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18.01.2016
This method has reached a very advanced level of sophistication in the last ten years due to improvements in ultrasound imaging of the prostate during the procedure (allowing direct visualisation of the deposition of the seeds) and better computer assisted planning and seed delivery methods.
The great attraction of brachytherapy is that it is a single procedure, a small operation, with the patients almost always leaving hospital next day.
The inclusion of patients for brachytherapy is defined by relatively strict criteria.  Usually, we accept those biopsy proven patients with a Gleason score less than 8, a gland of less than 50cc, good urinary flow rates and a PSA of less than 15. Sagittal view of the Seattle low dose radiation seed implant technique for prostate cancer with the transrectal probe in situ, and the implant taking place via the transperineal route through a template (seen ‘side-on’ in the main diagram but ‘ en face’ in the ‘bubble’ top right), the depth coordinate being called by the rectal ultrasound probe.
The delivery of interstitial brachytherapy is nowadays carried out with great precision, utilising trans-rectal ultrasound to visualise the prostate and allow the radioactive seeds to be placed under direct supervision. After initial assessment and fulfilling the entry criteria for inclusion in brachytherapy treatment, the patient is usually admitted to hospital for thirty six hours. The metal grid is set up and secured to the operating table.  Through the grid, needles are inserted through the skin of the perineum into the prostate gland, under direct vision using thtetransrectal probe. When the positioning of the needles is satisfactory and matches the defined radiotherapy treatment plan, the seeds are deposited. In the ward and for the next 3 months (as the half life of the isotope is 2 months) there will be no restriction on visiting, excepting close proximity to pregnant women and infants, as there is no significant radiation risk to the patient’s visitors.
5% of patients require a catheter to be re-inserted (and more commonly in those with a weak stream prior to the procedure – hence the selection of patients by whether they can produce a reasonable stream prior to the procedure). We have experienced no cases of urinary incontinence and no major rectal problems (exacerbation of haemorrhoids with bleeding may occur). The largest clinical work and the longest follow up of patients treated with iodine-125 seeds (our own method) comes from Seattle and the results are entirely comparable with those of surgery or other radiatiom methods in terms of cure. Science, Technology and Medicine open access publisher.Publish, read and share novel research. A Novel Therapy for Melanoma and Prostate Cancer Using a Non-replicating Sendai Virus Particle (HVJ-E)Toshihiro Nakajima1, Toshimitsu Itai1, Hiroshi Wada1, Toshie Yamauchi1, Eiji Kiyohara2, 3 and Yasufumi Kaneda2[1] GenomIdea, Inc., Midorigaoka, Ikeda, Osaka, Japan[2] Division of Gene Therapy Science, Department of Molecular Therapeutics, Graduate School of Medicine, Osaka University, Yamada-oka, Suita, Osaka, Japan[3] Department of Dermatology, Graduate School of Medicine, Osaka University, Yamada-oka, Suita, Osaka, Japan1. Once prostate cancer has been diagnosed, the right treatment option can vary greatly depending on a number of factors. This post is part of a series dedicated to addressing one of the most important health issues facing men today. Philadelphia CyberKnife is a service of Delaware County Memorial Hospital, a member of the Crozer-Keystone Health System.This Site Does Not Provide Medical Advice. Comfort Pal Donut Cushions - The Original Heavy Duty18" Inflatable Ring Travel Cushion (Gray) - Perfect for Bed Sores, Hemorrhoid Treatment, Tailbone Pain, Child Birth, and much more. When he finished the whole treatment, he shared that "All my symptoms are gone and never come back. However, when an ailment of an organ becomes chronic, it must be treated in this organ locally – and this is exactly what Dr.
Symptoms of prostatitis exposed: Prostatitis treatment tends to come in all sizes, colors and flavors.
Prostatitis: Causes, Symptoms, Diagnosis, Tests, and Treatment A description of prostatitis including the causes, symptoms, and treatments available. Treatments for prostate cancer can be done depending on the stages and types of the cancer itself. Prostate cancer patients might have varied situations which include economical, physical, and psychological aspects. After getting a test, doctors will tell you the stage of your cancer and also the type of it. PROVENGE is a treatment option for certain men with metastatic castrate resistant prostate cancer.
PROVENGE® (sipuleucel-T) is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer. Take any other medicines including prescription and nonprescription drugs, vitamins, and dietary supplements. Have breathing problems, chest pains, racing heart or irregular heartbeats, high or low blood pressure, dizziness, fainting, nausea, or vomiting after getting PROVENGE. Develop numbness or weakness on one side of the body, decreased vision in one eye or difficulty speaking. The most common side effects of PROVENGE include chills, fatigue, fever, back pain, nausea, joint ache, and headache.
For more information on PROVENGE, please see the Full Prescribing Information or call 1-877-336-3736. By submitting an e-mail address above, you are requesting that we contact the person you specify here on your behalf.
The middle panel shows the axial CT cuts through the prostate at various levels from base to apex demonstrating the deposited seeds around the urethra. In a consecutive series of 400 patients implanted by our team, only one individual required a catheter after one month. Discussion and conclusion The major disadvantages associated with oncolytic viruses are safety concerns because viral replication could theoretically cause the emergence of new pathogenic viruses [43]. Not only is the stage and grade of the tumor important, but also the age, health and lifestyle of the patient. Check our blog for additional information about prostate cancer and the unique benefits of CyberKnife® treatment. The Content is not intended to be a substitute for professional medical advice, diagnosis, or treatment.
Supports Reduced Inflammation, Healthier Cholesterol Levels, and Improved Urinary Function.
There are a lot of things that need to be considered before doctors make a decision about the treatments. From physical aspect – health condition, stages, and types, there are some treatment options which can be taken.
Therefore it is better to consult your condition to one doctor that knows your medical record. The right panel demonstrates the template coordinates, through which holes the needles were inserted to achieve this distribution – the middle two pictures showing these coordinates superimposed on ultrasound pictures.
A medicine called an alpha blocker is usually prescribed for three months to assist the urinary flow that may be (usually temporarily) less strong. Conventional anti-cancer therapies are problematic and a 2-step therapeutic strategy is proposed for effective cancer treatment. It is based on the case reports since 1950s, which reported the regression of cancers including leukemia, Hodgkin’s disease, and Burkitt’s lymphoma after the infection of wild type viruses [1-11]. A time course study of change in tumor volume was performed, and the difference in tumor volume among the three groups was statistically analyzed at the end of the study.
The use of non-replicating oncolytic viruses is expected to resolve the safety issues associated with conventional oncolytic viruses because they are unable to replicate in target cells.The modes of action underlying the anti-cancer effects of non-replicating virus on cancer cells and immune cells have been analyzed. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.
The device works 24 hours a day and creates an ideal environment for blood to clean inflammation in the prostate tissue. Some patients who are very depressed about their situation might need to make the decision as quickly as possible. They include active monitoring, surgery, radiation therapy, hormone therapy, chemotherapy, vaccine treatment, and bone treatment.
It is totally normal to be terrified by the fact, but it is more important to tell yourself that you need to fight the disease. Doctors whom you can talk to are urologists, radiation oncologists, and medical oncologists. The earliest virotherapies involved injection of wild-type viruses and evaluation of their efficacies [1-3]. These proof-of-concept studies in melanoma and CRPC using the non-replicating oncolytic virus were initiated in July 2009 and July 2011, respectively [55, 56].
Consult your doctor and physicians with an expertise in each of these fields to make a fully informed decision.
Provides prolonged disease freeinformation about treatments and symptoms, diagnosis, treatment,sep .


However, it is important to take time for getting the process and knowing deeper about the information about the disease. These treatments can be used one in a time; however, in some cases they need to be combined.
Urologists are the surgeons who are specialists in treating diseases within urinary and male reproductive system – also includes prostate.
Problems associated with conventional anti-cancer drugs and immune therapies, including cancer vaccines, are shown.3.
Ex vivo therapies using autologous irradiated tumors infected with oncolytic viruses were also investigated [12-18].
RIG-I is a cytosolic nucleic acid receptor that acts as a sensor that detects virus infection [82-84]. Here are some prostate cancer treatment options that can be taken depending on the patients’ situation. In addition, the body of the sufferer itself can experience side effect symptoms of the treatments. Furthermore, the prostate cancer can be handled way much easier if it is found in early stage. Radiation oncologists are doctors who are specialized in giving radiation therapy for cancer patients.
Deletion mutants of oncolytic viruses [19-24], and recombinant viruses carrying a therapeutic gene [25-32] that induce cancer apoptosis or cancer immunity have been developed and evaluated in the clinical setting.Oncolytic viruses derived from adenovirus, poxvirus, reovirus, picornavirus, paramyxovirus, and herpes simplex virus are currently available and have been clinically evaluated [33-35]. A survival study was performed and the difference among the three groups was statistically analyzed at the end of the study. The primary endpoints of these studies were safety and tolerability based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, whereas the secondary endpoints were efficacy and confirmation of the mode of action. While medical oncologists are doctors are specialists in medical therapy such as chemotherapy and hormone therapy. RIG-I is a cytosolic receptor for nucleic acids: it usually functions as a sensor to recognize viral infection. In China, two adenovirus-based products (Gendicine and Ocorine) have been commercialized [36], while randomized phase III studies of two oncolytic viruses (reovirus and poxvirus) are ongoing in advanced countries [33-35]. The major difference between the regimens for the melanoma and CRPC studies was the route of administration and number of administrations. Thus, virotherapy is expected to become available as a new approach for cancer treatment, and specific product approval is anticipated in the US, EU, and Japan [37].The major drawback associated with virotherapy is safety since replicating viruses are used in this therapy. A combination of intratumoral and subcutaneous routes of administration (one intratumoral and three subcutaneous injections) was adopted in the CRPC study. Genetic analyses suggest that differences in the expression of apoptosis-related genes define the sensitivity to the treatment with a non-replicating virus (HVJ-E) [54]. In order to reduce the toxicity to normal cells, oncolytic viruses with strict specificity for cancer cells were constructed [29, 38-42]. In addition, a new injection system developed by Okayama University was used in the CRPC study.
Therefore, you can also know about the side effects of each treatment by seeing your medical records.
However, the use of these viruses is still considered to be high risk because it is theoretically possible that a virulent infection may occur after recombination with wild-type viruses [43]. This system permits stable refrigerated storage of the test article, and accurate injection into the prostate [91]. An alternative option to avoid such a risk is to use a non-replicating oncolytic virus [44].
The non-replicating virus (HVJ-E) activates DCs to produce IL-6, which suppress the function of Treg [45]. We found that a non-replicating oncolytic virus (HVJ-E: hemagglutinating virus of Japan-envelope) is able to induce cancer cell-specific apoptosis and immunity [45]. This effect is expected to maintain the induced cancer immunity because Treg is known to be a negative regulator of immune responses [92-94]. The induction of apoptosis and activation of dendritic cells in vitro, and anti-tumor activity in vivo are similar to the wild-type hemagglutinating virus of Japan (also known as Sendai virus, HVJ) [45].The hemagglutinating virus of Japan was discovered in Sendai, Japan, in the 1950s [46].
It has been reported that cancer cells escape cancer immunity by the recruitment and activation of Treg. Therefore, it will be important to control the function of Treg for long-term effective induction and maintenance of cancer immunities. The virus has fusogenic activity [47, 48], and is used to prepare hybridoma cells for the production of monoclonal antibodies, and heterokaryons for chromosome analysis [49-51].The hemagglutinating virus of Japan-envelope is an inactivated HVJ particle [52].
A time course study of change in tumor volume was performed and differences in tumor volume between the two groups were statistically analyzed at the end of study.
Good manufacturing practice (GMP)-regulated processes have been established in their production for use in preclinical and clinical studies [53]. The attachment of the HVJ-E particle to the surface of DCs was sufficient for the production of IL-6, suggesting that the RNA fragments are unnecessary for the induction of this cytokine [95]. We conducted dose-setting efficacy studies for HVJ-E in a murine cancer model in which dose-dependent anti-cancer activity was observed. Detailed analyses identified that the F protein on the surface of HVJ-E is involved in the production of IL-6 [95]. We also conducted safety studies following good laboratory practices (GLP), including pharmacological safety studies and toxicokinetic (TK) studies in rats and monkeys, as part of an investigational new drug (IND) application.Osaka University Hospital is currently conducting two investigational clinical studies with HVJ-E for the treatment of advanced melanoma and castration-resistant prostate cancer (CRPC) [54-56]. These clinical trials are the first human studies for HVJ-E and will reveal the safety and efficacy of the non-replicating virus (HVJ-E).
A time course study of change in tumor volume was performed and differences in tumor volume between the two groups were statistically analyzed at the end of the study. Several gangliosides, such as GD1a and sialyl paragloboside, are implicated in the association of the HVJ-E particle and cancer cells because the HN protein binds the sialic acids of gangliosides. Virotherapy with a non-replicating oncolytic virus is a new approach that is anticipated to provide a new strategy for cancer therapy.2. A new strategy for cancer therapyMost cancers are still incurable and new approaches are required to improve the efficacy of cancer treatments.
However, conventional cancer therapies are problematic.Chemotherapy with anti-cancer agents is useful in achieving tumor regression.
In case of HVJ-E, the virus is inactivated by treatment with an alkylating agent and UV irradiation, a process used for the production of vaccines against viral diseases. However, the immune system, which is important in the removal of residual cancer cells, is also suppressed by these agents (Figure 1). Thus, the development of oncolytic viruses could be converted to the development of non-replicating oncolytic particles by similar manufacturing processes.A disadvantage associated with non-replicating oncolytic viruses may be the defect in transmission ability. Therefore, surviving cancer cells and cancer stem cells (CSC) eventually acquire drug resistance, resulting in tumor relapse (Figure 1) [57]. Therefore, it is possible that a greater amount of non-replicating oncolytic virus may be required for effective treatment compared with a live oncolytic virus. Alternatively, more frequent injections may be necessary for complete tumor eradication compared with the use of live oncolytic viruses.
However, it is important to achieve a balance between the risks and benefits associated with the therapy. Problems associated with conventional anti-cancer drugs and immune therapies, including cancer vaccines, are shown.Immune therapies for cancer offer a new approach to cancer treatment, and several products, including sipuleucel-T, are currently approved in advanced countries [58, 59]. Future perspectivesThe first non-replicating oncolytic virus (HVJ-E) is currently under evaluation in clinical studies. Proof-of-concept data for non-replicating viruses in both clinical and non-clinical studies are necessary for further development of this approach. However, these agents are not potent because of lack of cytotoxic effect on cancer cells (Figure 1).These observations suggest that a two-step strategy is necessary for the eradication of cancer cells (Figure 1).
During the first step, the direct killing of cancer cells is necessary for reduction of tumor volume.
Indeed, an increase in therapeutic efficacy has been reported for virotherapies combined with photodynamic therapy [98, 99], radiotherapy [100], chemotherapy [101, 102], or gene therapy [103].
CSCs are usually resistant to conventional anti-cancer drugs and continue to proliferate during chemotherapy.


Kiyohara and Kaneda reported that combination of the non-replicating virus (HVJ-E) and gene therapy (IL-12) increased efficacy in a murine model of melanoma [104]. Therefore, an agent that targets and kills CSCs is required for effective cancer treatment.During the second step, the removal of residual cancer cells (and CSCs) from the body by a cancer-specific immune response is necessary to avoid relapse of the condition [57].
Furthermore, it was reported that a combination of non-replicating virus (HVJ-E) and chemotherapy [bleomycin or cis-diamminedichloroplatinum (CDDP)] increased efficacy in murine models of colon and bladder cancers [78, 105].Technologies for systemic administration and targeting for HVJ-E are under development. However, it is difficult for immune cells to recognize and remove CSCs because they exist as a minority population within the tumor, and possess a lower antigenicity than differentiated cancer cells [57]. The HN protein of HVJ-E has hemagglutinating activity and causes agglutination and lysis of erythrocytes in vitro.
Oncolytic viruses have the capability of both directly killing cancer cells and inducing cancer immunity.
Currently, inactivation of the HN protein, decreased expression of the HN protein, and “masking” with platelets is being developed for intravenous injection of HVJ-E. It has been reported that several oncolytic viruses have the capability to kill CSCs [60-67].
The reovirus-based oncolytic virus [61], telomerase-specific oncolytic adenovirus [62], and herpes simplex virus-based oncolytic viruses (G47Delta and Delta 68H-6) [63, 64] reduced CSCs in murine models of breast cancer, esophageal cancer, and malignant glioma, respectively. Thus, a virotherapy approach in patients is expected to kill cancer cells and eradicate cancer cells including CSCs (Figure 1).3.
Non-replicating virus particles as anti-cancer agentsThe use of non-replicating virus particles is a new approach in virotherapy. A non-replicating virus particle, HVJ-E, is currently being developed as a potential new agent for the treatment of advanced melanoma and CRPC [44, 55, 56]. The HVJ-E particle is prepared by inactivating the wild-type virus (HVJ) by treatment with an alkylating agent and UV irradiation [52, 53].
HVJ-E was originally developed as a drug delivery system (vector) for various biopharmaceuticals such as plasmid DNAs, siRNAs, decoy oligonucleotides, antibody proteins, and anti-cancer drugs [52, 68-75]. Kurooka and Kaneda discovered that the HVJ-E particle itself displayed anti-cancer effects in a murine model of colon cancer [45]. Similar to the live (replicating) virus, HVJ-E induced maturation and differentiation of human and murine dendritic cells (DCs). It also induced infiltration of immune cells into the tumor tissue followed by activation of cancer cell-specific cytotoxic T cells. Furthermore, HVJ-E suppressed the function of regulatory T cells (Treg), which have been reported to be negative regulators of cancer immunity.
Intratumoral injection of HVJ-E promoted infiltration and activation of natural killer (NK) cells by the induction of C-X-C motif chemokine 10 (CXCL10) and type I interferons.
When HVJ-E was injected into the tumor of a murine model of renal cell carcinoma (RCC), NK cells exhibited cytotoxic activity against the RCC cell line in vivo [76]. The involvement of NK cells in the anti-tumor effect was also confirmed by showing the depletion of NK cells using an asialo-GM1 antibody [76]. Activated NK cells produced interferon-?, which induces cancer-specific cytotoxic T cells [76].
These results indicated that HVJ-E is able to induce both innate and adaptive immunities.In addition to the induction of cancer immunities, HVJ-E has the capability to induce cancer cell-specific apoptosis. In contrast, it showed no suppression of normal human prostate epithelium proliferation [77]. HVJ-E also induced apoptosis of prostate cancer cells in vivo because it showed an anti-tumor effect in severe combined immunodeficiency (SCID) mice that lack B lymphocyte- and T lymphocyte-mediated immunities [76, 77]. When NK cells were depleted from SCID mice by injection of the asialo-GM1 antibody, intratumoral injection of HVJ-E still showed an anti-tumor effect in a murine model of CRPC [77].
These results are inconsistent with results obtained with HVJ-E [45, 76, 77, 79], and the putative reason is the difference between the number of particles used in the studies. In studies with NDV, 5 ? 109 PFU of oncolytic virus were systemically or locally administrated [81], whereas the number of HVJ-E particles administered was estimated to be higher.Another possibility is the difference in the capability of the virus to deliver its RNA fragments to target cancer cells. The Z strain-derived HVJ-E used in our studies has the highest level of membrane fusion activity [52]. Therefore, it is possible that HVJ-E has the ability to deliver more RNA component to the target cancer cells than the UV-inactivated NDV particle.
The difference in process of inactivation may be responsible for the activity of non-replicating oncolytic viruses. The Newcastle disease virus was inactivated by UV irradiation, whereas HVJ-E was inactivated by a combination of treatment with an alkylating agent and UV irradiation [53]. Inactivation conditions affect the efficiency of delivery, and strictly regulated processes are necessary to obtain suitable performance [53].4. Interestingly, no apoptotic effects were observed on normal epithelial cells derived from murine prostate [54, 77].
Thus, the apoptotic activity of HVJ-E is considered to be specific to cancer cells [54, 77]. Retinoic acid inducible gene-I is a cytosolic nucleic acid receptor and was originally identified as a sensor that recognizes infection by single strand RNA viruses [82, 83]. Thus, RIG-I has been recognized as an inducer of immune response against infected viruses [82-84].The RNA fragments delivered by HVJ-E bind the helicase domain of RIG-I in the cytoplasm and change the conformation to unmask the caspase activation and recruitment domain (CARD) (Figure 3B). After binding with the RNA fragments, RIG-I interacts with the mitochondrial antiviral signaling (MAVS) protein on the mitochondrial membrane (Figure 3B) [84]. It also stimulates kinases of regulator protein of transcription factor NK-?B, resulting in increased expression of cytokines, chemokines, and other genes (Figure 3B) [45, 54, 76, 77]. Transfection of isolated RNA fragments from HVJ-E particle also induced apoptosis of cancer cells in vitro [54]. Thus, HVJ-E uses a natural oligonucleotide (RNA fragment from the inactivated virus genome) as an active ingredient, and a natural virus particle (envelope of HVJ) as a delivery system for a nucleic acid medicine (RNA fragments).
The apoptosis induced by HVJ-E was cancer cell-specific because normal endothelial cells showed no apoptosis after the treatment with HVJ-E [54, 77].Involvement of RIG-I in cancer cell-specific apoptosis has also been indicated in ovarian cancers and melanoma.
Similar to sensitivity of HVJ-E, epithelial cells derived from ovarian surface was resistant to apoptosis mediated by RIG-I signal pathway. The authors used pppRNA and poly(I:C) as ligands for RIG-I and MDA-5, and showed the involvement of caspase-9 and Apaf-1 during apoptosis. Details of the underlying pathways are currently being analyzed using siRNAs of apoptosis-related factors [54]. It has been suggested that differences in the expression of apoptotic genes such as Noxa, TRAIL, and TRAIL receptors in cancer cells and normal cells determine the specificity of apoptosis induced by HVJ-E (Figure 3B) [54].HVJ-E also induced differentiation and maturation of murine and human DCs [45].
It induced the expression of surface markers on mature DCs, and the production of various cytokines and chemokines from DCs [45, 76, 77]. Activated DCs induce both innate (NK cell-mediated) and adaptive (cytotoxic T cell-mediated) immunities (Figure 3A) [45, 76].
The data have indicated that the anti-tumor effect is dose-dependent similar to other non-viral anti-cancer agents (Figure 5B). This feature is important for the development of non-replicating oncolytic virus as a novel therapeutic agent; identification of the optimal dose for non-replicating oncolytic viruses is easier than determining the optimal dose for replicating oncolytic viruses as the latter are subject to change (increase) resulting from replication in target cancer cells. The effects of administration in a xenograft model of human CRPC were also examined (Figure 5A).
It is known that the SCID mice lacks B lymphocyte- and T lymphocyte-mediated immunities such as antibody production, and induction of cytotoxic T cells but retains monocytes and NK cells important for innate immunity. Efficacy by subcutaneous administration is important for the development of a non-replicating virus because subcutaneous administration is more common than intratumoral administration. Intratumoral administration kills cancer cells directly and promotes the release of tumor antigens, which are recognized by immune cells. Results from single dose general toxicity studies revealed that no death or severe finding was observed even in the maximum dosage groups.
Similar to the single dose studies, no severe finding was observed in repeated dose, general toxicity studies (Table 1A).Results from immunological and genetic toxicity studies in rat and monkeys revealed that no abnormal symptoms related to the test agent were observed.



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