Most Effective Prostate Home Remedies

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 Summary


4.6 stars out of 11 votes

Contents: Ebook
Author: Radu Belasco

My The 21 Day Prostate Fix Review

Highly Recommended

Recently several visitors of blog have asked me about this manual, which is being advertised quite widely across the Internet. So I purchased a copy myself to find out what all the excitement was about.

This e-book served its purpose to the maximum level. I am glad that I purchased it. If you are interested in this field, this is a must have.

Download Now

Hypofractionation for Prostate Tumors

There is another situation in which the biology of the tumors makes hypofractionation the best clinical rationale available, as well as a convenient one. That is in the exceptional situation of tumors proliferating so slowly that their a p ratios are significantly lower than those of late-responding normal tissue complications. This has been reported for malignant melanomas (Bentzen et al. 1989), although these are notoriously variable in response. The outstanding example is prostate tumors, with a median Tpot of 42 days (range 15 days to 70 days) compared with Tpot 4-10 days in most other types of tumor, especially carcinomas (Haustermans and Fowler 2000). The a p ratio for prostate tumors was reported as 1.5 Gy ( 0.8 Gy 95 confidence interval) in 1999 (Brenner and Hall 1999, 2000 BrenneR 2000) and 1.5 0.3 Gy in 2001 when updated with more patients and centers (Fowler et al. 2001). Some other estimates have however suggested a p to be about 3 Gy, similar to the commonly accepted a p...

Morphogenetic Factors Implicated In Prostate Cancer Progression And Hormone Therapy Failure

Common prostatic adenocarcinoma is mainly composed of exocrine tumor cells that express PSA and CKs 8 and 18 and share phenotype similarity with secretory luminal cells of the normal prostatic epithelium (Nagle et al., 1991). These exocrine tumor cells generally express the nuclear AR and 5 a reductase isoenzymes 1 and 2 in primary, metastatic, and recurrent lesions (Bonkhoff et al., 1993c, 1996c Koivisto et al., 1998). This observation suggests that exocrine tumor cells are androgen responsive and maintain the dihydrotestosterone-forming process even in hormone-refractory stages of the disease. The continuous expression of the nuclear AR in androgen-insensitive tumors can be explained partially by AR gene amplification, which has been identified in at least 30 of recurrent lesions (Koivisto et al., 1998). The presence of the nuclear AR in prostate cancer tissue, however, does not imply androgen-dependent growth. Point mutations in the steroid-binding domain of the AR gene can...


The effects of surgical and radiation injury are not seen until puberty, because the gland is nonfunctional during the prepubescent years. Atrophy of the normal glandular tissue in the prostate can be seen following moderate or high doses of radiation 48 . Impaired growth of the seminal vesicles, with consequent decreased production of and storage capacity for seminal fluid, may result in a diminished ejacu-lum volume. Since the normal ejaculate is a combination of fluids derived from the gonads, seminal vesicles and prostate, dysfunction of any of these structures theoretically can lead to abnormalities in ejaculation or the ejaculate volume.

Cancer Therapy And The Cycle Classical Chemotherapies

Sex hormones stimulate the growth of some breast, ovarian and prostate cancer cells. Blocking these hormones' action can kill these cells. Tamoxifen is chemically related to the sex hormone oestrogen, with which it competes for binding to oestrogen receptors in a cell. Since tamoxifen blocks the stimulation by oestrogen and does not activate growth, it is in fact inhibitory.

Is This a Mistaken Dose Prescription

Peutic ratio becomes worse (for most types of tumor except prostate Ca) when larger doses per fraction are used. The late BED is then 20 above the normally safe upper limit of 117 Gy3, so it is far from safe and this schedule should not be used. This criterion alone is sufficient to exclude this schedule from practical use. Further, the tumor BED is only raised to the same BED of 84 Gy10 as would be given by a 70 Gy NTD schedule (with 2 Gy fractions). The increase in late effects would be obviously dangerous, without giving a proportionately high gain in tumor BED. It demonstrates the loss of therapeutic gain that occurs for most tumors when hypofractionation (larger and fewer fractions) is used. There are certain exceptional circumstances in which hypofractionation could give an increased therapeutic gain - especially in prostate cancer - and these are discussed in Section 1.6 of this chapter.

Clinical Correlations

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

The Impact of IMRT on the Incidence of Radiation Induced Second Cancers

Dose volume histograms for two typical treatment plans for prostate cancer a four-field conformal plan and a nine-field plan using intensity modulation (IMRT) Fig. 2.3. Dose volume histograms for two typical treatment plans for prostate cancer a four-field conformal plan and a nine-field plan using intensity modulation (IMRT)

Nonbiogenic Toxic Substances Metals

Some of the toxic effects of these metals involve hematopathies, neuropathies, nephropathies, and carcinogenesis attributed to lead pulmonary edema, nausea, vomiting, abdominal pain, prostate, and lung cancer attributed to cadmium neuropathies, teratogenesis, and mutagenesis attributed to mercury and both central nervous system (CNS) and peripheral nervouos system (PNS) pathologies, including muscle weakness and loss of sensory perception, attributed to arsenic.47

Wnt Signaling in Cancer

In addition to upregulation of expression levels of activators of Wnt signaling downregulation of expression has been demonstrated for the secreted inhibitors of Wnt signaling sFRPs and WIF-1. sFRPs have been found to be downregulated in breast, bladder, and colorectal cancers as well as in mesothelioma (96-99). WIF-1 expression has been reported as being repressed in prostate, breast, lung, bladder, and colorectal cancers (100-102). Axin, which serves as the scaffold in the multiprotein complex facilitating phosphorylation of P-catenin, has been found to be biallelically mutated and hereby inactivated in a subset of hepatocellular and col-orectal cancers as well as in medulloblastoma (103-107). Mutation of one of the four serine or threonine residues in the destruction box or deletion of the whole box in the amino terminus prevents the phosphorylation and subsequent degradation of P-catenin. These molecular changes give rise to the cytoplasmic accumulation of P-catenin and after...

Evaluation of Lymph Node Status N

A recent study 35 showed the utility of a lymph node-specific contrast agent (ultrasmall particles of iron oxide) used in the detection of lymph nodes in patients with prostate cancer. The results regarding the accuracy of this study are excellent but this agent has not yet been introduced in clinical practice.

Structure And Function Of Oestrogen Receptors a AND p

The ERft gene is located on chromosome 14q22-24 and encodes a protein of 530 amino acids with a molecular mass of 60kDa (Mosselman et al., 1996). Unlike ERa, several studies indicate that ERft is transcribed as multiple mRNAs and also translated into proteins from at least two reading frames resulting in a second ERft protein which lacks 53 amino acids of the N-terminus. Overall, ERa and ERft are highly homologous (49 amino acid identity), but appear to be expressed in different organs and at different developmental stages. Interestingly, ERa is expressed in female organs such as the mammary gland, uterus, ovary, vagina and certain areas of the hypothalamus, whereas ERft is found in the male in different areas of the hypothalamus when compared with ERa, and in the cerebral cortex. Additionally, ERft mRNA has also been detected in prostate, ovary, uterus, lung, testis and artery.

In Vivo Function of the Oestrogen Receptors

Sexual behaviour, but have fewer and smaller litters owing to reduced ovarian efficiency, and multiple resorbed fetuses. Older males lacking ERft display signs of prostate and bladder hyperplasia. In contrast to the aERKO animals, the ftERKO females exhibit normal breast development and lactate normally, while all components of sexual behaviour in ftERKO mice were found to be intact. These observations indicate that unlike ERa, ERft is essential for normal ovulation efficiency but not for female or male sexual differentiation, fertility or lactation.

Management of Patients with Visceral Sarcoma

Genitourinary STSs behave like retroperitoneal sarcoma (kidney, ureter) or visceral sarcomas (prostate) and should be managed accordingly. Bladder sarcomas have a more favorable prognosis as they often present earlier due to hematuria and can be completely resected. Selected patients with small ( 2 cm) bladder sarcomas may be successfully managed with a transurethral resection alone.

New Experimental Designs Sample Pooling

Comparison between cultured clonally selected human prostate tumour cells and the patient-matched primary tumour epithelium from which they were derived (Ornstein et al. 2000). This revealed only a 25 similarity between the two protein populations even though they came from the same person. Therefore, molecular analysis of cells in their native tissue environment provides the most accurate picture of the in vivo disease state, with primary cell cultures established from fresh tissue being unable to duplicate the environment of cells in the actual tissue from which they are derived. Because of that, especially in experiments investigating clinical samples where the amount of tissue sample is particularly problematic, pooling of samples might be advantageous. Another reason for the pooling of samples is to reduce the costs of screening large numbers of samples. For proteomic analysis of microdis-sected clinical cancer samples, both of these situations apply, because proteins cannot be...

Vascularization Of Ebs

ES cells to study tumor-induced angiogenesis. (A) PECAM-1 immunostaining in a 10-d-old outgrown EB. The bar represents 50 lm. (B) Confrontation culture established between an EB (right) and a multicellular prostate tumor spheroid (left) stained with long-term cell tracker CMFDA. After 24-48 h of confrontation culture, endothelial cell structures (red) appear in the contact region of both objects and start to invade into the tumor tissue. The bar represents 150 m. (C) Invasion of ES cell-derived endothelial cells (red) into the tumor tissue. The bar represents 50 m.

Protein Profiling With Total Protein Arrays

Total protein arrays, also referred to as reverse phase protein arrays, consist of immobilized extracts of cells, tissues, or sera that are probed using a given antibody, followed by detection with a labeled secondary antibody (fig. 10.2C). This format allows numerous protein samples to be analyzed simultaneously with one or two antibodies under the same experimental conditions 24,27,53 . Such protein arrays were used to study cancer progression from normal prostate epithelium to intra-epithelial neoplasia and to invasive prostate cancer 24 . A remarkable reduction was observed in the ratio of phosphorylated ERK to total ERK during the longitudinal progression of the cancer. In a similar way, protein microarrays were employed to

Stem Cells and Cancer

We have noted that adult stem cell populations exhibit functional decline with age. Ageing is also associated with a dramatic increase in the incidence of cancer, and several recent studies support a stem cell origin for cancer (Campisi 2003, Campisi 2005, Kaplan et al. 2006, Li and Neaves 2006, Rizo et al. 2006, Li et al. 2007). Together, these findings offer strong support to the stem cell theory of ageing by connecting functional decline in the stem cell population to malignancy resulting in limited organismal longevity. Interestingly, from the cell surface, stem cells from a variety of tissues resemble their malignant counterparts. Hematopoietic, mammary, neural, lung, skin, and prostate stem cells can be identified by some of the same cell surface markers used to identify cancer stem cells in these tissues (Li et al. 2007). In addition to cell intrinsic similarities between normal stem cell and cancer cells, an enormous body of literature describes intricate relationships between...

Trks As Therapeutic Targets

All Trk mediated events commence with the activation of the Trk tyrosine kinase. Therefore blocking this enzymatic activity could inhibit all Trk responses. This could be of great advantage in the treatment of malignant prostate cancer or advanced stage neuroblastoma. Several drugs are known to inhibit Trk kinase activity. The family of indolocarbazoles, including the naturally occurring parent compound K252a (Koizumi et al., 1988) and its synthetic analogues CEP-701, CEP-751 (Camoratto et al., 1997) and CEP-2563 (Ruggeri et al., 1999) are competitive antagonists for ATP binding and function as inhibitors of protein kinase C, Trk, Flk 1 and PDGFR receptor kinases (George et al., 1999). In addition monoamine-activated a 2-macroglobulin functions as a pan-Trk inhibitor (Hu and Koo, 1998 Koo et al., 1994) and endocannabinoids (Melck et al., 2000) can promote the downregulation of TrkA and thus decrease its activity.

The Money Shot in Pornography and Prostitution

Although male callers rarely asked about their semen, in our training, we were instructed to provide them with these facts. Spermatogenesis, or the production of the sperm cell, takes approximately 72 days. Both Cowper's and Littre's glands, which are located in the genital area, contribute secretions in the processes of ejaculation. The prostate also adds fructose and liquefying enzymes.1 When a man comes, a range of 2-10 milliliters of fluid is produced though his ejaculation at about 10 miles per hour. Between 200 and 500 million sperm cells are contained in most ejaculates, the equivalent of about 5-15 calories. It is estimated that a man ejaculates 5,000 times in his lifetime.2 Theoretically any man could repopulate the United States with just a few ejaculates (and the participation of 290 million women or less if multiple births occur).

Identification Of Renal Stem Cells

Markers for stem cells in other branching organs may provide some insight into potential markers for renal stem cells. For example, in the prostate, a2P1-integrin, p27Kip1, P-cadherin, In the polarized epithelium of the kidney collecting ducts, as in the prostate, it has long been assumed that stem cells of normal kidney epithelia undergo asymmetric cell division to produce one copy of the stem cell and one amplifying intermediate cell that in turn terminally differentiates (reviewed in Al-Awqati and Oliver, 2002). However, this concept was recently revisited in the prostate, providing new insights into prostatic epithelial cell lineages. This may serve as a template on which to build an alternative model of renal stem cell lineages. As in the kidney, the most common prostatic stem cell model is one in which prostatic stem cells in the undifferentiated state are located in the basal layer and give rise to intermediate and then secretory cells, in a direct precursor-progeny...

Renal Stem Cells And Potential Therapeuticsa Challenge For The Future

The issue of the adult stem cell is central to the development of therapeutic agents. The confusion that currently surrounds the issue of the ES cell will greatly impact our understanding of the biology of the mature organ. Using the prostate as an example, we may assume that the renal ES cell is retained during adulthood and contributes to disease. The exact lineage of renal stem cells cannot be assumed to operate in a direct precursor-progeny relationship, whether they be epithelial stem cells, MSCs, or a common progenitor of both cell types. Further work using inductive factors to differentiate tagged pluripotent ES cells into kidney will allow tracking of renal cell lineages by comparing subsets of markers at each stage of development. Furthermore, it must be determined whether mesenchyme-to-epithelium or epithelium-

With Proteasome Inhibitors

The first evidence of the broad antitumor potential of proteasome inhibitors was given in 1999 by the National Cancer Institute screen of 60 tumor cell lines (Adams et al. 1999). Mean IC50 values for bortezomib were found in nanomolar range. For further evaluation of mechanisms of proteasome inhibitor mediated cytotoxicity, the authors used the prostate tumor PC-3 cell line. In an in vitro assay, the induction of apoptosis was independent of p53 status, but was accompanied by p21 stabilization, G2-M arrest, and poly-(ADP-ribose-)polymerase (PARP) cleavage. Using a PC-3 nude mouse model, treatment with bortezomib significantly suppressed tumor growth at well-tolerated doses (Adams et al. 1999).

Cancer As A Genetic Disease

The multistage theory of cancer has become further complicated with the recent discovery of cancer stem cells (Reya et al., 2001). Normal stem cells repair and renew our tissues, but recent research has focused on the idea that these have a kind of 'evil twin', a cancer stem cell (Abbott, 2006). These would make up just a tiny subset of the cells in a cancer, but are proposed to be able to proliferate and self-renew extensively, thus sustaining tumour growth. These cells were first isolated in leukaemias (Bonnet and Dick, 1997), but have now also been found in some solid tumours, including brain (Clarke, 2004) and prostate (Collins et al., 2005) cancers. This has very important implications for treatment as, rather as a weed can grow back from its roots, it is very conceivable that only the eradication of these cells can lead to an effective cancer cure. Cancer stem cells might arise from the mutational transformation of normal stem cells, while in other cases mutations might cause...

Stem Cells in Glandular Organs

The interaction of stroma and glandular tissue determines the phenotype of the glandular organ. The gastrointestinal (GI) stem cell model system is presented as an example of epithelial tissue turnover. In the GI epithelium, there are approximately four to six functional stem cells per crypt. These give rise to transit-amplifying cells that can differentiate into the different mature cells of the GI tract including mucous, absorptive, secretory, and neuroendocrine cells with different proportions at different levels of the GI tract. About 80-90 of the long-lived clones in the GI tract are unipotent, with the remainder being multipotent. Other glandular organs have similar cell lineage arrangements with different differentiation potentials. The differentiation potential of immature epithelial cells is controlled by the mesenchymal stroma through permissive or instructive effects. For example, embryonic mammary mesenchyme can induce mammary gland differentiation of skin epithelium...

Posttreatment Surveillance

In conjunction with history and physical, most physicians monitor CEA. Carcinoembryonal antigen was first described in the 1960s. The hope was that it would serve as a screening test, much like PSA does for prostate cancer. Unfortunately, approximately one third of colorectal cancers are not associated with an elevated CEA. Further, there are many reasons to have an elevated CEA other than colon cancer. The relatively wide range of normal values further hinders the utility of CEA as a screening test.

What are tumour markers

Tumour markers are biological or molecular substances (protein, carbohydrates, hormones, etc.) that can be produced and attributed to the events in tumorigenesis. They may be produced by the tumour cells themselves, or by the body in response to the presence of cancer, or in certain benign conditions, e.g. dermatofibroma, benign prostatic hyperplasia and benign prostatic hypertrophy. Those produced intra-cellularly, or on the cell membrane (oestrogen receptor - ER) are detected by immunohistochemistry (IHC) on the tumour tissue. Those secreted into body fluids can be quantified by immunoassay methods. The production of tumour markers can result from Prostate-specific antigen (PSA) Prostate cancer Prostate cancer

Normal Organ Development

Normal fetal development of the GU structures begins with successive development of pronephric, mesonephric and metanephric tubules around the third, sixth, and twelfth weeks of gestation in the em-bryo,respectively.After 12 weeks,the urinary bladder has developed and separated from the rectum. The prostate and testes in boys, and the ovaries and uterus in girls, are also formed at approximately 12 weeks gestation. The vagina develops somewhat later. After birth, prostatic and vaginal-uterine growth proceeds very slowly until adolescence, when the organs enlarge during pubertal growth.

Bladder Ureter and Urethra

Radiation can induce inflammation and fibrosis and cause dysfunction due to a reduction in bladder capacity and contractility. Although it is not certain, the underlying etiology seems to be radiation-induced vascular ischemia of the muscular wall 9-11 . The risk of developing bladder dysfunction is related to both the radiation dose and the percentage of the bladder wall irradiated 9, 12 . In data compiled in adults, it is clear that a small volume of the bladder can tolerate fairly high does of radiation 9, 12 , (Radiation for prostate or bladder cancer in adults routinely results in irradiation of portions of the bladder with 60-70 Gy.) However, high doses may cause focal injury to part of the bladder wall, resulting in bleeding and stone formation 13-17 . It is believed that stone formation is associated with bac-teruria, which can occur after damage to the bladder. When the entire bladder is irradiated, doses of 50 Gy may result in severe contraction and secondary whole organ...

What is the usefulness of tumour markers in disease management

The decision to test for tumour markers can depend ultimately on a clinician's management for a patient. To provide patient care, several guidelines have now been produced by a number of expert panels. Examples include guidelines by the ASCO. It recommends that only oestrogen receptor and progesterone receptor values are of benefit in predicting which breast cancer patients are suitable for endocrine therapy (ASCO, 1996, 1998 Hammond and Taube, 2002). The College of American Pathologists (CAP) has evaluated tumour markers, in both 1994 and 1999, and has identified those that it recommends for clinical use for breast, prostate and colon cancer (Henson et al., 1995 Hammond et al., 2000 Hammond and Taube, 2002).

Useful markers for disease management

The guidelines agreed, with the exception of prostate cancer, that tumour markers, (primarily as a result of specificity and sensitivity) should not be used for screening. Otherwise, they are involved in staging and prognosis, detection of recurrence, follow-up and monitoring. The most common serum tumour markers used as surrogates, to monitor the course of disease during and after treatment, in clinical use are CA-125 for ovarian cancer, CA19-9 for ovarian cancer, CEA for colorectal cancer, prostate-specific antigen (PSA) for prostate cancer, and AFP and p-human chorionic gonadotrophin (p-hCG) together with the isoenzyme lactic acid dehydrogenase (LDH) for germ-cell tumours. Prostate-specific antigen (PSA) is another controversial marker as a result of the false-positive and false-negative results when used as a screening test. When used for screening in men aged over 50 years, or those at high risk (family history of prostate cancer), it is necessary to include a digital rectal...

Comparison of Technologies

Ribozymes as well as siRNAs can lead to nonsequence-specific effects (offtarget effects) that are strongly dependent on the concentration of oligomers. However, it should be stressed that the double-stranded siRNAs may result in two single-stranded oligomers, which yield more pronounced off-target effects than those obtained with an equal molar amount of ribozymes (89). Furthermore, it has been reported that ribozymes are much more sensitive to polymorphisms at the cleavage site level (89). This phenomenon can contribute to reduce the possibility of ribozyme-mediated off-target effects with respect to siRNAs. Although in a large number of studies reported thus far siRNAs have been shown to be effective in a broad range of experimental models, they can be potent inducers of stress-response pathways. Such a phenomenon that could depend on the different cellular environments would compromise the efficacy of the siRNA-mediated gene silencing. In fact, it has been demonstrated that...

Transforming Growth Factora

HER2 can be overexpressed on epithelial tumor cells, including breast, non-small cell lung, prostate, ovarian, bladder, and pancreatic carcinomas, and Wilm's tumor (Agus, Bunn, Franklin, Garcia, & Ozols, 2000 Menard, 2001). The correlation between HER2 gene amplification and its overexpression in breast cancer is undisputed. In a landmark study, Slamon et al. (1987) demonstrated that the HER2 neu oncogene was amplified from 2- to greater than 20-fold in 30 of breast cancers. HER2 neu gene amplification is associated with a more aggressive form of breast cancer characterized by significantly diminished disease-free and overall survival rates. A variety of studies using transfected cells improved understanding The roles of HER3 and HER4 in human cancers are not as well described as for EGFR and HER2. A product of erb-b3 expression is the pl80e,bB3 protein, which can be overexpressed in a variety of cancers, including breast, ovarian, cervix, pancreas, stomach, colon, and prostate...

Relevant Pelvic Anatomy

To describe the node-bearing fatty tissue that surrounds the extraperitoneal rectum. It is covered by a visceral fascia. Between this visceral fascia and the lateral pelvic wall is an areolar plane, the identification of which is essential for sharp mesorectal excision. Posteriorly, the visceral and lateral or parietal fasciae fuse into the rectosacral fascia. This tethers the posterior rectum into the sacral hollow, and the division of this is required for low anterior resection. Anteriorly, the perirectal fat abuts Denonvilliers' fascia. Denonvilliers' fascia envelops the seminal vesicles and fuses with the prostate fascia. In women, the perirectal fat abuts the rectovaginal septum. In the upper pelvis posterior to the superior hemorrhoidal vessel is nerve-bearing tissue. This is within Waldeyer's fascia. The sympathetic nerve trunks reside within this plane. The main parasympathetic nerve trunk necessary for erection and orgasm is S3. This nerve exits in the mid pelvis just distal...

Preparation Of The Patient

It is important to stage the patient as accurately as possible. Preoperative staging should include a physical examination, rigid proctoscopy (the preferred method of scoping the rectum) or flexible sigmoidoscopy, documentation of the location of the tumor as measured from the anal verge, and other features such as the configuration of the tumor (i.e., sessile, ulcerated, or exophytic), circumferential, its location along the rectal circumference, the presence or absence of extramural palpable disease (i.e., mesorectal nodes), attachment to the vagina or prostate, and whether there was prior pelvic surgery or radiation therapy. Preoperative colonoscopy or double-contrast barium enema is indicated to rule out synchronous cancers.

Posterior Lobe or Neurohypophysis

The paraventricular nuclei predominantly manufacture oxytocin, which is a smooth muscle-contracting hormone. Oxytocin plays an important role in inducing the contractions of the uterine walls during the birth process that is, oxytocin is responsible for labor pains. In addition, it is required for the release of milk in response to suckling. In males, oxytocin regulates prostate gland function.

Molecular Monitoring Of Human Cancers In Blood And Prognostic Implications

From patients with colon cancer, and MGMT, DAPK, or GSTP1 hypermethylation was found in plasma and serum from patients with lung cancer, prostate cancer, or head and neck cancer (Table 14.1).30'313435 The peripheral blood MSP analysis can be easily conducted for widespread cancer screening and the monitoring of patients' response to therapies, such as surgical resection, chemotherapy, or radiotherapy.56

Dna In Urine From Patients With Cancer

As compared to urinary cytological analysis, the methylation analysis of DNA in urine from patients with bladder cancer may predict tumor recurrence with higher sensitivity.5758 Moreover, tumor DNA may be enriched in urine of patients with bladder cancer, enabling the detection of tumor cells at very early stages. Methylated DAPK, A p, E-cadherin, and p16INK4a sequences were frequently found in the urine of patients with bladder cancer (Table 14.2).59 Tumor DNA was also found in urine from patients with renal cell carcinoma or prostate cancer,44 and hypermeth-ylation of six genes was detected in urine of patients with kidney cancer with very high specificity and sensitivity.60

Methylation Profiling Of Tumor Cells And Tumor Dna In Other Body Fluids From Patients With Cancer

Prostate cancer ples from patients with a variety of cancers (Table 14.2).2 Epigenetic alterations occur early in primary neoplasia, and promoter hypermethylation is an early phenomenon in premalignant or morphologically benign lesions. Many research groups have analyzed epigenetic markers in body fluids of patients with cancer as compared with healthy individuals. Tumor-associated methylated DNA was detected in exfoliated tumor cells isolated from body fluids (Table 14.2).62 Thus far, DNA hyperm-ethylation has been found in body fluids from patients with different cancer types, including lung cancer, liver cancer, breast cancer, prostate cancer, head and neck cancer, colon cancer, and acute leukemia.12'29-31'34'55'6364 As opposed to conventional immunocytological detection, molecular detection in body fluids offers higher sensitivity. Prostate specific antigen (PSA) has been applied as a protein tumor marker for the diagnosis of prostate cancer with low specificity. Compared to...

Antioxidant Antiinflammatory Activity

Moreover, COX-2 regulates or participates in a number of different cellular pathways and biological processes important in carcinogenesis. Expression of COX-2 is increased in many types of human cancers (e.g. colon, oesophagus, lung, breast, pancreas, prostate) and precancers. COX-2 inhibitors have potent chemopreventive activity in animal models of colon, bladder and skin carci-nogenesis. In a recent clinical study the COX-2 inhibitor celecoxib significantly reduced the number of colorectal adenomas (which are precancers) in patients with familial adenomatous polyposis (FAP), supporting the concept that COX-2 inhibitors may have therapeutic utility against colorectal cancer and gaining FDA approval for celecoxib use in treatment of FAP (see the chapter Chemoprevention).

Theodore J Saclarides

The benefits of pelvic radiation for prostate, endocervical, and anorectal malignancies have been well established, but many patients experience distressing side effects of treatment. The rectum is most frequently injured by radiation because of its fixed location within the pelvis and its proximity to the treated area. Such injuries include rectovaginal fistulas, anorectal strictures, and hemorrhagic proctitis. Although the treatment of rectovaginal fistulas is covered in detail elsewhere in this text, the principles of surgery are mentioned here. The small bowel may be injured as well, but this occurs much less commonly than rectal injuries, because modifications of the treatment method can be implemented to reduce the possibility of injury. Small bowel injuries may be manifested by obstruction, diarrhea and malabsorption, and fistulas to adjacent organs these are not discussed here.

Incidence Of Complications

Fortunately, only a small percentage of patients develop chronic problems. After radiation for prostate cancer, the incidence of moderate complications of proctitis is 5 enteritis, 1 and anorectal stricture or fibrosis, 1 . The incidence of severe complications is less than 1 . Most injuries become manifest within 2 to 5 years after radiation.1 Risk factors for the development of injuries include widening the radiation field to include pelvic lymph nodes in addition to the prostate, a history of diabetes and prior pelvic surgery, age of less than 60 years, and the use of split course rather than a continuous course of treatment. After radiation for cervical cancer, approximately 1 of patients develop proctitis and 1.5 develop rectovaginal fistulas. If high-

Screening And Early Detection

There are three primary types of screening programmes, based on the stage of malignancy that is targetted. Some screening programmes are designed to detect precursor lesions, before they become invasive cancers and are very effective when removal of the pre-invasive lesion is curative. The Papanicolaou (PAP) test for cervical cancer is the model for this type of cancer screening and has significantly contributed to reduction in death from cervical cancer in developed countries by identification and treatment of the preinvasive lesion (cervical intraepithelial neoplasia) (Miller et al, 2000). 'Organ-confined' invasive cancer screening is exemplified by detection of prostate cancer by elevated levels of serum prostate-specific antigen (PSA). Screening for breast cancer by mammography detects both small invasive breast cancers that cannot be identified by physical examination as well as the preinvasive ductal carcinoma in situ. As our understanding of cancer on the molecular level...

Tumour Classification

One of the most challenging problems to a surgical pathologist is the diagnosis of a poorly differentiated tumour when no primary site is clinically evident. From a therapeutic perspective, it is most critical to correctly identify those tumours for which there is effective specific systemic chemotherapy or hormonal therapy, such as for lymphomas and metastatic carcinomas of the breast, prostate and ovary. Although extensive radiological and endoscopic work-ups can be done, these are often uninformative, expensive and may have significant morbidity. Frequently the use of antigenic markers can be helpful in narrowing the possibilities and a likely site can be suggested based on clinical setting, subtle morphological features of the tumour combined with a limited immuno-histochemical panel of antibodies. Among the most useful antigens in this setting are the intermediate filaments that composed the cell's cytoskeletal framework (Table 3). A large number of antibodies that are helpful in...

Tumour Markers and Prognostic Markers

In a broad sense, tumour markers are molecules or substances that are produced by tumours or in response to tumours that can be used for early detection, diagnosis, prediction of disease progression and monitoring response to therapy. Many tumour markers are substances normally produced by the tissue of origin such as prostate specific antigen (prostate) or a-fetoprotein (liver and germ cell tumours) and can be elevated in both benign and malignant processes. A great number of tumour markers have been Markers are most useful when linked to specific pharmacological therapy or other forms of intervention based on the results. Her2 neu amplification in breast cancer predicting responsiveness to therapy with Herceptin has already been mentioned and is now also being evaluated in other cancers such as lung and prostate. Similarly for lymphomas that express CD20 antigen, antibody therapy with Rituximab is effective. On an investigational basis,

Minimal Residual Disease

Unfortunately, the genetic abnormalities are much more heterogeneous in the common malignancies of adults such as breast, prostate, lung and colon cancers. However, these malignant cells continue to express markers characteristic of their cell of origin and identification of a tissue-specific mRNA can be used to recognize MRD. For example, even very poorly differentiated metastatic prostate cancer to lymph nodes often express PSA mRNA, sometimes even when no protein is detectable by antigenic methods. Detection of micrometastasis by molecular methods is likely to have a profound impact on how cancer patients are treated and monitored in the future. For further information, the reader is referred to a recent review (Ghossein et al., 1999).

Formulation Applications

Leuprolide, used for the palliative treatment of prostate cancer, was formulated at 370 mg ml in DMSO within an osmotically-driven implantable pump lasting 1 year, where the choice of DMSO provided 2 year room temperature shelf life, plus 1 year of implant life at 37 C (Stevenson et al., 1999 Wright et al., 2001).

Causes of Pelvic and Rectal Pain

In the male patient, chronic or acute prostatitis may present as rectal or pelvic pain. Urinary symptoms are often present and should be elicited in questioning. Digital rectal examination in men should always include careful prostatic palpation to exclude these conditions. Transrectal ultrasound may be helpful to diagnose pelvic pain, revealing pathology of the male reproductive organs. In women, tubo-ovarian infections, ectopic pregnancy, endometritis, and endometriosis are potential sources of pelvic pain. Bimanual pelvic examination with speculum visualization of the cervix will usually suffice to eliminate these concerns. Occasionally, ultrasonography or CT of the pelvic viscera is necessary to complete the evaluation.

Presentation and diagnosis

Patients with vasculitis may present with isolated pulmonary haemorrhage, but usually there is also systemic involvement. Most patients with Wegener's granulomatosis have granulomatous lesions in the upper respiratory tract which result in chronic sinusitis, epistaxis, chronic otitis media, and deafness. Involvement of the trachea can present with life threatening stridor. Granulomas are also found in many sites outside the respiratory system including the kidney, central nervous system, prostate, parotid and orbit.3 Patients with microscopic polyangiitis and Wegener's granulomatosis also present with systemic symptoms secondary to the small vessel vasculitis. Urine abnormalities include microscopic haema-turia and proteinuria, with red cell casts on microscopy. The serum creatinine may initially be in the normal range, but acute renal failure tends to develop quite rapidly. Renal and respiratory involvement both have a significant effect on mortality.3 24 25 Other organs in which...

Evidence as the dominant driver

The casual reader of the article by Stern et al might erroneously construe that ACS supports mass screening. Studies have shown that when men are provided with more formal information regarding early detection testing for prostatic cancer, many decline it. The ACS is concerned that men may be undergoing screening without proper pre-test guidance and education and agreed that routine serum prostate specific antigen (PSA) measurement is not appropriate without such education. As was the case with testing for the human immunodeficiency virus, serum PSA measurement should not be bundled in among other routine blood studies that do not require any preamble discussion. The ACS is also concerned that clinicians who do not let men know that early detection testing for prostate cancer is available vitiate a man's right to choose to undergo a relatively simple test that could conceivably save his life.7

Who should make valuedrive decisions

4 Selley S, Donovan J, Faulkner A, Coast J, Gillatt D. Diagnosis, management and screening of early localised prostate cancer. Health TechnolAssess 1997 1(2) 1-96. 5 Chamberlain J, Melia J, Moss S, Brown J. The diagnosis, management, treatment and costs of prostate cancer in England and Wales. Health Technol Assess 1997 1(3) 1-53. 6 Stern S, Altkorn D, Levinson W. Detection of prostate and colon cancer. JAMA 1998 280 117-18. 7 Rosenthal DS, Feldman G. Talking with patients about screening for prostate cancer. JAMA 1999 281 133.

Pathogenesis Of Stromal Invasion

Adhesive interactions in premalignant lesions do not differ significantly from those encountered in benign prostate tissue. Dramatic changes occur during early stromal invasion when the transformed epithelium loses basal cell differentiation (Bonkhoff, 1998c). This process is associated with the loss of a number of hemidesmosome-forming proteins and associated adhesive molecules, including collagen VII, P3 and y2 subchains of laminin 5, Another important event in early stromal invasion refers to the synthesis of tumor-associated basement membranes (Bonkhoff et al., 1991b, 1992). Invasive prostate cancer cells produce basement membrane-like matrices to invade the host tissue, and express associated integrins (a6P1, a2P1) that mediate attachment to this newly formed matrix (Bonkhoff et al., 1991b, 1992, 1993a) (Fig. 5). This particular tumor-host relation encountered in prostate cancer is maintained through the various stages of the disease, including high-grade, metastatic, and...

Novel Integrated Approach to MicroRNA Identification

We started out by computationally scanning the entire human genome for hairpin structures. This was a daunting computational task that had not been attempted before. We then scored each hairpin for its similarity to known microRNAs, using PalGrade, a novel algorithm we developed. Next, we determined the expression levels of high-scoring postulated microRNAs in six tissues (placenta, testis, thymus, brain and prostate). Finally, we validated microRNAs, the expression of which was detected by the microarray, using a novel sensitive sequencing technique we developed. This sequencing technique uses a specific biotinylated capture oligonu-cleotide, designed for the predicted microRNA to be cloned, to 'fish out' the

Paraneoplastic Syndromes

Figure 47-4 Evaluation of paraneoplastic syndromes. AFP, alpha-fetoprotein CEA, carcinoembryonic antigen CT, computed tomography CXR, chest x-ray study EEG, electroencephalogram EMG NCV, electromyography nerve conductor analysis hCG, human chorionic gonadotropin LDH, lactate dehydrogenase LEMS, Lambert-Eaton myasthenic syndrome PSA, prostate specific antigen MRI, magnetic resonance imaging. TAH BSQ, total abdominal hysterectomy bilateral salpingo-oophorectomy.

Incidence And Epidemiologic Associations

Modified Dukes Staging

Colorectal cancer ranks third behind prostate and lung cancer in men and behind breast and lung cancer in women as the most common malignancy in the United States. It is the second leading cause of cancer deaths, accounting for approximately 10 of deaths from cancer. An estimated 130,000 patients will be newly diagnosed with bowel cancer in 1999, and 57,000 deaths will occur.1 The probability of colorectal

Cell Divisions During Spermatogenesis

Cross Sectional Seminiferous Tubules

Prostate gland Function of the Prostate Gland The prostate gland secretes a thin, milky fluid that contains calcium, citrate ion, phosphate ion, a clotting enzyme, and a profibrinolysin. During emission, the capsule of the prostate gland contracts simultaneously with the contractions of the vas deferens so that the thin, milky fluid of the prostate gland adds further to the bulk of the semen. A slightly alkaline characteristic of the prostatic fluid may be quite important for successful fertilization of the ovum, because the fluid of the vas deferens is relatively acidic owing to the presence of citric acid and metabolic end products of the sperm and, consequently, helps to inhibit sperm fertility. Also, the vaginal secretions of the female are acidic (pH of 3.5 to 4.0). Sperm do not become optimally motile until the pH of the surrounding fluids rises to about 6.0 to 6.5. Consequently, it is probable that the slightly alkaline prostatic fluid helps to neutralize the acidity of the...

Anticipate a Long Difficult Case and the Need for Other Specialists

Figure 40-2 Close view of narrow pelvic retractor. Unlike the lighted Goligher straight-blade retractor, this allows for vigorous elevation of the prostate and bladder base away from the rectum or the low rectum and mesorectum from the sacrum. (This is the senior author's preferred retractor.)

Cellular Biology Of Prostatic Epithelium

The prostatic epithelium has a complex composition of three cell types differing in their hormonal regulation and marker expression (Fig. 2). The most prevalent phenotype consists of secretory luminal cells expressing prostate-specific antigen (PSA) and cytokeratins (CKs) 8 and 18 (Nagle et al., 1991 Xue et al., 1998). Basal cells, the second most important phenotype, maintain normal epithelial-stromal relation and express high-molecular-weight cytokeratins (Wernert et al., 1987 Bonkhoff, 1996). The third phenotype shows neuroendocrine differentiation. Neuroendocrine cells express chromogranins and secrete a number of neurosecretory products that may have growth-promoting properties (Di Sant'Agnese, 1992 Di Sant'Agnese and Cockett, 1996). Although these basic cell types clearly differ in their biological functions, they obviously share a common origin from pluripo-tent stem cells located in the basal cell layer (Bonkhoff, 1996a Fig 1. Zonal anatomy of prostate. The prostate of a...

Syndromes of Lesions Involving Peripheral Branches of Cranial Nerve V

The numb chin syndrome (mental neuropathy) often reflects a bony lesion affecting the mental foramen through which V3 passes to innervate the chin and mandible.y , y Patients often report numbness or pain on one or both sides of the chin, which may extend to the lip or submandibular region. Frequent causes include granulomatous diseases such histiocytosis X primary bony malignancies such as osteosarcoma, fibrosarcoma, and plasmacytoma and metastatic lesions from lung, breast, and prostate carcinomay as well as lymphoma (especially Burkitt's lymphoma). Development of a numb chin in a patient with cancer in remission may indicate relapse. Nonmalignant etiologies include collagen vascular disorders, trauma, periodontal disease, benign bony cyst, focal idiopathic osteolysis (Gorham's disease),y and sickle cell disease. A variant of the numb chin syndrome is the numb cheek syndrome, which results from a bony lesion affecting the infraorbital foramen or the maxillary sinus and trigeminal...

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

In patients with lung cancer, APC hypermethylation was commonly detected in plasma or serum by quantitative real-time methylation-specific PCR (MSP).40 DNA methylation was also found in plasma or serum from patients with colorectal cancer, liver cancer, or esophageal cancer.29344142 Circulating tumor DNA was detectable in plasma or serum of patients with bladder cancer, renal cell carcinoma, or prostate

Incidence of Somatostatin Receptors in Human Tumors

Colony Forming Ells

Somatostatin receptors are expressed or even over-expressed also in several nonendocrine cancers. They were revealed, among others, in breast cancer tumor samples and cell lines. The positive immunostaining with sst2A and or sst2B antibodies was detected in 85 of breast cancer samples.21 Even the higher percent of the investigated samples (98 ) expressed sst2 mRNA.22 The remaining subtypes were also identified, either by immunohistochemis-try, or by PCR. The immunopositivity for sst1 were detected in 52 and in 42 for sst3.21 The presence of mRNA for sst1 was detected in 91 of samples, and for sst3, sst4 and sst5, in 96 , 76 and 54 of samples, respectively.22 The expression level of sst2 receptors is higher in cancer tissue than in nonneoplastic surrounding tissues.23 The incidence of sst1, 2 and 4 correlate positively with estrogen receptor levels, and sst2 additionally with progestrone receptors.22,23 Moreover, high level of sst2 negatively correlated with proliferative potential of...

Routine laboratory tests

These should include a blood sugar and a fasting lipid profile in all men with ED without a diagnosis of diabetes mellitus or dyslipidemia, respectively. A PSA should be determined in the case of abnormal findings during palpation of the prostate, or as per the physicians' PSA screening protocol. A urinalysis is also helpful to look for glucose, ketones and protein-uria, as well as blood and white blood cells.

Differentiation And Proliferation Disorders In Early Phases Of Prostatic Cancerogenesis

HGPIN is the most likely precursor of prostate cancer (Bostwick, 1996 Montironi et al., 1996). This lesion usually arises in preexisting ducts and duct-acinar units of the peripheral zone and shares cytological features with intermediate and high-grade carcinoma but retains basal cell differentiation (Bostwick, 1996). Autopsy studies indicate that PIN precedes carcinoma by 10 yr and more. HGPIN is currently the most significant risk factor for prostate cancer. Its identification in prostatic biopsy specimens warrants further searches for concurrent cancer (Bostwick, 1996). The role of estrogens in the malignant transformation of the prostatic epithelium appears even more complex. Epidemiologi-cal and experimental data suggest that estrogens may exert can-cerogenic and chemopreventive effects on the prostatic epithelium (Chang and Prins, 1999 Griffiths, 2000 Steiner et al., 2001). This apparent contradiction obviously reflects the presence of two distinct estrogen receptors (ERa and...

Penile Length Alterations

There are a total of three analyses on this issue in the literature. Fraiman et al. studied 100 men less than six months after radical prostatectomy, and took preoperative and postoperative flaccid and erect measurements and demonstrated an overall mean reduction in erect penile length of 9 but a mean reduction in volume of 22 1 . Munding et al. studied 31 men and measured penile length in the stretched flaccid state (accepted as equivalent to erect length) and showed that 71 had a decrease in penile length compared to preoperatively, with 48 of men demonstrating greater than a 1 cm loss and a range of loss of 0.5-4cm 2 . Finally, Savoie et al. studied 63 patients with preoperative measurements followed by repeat measurement, at three months postopera-tively, and demonstrated that 68 of patients had some degree of length loss. The authors also showed that in this population there was no difference between patients with erectile dysfunction (ED) and those without, postoperatively 3 ....

Reproductive and Hormonal Functions of the Male and Function of the Pineal Gland

Figure 80-1A shows the various portions of the male reproductive system, and Figure 80-15 gives a more detailed structure of the testis and epididymis. The testis is composed of up to 900 coiled seminiferous tubules, each averaging more than one half meter long, in which the sperm are formed. The sperm then empty into the epididymis, another coiled tube about 6 meters long. The epididymis leads into the vas deferens, which enlarges into the ampulla of the vas deferens immediately before the vas enters the body of the prostate gland. Two seminal vesicles, one located on each side of the prostate, empty into the pro-static end of the ampulla, and the contents from both the ampulla and the seminal vesicles pass into an ejaculatory duct leading through the body of the prostate gland and then emptying into the internal urethra. Prostatic ducts, too, empty from the prostate gland into the ejaculatory duct and from there into the prostatic urethra. Prostate gland

Preclinical Studies

The non-nucleoside telomerase inhibitor BIBR1532 was identified by Boehringer Ingelheim and their academic partners (Damm et al. 2001). Long-term culture in BIBR1532 reversibly inhibited telomerase activity and decreased telomere lengths in lung, breast, prostate, and fibrosarcoma cancer cells. No short-term effect on cell proliferation was observed, but delayed onset growth retardation was shown, consistent with the predicted phenotypic lag expected of classic telomerase inhibitors. Growth inhibition was independent of p53 status, and the drug also inhibited growth of xenografts after oral administration. The authors stated that no effects on growth of normal lung fibroblasts were observed. BIBR1532 inhibits recombinant telomerase in vitro by a mixed-type noncompetitive mechanism, reducing the affinity of telomerase for deoxyribonucleotides and inhibiting formation of long reaction products without significantly affecting binding to the DNA primer (Pascolo et al. 2002). High...

Alterations in Orgasm

Most of the post-radical prostatectomy sexual dysfunction literature has focused specifically on erectile dysfunction, and changes in orgasm have been reported in post-prostatectomy patients 14-16 . Orgasm, which is often considered to be a goal and reinforcer of sexual behavior, remains the least understood phase of the sexual response cycle. Alterations in orgasm, and in particular its absence, are associated with significant reductions in emotional and physical satisfaction, which in turn may lead to sexual avoidance behavior and secondary relationship discord 17-18 . (dysorgasmia) at some time after surgery. Goriunov etal. have reported on orgasm alterations in surgically-treated BPH patients 15 . This group reported that 188 of 818 (23 ) such patients suffered from dysorgasmia after their surgery. Koeman reported pain during orgasm in 11 post-radical prostatectomy patients, and 82 complained of diminished orgasmic intensity after surgery 16 . Bergman's study of 43 men who had...

Trks And The Regulation Of Cancer Growth

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

Embryology of the Penis

The penis develops from the genital tubercles and the urethra from the genital folds (in the female labia minora). The genetic sex (XY) induces testicular development, with the help of the sex-determining factor located on the Y chromosome 1 . Differentiation of the external genitals (male phallus female clitoris) from the genital tubercles occurs when testosterone production begins in the Leydig cells in the 8th 9th embryonal week. The penis grows very rapidly and is fully developed along with the urethra at the 4th fetal month. Growth of the penis and the scrotum, as well as differentiation of the prostate from the urogenital sinus, are regulated by dihydrotestosterone (DHT), which is converted from testosterone by 5a-reductase in peripheral tissues. Androgen-induced genital development occurs via specific androgen receptors, which have increased affinity to DHT. The gene for the androgen receptor is located on the long arm of the X chromosome 2 .

Clinical picture of hypogonadism

Androgen production is minimal and hypogonadism will not manifest itself. Hypogonadism at the normal time of puberty will result in a typical syndrome of eunuchoidism. Epiphyseal cartilage does not stop growing, so the long bones continue to grow, resulting in a ratio of upper to lower body

Evidence For Renal Stem Cells

They demonstrated that the number of potential contaminating mesenchymal cells was not sufficient to account for the quantity of nephron-like cells generated by the isolated ureteric buds. Assuming then that contamination was highly unlikely, they hypothesized that the collecting system forms, at least in part, from recruitment of metanephric mesenchymal cells. In contrast to the previous studies, they postulated that the metanephric mesenchymal cells are the progenitors of the entire kidney (Qiao et al., 1995). They proposed that this occurs via a series of mesenchyme-to-epithelium and epithelium-to-mesenchyme transitions whereby the metanephric mesenchyme gives rise to ureteric bud epithelium, which then switches back to metanephric mesenchyme, which, in turn, eventually converts again to nephron epithelia (Fig. 2). The exact sequence of events is as yet unknown. Simplis-tically, the metanephric mesenchyme is an intermediate through which both types of epithelia arise therefore, it...

Angiogenesis Inhibitors Encrypted within Larger Proteins

More recently discovered endogenous angiogenesis inhibitors are angiostatin and endostatin (for reviews, see Kim Lee Sim, 1998 Oehler and Bicknell, 2000). Angiostatin is a 36-kDa fragment of plasminogen which is cleaved by macrophage-derived MMPs or proteases derived from tumours (e.g. prostate carcinomas). Endo-statin is a 20-kDa fragment of collagen XVIII. Systemic administration of both angiostatin and endostatin induces tumour regression by destruction of the tumour vascu-lature. They also inhibit the formation of new blood vessels in a tumour. They therefore maintain a tumour in a state of

In Vivo Delivery of Antisense Oligonucleotides

Cells With Confluency

Inhibition of Raf-1 protein expression in human prostate (DU-145) and breast cancer cells (MDA-MB 231). Tumor cells were treated with indicated concentration of phosphorothioate c-raf ASO (ASR1, ISIS 13650 ASR2, ISIS 5132) or a mismatch ASO (MM, ISIS 10353). Cells were grown to 80 confluency in improved minimum essential medium containing 10 fetal bovine serum (FBS) and 2 m L-glutamine. For ASR1 treatment, on day 1 cells were treated with indicated concentration of ASO or MM for 6 h in the presence of lipofectin (15 pg mL) in medium containing 1 FBS. Cells were then washed twice with 10 FBS containing medium and maintained overnight in 1 FBS containing medium in the presence of indicated concentration of antisense oligonucleotides (ASO) or MM. On day 2, cells were treated as on day 1. On day 3, Raf-1 expression was detected in cell lysates by Western blotting using monoclonal anti-Raf-1 antibody. The blots were reprobed with polyclonal anti-GAPDH antibody. For ASR2 treatment,...

Lower Urinary Tract Symptoms LUTS

There has been a recent increased interest in the association between LUTS and ED, both conditions being prevalent among older men. Recent epidemiologic data support such a link. El Sakka recently studied 476 male patients with ED and reported that 77 suffer from LUTS of those, 22.8 had mild, 42 had moderate, and 35.2 had severe grades of ED. Significant associations between LUTS and both the longer duration and the increased severity of ED, were also observed 69 . Suggested mechanisms for the postulated LUTS-ED association include (1) decreased or altered NOS NO levels in the prostate and penile smooth muscle (2) increased adrenergic tone effects on LUTS, prostate growth and ED (3) alternate pathway mechanism Rho kinase activation endothelin activity and (4) pelvic atherosclerosis 70 .

Risks of androgen therapy

Benign prostatic hyperplasia It is well recognized that the development of benign prostatic hyperplasia requires the presence of andro-gens and that the marked reduction in serum T caused by chemical or surgical castration reduces prostate volume. However, multiple studies 176 have failed to demonstrate exacerbation of voiding symptoms attributable to benign prostatic hyperpla-sia during T therapy, and complications such as urinary retention have not occurred at higher rates than in controls receiving placebo. The literature on the effect on prostate volume with exogenous T in middle-aged and older men with clinical features of symptomatic LOH (SLOH) is controversial. Pechersky et al. found that prostate growth can be retarded or even reversed with androgen therapy 177 . Others found that prostate volume, as determined by ultrasonography, increases significantly during T therapy, mainly during the first six months, to a level equivalent to that of men without hypogonadism. However,...

Overlapping Diseases and Points of Confusion

And twenty men with ED or benign prostatic hyperplasia (BPH) were divided into three groups. Group 1 had ED only, group 2 had BPH only, and group 3 had both ED and BPH. Patients were screened for depressive symptoms using Primary Care Evaluation of Mental Disorders (PRIME-MD) and the Beck Depression Inventory (BDI). They were also surveyed for comorbidity, marital status, severity of ED, levels of libido, prior ED treatment choice (if any), success of treatment, and others. Depressive symptoms were reported by 26 (54 ) of 48 men with ED alone, 10 (56 ) of 18 men with ED and BPH, and 7 (21 ) of 34 men with BPH alone. Patients with ED were 2.6 times more likely to report depressive symptoms than men with BPH alone (P 0.005). Patients with depressive symptoms reported lower libido than other patients (P 0.0001). Severity of comorbidities did not differ among the three groups. The conclusion is that ED is associated with high incidence of depressive symptoms, regardless of age, marital...

Screening for hypogonadism in sexual dysfunctions

Testosterone determination is not necessary in the other sexual dysfunctions, unless clinical signs of hypogonadism are associated. Some men using the 5a reductase inhibitor, finasteride, for benign prostate hyperplasia, experience an impact on sexual function, especially on ejaculation, although these effects are relatively rare 158 .

Chronic daily dosing of PDE5 inhibitors

Although all three PDE-5 inhibitors were developed and approved for as-needed use, many experts in this field moved to daily dosing, provided the patients could afford it. Daily dosing of PDE-5 inhibitors at bed time became a successful treatment option in early sexual rehabilitation of patients after nerve-sparing radical prostatectomy 116-118 . But beyond this indication, daily dosing with PDE-5 inhibitors turned out to be very successful in non-responders to on-demand treatment 113 , supported by personal observations and also increased nocturnal erection events in healthy men 119-120 . According to personal experience with more than 100 patients currently on daily dosing with tadalafil 5-10 mg, this concept is very promising for organic ED patients with several cardiovascular risk factors, and relieves the patients from scheduling sexual activities. This is especially welcomed by their partners. In addition, chronic dosing with PDE-5 inhibitors, either short-acting (here...

Cavernous nerve interposition grafting

The first report was by Kim et al. from Baylor discussing their experience with nine men, with excellent preoperative erectile function, who underwent non-nerve-sparing RP for locally extensive, highgrade prostate carcinoma 52 . All underwent bilateral sural nerve interposition grafting (SNG). Postoperative erectile function was assessed using patient interview, a questionnaire and Rigiscan analysis. Of the nine patients, one had spontaneously functioning erections at 14 months postopera-tively. This experience demonstrated feasibility and encouraged these investigators to continue to accrue patients for SNG. The following year, they reported on their experience in 12 men in whom SNG and genito-femoral nerve interposition grafting (GNG) was performed 53 . The data from this analysis indicated that erections unassisted by medication and sufficient for sexual intercourse occurred in one third of patients partial erections occurred in 42 , while the remainder had no return of erections....

Etiology of Hypoactive Sexual Desire

Hypoactive sexual desire is frequent in men with erectile dysfunction. In a series of 428 men with erectile dysfunction, Corona and co-workers (2004) 5 reported that 43.3 of their participants had the condition. This group found no correlation for patient or partner's age. Men with HSD in this study were not diagnosed as hypogonadic more frequently than men without HSD however ANOVA showed a significant (P 0.005) difference of total, free testosterone and prolactin levels among patients with different severities of HSD. No significant correlation was found for follicle-stimulating hormone (FSH) (r 0.04), luteinizing hormone (LH) (r 0.04), thyroid-stimulating hormone (TSH) (r 0.06), or testis volume (r -0.08). No correlation was found for prostate specific antigen (PSA), blood pressure, lipid profile, glycemia, and parameters derived from

Initiation of treatment and followup

The second annual Andropause consensus meeting recommended performing DRE and serum PSA before treatment, at three and six months, and yearly thereafter 215 . In addition to that recommendation, a PSA level could be obtained one month after initiation of therapy to capture the patient with a previously undiagnosed prostate cancer that may be behaving in a very aggressive fashion following T-replacement. ISSAM and WHO guidelines also recommend periodic hematologic assessment, i.e.

Mechanism of action and conversions

The testis has a dual function spermatogenesis and the production of T. The latter takes places in the Leydig cells. The daily production of T in adulthood is about 5-7 mg. T diffuses passively into cells of the target organs of androgens. To exert its biologic action, it must bind to the androgen receptor, though there are also a number of biologic actions of T that do not require receptor activation. For some of its biologic actions T is a prohormone. After diffusion into the cell, T may be converted to 5 a-dihydrotestosterone (DHT) or estradiol. There are two types of 5 a-reductase enzymes that convert T to DHT. 5a reduc-tase type 1 is predominantly located in skin, liver, and brain whereas 5a reductase type 2 is almost exclusively distributed in the classical androgen-dependent organs such as prostate,seminal vesicles, and testicles. DHT and T bind to the same androgen receptor, although DHT has an approximately tenfold greater affinity for the receptor and its dissociation is...

Table 9 Aspects of chemoprevention at major cancer target sites3

Prostate Age 50 years familial history of prostate cancer high serum testosterone high-fat diet high red meat consumption population geographical background (highest incidences in Canada and northwest Europe) prostatitis, genetic polymorphisms (e.g. in SRD5A2, gene for steroid 5-reductase) low micronutrient levels (e.g. selenium, carotenoids, vitamin D) Patients scheduled for radical prostatectomy patients with PIN patients with cancer on biopsy, treated by watchful waiting patients at high risk of biochemical failure or rising PSA postradical prostatectomy subjects with positive family history

Monoclonal Antibodies That Are Currently Used In Cancer Therapy

(EGFR), which were approved by the FDA for the treatment of colorectal cancer ( ). The EGFR transmits the mitogenic action of the EGF family of growth factors, such as EGF, transforming growth factor TGFa, HB-EGF (heparin-binding epidermal growth factor), BTC (betacellulin) and epiregulin (Modjtahedi and Dean, 1994 Mendelsohn, 2001). From histological examination of human tumour biopsies, it has become evident that overexpression of EGFR, accompanied by co-production of one or more of its ligands, is a common feature of human tumours of epithelial origin (Modjtahedi and Dean, 1994). Overexpression of EGFR has been detected in cancer of the bladder, breast, lung, brain, stomach, prostate, ovary, pancreas and head and neck. It has been associated with a poor prognosis, as well as resistance to chemotherapy and or radiotherapy, in many patients with these cancers (Modjtahedi and Dean, 1994 Nicholson, Gee and Harper, 2001). Consequently, several laboratories have generated a...


In male rats, castration or the administration of androgen synthesis inhibitors, like cyproterone acetate, disrupt and ultimately eliminate copulatory behaviors and penile reflexes progressively over time. They also shrink androgen sensitive peripheral tissues (e.g. penis and prostate). Although the degree of disruption depends on the amount of androgen synthesis inhibition that is induced (e.g. moderate following low doses of cyproterone acetate to total disruption following castration), the amount of time it takes to reach an asymptotic level of behavioral or reflexive performance depends on the level of sexual experience male rats have prior to treatment. In each case, subsequent exogenous administration of androgens or estrogens can restore sexual interest and copulatory behavior, with nonaromatizable androgens (such as dihydrotes-tosterone) restoring peripheral tissues, and aro-matizable androgens (e.g. testosterone) restoring behavioural measures. As with hypogonadal men,...

The Definition Of Cancer

Bone metastases are commonly associated with malignancies of the breast, prostate, kidney, lung and thyroid. Patients with bone metastases can often present with pain. Pathological fractures are not uncommon due to the damage caused to the bone by the malignant cells - that is, the cancer cells replacing the healthy cells and thereby weakening the bone, making it more prone to fracture (Wolfe, 1986 Walter, 1977).

Pet Imaging Of Reporter Gene Expression Driven By Endogenous Moleculargenetic Processes

Imaging regulation of endogenous gene expression in living animals (and potentially in human subjects) using noninvasive imaging techniques will provide a better understanding of normal and cancer-related biological processes. Modern molecular techniques provide the opportunity to design specific reporter gene constructs, in which the reporter gene is placed under the control of different promoter enhancer elements. For example, they can be always turned on by constitutive promoters (such as LTR, RSV, CMV, PGK, EF1, etc.). Alternatively, the promoter enhancer elements can be constructed to be inducible and sensitive to activation and regulation by specific endogenous transcription factors and promoters (factors that bind to and activate specific enhancer elements in the promoter region of the endogenous genes and reporter vector construct leading to the initiation of reporter gene transcription). Reporter gene expression can be made tissue specific, in which enhancer elements are...

Potentiality Of Adult Epithelial Tissues

Ef1a Promoter Region

Following gastrulation, the mammalian embryo is composed of cells representing the three germ layers that will give rise to all of the tissues of the body. In a simplistic representation, the external surface is covered with a layer of ectoderm that will give rise to the skin, as well as the sweat, mammary, and preputial glands. The endoderm will give rise to the GI tract and those structures, such as the liver, pancreas, prostate, and bladder, that are derived from it. The mesodermal layer, which occupies the space between these surfaces, will give rise to all of the mesen-chymal tissues, including the muscles and connective tissues. As a result of mesenchymal-to-epithelial transitions, mesoderm also gives rise to epithelial structures including the urogenital tract derivatives of the Wolffian and Mullerian ducts (the ureters, epididymis, ductus deferens, and seminal vesicles, and the fallopian tubes and uterus, respectively). The phenomena of metaplasia and transdifferentiation...

What are the symptoms and complications of gonorrhea

When initially infected, about 50 of men have some signs or symptoms. Symptoms and signs include a burning sensation when urinating and a yellowish white discharge from the penis. Sometimes men with gonorrhea get painful or swollen testicles. In men, gonorrhea can cause epididymitis, a painful condition of the testicles that can sometimes lead to infertility if left untreated. Without prompt treatment, gonorrhea can also affect the prostate and can lead to scarring inside the urethra, making urination difficult.

Assessment Of Immune Response With Antigen Arrays

Antigen microarrays have been employed to target other human diseases as well. Different sets of potential antigens and allergens (both peptides and proteins) were used to evaluate auto-antibodies in the sera of patients with systemic rheumatic diseases, autoimmune encephalomyelitis, or multiple sclerosis 69-71 . Recently, tumor-derived proteins have been arrayed and incubated with sera obtained from cancer patients and healthy controls 72-74 . Positive responses have been observed in prostate cancer and lung cancer patients, indicating the wider applicability of antigen microarrays to elicit specific antibodies in complex biological fluids.

ED Minimizing Maneuvers Nervesparing surgery

Nerve injury can occur at four time points during radical retropubic prostatectomy at the time of urethral dissection, during lateral pedicle division, during dissection along the base of the prostate, and at the time of seminal vesicle dissection. Nerve trauma is classically thought of as occurring with cautery, ligation or avulsion however, overly aggressive traction may lead to neuropraxia, and even this temporary trauma may result in structural sequelae in the corporal bodies that may limit the recovery of erectile function 7,8,33 . Donohue et al., using a rat model of cavernous nerve injury, demonstrated that nerve exposure alone without any direct manipulation results in a significant reduction in erectile function as measured by intracavernous pressure generation in response to cavernous nerve stimulation 34 . There is a plethora of robust data supporting the concept that the greater the volume of nerve tissue preserved the better the spontaneous erectile function and the...

Endogenous Substances Single Protein Analysis 9411 Hormones and Growth Factors

Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are two of the most important angiogenic factors that stimulate tumor growth (Folkman and Klagsbrun, 1987 Folkman and Shing, 1992). A preliminary report that analyzed 10 patients with breast cancer and 10 controls found that bFGF levels in NAF were higher in women with breast cancer than in normal subjects (Liu et al., 2000). A larger study, which evaluated 143 NAF specimens (Hsiung et al., 2002), also found that mean NAF bFGF levels were significantly higher in women with breast cancer than in those without. VEGF levels in NAF were not associated with breast cancer. A logistic regression model including NAF levels of bFGF and clinical variables was 90 sensitive and 69 specific in predicting which women had breast cancer. Adding another biomarker linked to breast cancer, prostate-specific antigen (PSA), increased the sensitivity to 91 and the specificity to 83 .

Chuanbo Zhang Jin Pei Deepak Kumar Isamu Sakabe Howard E Boudreau Prafulla C Gokhale and Usha N Kasid

Antisense oligonucleotides (ASO) against specific molecular targets (e.g., Bcl-2 and Raf-1) are important reagents in cancer biology and therapy. Phosphorothioate modification of the ASO backbone has resulted in an increased stability of ASO in vivo without compromising, in general, their target selectivity. Although the power of antisense technology remains unsurpassed, dose-limiting side effects of modified ASO and inadequate penetration into the tumor tissue have necessitated further improvements in ASO chemistry and delivery systems. Oligonucleotide delivery systems may increase stability of the unmodified or minimally modified ASO in plasma, enhance uptake of ASO by tumor tissue, and offer an improved therapy response. Here, we provide an overview of ASO design and in vivo delivery systems, and focus on preclinical validation of a liposomal nanoparticle containing minimally modified raf antisense oligodeoxynucleotide (LErafAON). Intact rafAON (15-mer) is present in plasma and in...

Methylation Profiles In Circulating Tumor Cells Isolated From Blood Of Patients With Cancer And Biological Implications

Prostate cancer rates for tumor cells and tumor DNA in blood are exceptionally high in patients with liver cancer or prostate cancer.2930 With high specificity and sensitivity, molecular analyses of tumor-derived epigenetic alterations in blood of cancer patients may possibly create a profound impact on noninvasive diagnosis of cancers among high-risk populations, cancer monitoring, and prognostication.293132 Also, the circulating tumor burden is much greater among patients with cancer with metastases as compared with those without metastases. Biologically, the epigenetic change is heritable and associated with transcriptional silencing and hence the loss of function. As mentioned previously, a panel of genes encoding tumor suppressors, DNA repair proteins, and metastasis inhibitors has been found hypermethylated in multiple human cancers. Epigenetic changes of p16, p15, and GSTP1 have been detected in blood cells from patients with cancer with tumoral methylation (Table 14.1).12 29...

Models Of Stem Cell Biology

Stem cell-based models of development and proliferation have been proposed in a number of organs. These models have generally suggested the presence of a stem cell compartment with the potential to undergo many rounds of division. Divisions of stem cells are proposed to give rise to daughter cells that are stem cells or that join a population of transient-amplifying cells capable of undergoing clonal expansion, finally giving rise to a cell population that is fully differentiated but has limited potential for proliferative activity (Hume and Potten, 1979 Lavker and Sun, 1983). Isaacs (1985) proposed such a stem, amplifying, transit cell model for the prostate, which is summarized in Fig. 1. The prostate is potentially a good model in which to study stem cell biology because it is dependent on androgenic stimulation for its development and for maintenance of its glandular structure in adulthood. If androgens are removed, the prostate will regress, and if they are reintroduced, it will...

Antiproliferative Activity via Signal Transduction Pathways

Particularly, their function is associated with control of abnormal growth in carcinogenesis. Several of these genes have been identified and implicated in pathogenesis by the presence of mutated or otherwise dysfunctional forms in specific cancers. For example, the tumour suppressor Rb is involved in retinoblastoma, osteosarcoma and tumours in lung, bladder, prostate and breast p53 in adenocarcinomas in colon and breast, human T cell leukaemias, glioblastomas, sarcomas, and tumours in lung and liver WT in Wilm tumour and DCC (Deleted in Colorectal Cancer) in colon tumours. There is potential for treating cancer patients with exogenous functional tumour-suppressor genes to inhibit tumour growth and spread. Possibly, it also will be found that chemicals can modulate the expression and activity of tumour suppressors and inhibit carcinogenesis by this mechanism. CP-31398 stabilizes the DNA binding domain of both normal and mutant p53 in an active conformation,...

Of Normal Gonadal Development

The first stage of testis differentiation is the formation of testicular cords consisting of Sertoli precursor cells packed tightly around germ cells. The diploid germ cells, the pre-spermatogonia, undergo meiosis in the fetal testis and remain in meiotic arrest until puberty. Sertoli cells, which provide a location for support and proliferation of spermatogonia, are derived from the mesonephros and proliferate only during fetal life and in the neonatal period 83 . After the 8th week of fetal life, the Leydig cell of the fetal testis secretes testosterone. Luteinizing hormone (LH) release is suppressed, and masculiniza-tion of the external genitalia and urogenital sinus of the fetus results. By the third month, the penis and prostate form 17 . Normal testes descend by the seventh month of gestation with little likelihood of continuing spontaneous descent after 9 months 19 .

Malignant Bone Tumors

Tumors that commonly metastasize to bone include thyroid, breast, prostate, bronchus, kidney, bladder, uterus, ovary, testicle, and adrenal tumors. Lymphomas most commonly spread to bone from primary involvement of lymph nodes but also are seen rarely primarily in the skeleton. Bone scans are thought to be the best screening test for patients suspected of having skeletal metastasis.31 Patients with metastatic bone disease most often present with pathological fracture or pain. The radiographical appearance of these lesions tends to be sclerotic in prostate and breast metastasis and lytic in lung, bowel, kidney, and thyroid. Biopsy of the bony lesion is helpful for determining whether the lesion is metastatic.

Secondary tumours Liver form at new sites

Metastasize requires that the tumour cells produce proteases that degrade the basement membrane of blood vessels through which the tumour cells will travel. Metastatic tumour cells are also able to escape immune surveillance of the host organism and then to grow again in another part of the body. Factors produced at these distal sites are thought to provide a favourable environment for the continued proliferation of the tumour cells. Evidence for this comes from the finding that specific types of tumours have a propensity to metastasize to the same sites, e.g. prostate cancer commonly targets bone. Moreover, tumour cells also have the ability to affect the underlying layer of stroma, or fibroblast cells, stimulating them to produce growth factors and cytokines that enhance tumour growth. Figure 1 depicts how a cell breaks away from the primary tumour and generates a secondary neoplasm within the organism. (See also chapter on Invasion and Metastasis.)

Targeting Downstream Effectors of PCatenin

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

Ribozymes Targeting Survivin

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