatment

Although the mitochondrial pathway is central to the apoptogenic action of VE analogs, there are other pathways that may play an important role in the effects of the agents. Kline's group reported regulation of the AP-1 and mitogen-activated protein kinase extracellular-regulated protein kinase pathways as additional signaling routes for apoptosis induced by a-TOS.82-86 Some but not all papers suggested that a-TOS induces apoptosis by interfering with the tumor necrosis factor-P (TGF-P) signaling, compromising the expression of pro-survival factors.87-89 These findings may be related to the effect of the VE analog on transition of cell through the cell cycle. Several reports showed that the agent caused arrest in G1 or G2. Turley et al.90 presented evidence that a-TOS inhibited proliferation of breast cancer cells by interfering with the cyclin A-E2F restriction point machinery. Yeh's group reported that a-TOS inhibited proliferation of cancer cells by modulation of the cell cycle...

Conclusions

Lifestyle factors play a significant role both in the promotion of most cancers and in the protection from these cancers. Diet and nutrition are perhaps among the most significant of these lifestyle factors. We have reviewed the effects on cancer prevention of one specific dietary component, the phytosterols. Dietary phytosterols, or plant sterols, have been shown by the majority of the experimental data to be protective against specific cancers, including colorectal, breast, prostate, lung, and stomach carcinomas. This protective role of dietary phytosterols appears to be independent on their effects on cholesterol absorption and is supported by the results from large epidemiological studies, as well as from animal studies and laboratory experimentation with in vitro tissue culture models. Epidemiological studies have included case-control studies, cohort studies, and randomized placebo-controlled trials. Although one cohort study showed no association between phytosterol intake and...

Rat Models

Adlercreutz20 in a review of the literature concluded that there was no convincing evidence to suggest that soy or isoflavone consumption during adult life was protective against breast cancer for women living in Western countries. However, moderate lifelong intake of soy products or isoflavone supplements may have beneficial effects on the cardiovascular system and bone metabolism, but negative effects on the breast could not be completely excluded, although equally positive findings are also present in the literature.20 The epidemiological data indicate that in the context of a healthy lifestyle soy consumption does not preclude low levels of breast cancer incidence. Furthermore, affluence and Westernization, in the absence of increased soy consumption seem to be the major drivers for increases in breast cancer. For other cancers such as prostate, and possibly colon and stomach, soy may well turn out to have beneficial effects. The alarming rise in colon cancer in Japan at a time of...

Hormone Activity

The majority of circulating hormones are bound to sex hormone-binding globulin (SHBG also known as plasma sex steroid-binding protein, SBP). Free hormones, i.e., hormones not bound to SHBG, are available to migrate into cells and initiate hormonal responses. It is theorized that if there is a decrease in plasma concentrations of SHBG, a decrease in the SHBG rate of metabolism, or an increase in hormone production, there is an associated increase in risk of developing hormone-dependent cancers. Phytoestrogens are known to increase plasma levels of SHBG, thus decreasing the plasma concentration of free estrogen and testosterone. The reduced availability of free androgens and estrogens to the target cells would therefore reduce the risk of hormone-dependent cancers.83 This relationship is based on evidence that high levels of circulating estrogen and low levels of SHBG appear to be associated with increased risk of hormone-dependent cancers involving estrogen such as breast and ovarian...

Inflammation

There are two known COX isoforms, referred to as COX-1 and COX-2. COX-1 is commonly regarded as a housekeeping enzyme and is expressed in most cells, performing protective functions. COX-2 is highly inducible by inflammatory stimuli and is associated with deleterious effects when expressed at high levels. COX-2 is present in low concentrations under basal conditions however, under inflammatory conditions it is subject to induction in the presence of mitogens and cytokines resulting in overexpression. The overexpression of COX-2 has been reported in neoplasms of the colorectum, prostate, gastric tissue, liver, lung, breast, and skin, thereby suggesting its role in tumorigenesis. COX-2 is therefore recognized as a potential enzyme to target for preventative interventions against cancer.90,91

In Vitro Studies

Inhibition of cell growth and modulation of the cell cycle have been reported for allyl ITC (AITC) (10 M), benzyl ITC (BITC) (5 M), and PEITC (2.5 M) in HeLa cells,20 and similar effects have been reported for SF (15 M) in HT-29 cells. Similar results have been reported in other cell lines including human leukemia HL60 and prostate cancer cell lines LNCaP and DU-145 (reviewed by Reference 21). A comprehensive study of the effect of ITCs on the growth of different cancer cells reported that AITC, BITC, and PEITC were able to inhibit cell growth.22 The results of some recent studies are summarized in Table 21.2. While some studies have demonstrated similar cytotoxicity in cancer and normal cells,23,25 others have reported differences. A synthetic ITC 4-(methylthio) butyl ITC has shown selective action against human leukemia cells, and almost no effect on lymphocytes.26 AITC also has an inhibitory effect in the human prostate cancer cell lines, while normal cell line PrEC remained...

Replicative Senescence

Thus, specifically targeting each of the barriers of immortalization by introduction of the SV40 Early Region, which encodes the large T oncoprotein, in combination with the hTERT gene into normal human fibroblasts and kidney cells suffice for immortalization (48,49). Since the SV40 Early Region also encodes for small t onco-protein, subsequent transduction with oncogenic RAS results in the ability to develop tumors in immunocompromised mice, hence transformation. Additional studies have revealed this combination of genetic alterations to be sufficient to transform multiple cell types, including cells of mammary (50), lung (51), prostate, ovarian, mesothelial (52), endothelial, and neuroectodermal (53) origin. Thus, it is necessary to understand the roles of these basic genetic elements involved in transformation in regards to the critical pathways that they effect. For example, the large T oncoprotein may functionally inactivate the p53 and RB pathways, but the inactivation of these...

Applied Shortread Genomic Sequencing

Importantly, Oudes et al. (2005) undertook comparison of two high-throughput methods frequently used to profile transcriptomes - DNA hybridization analysis by Affymetrix GeneChip Array and MPSS. Each method has certain strengths and weaknesses and this study undertook a direct comparison between both the analysis systems. The transcriptome of two lineage-related prostate cancer cell lines, LNCaP and C4-2, was analyzed to identify genes associated with prostate cancer progression. All together, the LNCaP and C4-2 cell lines were found to express 10,308 genes. Figure 7 illustrates the data acquisition by the two methods. Both technologies detected genes that the other Fig. 7. Comparison of Affymetrix and MPSS gene expression signals for the analysis of two prostate cancer cell lines, LNCaP and C4-2. Unique gene expression signals were found with the two analysis systems. In cell line LNCaP, 3180 genes were only detected by Affymetrix array and 1169 genes were only detected by MPSS....

Clinicopathological Features Of Brca1related Breast Cancer

Cytogenetic analyses of clinical samples also shed some intriguing light on the genetic instability of BRCA1 -associated tumor and the surrounding stroma in the same microenvironment. In a recent report, Weber et al. found that, on a total-genome scale, LOH in BRCA1 mutation carriers was similar between the breast tumor cells and the associated stroma (106). Further, LOH at the BRCA1 locus of several patients was only observed in the breast tumor stroma (106). These observations suggest a role for stromal BRCA1 in suppressing tumor progression that may be independent of LOH at the BRCA1 locus in the epithelium. The potential tumor-promoting effect of BRCA1 loss in the stromal compartment may be similar to that of stromal p53 mutations recently demonstrated in breast and prostate tumors (107, 108). Lastly, it has been recently reported that malignant human breast cancer epithelial cells can fuse with and transform mouse stroma (109). Therefore, it will be of interest to see whether the...

Adenosquamous Carcinoma

Adenosquamous carcinoma (ASC) is a rare malignant epithelial tumour characterised by the presence of both SCC and adenocarcinoma, and aggressive behaviour. It occurs in various sites, such as the pancreas 68 , lung 262 , uterine cervix 132 , prostate 310 , stomach 44 and breast 305 . In the head and neck, it was first reported by Gerughty et al. 131 who described a series of 10 patients with nasal, oral and laryngeal ASC.

Image Guided Radiation Therapy

In the past, large target margins and treatment volume were used to accommodate the positioning error and organ motion associated with radiation therapy treatment. Because highly conformai radiation therapy can now be delivered, accurate target determinations (i.e., CTV, GTV, PTV) have become a very important issue. Various image modalities can now guide highly conformal therapy such as IMRT by locating the target before daily fractionated radiation therapy. Ultrasound imaging is often used for internal target positioning, mostly for localized prostate cancers.45 However, because the ultrasound cannot penetrate air or bone, its use is limited to certain anatomic sites. Additionally, ultrasound, similar to CT, does not provide any functional information on tumor biology. Traditionally, the determination of tumor volumes for radiation treatment planning, as well as determining responses following radiation therapy, has been limited to imaging techniques such as CT and magnetic resonance...

Neuropilin in Pathological Angiogenesis

Many tumor cell types express NRP1 and NRP2 and bind VEGF165. NRPs are the only VEGF receptors expressed by these tumor cells, so that any VEGF 165 activity must be mediated by NRPs. In several clinical studies, NRP1 and NRP2 expression was correlated with increased aggressiveness, malignancy, and or hypervascularity. For example, NRP1 was upregulated in primary sporadic prostate tumors at different clinical stages. The correlation between NRP1 overexpression with advanced disease suggested that NRP1 overexpression might be a marker of aggressiveness. The function of NRP1 in tumor cells has been analyzed directly by expressing NRP1 in tumor cells under the control of a tetracycline-inducible promoter. Concomitant with increased NRP1 expression in response to tetracycline, tumor cell migration and VEGF165 binding was increased. However, induction of NRP1 did not affect tumor cell proliferation. When rats injected with rat prostate carcinoma cells were fed tetracycline, NRP1 synthesis...

P450s Identified Only by Catalytic Activities 3P 5aDiol Hydroxylase

Interestingly, one of the major constitutive forms of P450 in the brain is not listed in either Table 1 or 2 because its cDNA has not yet been cloned. This P450 that is known to metabolize steroids with 3p, 5a configuration, is abundantly expressed in prostate (48), brain (18), and pituitary gland (49), but is absent in liver and kidney (18). It is distributed evenly throughout the brain, is not sexually differentiated, and is not regulated by the adrenal or gonads. It does not metabolize steroids such as testosterone, corticos-terone, aldosterone or estradiol. It catalyses the 6a and 7a hydroxylation of 5a-andros-tane-3p,17 -diol (3p, 5a-diol) and its catalytic activity in the brain (300 nmol triols formed h g tissue) is much higher than that of any other microsomal steroid hydroxylase measured in the brain to date. In the prostate, it is the 3p- and not the 3a, 5a-diol that represents the major pathway for the formation of more polar metabolites and thus the elimination of...

Genetic Variation and Pharmacology

Diseases with complex patterns of inheritance, and where genetic variation comes into play after an exposure, account for the vast majority of the disease burden in the population. Examples of both the strategies and the problems involved in identifying genes with roles in these complex diseases can be appreciated from reading recent papers describing efforts to identify genes associated with risk for prostate cancer (Nwosu et al., 2001), type 2 diabetes, (Cox et al., 2001), and asthma (Xu et al., 2001). Cox (2001) outlines the challenges in moving from the identification of a chromosomal region associated with an elevated risk of disease via linkage mapping to the definitive estimate of risk associated with specific variants in specific genes. It should be noted that common refers to the relatively high incidence of the disease in the population and complex describes the pattern of inheritance of the genetic factors neither term relates to the clinical characteristics of a disease....

Diagnosis screening and staging

Elevated levels of PSA (> 4 ng ml-1) occur in about 53 of men with intracapsular microscopic and 77 of men with intracapsular macroscopic prostatic cancer, but can also occur in 30-50 of men with benign prostatic hypertrophy (BPH). A combination of PSA and digital rectal examination, followed by prostatic ultrasound in patients with abnormal findings, is commonly used for screening in US but is not recommended in the UK. As yet, there is no definite evidence of survival benefit from screen detection of early prostate cancer. About 40 of patients with PSA levels of 4.0-9.9 ng ml-1 at screening will already have tumour spread outside the prostate. The ratio of free to total PSA is being used to improve diagnostic specificity more of the PSA is protein-bound in patients with prostate cancer compared with BPH. The ratio of free to total PSA is low (about 10 ) in prostate cancer compared to > 16 in BPH and prostatitis. Bone or lymph node metastases are usually, but not always,...

Prognosismonitoring responserecurrence detection

A high pre-treatment PSA is associated with a poor prognosis. PSA levels fall rapidly to undetectable levels after complete removal of a tumour by radical prostatectomy. The rate of fall is slower and the nadir higher after successful radiotherapy or endocrine therapy. A serial rise in PSA frequently precedes other evidence of disease progression in the patient with a past history of prostate cancer. Development of bone pain in the presence of an elevated PSA level suggests the development of bone metastases.

Paraneoplastic Syndromes

Paraneoplastic syndromes such as hyponatremia due to inappropriate secretion of antidiuretic hormone such as seen in small cell lung cancers, prostate, pancreas, and other cancers, or hypercalcemia such as seen in squamous cell carcinomas of the lung, breast, or kidney, will alter nutritional and fluid and electrolyte management. Although mild hyponatremia can be associated with mild symptoms such as nausea and headaches, severe, acute hyponatremia can lead to more severe symptoms, even seizures or coma. Hypercalcemia is most often associated with bone metastasis, but it may be related to a paraneoplastic syndrome and can lead to neuro-muscular symptoms such as weakness and fatigue and gastrointestinal symptoms such as nausea, ileus, and abdominal pain. Severe hypercalcemia can disturb cardiac conductivity. Given the tendency to malnutrition and low serum albumin in cancer patients, serum calcium levels are often best determined by measuring ionized calcium.

Effects of Low Glycemic Index Diets

Situations where insulin resistance and insulin-like growth factors have been implicated are the so-called diet-related cancers - colon, breast and prostate 21 . It has been hypothesized that the risk of these cancers may be increased by insulin resistance 21 . Recently an Italian case-control study reported that the dietary glycemic index was related to colon cancer risk the higher the glycemic index the greater the risk. Of particular interest was the finding that the association was only significant for white bread (high glycemic index food) which contrasted with pasta (low glycemic index food) where no association existed 21 .

Metastatic Disease In The Orbit

Metastatic tumors constitute approximately 3 of all orbital diseases and 10 of orbital neoplasms in most series.23'34-36 The prevalence of ocular and orbital metastasis in patients with cancer varies from 0.7 to 12 , depending on whether the analysis was clinical or performed in autopsy series.37-39 The frequency of the site of origin parallels the general incidence of tumors.40 The most frequent primary organs are breast in women, and lung and prostate in men, and cutaneous melanoma. However, metastases from a large variety of tumors have been reported to occur in the orbit (Table 4.2).23 The spatial and tissue location of metastasis within the orbit is variable. Frequency analysis suggests that tumors from different primary sites tend to metastasize predominantly within certain tissues of the orbit. The orbit is bordered by bone and contains fat and muscle tissues. Melanoma has a strong tendency to metastasize muscle (41-76 of the cases), whereas thyroid and prostate carcinomas...

Development of Targeted Therapies

With our ever-increasing understanding of the pathogenesis of cancer, there are now a plethora of potential molecular targets in human cancer cells that are being utilized for the development of novel anticancer therapies (Table 5.1). Perhaps the oldest and most established targeted therapy is endocrine treatment for breast and prostate cancer, taking advantage of the estrogen receptor (ER) and androgen receptor (AR) that can readily be detected in many breast and prostate carcinomas, respectively. More recently, peptide growth factor receptors (EGFR and HER2) have become viable targets in human solid epithelial tumors such as lung, head and neck, breast, and colon cancer. The unraveling of the signal transduction cascade within cells has resulted in various small molecule signal transduction inhibitors (STIs) entering clinical development, whereas the complex protein interactions that regulate the cell cycle may allow various modulators to be developed to restore cell-cycle control...

Musculoskeletal Morphology

The pelvic sidewalls are composed of a horseshoe shaped muscular sling covered with pelvic fascia. The iliopsoas muscles form the walls of the false pelvis while the obturator internus and piriformis muscles form the walls of the true pelvis. The pelvic floor is a fibromuscular diaphragm formed from the paired levator ani muscles anteriorly and the paired coccygeal muscles posteriorly. The levator ani muscle arises from the superior and posterior aspects of the pubis, the pelvic fascia covering the obturator internus muscle and the inner surface of the ischial bone and ischial spine. It inserts into the perineal body, coccyx and the anococcygeal body. The levator ani is divided into three groups of muscles. The anterior group (levator prostate or sphincter vaginae) forms a sling around the prostate and vagina and inserts into the perineal body. The middle group (puborectalis) forms a sling around the junction of the rectum and anal canal and blends with the external anal sphincter....

BOX 42 Clinical Presentations of Orbital Metastases

The mean interval from the diagnosis of the primary tumor to the development of the ophthalmic sign or symptom is highly variable and is related to the biology of the primary tumors and the development and application of diagnostic methods and ther-apy.23 An interval of more than 3 to 5 years is expected in breast, thyroid, and prostate carcinoma, and carcinoids. Lung, renal, and gastrointestinal tumors are more frequently diagnosed after the appearance of orbital metastatic signs and symptoms and usually follow a fulminant course with short survival.

Signal Transduction Targeted Therapies

The FTI lonafarnib (SCH66336 or sarasar) is a tricyclic compound that inhibits the growth of several tumor cell lines as well as K-ras-transformed xenografts in vivo.39 In human xenograft studies a wide variety of tumors including colon, bladder, lung, prostate, and pancreas were growth inhibited in a dose-dependent manner, while prophylactic administration of SCH66336 delayed both tumor onset and growth.40 In patients with solid tumors, efficacy has been reported in early Phase I clinical studies in a variety of tumor types including lung and head and neck cancer,41 and confirmation of biologic efficacy has been demonstrated by inhibition of prenylation of prelamin A in buccal mucosa cells in treated patients42 (Table 5.5). Based on promising preclinical evidence that

Cell CycleTargeted Therapies

Flavopiridol targets the ATP-binding pocket of cdk2 and arrest cells at either the G S or G2 M checkpoints and may inhibit other cdks including cdk1, cdk7, and cdk9. The initial Phase I trial explored a 72-hour continuous infusion of flavopiridol, but dose-limiting toxicities included secretory diarrhea and symptomatic hypotension62 (Table 5.6). In three separate phase II studies with this schedule, objective tumor responses were rare, although disease stabilization was seen in a number of patients.63-65 Previous preclinical studies had shown synergy and induction of apoptosis when flavopiridol was combined with standard cytotoxic therapies,66 and clinical activity using combination therapy has been seen in patients previously resistant to the given cytotoxic drug alone.67,68 Preclinical evidence of synergism with paclitaxel therapy followed by flavopiridol in animal models further supported clinical studies of this combination,69 and Phase I combination studies have demonstrated...

Strategies to Modulate Apoptosis TRAILR1 Monoclonal Antibody

Sphingosine kinase promotes the activity of the caspase inhibitory proteins XIAP and FLIP. The isoflavone phenoxo-diol targets a regulator of sphingosine kinase thereby reducing XIAP and FLIP activity. Phase Ib II data have recently been presented demonstrating promising activity of oral phe-noxodiol in hormone refractory prostate cancer and late-stage ovarian cancer refractory to chemotherapy.90,92

Historical Perspective

To lack of sensitivity but is largely through the heterogeneity of malignancies precluding the discovery of widely expressed markers. The estrogen receptor (ER) is currently the most reliable predictor of therapeutic response, based on hormone sensitivity in breast cancer (1). The epidermal growth factor receptor (EGFR) holds an equivalent but inverse prognostic value in conjunction with the ER status (2). Urokinase plasminogen activator (uPA), a serine protease causally involved in cancer invasion and metastasis, is also prognostic for poor outcome in breast cancer and other adenocarcinomas, such as gastric, colorectal, esophageal, renal, endometrial, and ovarian cancers (3). Carcinoembryonic antigen (CEA) is used in postoperative monitoring of colon carcinoma where preoperative levels are known (4). The increment of prostate-specific antigen (PSA) due to proliferation of cancerous prostatic epithelial cells is considered a useful marker of disease indeed, the serine protease family...

Preoperative Evaluation Choice of Imaging Modality for Guidance

FIGURE 3 Prostate carcinoma metastatic to the scapula. Although primarily a bone lesion, there is a large soft-tissue mass displacing the infraspinatus (A), amenable to a soft-tissue biopsy with a spring-loaded gun (B). FIGURE 3 Prostate carcinoma metastatic to the scapula. Although primarily a bone lesion, there is a large soft-tissue mass displacing the infraspinatus (A), amenable to a soft-tissue biopsy with a spring-loaded gun (B).

GSTT1 and Health Conditions

The deletion is associated with an increased risk of lung, larynx, prostate, cervical, and bladder cancers (34,80,86-89), and asthma (90). When broccoli consumption was factored into a study of the incidence of colorectal adenomas, a protective effect was observed in GSTT1 ( ) with individuals consuming highest amounts of broccoli (91).

Fascia and Ligaments of the Pelvic Floor

Posterior to the rectum is the mesorectum, which contains both blood vessels and lymphatics that supply and drain the rectum. This is loosely bound down the front of the sacrum and coccyx by connective tissue known as the fascia propria. The lateral ligaments, which attach the rectum to the pelvic walls, are condensations of the fascia propria and contain loose areolar tissue, nerves, and small blood vessels. Thus, the mesorectum can be mobilized by dissection in the mesorectal plane leaving the mesorec-tum invested in this thin layer of fascia. The sacrum and coccyx are also covered in a thicker fascia, which extends downward and forward, just superficial to the anococ-cygeal ligament known as Waldeyer's fascia. Anteriorly the rectum is covered with a layer of visceral fascia that extends from the anterior peritoneal reflection to the urogenital diaphragm. This is Denonvilliers fascia and lies between the rectum and vagina (or prostate in men). Nerves important to bladder control and...

Vascular Endothelial Growth Factor

Structural alterations of FGFRs may play a role in human tumorigenesis. FGFR1 is highly expressed in the brain (41) but the shorter (2 Ig-domain) form of FGFR1 is more abundant in some CNS glioblastomas (42). Anti-sense targeted interruption of FGFR1 reduces malignant melanoma cell proliferation and differentiation (43). FGFR2 exon switching has been observed to accompany prostate cell transformation (44).

Basic Fibroblast Growth Factor

Basic fibroblast growth factor (bFGF), like VEGF, is a potent angiogenic factor. Excessive concentrations of bFGF have been identified in the plasma, urine, and or tumor tissues of patients with a variety of cancers, including those of the uterus, prostate, kidney, liver, en-dometrium, and stomach. Its presence has also been positively correlated with reduced survival of patients with breast, kidney, and uterine cancer.116,117 Unfortunately, few studies on bFGF inhibition by natural compounds have been conducted. Studies on the polysaccharide PSK reported it may inhibit production of bFGF in rat prostate cancer cells.118,119 One study on curcumin reported that oral administration of about 1.2 grams per day (as scaled to humans) inhibited angio-genesis induced by fibroblast growth factor-2 (FGF-2) in the corneas of mice.120 FGF-2 is similar to bFGF. This mouse study, and another, also reported that direct treatment of the cornea with curcumin inhibited angio-genesis induced by FGF-2 or...

Boneseeking radiopharmaceuticals for intractable bone pain

Bone metastases occur in up to 85 of patients who have breast, lung, or prostate cancer. Bone-seeking radiopharmaceuticals have pharmaco- Application of 32P-orthophosphate for the treatment of bone pain was effective, but bone marrow toxicity limited its widespread use. 89Sr was the first radioisotope employed as a systemic treatment for bone metastases in prostate cancer. After IV administration of l50 MBq of 89Sr the radiopharmaceutical is avidly accumulated in areas of high bone turnover, such as reactive bone surrounding a metastasis. A transient leucopaenia can be expected after 6 weeks. After a single administration of 89Sr, in 75-80 of patients pain is promptly relieved and progression of further bone disease is delayed, with the response lasting 1-6 months.

General Consideration on the 5aReductases

It is well known that the transformation of T into 5a-DHT by the NADPH-dependent enzyme, 5a-R, has an established physiological role in peripheral androgen-dependent structures, and especially in the control of the development and function of the prostate. The intracellular formation of 5a-DHT precedes the binding of this 5a-reduced steroid to the AR, allowing the receptor-mediated activation of target genes. In the prostate, this metabolic transformation is a mechanism of amplification of the androgenic signal, since 5a-DHT possesses an affinity for the AR about four times higher than that of T (88-91). Moreover, the activated AR appears to be more stable when 5a-DHT is bound (90,91), because this compound exhibits a fivefold slower dissociation rate from the AR than T. 5a-DHT is consequently able to activate transcription at concentrations significantly lower than those of its precursor.

Structure and Biochemical Properties of the 5aReductase Isozymes

The human type 1 gene (gene symbol SRD5A1) is located at the extreme tip of the short arm (p15) of chromosome 5. An apparently nonfunctional pseudogene, lacking introns and containing a premature translation termination codon, is present on the long arm of the X chromosome. The human type 2 gene (gene symbol SRD5A2) is present on the short arm of chromosome 2. The exon-intron structures of the two functional genes is identical, indicating an ancient gene duplication. In humans, the type 1 gene appears to be expressed at high levels in the liver and in the nongenital skin, and at low levels in the androgen target tissues (105). In the rat, the expression of this isoform is widely distributed throughout the various genital and nongenital tissues, with the highest levels in the liver. Both in rat and in humans, the type 2 isoform is concentrated especially in andro-gen-dependent structures, such as the epididymis (especially in the basal cells), the seminal vesicles, the genital skin,...

Overview of Various Cancers

A total of 19 prospective studies were published between 1994 and 2005 and were used for data analysis. These comprised 3,004 lymph nodes in 631 patients who underwent comparable MR imaging with histological verification as shown in Table 3.1. The overall sensitivity and specificity for MRI with USPIO (17 studies) were 88.1 and 96.2 respectively, with an area of 84.2 under the ROC curve and a diagnostic odds ratio of 123.1. When unenhanced MRI was evaluated, there was a significant reduction in the overall sensitivity and specificity (63 and 92.7 respectively), with an area of 84.2 under the ROC curve and a diagnostic odds ratio of 26.7 (Table 3.2). When analyzed specifically by body region, USPIO-enhanced MRI had a high sensitivity and specificity for lymph node status in the abdomen and pelvis compared with the chest or head and neck. The highest sensitivity and specificity was noted for the two studies, reporting results only for prostate cancer. This may be explained by the fact...

Hepatocyte Growth Factor And Its Receptor Cmet

The c-Met receptor is expressed by a wide variety of epithelial cells, whereas its ligand, HGF, is normally produced by the stromal tissues. Interestingly, possible autocrine signalling mechanisms have also been demonstrated in human carcinomas of the breast, lung, colon, and prostate through the co-expression of HGF and c-Met in the tumour tissue (26, 28, 48-52).

Endometrioid Type I Carcinoma

PTEN is located on chromosome 10q23.3, a region of the genome that undergoes loss of heterozygosity in approx 20-30 of endometrioid carcinomas and 30-80 of tumors having intragenic mutation (1). In addition, mutations have been detected in approx 20 of hyperplastic lesions, both with and without atypia, suggesting that mutations in PTEN occur relatively early in the pathogenesis of endometrioid carcinoma (2,3). This is in contrast to other tumor types (e.g., prostate cancer, melanoma, and gliomas), in which PTEN is believed to be inactivated later in their development. Initially, based on sequence homology, it was believed that PTEN encoded a dual specificity protein phosphatase. It was later shown that in vitro it had lipid phosphatase activity (4). Presently, its most well-documented substrate is the lipid molecule phosphatidylinositol 3,4,5-triphosphate. This lipid molecule is an important second messenger that regulates the phosphorylation of a protein...

Intracellular And In Vivo Applications

In a recent paper, Gao et al. (2004) reported in vivo cancer imaging and targeting with a new class of bioconjugated quantum dots. Antibodies specific to a prostate cancer marker called PSMA were conjugated to QDs coated with a PEGylated ABC triblock copolymer. The probes were injected into nude mice implanted with human prostate cancer cells and in vivo imaging was performed. The results showed QDs accumulated specifically at the implanted tumor site as shown in Figure 4.8. Due to high autofluorescence from the mouse skin, a spectral unmixing algorithm was applied to subtract the background fluorescence. This would not be necessary if NIR QDs are used because autofluorescence emission has been shown to taper off at 800 nm and NIR spectral region lies in the range 700-900 nm. To that effect, another paper reported the use of NIR QDs for sentinel lymph node mapping (Kim et al., 2004). By injecting NIR QDs into pigs and mice and then imaging with an NIR imaging setup, a surgeon was able...

Mr Imaging Imaging Plane

Example, when evaluating pelvic nodes in patients with prostate cancer, additional imaging in an oblique plane parallel to the psoas muscle allows surgeons to precisely locate the lymph nodes in relation to the obturator nerve an important surgical landmark (Fig. 3). Furthermore, this imaging plane enables the nodes to be optimally distinguished from vessels. Surgeons usually remove nodes from the so-called obturator fossa,'' an area anterior and slightly posterior to the obturator nerve. An extended, more aggressive dissection is indicated when there is evidence on the postferumoxtran-10 MRI of nodal disease more than 2 cm posterior to the nerve. Figure 3 Oblique imaging for delineating the obturator fossa. (A) Coronal Tl-weighted 3D-GRE MRI. The plane of Figure 3B (parallel to the psoas muscle) is indicated by the line. (B) Tl-weighted SE MR image, obtained 24hours postferumoxtran-10 (which is insensitive to iron oxide particles), shows normal size nodes (arrows and circle) of...

Emerging Role Of Hai1 And Hai2 In The Regulation Of Metastasis

The significance of HGF in human cancer metastasis is well established. However, the role of the HAI inhibitors is less clear. The fact that HGF plays such a pivotal role, suggests that the HGF activators (HGFA and matriptase), and HGF activation inhibitors (HAI-1 and HAI-2), are important factors that can influence the metastatic spread of tumours. Recently, a number of studies demonstrate that the ratio between HAI-1 2 and matriptase HGFA expression is a crucial factor governing the malignant progression of tumour cells in a variety of human cancers including breast, prostate, renal, and colorectal (26, 144, 146, 157, 159, 160). These reports reveal a shift in the balance between HGF activation and inhibition and demonstrate the malignant progresssion of tumour cells may be a consequence of protease and or inhibitor dysregulation. our studies have shown that low levels of HAI expression within breast tumours are associated with a poor prognosis for the breast cancer patient (26). We...

The 2004 Clinical and Research Challenges in Economics and How the Principles and Practice of Oncology May Be Changing

The impact of cost-effectiveness studies has been hard to gauge. Reflecting over the past years, we can think of only several examples of the importance of cost-effectiveness studies. When adjuvant chemotherapy for women with node-negative breast cancer was first endorsed, a major objection was the cost, estimated at 300 million or more yearly in the United States.36 Subsequent studies showed that adjuvant treatments had similar cost-effectiveness ratios to the treatment of hypertension, and were clearly acceptable.37,38 Similar objections were raised to the use of chemotherapy for advanced non-small cell lung cancer, with only a few months of time gained compared to best supportive care, but subsequent analyses showed that chemotherapy could actually be cost saving39 or have very acceptable cost-effectiveness ratios.40 Chemotherapy with mitoxantrone in advanced prostate cancer showed no survival benefit41 but actual cost savings due to avoided radiation and hospitalizations.42 Royle...

Magnetic Resonance in Cancer Diagnostics Generalities

The real strides made by in vivo MRS and MRSI in clinical oncology are, in fact, highly tumor- or site specific. The most dramatic achievements have been made with respect to brain tumors, for which this molecular imaging modality has become an indispensable diagnostic component. MRS and MRSI are also now becoming very important in various aspects of prostate cancer diagnostics. For other malignancies, in vivo MRS and MRSI while showing promise, still have had relatively limited applications. On the other hand, MRI is widely used in staging many, if not most, solid cancers. Moreover, for some special indications, notably young women at high risk for breast cancer, MRI is being explored as a possible first-line diagnostic modality. In the subsequent chapters of Part B of this book, we will provide an in-depth review of the state-of the art of molecular imaging through MR in clinical oncology, on a tumor- or site-specific basis. In this chapter, we first present some generalities...

EGFR signalling in ERpositive acquired endocrineresistant breast cancer cells

Tumour progression and spread requires a cell phenotype that displays altered biological activities other than simply deregulated proliferation, such as invasiveness and motility, and it has been speculated that the EGFR may play a role in this process. High levels of EGFR have been demonstrated in a number of aggressive tumour types including head and neck cancer, non-small-cell lung cancer, colorectal cancer, and ovarian tumours (7). Furthermore, elevated levels of EGFR correlate with increased invasiveness and metastasis and are associated with a poor clinical prognosis (11, 20, 21). Although expression of the EGFR protein may be increased in tumour tissue, it is likely that its activation state has a greater bearing on prognosis than expression of the protein alone. Constitutive activation of the EGFR may arise from autocrine production of EGFR ligands such as TGFa. Indeed, co-expression of EGFR and TGFa has been reported in non-small-cell lung cancers (22), prostate cancer (23),...

The Idea of Cancer and the Idea of Screening

Expression profiling using DNA microarrays4,5 has shown the genetic heterogeneity of individual breast cancers. There is not one type of breast (or colorectal or prostate) cancer, but a number of types, each with a different natural history. Together with the probable but largely unknown ways in which individual susceptibility varies, these cancer types produce great variation in the ways a particular cancer is expressed. Some cancers in certain individuals grow rapidly and are lethal within a short time, regardless of our best treatments. Screening is unlikely to make a difference for people with such cancers, which may metastasize from the first cell.

Relaxation rates of neoplastic tissues

Many cancers appear hyper-lucent on T2 weighted images. However, if the surrounding tissue, e.g. endometrium is hyper-intense on T2 weighted images, neoplastic tissue, i.e. endometrial carcinoma, can be of intermediate intensity 1 . Prostate cancer, on the other hand, is generally of low signal intensity on T2 weighted images. There are also exceptions based upon histological type. Sometimes, tumors may be iso-intense to their surroundings. On the other hand, a difference in signal intensity compared to surrounding tissue is by no means pathognomonic for neoplasia.

Image Measurement And Quantification

The distribution and statistics of pixel intensity within a region can reveal the smoothness, contrast, regularity, or homogeneity of tissues. Texture analysis such as statistical moments, and co-occurrence matrix provides ways to describe the tissue appearance (12). The statistical moments are computed based on the intensity histogram. The second moment of the histogram measures the intensity variance within the region, which correlates with the roughness perception. The third and fourth moments, skewness and kurtosis, reflect the asymmetry and uniformity of the intensity distribution. The co-occurrence matrix is also known as spatial gray level dependence matrix in the sense that it combines spatial information and intensity statistics (14). The inertia of the co-occurrence matrix characterizes the texture contrast of a region. The entropy of the matrix quantifies the level of randomness in the region. The angular second moment of the co-occurrence matrix can be used to describe the...

Overdiagnosis and Overtreatment

A problem with this formulation, however, is that many cancers can only be placed in their proper category retrospectively. That is, the people in category 3, who do not need to be detected or treated, are often initially difficult to distinguish from the other groups. Thus, people in this category are still treated. An example is men with prostate cancer detected by screening. The majority of men with screening-detected prostate cancer have tumors that are moderately differentiated. Some cancers of this type are potentially lethal whereas others will never cause clinical problems. Because it is impossible to distinguish these cancers with high confidence at the time of diagnosis, virtually all men with this type of cancer are treated. This constitutes overdiagnosis, as we are diagnosing some men with cancer who do not need to be diagnosed, and overtreatment, as we are treating some men who do not need treatment. The fact of overtreatment is undeniable and likely occurs with many...

Image Display And Visualization

Figure 5 Functional parameter maps. (A) Amplitude map of breast study (B) k21 map of breast study (C) uptake slope map of prostate study. (See color insert.) Figure 5 Functional parameter maps. (A) Amplitude map of breast study (B) k21 map of breast study (C) uptake slope map of prostate study. (See color insert.)

Agonistssupraphysiological doses of hormone

This approach is epitomized by the use of gonadotrophin-relating hormone agonists (GnRHa or LHRHa). The gonadotrophins LH and FSH provide the stimulus for gonads to produce steroid hormones in turn their synthesis and release from the pituitary is regulated by the hypothalamic factor GnRH (or LHRH). Highly potent agonist analogues of GnRH have been synthesized by introducing unusual amino acids into the native peptide. When administered for short periods they cause a rapid release of gonadotrophins, but in the long term these agonists down regulate gonadotrophic receptors and desensitize the pituitary. As a result circulating gonadotrophins fall, the trophic drive to the gonads is abolished, and circulating sex hormones are reduced to castration levels. Depot formulations of LHRH agonists are available so that a single injection can maintain effective medical castration over prolonged periods. The use of GnRH analogues in pre-menopausal women with breast cancer and men with prostate...

MRSIImportance of full volumetric coverage

The advantages of MRSI as compared to MRS for tumor diagnostics cannot be overemphasized. As will be seen in the next chapters, the major breakthroughs in brain and prostate cancer diagnostics have relied heavily upon assessment of the metabolic characteristics of larger areas of suspected tumor, peritumoral regions and normal tissue. This is provided by MRSI. Spielman 10 states the spatial resolution of in vivo MR spectroscopy is simply too coarse to avoid false negative findings resulting from small lesions partially volumed with normal tissues(p. 30) and emphasizes the need for volumetric coverage using proton MRSI for central nervous system (CNS) tumor diagnostics. Complete volumetric coverage of a suspected lesion is critical for accurate diagnosis, and Spielman notes that metabolically abnormal regions may not precisely correspond to much larger T2 abnormalities. Thus, he concluded sampling the most 'metabolically' abnormal tissue may be a better choice than just sampling the...

Paradigm Shift Involving Patients in Healthcare Decisions

Many clinical decisions are not purely scientific matters, but also involve value judgments that vary from person to person. For example, the right choice, for a patient choosing between surgical and radiation treatment of his prostate cancer, depends on how much he thinks he would be bothered by surgical complications such as impotence or incontinence and on how important he feels it is to have the cancer physically removed from his body. Similarly, whether a woman should begin receiving annual mammography at age 40 or 50 depends on how she feels about the inconvenience and discomfort of mammography, the financial costs of screening, the consequences of false-positive testing, and the benefits of receiving more aggressive screening.

Introduction The Problem

The incidence of cancer in the United States is over a million new cases a year (excluding cancers of the skin), of which over 100,000, perhaps up to 150,000 patients a year, develop bone metastases. The frequently occurring tumors that spread to the bone are prostate, breast, and lung cancer. The presence of bone metastases obviously signals reduced survival but also heralds a number of clinically significant complications, including bone pain which will afflict up to two-thirds of those with bone metastases. Other complications include fracture, hypercalcemia, and spinal cord compression. This chapter will discuss the role of nuclear medicine in pain control of these painful osseous metastases.

Lymphangiogenic Factors 31 VEGFs

Membrane of chicks, to mouse cornea or to ischaemic hindlimbs of rabbits (50, 78). Therefore, VEGF-C is likely to play a dual role both as an angiogenic and a lymphangiogenic growth factor. If VEGF-C induces lymphangiogenesis, is it sufficient enough to increase the rate of metastasis to the lymph nodes It has recently been reported that lymphatics surrounding a VEGF-C overexpressing tumour are enlarged, and it has been suggested that the in crease in lymphatic diameter may be sufficient to increase metastasis (7). Clinical studies correlating the levels of VECF-C in tumours and their metastatic potential have revealed controversial results. However, a significant correlation between VEGF-C expression and lymph node metastasis have been observed in a variety of carcinomas including breast (79), oesophageal (80), gastric (81, 82), colorectal (83), thyroid (84, 85), head and neck (86), prostate (87), and lung (88,89).

Emotional Mispredictions

Such mispredictions are common in health settings.49 For example, patients with inflammatory bowel disease expect that having a colostomy would make them miserable, and yet patients emotionally adapt to colostomies relatively quickly.50 People predict that they would be miserable if they had kidney failure, and yet most dialysis patients are happy.51 Such mispredictions could influence patients' healthcare decisions. If a prostate cancer patient overestimates how much he will be bothered by impotence or incontinence, he may forgo potentially beneficially treatments.

Taking Advantage of Time

Clinicians should remind themselves that strong emotions often dissipate over time. Furthermore, the ability to retain and process information about a cancer diagnosis increases over time. When possible, clinicians should rely on time as a useful clinical intervention. For example, men with new diagnoses of localized prostate cancer often find out about their diagnosis at the same clinic visit that they decide how to treat the cancer. It is doubtful that these patients have had time to absorb all the information in one sitting, especially given their likely shock at receiving a cancer diagnosis. Perhaps a better goal at such a visit is to communicate their diagnosis and prognosis to patients, and let them know that good treatment options are available, which they can decide about over the next few weeks. When delivering bad news to patients, clinicians should expect that many patients will not be able to process much clinical information during the initial visit, and will usually be...

Therapy Of Bone Pain Due To Osteoblastic Metastases

An effect of appropriate chemotherapy can be to reduce bone pain, as has been documented for mitoxantrone in prostate cancer and the taxanes in breast cancer in up to 30 of patients. Another sort of chemotherapy is the use of the bisphosphonates to treat bone pain. Oral and intravenous bisphosphonates have been shown to reduce bone pain, especially in osteolytic cancers, as well as to reduce the risk of pathologic fracture and treat hypercalcemia. Nitrogen-containing bisphosphonates inhibit farnesyl diphosphate synthase, an enzyme involved in osteoclast cholesterol biosynthesis. This leads to a reduction in the lipid geranylger-anyldisphosphate which prenylates guanosine triphosphatases (GTPases) required for normal cytoskeletal organization and vesicular traffic in the osteoclast. In addition, bisphosphonates modulate the expression of bcl-2, leading to caspase-dependent osteoclast apoptosis. This multifaceted osteoclast inhibition and destruction lead to reduced bone turnover, and...

Controversies in Multimodality Treatment

For patients with muscle-invasive bladder cancer, chemoradiotherapy can be used selectively to achieve bladder preservation.77 However, the application of limited surgery, chemoradiotherapy, and radical cystectomy remains highly variable.78 The management of prostate cancer is complex, as options often include observation, hormonal therapy, surgery, or radiation (external beam or brachytherapy).79 Clinically node-negative nonseminomatous testicular cancer can be managed with initial chemotherapy or with observation treatment varies with the preference of the treating physician and the details of the patient's disease.80

Diagnostic Applications Of Dna Methylation

Prostate cancers but not in benign prostatic hyperplasia (99). For other cancers, markers showing this degree of specificity remain to be identified. An alternative approach is to use a small panel of recurrently methylated markers rather than a single marker. By assembling a panel of four to five loci, it might be possible to cover close to 100 of tumors. It is critical to verify that the markers are generally not methylated to any significant degree in normal tissue. Methylation markers can be used for early detection of cancer or for monitoring response to treatment. Sensitive techniques can be used to detect methylation in biological fluids such as (1) blood for the detection of disseminated carcinoma cells or tumor-derived DNA, or (2) various lumenal fluids such as urine for the detection of cells from bladder, kidney, and prostate cancers, or (3) washings such as bronchioalveolar and ductal lavages for the detection of early malignant cells in lung and breast cancer,...

Phosphorus32sodium Phosphate

This radiopharmaceutical was the most widely employed agent for the treatment of bone pain from osseous metastases between 1950 and approximately 1980. It is usually administered intravenously, but there are studies showing equal efficacy with oral administration, where absorption varies between 40 and 80 . Oral P-32, which is much less expensive than any of the radiotracers to be discussed (and therefore suitable for developing countries) was compared in 1999 with intravenous Sr-89 in an study sponsored by the International Atomic Energy Agency (IAEA). There was no significant difference found in response rates from P-32 or Sr-89 treatment both were about 90 efficacious. In the early years of P-32 utilization, it was employed after a week of androgen therapy in the belief that tumor and bone uptake would be stimulated. However, the data on which this supposition was made were flawed. Androgen administration can lead to severe side effects, such as spinal cord compression in the...

Inhibition of PSecretase

A number of cellular factors have also been reported to regulate BACE-1 activity. For example, members of the reticulon family of proteins (also known as Nogo proteins) have been shown to bind to BACE-1 and inhibit its activity (He et al., 2004). The leucine zipper protein PAR-4 (prostate apoptosis response-4) has been shown to form a complex with the cytosolic domain of BACE-1, and upon binding increases its activity (Xie & Guo, 2005). The vacuolar protein-sorting protein sorLA interacts with the cytoplasmic domains of both BACE-1 and APP, disrupting BACE-1-APP interactions and reducing the BACE-1 cleavage of APP (Andersen et al., 2005 Spoelgen et al., 2006). Also, the cellular form of the prion protein downregulates the BACE-1 cleavage of APP (Parkin et al., 2007). It remains to be seen whether any of these biological interactions can be exploited to design therapeutics that will inhibit BACE-1 activity. Recently, inhibition of the BACE-1 cleavage of APP with antibodies raised...

Andrew J Vickers and Barrie Cassileth

CAM is widely used by the general public in the United States2,3 and in other industrialized countries.4-7 CAM use is markedly prevalent among cancer patients a systematic review located 26 surveys of cancer patients from 13 countries, including 5 from the United States. The average prevalence across all studies was 31 , with prevalence rates as high as 64 in published reports.8 Research published subsequent to the systematic review showed similar or slightly increased rates of CAM use.9-15 Particularly popular today among cancer patients is the use of herbs, vitamins, and other dietary supplements. For example, more than one in four prostate cancer patients at a Canadian cancer clinic16 and at a veterans' affairs medical center17 used supplements or herbal treatments. A review of several studies reporting CAM product use in breast cancer patients found rates as high as 50 for herbs and 60 for other supplements.18