Wednesday, August 25, 2010

SMELL of cancer - detector from Japan

Highly sensitive and selective odorant sensor using living cells expressing insect olfactory receptors

1. Nobuo Misawaa,b,1,
2. Hidefumi Mitsunob,c,1,
3. Ryohei Kanzakic, and
4. Shoji Takeuchia,b,2

+ Author Affiliations

1.
a Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan;
2.
b Life Bio Electro-mechanical Autonomous Nano Systems (Life BEANS) Center, The BEANS Project, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan; and
3.
c Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan

1.

Edited by Katepalli R. Sreenivasan, New York University, New York, NY, and approved July 20, 2010 (received for review March 31, 2010)
2.

.1N.M. and H.M. contributed equally to this work.

Abstract

This paper describes a highly sensitive and selective chemical sensor using living cells (Xenopus laevis oocytes) within a portable fluidic device. We constructed an odorant sensor whose sensitivity is a few parts per billion in solution and can simultaneously distinguish different types of chemicals that have only a slight difference in double bond isomerism or functional group such as .OH, .CHO and .C(.O).. We developed a semiautomatic method to install cells to the fluidic device and achieved stable and reproducible odorant sensing. In addition, we found that the sensor worked for multiple-target chemicals and can be integrated with a robotic system without any noise reduction systems. Our developed sensor is compact and easy to replace in the system. We believe that the sensor can potentially be incorporated into a portable system for monitoring environmental and physical conditions.

Hebrides olfactory machinery

Matthias Gräbner 25/08/2010
Researchers combine living cells with evaluation electronics,
creating an olfactory-machine whose performance technically
not be reached so far is
Technical devices are better than man.
Whether in the universe or in the nano world,
much remains hidden from the eye, can make the technology visible.
The same goes for listening: Machines take sound true
in areas that we do not remain closed for reasons of age.
But when it comes to smell, not even the comparatively
poor man is now equipped to fight from the electronics.

Not to mention many of us far superior animals.
Even individual cells can register chemicals - say,
smelling. The sperm, for example, is based on the search
for the egg to lily of the valley fragrance, as researchers
have found. The fact that the olfactory perception is probably
the worst so far investigated has meaning for several reasons.
First, it has historically been given less attention - smells
long regarded as something that aroused than unpleasant associations.
Painting and music refer to visual and auditory senses,
but how popular are odor-art?

The fact is, however, that the olfactory sense is also not easy to tap. It is not enough to understand the basis. It depends on more than wavelengths and amplitudes: odors are mediated by different chemical substances. When we found out what makes Lily of the Valley Sun smell how we perceive it in the spring, then we know for a long time not see why violets smell of violets. Even the man has over 400 different receptors that are distributed to the olfactory mucosa in an area of five square centimeters. They allow up to 10,000 different smells. As a rule, have to dock only a few molecules of the substance at the receptors to produce an impression.

Oocytes of the African clawed frog as a chemical sensor for a machine

How can this potential best use of technology? One way would be to replicate the mechanism that has the nature as conceived. Another way to show Japanese researchers in the current issue of the Publications of the U.S. Academy of Sciences (PNAS). In their [external] Paper describing how eggs of the African clawed frog [external] Xenopus laevis may act as a chemical sensor for a machine.

The researchers calculated that chose this egg is on their mobile application for the practical size of about one millimeter in diameter. Genetically, the scientists took cells for receptors for a variety of training materials that have been borrowed from various insects. Then docks to a corresponding molecule on the receptors of the cell, creating a tiny current - which it will have to enhance and evaluate. The researchers succeeded in surprisingly good

The eggs were found to be very robust in the experiment. At the same time they were able to distinguish between the different, chemically very similar substances. The conventional way you would for a gas chromatograph must try. Since so far about 50 receptors of insects in the required manner are known, it would be a based on the claw frog egg system quite well. Therefore it is not even necessary to understand the detailed operation of the receptors. The microfluidic apparatus, the researchers have constructed is, while just 5 x 30 x 45 millimeters in size. It could, so the idea, well suited as a portable sensor for example for environmental monitoring. In a typical Japanese experiment, the researchers built their device in a robot-head: whenever the sensor is then registered a certain smell, led the head of defined movements.

Tuesday, August 17, 2010

Russia approved CANCER VACCINE (made from YOUR cancer)

April 09, 2008

Tuesday morning, a little biotech company, Antigenics (AGEN), announced that Russia has approved its kidney cancer drug, Oncophage. It's the first so-called therapeutic cancer vaccine to win full-out approval anywhere in the world.

This is not a traditional preventive vaccine where you'd get a shot to stave off coming down with something. Therapeutic means you'd unfortunately have to get the cancer first and then your own cells are mixed with the "vaccine" to empower your body's immune system to fight off the disease.

Anyway, a test showed that a subset of patients on Oncophage lived 1.7 years longer without the cancer coming back. But because the clinical trial didn't meet its main goal and the aforementioned benefit was only discovered in a re-analysis of the data, the drug didn't pass muster with the Food and Drug Administration.

The agency wanted AGEN to do a bigger, longer and expensive study. But like most baby biotechs, Antigenics didn't have that kind of cash. So, the company turned to Russia where it had enrolled 125 patients in the same clinical trial. And after a 10-month process, AGEN won approval of the drug there making Russia the first country in the world to allow a therapeutic cancer vaccine onto the market.

The lead clinical trial investigator, Dr. Christopher Wood at the MD Anderson Cancer Center, says the company has given him verbal assurances that it will use the Russian revenue to pay for another study here that might eventually satisfy the FDA. Dr. Wood, an associate professor of urology and cancer biology, says he doesn't own AGEN stock--he just consults for Antigenics and ran the clinical trial.

Over the phone he told me, "Absolutely no question about it (that the drug works). I've looked at the data," he said, "and there's clear activity in the intermediate risk subgroup." That means he believes the drug works on patients whose tumors are of a certain size and confined to the kidney and the fatty tissue around the organ. If it has spread, then this drug, he said, is not for you. Dr. Wood says he and his colleagues have just submitted the study for possible publication in a major, but unidentified, peer-reviewed medical journal. That could give the drug even more cred.


There are many companies working on various types of therapeutic cancer vaccines. The most famous is Dendreon (DNDN). Please keep in mind many of these stocks are micro caps, but some of the others are Cell Genesys (CEGE), Geron (GERN), Vical (VICL), and Favrille (FVRL)

Vitespen


Oncophage (vitespen; formerly HSPPC-96) is a patient-specific therapeutic cancer vaccine tested in over 800 patients in multiple cancers in more than 15 Phase 1, 2 and 3 clinical trials. Oncophage is approved in Russia for the adjuvant treatment of kidney cancer patients at intermediate-risk for disease recurrence. Oncophage contains the heat shock protein, gp96, and associated peptides which are purified from the patients' own tumor tissue and has been the primary focus of Antigenics' research and development efforts since the company's founding. Treatment with Oncophage is designed to target only cancerous cells — not healthy normal cells. As a result, Oncophage is designed to limit the toxicities associated with traditional broad-acting cancer treatments.

Oncophage first entered the clinic in the 1990's where it was studied in a number of different tumor types in advanced disease settings. The objectives of these early Phase 1/2 trials were to assess the feasibility of vaccine manufacture and corresponding logistics, safety and to identify signals of activity. The early findings supported the initiation and completion of two Phase 3 randomized trials in stage IV melanoma and adjuvant renal cell carcinoma (RCC).

The accumulated clinical data has revealed a pattern of findings that is entirely consistent with the biological premise:

  • Oncophage is well tolerated and has demonstrated a very low toxicity profile
  • Oncophage elicits tumor-specific T cell responses and innate immune response irrespective of tumor type
  • Oncophage efficacy is most significant in patients with early-stage disease/ low tumor burden (patients with better prognostic features)

To make Oncophage, patients first have surgery to remove part or all of the cancerous tissue, and the tumor tissue is shipped frozen to Antigenics' state-of-the-art GMP manufacturing facility in Massachusetts. The facility is capable of making vaccine for 10,000 patients with on site expansion to enable vaccine production for 100,000 patients. Using a proprietary, standardized, quality-controlled procedure, the product is isolated from the tumor in 8-10 hours. The product is sterile-filtered, packaged in vials, and shipped frozen back to the hospital pharmacy or clinician for use when the patient has recovered from surgery.

Oncophage is administered as a simple weekly or biweekly intradermal injection during an office visit.

Oncophage received fast track and orphan drug designations from the US Food and Drug Administration (FDA) for both kidney cancer and metastatic melanoma as well as orphan drug designation from the EMEA for kidney cancer. In 2009, Oncophage also received orphan drug designations from the FDA and EMEA for glioma. Antigenics has developed crucial management and logistics expertise in patient-specific vaccines.


Vitespen (HSPPC-96) for Immune Response Assessment Following Treatment of Resectable Renal Cell Carcinoma
This study is currently recruiting participants.
Verified by M.D. Anderson Cancer Center, August 2010
First Received: February 19, 2010   Last Updated: August 3, 2010   History of Changes
Sponsor: M.D. Anderson Cancer Center
Information provided by: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01073254
  Purpose

The goal of this clinical research study is to learn if patients receiving HSPPC-96 after surgery have an immune response against kidney cancer and how long the immune system response may last.

Primary Objective:

  • to determine whether patients exhibit a measurable immune response after multiple administrations of HSPPC-96, including evaluation of immune response after 12 weeks of treatment (corresponding to 8 doses of HSPPC-96) as assessed by ELISPOT assay.

Secondary Objectives:

  • to assess if the immune response is durable beyond 12 weeks of treatment with the administration of 2 additional doses of HSPPC-96 or placebo at 6 and 12 months.
  • to assess natural killer (NK) cell activity during the treatment with HSPPC-96.
  • to assess safety following administration of HSPPC-96.

Condition Intervention Phase
Kidney Cancer
Renal Cell Carcinoma
Biological: Vitespen (HSPPC-96)
Phase II

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Randomized, Single-Blind Study of Vitespen (HSPPC-96, Oncophage) for Immune Response Assessment Following Treatment of Patients With Resectable Renal Cell Carcinoma at Intermediate Risk of Recurrence


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Number of patients who exhibit a measurable immune response after multiple administrations of HSPPC-96 [ Time Frame: After 12 weeks of treatment (corresponding to 8 doses of HSPPC-96) ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: January 2010
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Part 1A: Experimental Biological: Vitespen (HSPPC-96)
8 administrations of HSPPC-96 over 12 weeks (weeks 14-17, 19, 21, 23, 25)
Part 1B: Experimental Biological: Vitespen (HSPPC-96)
8 vaccine doses (4 weekly doses, followed by 4 bi-weekly doses at study weeks 1-4, 6, 8, 10, 12) over 12 weeks
Part 2: Experimental Biological: Vitespen (HSPPC-96)
8 vaccine doses (4 weekly doses, followed by 4 bi-weekly doses at study weeks 1-4, 6, 8, 10, 12) over 12 weeks



Criteria

Inclusion Criteria:

  1. Patients with higher risk MDS (IPSS int-2 or high, or >/= 10% blasts as defined by WHO or FAB). - No prior intensive chemotherapy or high-dose cytarabine (>/= 1 g/m2). - Prior biologic therapies (</= 1 cycle of prior decitabine or azacitidine), targeted therapies, or single agent chemotherapy is allowed. - Off chemotherapy for 2 weeks prior to entering this study with no toxic effects of that therapy, unless there is evidence of rapidly progressive disease. - Hydroxyurea is permitted for control of counts prior to treatment. - Hematopoietic growth factors are allowed. .
  2. Age >/= 18 years.
  3. ECOG performance status </= 2.
  4. Have adequate renal function as indicated by the following laboratory values: Serum creatinine </= 1 mg/dL; if serum creatinine > 1 mg/dL, then the estimated glomerular filtration rate (GFR) must be > 60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73m2) = 186 x (serum creatinine)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is black).
  5. Serum bilirubin </= 1.5 x upper limit of normal (ULN)
  6. Aspartate transaminase (AST) or alanine transaminase (ALT) </= 2.5 x ULN
  7. Alkaline phosphatase </= 2.5 x ULN
  8. Provide signed written informed consent.
  9. Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent.
  10. Female patients of childbearing potential must have a negative pregnancy test within 2 weeks prior to enrollment.
  11. Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.

Exclusion Criteria:

  1. Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
  2. Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea. The patient must have recovered from all acute toxicities from any previous therapy.
  3. Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment.
  4. Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
  5. Pregnant or lactating patients.
  6. Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results
  7. Have had a diagnosis of another malignancy, unless the patient has been disease-free for at least 3 years following the completion of curative intent therapy with the following exceptions:
  8. a) Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed; b) Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01073254

Contacts
Contact: Stefan Faderl, MD 713-745-4613

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Stefan Faderl, MD            

GERMAN: RUSSIsCHES SERUM 'Oncophage' gegen Nierenkrebs gefunden


GEWEBE WIRD ENTNOMMEN UND IN DIE USA GESCHICKT.
DORT WIRD DAS SERUM ERZEUGT.



FORSCHUNG AKTUELL
24.04.2008
Mit neuen Medikamenten nimmt die Wissenschaft Tumorzellen aufs Korn. (Bild: Universität Münster)
Mit neuen Medikamenten nimmt die Wissenschaft Tumorzellen aufs Korn. (Bild: Universität Münster)

Durchbruch unter Vorbehalt

Erster therapeutischer Impfstoff gegen Krebs in Russland zugelassen

Von Arndt Reuning

Medizin. - Eine US-Firma hat nach eigenen Angaben einen Impfstoff gegen Krebs gefunden. In den USA ist er allerdings nicht zugelassen, deshalb ist das Unternehmen jetzt einen anderen Weg gegangen: Es will den Impfstoff in Russland auf den Markt bringen. Die Genehmigung dafür hat man bereits. Auf dem Welt-Impfstoff-Kongress in Washington berichteten Vertreter über Einzelheiten.

Eine Schutzimpfung gegen Krebs gibt es bereits: Zwei verschiedene Mittel können verhindern, dass sich Frauen mit humanen Papillomviren infizieren, die Gebärmutterhalskrebs auslösen können. Der Impfstoff, den die Firma Antigenics aus New York nun in Russland auf den Markt bringen möchte, funktioniert anders: Er bekämpft die Krankheit, wenn sie bereits ausgebrochen ist - indem er das körpereigene Immunsystem der Krebspatienten dazu anregt, den Tumor zu bekämpfen, sagt Garo Armen, der Geschäftsführer von Antigenics.

"Unser Produkt ist auf jeden einzelnen Patienten zugeschnitten. Wir stellen den Impfstoff direkt aus dem Tumorgewebe des Patienten her. Theoretisch eignet es sich daher für jede Art von Krebs. Am weitesten fortgeschritten allerdings sind unsere Programme bei Nierenkrebs und Hautkrebs."

Die Krebszellen des Tumors sind gespickt mit kleinen Eiweißmolekülen, die sie von gesunden Körperzellen unterscheiden. Die sind gleichzeitig eine Art Steckbrief, mit dem das Immunsystem die Tumorzellen erkennen könnte, um sie dann abzutöten. Aber meistens finden Krebszellen Wege, sich der Immunabwehr zu entziehen. Deshalb ernten die Mitarbeiter der New Yorker Firma sozusagen diese Eiweißschnipsel und stellen daraus den Impfstoff her, der die körpereigene Abwehr aktiviert. Und weil diese sogenannten Antigene von Patient zu Patient unterschiedlich sind, isolieren die Wissenschaftler die Moleküle direkt aus dem Tumorgewebe. Dabei helfen ihnen biologische Substanzen, die überall im Körper vorkommen. Armen:

"Hitzschockproteine, auch bekannt als Chaperon-Proteine. Also die "Anstandsdamen" unter diesen Substanzen. Zu ihren Aufgaben im Körper gehört es, die kleinen Eiweißschnipsel an sich zu binden und zu transportieren. Und dabei sind sie nicht besonders wählerisch. Sie binden alles an sich, was ihnen in die Quere kommt. Und deshalb erwischen wir damit den gesamten Vorrat an Antigenen im Tumor."

In einer Studie mit rund 600 Krebspatienten konnte der Impfstoff beweisen, dass er tatsächlich die Lebenserwartung der Betroffenen erhöht. Allerdings wirkt er nur bei solchen Patienten, bei denen die Krankheit noch nicht zu weit fortgeschritten ist, die noch keine Metastasen entwickelt haben. Armen:

"Patienten in einem frühen Stadium stellen die beste Zielgruppe dar für Krebs-Impfstoffe. Denn die Belastungen durch die Krankheit sind noch gering. Je weiter die Krankheit voranschreitet, desto mehr Schwierigkeiten ergeben sich für die Behandlung. Zum Beispiel: Große Tumore können sich dem Immunsystem besser entziehen. Und ganz wichtig: Wenn man das Immunsystem aktiviert, und der Tumor schon sehr stark gewachsen ist, dann muss man einen sehr starken Gegner bekämpfen. Das ist sehr viel schwieriger."

Wenn Antigenics nun den Impfstoff in den USA zulassen wollte, dann müsste eine neue langjährige Studie nur für diese spezielle Patientengruppe angefertigt werden. Aus diesem Grund hat sich die Firma dazu entschlossen, das Mittel zunächst in Russland auf den Markt zu bringen. Das Gesundheitsministerium in Moskau hat vor wenigen Tagen die Genehmigung erteilt - auf der Basis jener Ergebnisse, die bei den Patienten im frühen Krebsstadium gewonnen worden sind. Armen:

"Der nächste Schritt direkt danach wäre es dann, in Europa einen Antrag zu stellen auf eine eingeschränkte Genehmigung. Unter der Hoffnung, auch in Europa eine Zulassung zu erhalten. In den USA wird da wohl weiterhin ein großes Fragezeichen bleiben."

Allerdings nicht das einzige Fragezeichen. So bezweifeln zum Beispiel einige Impfstoff-Forscher, dass das Präparat auf lange Frist seine Wirksamkeit behält. Es könnte zum Beispiel zu einer Art Abstumpfungsprozess des Immunsystems kommen, wie bei einer chronischen Viren-Infektion.


Oncophage®

Oncophage (vitespen; formerly HSPPC-96) is a patient-specific therapeutic cancer vaccine tested in over 800 patients in multiple cancers in more than 15 Phase 1, 2 and 3 clinical trials. Oncophage is approved in Russia for the adjuvant treatment of kidney cancer patients at intermediate-risk for disease recurrence. Oncophage contains the heat shock protein, gp96, and associated peptides which are purified from the patients' own tumor tissue and has been the primary focus of Antigenics' research and development efforts since the company's founding. Treatment with Oncophage is designed to target only cancerous cells — not healthy normal cells. As a result, Oncophage is designed to limit the toxicities associated with traditional broad-acting cancer treatments.

Oncophage first entered the clinic in the 1990's where it was studied in a number of different tumor types in advanced disease settings. The objectives of these early Phase 1/2 trials were to assess the feasibility of vaccine manufacture and corresponding logistics, safety and to identify signals of activity. The early findings supported the initiation and completion of two Phase 3 randomized trials in stage IV melanoma and adjuvant renal cell carcinoma (RCC).

The accumulated clinical data has revealed a pattern of findings that is entirely consistent with the biological premise:

  • Oncophage is well tolerated and has demonstrated a very low toxicity profile
  • Oncophage elicits tumor-specific T cell responses and innate immune response irrespective of tumor type
  • Oncophage efficacy is most significant in patients with early-stage disease/ low tumor burden (patients with better prognostic features)

To make Oncophage, patients first have surgery to remove part or all of the cancerous tissue, and the tumor tissue is shipped frozen to Antigenics' state-of-the-art GMP manufacturing facility in Massachusetts. The facility is capable of making vaccine for 10,000 patients with on site expansion to enable vaccine production for 100,000 patients. Using a proprietary, standardized, quality-controlled procedure, the product is isolated from the tumor in 8-10 hours. The product is sterile-filtered, packaged in vials, and shipped frozen back to the hospital pharmacy or clinician for use when the patient has recovered from surgery.

Oncophage is administered as a simple weekly or biweekly intradermal injection during an office visit.

Oncophage received fast track and orphan drug designations from the US Food and Drug Administration (FDA) for both kidney cancer and metastatic melanoma as well as orphan drug designation from the EMEA for kidney cancer. In 2009, Oncophage also received orphan drug designations from the FDA and EMEA for glioma. Antigenics has developed crucial management and logistics expertise in patient-specific vaccines.


COMBINATION VACCINATION for kidney cancer

COMBINATION CANCER VACCINATION

http://www.ncbi.nlm.nih.gov/pubmed/18060404

Vaccination of colorectal cancer patients with TroVax given alongside chemotherapy (5-fluorouracil, leukovorin and irinotecan) is safe and induces potent immune responses.

Harrop R, Drury N, Shingler W, Chikoti P, Redchenko I, Carroll MW, Kingsman SM, Naylor S, Griffiths R, Steven N, Hawkins RE.

Oxford BioMedica (UK) Ltd, The Medawar Centre, Oxford Science Park, Oxford OX4 4GA, UK. r.harrop@oxfordbiomedica.co.uk

Abstract

Modified vaccinia Ankara (MVA) encoding the tumor antigen 5T4 (TroVax) has been evaluated in an open label phase II study in metastatic colorectal cancer patients. The primary objective was to assess the safety and immunogenicity of TroVax injected before, during and after treatment with 5-fluorouracil, leukovorin and irinotecan. TroVax was administered to 19 patients with metastatic colorectal cancer. Twelve patients had blood samples taken following each of the six injections and were considered to be evaluable for assessment of immunological responses. Both antibody and cellular responses specific for the tumor antigen 5T4 and the viral vector MVA were monitored throughout the study. Administration of TroVax alongside chemotherapy was safe and well tolerated with no SAEs attributed to the vaccine and no enhancement of chemo-related toxicity. Of the 12 patients who were evaluable for assessment of immune responses, ten mounted 5T4-specific antibody responses with titers ranging from 10 to > 5,000. IFNgamma ELISPOT responses specific for 5T4 were detected in 11 patients with frequencies exceeding one in 1,000 PBMCs in five patients. Eight patients presented with elevated circulating CEA concentrations, six of whom showed decreases in excess of 50% during chemotherapy and four had CEA levels which remained stable for > 1 month following completion of chemotherapy. Of the 19 intention to treat (ITT) patients, one had a CR, six had PRs and five had SD. Potent 5T4-specific cellular and/or humoral immune responses were induced in all 12 evaluable patients and were detectable in most patients during the period in which chemotherapy was administered. These data demonstrate that TroVax can be layered on top of chemotherapy regimens without any evidence of enhanced toxicity or reduced immunological or therapeutic efficacy.

PMID: 18060404 [PubMed - indexed for MEDLINE]


ONCO VIRUS QUIZ:  http://www.science-projects.com/oncoquiz.htm


***  HERPES VIRUS AND CANCER (und KREBS) ***

Beschreibung (Re: Nachweis):
http://de.wikipedia.org/wiki/Zytomegalievirus

A sore throat is common!!!
http://en.wikipedia.org/wiki/Cytomegalovirus

Stimmt es, daß Herpes sich der Interferon Immunantwort bemächtigt?
Does Herpes URSURP the inferon reaction?
HV-5 (Cytomegalovirus): Mononucleosis, eye, kidney, brain and congenital infections
http://www.science-projects.com/V21.htm Herpes A type that breaks the rules!

But Interferon Injections HELP! 
http://content.karger.com/ProdukteDB/produkte.asp?Doi=9998


Rabbits:
Natural (good) / Recombinant (bad) Interferon:  http://www.iovs.org/cgi/reprint/25/7/874.pdf
Monkeys

July 1984 Natural human leukocyte interferon (natural HuIFN-a) and
recombinant leukocyte A interferon (recombinant A HuIFN-
a) were tested for prophylactic and/or therapeutic effects in
reducing the severity of keratitis in rabbit and monkey eyes
infected with McKrae strain herpesvirus. The results showed
that the two interferons acted differently in the rabbit eye;
combined prophylactic and therapeutic administration of
natural interferon mitigated the disease, while recombinant
interferon had no effect. In monkeys, the two interferons
acted similarly. Combined prophylactic and therapeutic ad-
ministration reduced disease findings, while therapeutic ad-
ministration alone had no effect. Thus, studies in rabbits are
not accurate predictors of primate study results;


***** VIRUSES and CANCER ??? **********


COMBINATION VACCINATION for kidney cancer

http://en.wikipedia.org/wiki/TroVax#Renal_cell_carcinoma

http://clinicaltrials.gov/ct2/show/NCT00083941

A Study of TroVax Vaccine Given in Conjunction With IL-2 for Treatment of Stage IV Renal Cell Cancer
This study has been completed  (IN 2008!).
First Received: June 3, 2004   Last Updated: July 31, 2008   History of Changes
Sponsor:     Oxford BioMedica  Collaborators:     Columbia University
ORION Clinical Services   Information provided by:     Oxford BioMedica
ClinicalTrials.gov Identifier:     NCT00083941

The purpose of this study is to test the safety of an investigational vaccine called TroVax when given in conjunction with Interleukin-2 (IL-2) treatment. TroVax is the experimental product in this trial and its value as a medicine has not yet been proven. Interleukin-2 (IL-2) is standard treatment for your cancer, which means that you could receive it even if you choose not to participate in this study. TroVax is being studied as a possible treatment for patients with cancer of the kidney.

TroVax belongs to a class of medicines called a vaccine. A vaccine helps the body's immune system to recognize and kill foreign invading organisms effectively. It is believed that one of the reasons why cancer can spread through the body is that the immune system cannot recognize them as being different from normal tissues and therefore cannot kill the cancer cells. A vaccine that alerts the immune system to the presence of cancer cells in the body could lead to the immune system being able to target and kill those cancer cells effectively. This trial is of a completely new way of trying to treat cancer in the future by the use of vaccination injections. TroVax consists of a virus that has been changed so that it is no longer infectious and carries a gene for a protein called 5T4. This protein is carried by many kidney cancer calls. When the virus is injected, it makes the protein, and the body's immune system is then able to recognize this protein and kill the cells that have it (i.e. the cancer cells).

The purpose of this study is to assess the safety and tolerability of TroVax injections and to understand whether TroVax could make such an immune response happen in patients with renal cell cancer while receiving Interleukin-2 (IL-2). This study will also observe and monitor any side effects experienced in patients who receive TroVax while being treated with IL-2.

Condition     Intervention     Phase
Carcinoma, Renal Cell     Biological: TroVax in combination with IL-2   Phase II

Study Type:     Interventional
Study Design:     Allocation: Non-Randomized
Control: Historical Control
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label  Primary Purpose: Treatment
Official Title:     Clinical Trial Phase II (Single Centre Study) : A Preliminary Study of the Safety, Immunogenicity, and Clinical Efficacy of TroVax Given in Conjunction With Interleukin 2 (IL-2) in the Treatment of Stage IV Renal Cell Cancer


GERMAN: RUSSICHES SERUM gegen Nierenkrebs - Impfung krebs


BITTE HELFT!   Das ZUGELASSENE Russische Serum zu identifizieren! (Siehe unten!)



 Prostata-, Nieren- und Magenkrebs Impfung verläuft erfolgreich
Samstag 25.10.2008, 10:26  FOCUS Magazin

Die Impfung gegen Gebärmutterhalskrebs ist bereits auf dem Markt

Neue Hoffnung zeichnet sich im Kampf gegen Prostata-, Nieren- und Darmkrebs ab. Im klinischen Test reagierten Patienten auf einen Impfstoff gegen die Leiden positiv.
Der Impfstoff besteht aus zwei wichtigen Komponenten: zum einem aus einem modifizierten Virus, das zum anderen ein Gen transportiert, das wiederum das Antigen 5T4 produziert. Dieses Antigen ist in Tumoren nachweisbar. Der Impfstoff ist für all jene Patienten geeignet, in deren Tumoren Ärzte das Antigen identifizieren konnten. „Das Virus dient sowohl als Transporter, um das 5T4-Antigen zu beliefern, als auch als Helfer, der eine starke Immunantwort auf das Antigen unterstützt", erklärt der Wissenschaftler Richard Harrop. Der Impfstoff macht die körpereigene Abwehr mobil gegen 5T4. Das Immunsystem bekämpft das Antigen und bremst dadurch ein weiteres Wachstum des Tumors – oder bringt ihn im Idealfall sogar zum Schrumpfen.

Diesen Effekt konnten Ärzte nun auch in klinischen Tests belegen. Sie untersuchten 189 Patienten, die in den USA und in England an insgesamt neun Versuchen teilgenommen hatten. Im Durchschnitt erhielten sie fünf Injektionen, maximal jedoch zwölf. Alle Probanden kamen mit dem Impfstoff gut zurecht – sowohl, wenn sie ihn „pur" erhielten, als auch wenn sie ihn in Kombination mit anderen Krebstherapien verabreicht bekamen. Im Anschluss ermittelten die Mediziner die Zahl der Antikörper im Blut von 180 Patienten. 88 Prozent (159 Personen) zeigten eine positive Immunantwort auf 5T4, 98 Prozent wiesen Antikörper für das modifizierte Virus des Impfstoffs auf. Die stärkste Immunantwort zeigte sich nach zwei Spritzen auf das modifizierte Impfvirus (MVA) und nach vier Spritzen auf 5T4. „Das hatten wir so erwartet", sagt Richard Harrop. „MVA ist ein fremdes Virus, auf das das Immunsystem schneller reagiert als auf eigene Antigene wie 5T4."

Überlebenschancen steigen

Je stärker die Reaktion auf 5T4 war, desto besser standen die Überlebenschancen für die Patienten. Verdoppelte sich die durchschnittliche Zahl der Antikörper zwischen der ersten und dritten Injektion, nahm ihr Risiko, frühzeitig zu sterben, um 17 Prozent ab.

In den letzten Jahren kamen die Impfstoffe gegen Krebs immer wieder in die Kritik, weil sie sich meist als nicht so vielversprechend erwiesen, wie es zunächst aussah. Abgesehen von Impfstoffen gegen Gebärmutterhalskrebs und einem in Russland zugelassenen Serum gegen Nierenkrebs gibt es bislang keine zugelassenen Impfstoffe gegen die Krankheit.
Die Ergebnisse wurden im Rahmen des 20. EORTC-NCI-AACR-Symposiums in Genf vorgestellt.

============================

WELCHES RUSSISCHE SERUM?

Bitte als Antwort einen KOMMENTAR hier drunter hinterlassen...

(Lesenzeichen setzen, wiederkommen)

Wir werden einen einfach zu googelnden Artikel darueber schreiben und hier veroeffentlichen.

Mehr info http://kidney-renal-cancer.blogspot.com/2010/07/german-1868-die-mbv-fiebertherapie.html


Sunday, August 15, 2010

Kidney Cancer DIAGNOSE - CT vs MRI

How is kidney cancer diagnosed?

Signs and symptoms of kidney cancer

Unfortunately, early kidney cancers do not usually cause any signs or symptoms, but larger ones may. Some possible signs and symptoms of kidney cancer include:

  • Blood in the urine (hematuria)
  • Low back pain on one side (not caused by injury)
  • A mass (lump) on the side or lower back
  • Fatigue
  • Unexplained weight loss
  • Fever that is not caused by an infection and that doesn't go away after a few weeks
  • Swelling of ankles and legs (edema)

These symptoms may be caused by cancer, but more often they are caused by non-cancerous diseases. For example, blood in the urine may be a sign of kidney, bladder, or prostate cancer, but most often it is caused by a bladder infection or a kidney stone. Still, if you have any of these symptoms, consult a doctor so that the cause can be evaluated and treated, if needed.

Medical history and physical exam

If you have any signs or symptoms that suggest you might have kidney cancer, your doctor will want to take a complete medical history to check for risk factors and symptoms. A physical exam can provide information about signs of kidney cancer and other health problems. For example, the doctor may be able to feel an abnormal mass when he or she examines your abdomen.

If symptoms and/or the results of the physical exam suggest kidney cancer might be present, more involved tests will likely be done. These might include imaging tests and/or lab tests.

Imaging tests

Imaging tests use x-rays, magnetic fields, or radioactive substances to create pictures of the inside of your body. Imaging tests may be done for a number of reasons, including to help find out whether a suspicious area might be cancerous, to learn how far cancer may have spread, and to help determine if treatment has been effective.

Unlike most other cancers, doctors can often diagnose a kidney cancer fairly certainly without the need for a biopsy (removal of a sample of the tumor to be looked at under a microscope). Often, imaging tests can give doctors a reasonable amount of certainty that a kidney mass is (or is not) cancerous. In some patients, however, a biopsy may be needed to be sure.

Computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, intravenous pyelograms, and ultrasound can be very helpful in diagnosing most kinds of kidney tumors, although patients rarely need all of these tests. Other tests described here, such as chest x-rays and bone scans, are more often used to help determine if the cancer has spread (metastasized) to other parts of the body.

Computed tomography (CT) scan

The computed tomography (CT or CAT) scan is an x-ray that produces detailed cross-sectional images of your body. Instead of taking one picture, like a regular x-ray, a CT scanner takes many pictures as it rotates around you while you lie on a table. A computer then combines these pictures into images of slices of the part of your body being studied.

Before any pictures are taken, you may be asked to drink 1 to 2 pints of a liquid called oral contrast. This helps outline the intestine so that certain areas are not mistaken for tumors. You may also receive an IV (intravenous) line through which a different kind of contrast dye (IV contrast) is injected. This helps better outline structures in your body.

The injection may cause some flushing (a feeling of warmth, especially in the face). Some people are allergic and get hives. Rarely, more serious reactions like trouble breathing or low blood pressure can occur. Be sure to tell the doctor if you have ever had a reaction to any contrast material used for x-rays.

CT scans take longer than regular x-rays. You need to lie still on a table while they are being done. During the test, the table moves in and out of the scanner, a ring-shaped machine that completely surrounds the table. You might feel a bit confined by the ring you have to lie in while the pictures are being taken.

CT scanning is one of the most useful tests for finding and looking at a tumor inside your kidney. It is also useful in checking whether or not a cancer has spread to organs and tissues beyond the kidney. The CT scan will provide precise information about the size, shape, and position of a tumor, and can help find enlarged lymph nodes that might contain cancer.

Magnetic resonance imaging (MRI)

Like CT scans, magnetic resonance imaging (MRI) scans provide detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed and then released in a pattern formed by the type of body tissue and by certain diseases. A computer translates the pattern into a very detailed image of parts of the body. A contrast material called gadolinium is often injected into a vein before the scan to better see details.

MRI scans are a little more uncomfortable than CT scans. First, they take longer -- often up to an hour. Second, you have to lie inside a narrow tube, which is confining and can upset people with claustrophobia (a fear of enclosed spaces). Special, open MRI machines can sometimes help with this if needed. MRI machines also make buzzing and clicking noises that many people find disturbing. Some centers provide headphones with music to block this noise out.

MRI scans are used less often than CT scans in people with kidney cancer. They may be done in cases where CT scans aren't practical, such as if a person is allergic to the CT contrast dye. MRI scans may also be done if there's a chance that the cancer has grown into major blood vessels in the abdomen (like the inferior vena cava), because they provide a better picture of blood vessels than CT scans. Finally, they may be used to look for possible spread of cancer to the brain or spinal cord if a person has symptoms that suggest this might be the case.

Ultrasound or ultrasonography

Ultrasound (US) uses sound waves to create images of internal organs. For this test, a small, microphone-like instrument called a transducer is placed on the skin near the kidney. It gives off sound waves and picks up the echoes as they bounce off the tissues in the kidney. The echoes are converted by a computer into a black and white image that is displayed on a computer screen. This test is painless and does not expose you to radiation.

Ultrasound can be helpful in determining if a kidney mass is solid or filled with fluid. The echo patterns produced by most kidney tumors look different from those of normal kidney tissue. Different echo patterns also can distinguish some types of benign and malignant kidney tumors from one another. If a kidney biopsy is needed, this test can be used to guide a biopsy needle into the mass to obtain a sample.

Positron emission tomography (PET) scan

Positron emission tomography (PET) scans involve injecting a form of radioactive sugar (known as fluorodeoxyglucose or FDG) into the blood. The amount of radioactivity used is very low. Because cancers use glucose (sugar) at a higher rate than normal tissues, the radioactivity will tend to concentrate in the cancer. A scanner can spot the radioactive deposits and can create a picture of areas of radioactivity in the body. The picture is not finely detailed like a CT or MRI scan, but it provides helpful information about your body.

This test can be helpful for spotting small collections of cancer cells and can be useful to see whether the cancer may have spread to lymph nodes near the kidney. PET scans can also be useful if your doctor thinks the cancer may have spread but doesn't know where. PET scans can be used instead of several different x-rays because they scan your whole body.

Some newer machines are able to perform both a PET and CT scan at the same time (PET/CT scan). This allows the radiologist to compare areas of higher radioactivity (suggesting an area of cancer) on the PET with the appearance of that area on the CT. PET and PET/CT scans are not a standard part of the work-up for kidney cancers.

Intravenous pyelogram

An intravenous pyelogram (IVP) is an x-ray of the urinary system taken after a special dye is injected into a vein. This dye is removed from the bloodstream by the kidneys and then concentrates in the ureters and bladder. An IVP can be useful in finding abnormalities of the urinary tract, such as cancer, but you might not need an IVP if you have already had a CT or MRI.

Angiography

Like the IVP, this type of x-ray also uses a contrast dye. A catheter is usually threaded up a large artery in your leg into the artery leading to your kidney (renal artery). The dye is then injected into the artery to outline blood vessels. This can allow the blood vessels that supply a kidney tumor to be identified and mapped, which can help in planning surgery in some patients. Angiography can also help diagnose renal cancers since the blood vessels usually have a special appearance with this test.

Chest x-ray

If kidney cancer has been diagnosed (or is suspected), a plain x-ray of your chest may be done to look for cancer spread to your lungs. Spread to the lungs is not very likely unless the cancer is far advanced. This x-ray can be done in any outpatient setting. If the results are normal, you probably don't have cancer in your lungs. The lungs are a common site of kidney cancer metastasis. If your doctor thinks there is a chance the kidney cancer has metastasized to your lungs, you may have a chest CT scan instead of a regular chest x-ray.

Bone scan

A bone scan can help show whether a cancer has metastasized (spread) to your bones. For this test, a small amount of low-level radioactive material is injected into a vein (intravenously, or IV). The substance settles in areas of damaged bone throughout the entire skeleton in a couple of hours. You then lie on a table for about 30 minutes while a special camera detects the radioactivity and creates a picture of your skeleton.

Areas of active bone changes appear as "hot spots" on your skeleton -- that is, they attract the radioactivity. These areas may suggest the presence of cancer spread, but arthritis or other bone diseases can also cause the same pattern. To distinguish between these conditions, your cancer care team may use other imaging tests such as simple x-rays or MRI scans to get a better look at the areas that light up, or they may even take biopsy samples of the bone.

Bone scans are done mainly when there is reason to think the cancer may have spread to the bones (like when the patient is having bone pain or blood test results show an increased calcium level). PET scans can usually show the spread of cancer to bones as well, so if you've had a PET scan you might not need a bone scan.

Lab tests

Lab tests are not usually used to diagnose kidney cancer, but they can sometimes give the first hint that there may be a kidney problem. They are also done to get a sense of a person's overall health and to help tell if cancer may have spread to other areas. They can help tell if a person is healthy enough to have an operation.

Urinalysis

Urinalysis (urine testing) is sometimes part of a complete physical exam, but it may not be done as a part of more routine physicals. It is likely to be one of the first tests done if kidney cancer is a possibility.

Microscopic and chemical tests are done on the urine to look for small amounts of blood and other substances not seen with the naked eye. About half of all patients with renal cell cancer will have blood in their urine. Sometimes special microscopic examination of urine samples (called urine cytology) will show actual cancer cells in the urine.

Complete blood count

The complete blood count (CBC) is a test that measures the different cells in the blood, such as the red blood cells, the white blood cells, and the platelets. This test is often abnormal in people with renal cell cancer. Anemia (having too few red blood cells) is very common. Less often, a person may have too many red blood cells (called polycythemia) because the kidney cancer makes a hormone (erythropoietin) that causes the bone marrow to make more red blood cells. Blood counts are also important to make sure a person is healthy enough for surgery.

Blood chemistry tests

Blood chemistry tests are usually done in people who may have kidney cancer, as it can affect the levels of certain chemicals in the blood. For example, high levels of liver enzymes are sometimes found, although the reasons for this are not known. High blood calcium levels may indicate that cancer is spread to the bones, and may therefore prompt a doctor to order a bone scan.

Fine needle aspiration and needle core biopsy

Biopsies are not often used to diagnose kidney tumors. Imaging studies usually provide enough information for a surgeon to decide if an operation is needed. However, fine needle aspiration (FNA) biopsy or needle core biopsy is sometimes used to get a small sample of cells from a suspicious area if imaging test results are not conclusive enough to warrant removing a kidney. Biopsy may also be done to confirm the diagnosis of cancer if a person's health is too poor for surgery and other local treatments (such as radiofrequency ablation, arterial embolization or cryotherapy) are being considered.

Fine needle aspiration and needle core biopsy are 2 types of percutaneous kidney biopsies (percutaneous means that a needle is placed through the skin to take a sample of some internal organ or tissue).

For either type of percutaneous biopsy, the skin where the needle is to be inserted is first numbed with local anesthesia. The doctor directs a hollow needle into the area while looking at your kidney with either ultrasound or CT scans. Unlike ultrasound, CT doesn't provide a continuous picture, so the needle is inserted in the direction of the mass, a CT image is taken, and the direction of the needle is guided based on the image. This is repeated a few times until the needle is within the mass.

For FNA, a small sample of the target area is sucked (aspirated) into a syringe. The needle used for FNA biopsy is thinner than the ones used for routine blood tests. The needle used in core biopsies is larger than that used in FNA biopsy. It removes a small cylinder of tissue (about 1/16- to 1/8-inch in diameter and ½-inch long). Either type of sample is checked under the microscope to see if cancer cells are present.

In cases where the doctors think kidney cancer may have spread to other sites, they may take a sample of the metastatic site instead of the kidney.

Fuhrman grade

The Fuhrman grade is found by looking at kidney cancer cells (taken during a biopsy or during surgery) under a microscope. It is used by many doctors as a way to describe how aggressive the cancer is likely to be. The grade is based on how closely the cancer cells' nuclei (part of a cell in which DNA is stored) look like those of normal kidney cells.

Renal cell cancers are usually graded on a scale of 1 through 4. Grade 1 renal cell cancers have cell nuclei that differ very little from normal kidney cell nuclei. These cancers usually grow and spread slowly and tend to have a good outlook (prognosis). At the other extreme, grade 4 renal cell cancer nuclei look quite different from normal kidney cell nuclei and have a worse prognosis.

Although the cell type and grade are sometimes helpful in predicting a prognosis, the cancer's stage is by far the best predictor of survival. The stage describes the cancer's size and how far it has spread beyond the kidney. Staging is explained in the section, "How is kidney cancer staged?"


Last Medical Review: 02/18/2010
Last Revised: 07/20/2010

IGNORE.. brainstorm material ONLY

Parasite?

quack_parasite cleaner


    * Black Walnut Hulls (from the black walnut tree)
    * Wormwood (from the Artemisia shrub)
    * Common Cloves (from the clove tree)

These three herbs must be used together.

Herbs

Desmodium styracifolium Mail Order USA &#37329;&#38065;&#33609; Guang Jin Qian Cao Desmodium styracifolium - Snowbelleaf Tickclover Herb

Shark?

supermaco Shark fat - olive oil- vitamine e


photo

http://en.wikipedia.org/wiki/Photodynamic_therapy

Body's own defences

[[http://scholar.google.co.nz/scholar?hl=en&q=coley's+toxins Coley's Toxins]]

Dendritic cells tell lymphnode which activates T-cells
german expl  Immuntherapie muss Tumoren nicht direkt angreifen Das Karzinom der Nebennierenrinde ist ein besonders bösartiger Tumor: Bei über 80 Prozent der Patienten treten im Laufe der Erkrankung Metastasen vor allem in Leber, Lunge und Knochen auf. Aus diesem Grund will Martin Fassnacht an der Medizinischen Klinik I der Uni Würzburg eine Immuntherapie gegen diese Krebsform etablieren.Es wird Blut entnommen, aus dem dann bestimmte Zellen ausgesondert werden, die so genannten Dendritischen Zellen. Die sind darauf spezialisiert, Krankheitserreger oder Tumorzellen zu erkennen, der Immunabwehr präzise zu beschreiben und dadurch eine gezielte Verteidigung in Schwung zu bringen. Im Labor werden die Zellen gegen den Feind aktiviert und dann dem Patienten als Tumor-Impfstoff zurückgegeben. Sein Immunsystem sollte daraufhin die Krebszellen verstärkt attackieren.

Fassnachts Strategie erscheint auf den ersten Blick ungewöhnlich, denn er will das Immunsystem nicht auf den Tumor selbst hetzen, sondern auf die Zellen, die ihn umgeben. Der Mediziner erklärt: "In den vergangenen Jahren hat sich zunehmend gezeigt, dass die Zellen, die um den Tumor herum wachsen, von entscheidender Bedeutung für den Verlauf der Erkrankung sind."

So gehe man beispielsweise davon aus, dass diese Zellen die Metastasenbildung fördern können. Sie sind zwar nicht entartet, unterscheiden sich aber trotzdem von gesunden Zellen. Beispielsweise bilden sie das Protein FAP, das im Körper sonst nur ganz selten vorkommt - und diese Eigenart macht sie zu einem guten Angriffsziel für die Therapie.  (FERNSEHSENDUNG august 2010, aufnahme habe ich) Gegen das seltene Protein lässt sich mit Hilfe der Dendritischen Zellen in der Tat eine Immunantwort auslösen. Das hat Fassnacht mit seinen Kollegen Jaewoo Lee und Eli Gilboa an der Duke University in North Carolina (USA) bewiesen: Die Forscher konnten in Zellkulturen und bei Mäusen das Wachstum von Haut- und Brustkrebs sowie Lymphomen deutlich verlangsamen. Ihre Ergebnisse wurden in den Zeitschriften "Clinical Cancer Research" (August 2005, 11: Seiten 5566-5571) und "Cancer Research" (Dezember 2005, 65: Seiten 11156-11163) publiziert. 


http://img.medscape.com/fullsize/migrated/430/327/cc430327.fig1.gif


more images: http://images.google.co.nz/images?q=Cancer%20immunotherapy

Fassnacht Wuerzburg

Monoclonal

http://en.wikipedia.org/wiki/Bevacizumab VERY HIGH PRICE

Fuda Cancer Hospital do Photodynamic therapy china chinese near hong kong

vascular targeted photodynamic therapy for renal tumors

LED light source

preserving kidney

read more


http://www.uni-stuttgart.de/izi/forschung/img/engineering1eng.gif


Saturday, August 14, 2010

KIDNEY DO'S AND DON'TS and Ayurveda


KIDNEY DO'S AND DON'TS

Do's
1) Drink plenty of water throughout the day.
2) Consume white variety of pumpkin and gourd.
3) Mung, wheat, barley and ginger juice is recommended.
4) Stay indoors in summer/ hot days.

Don'ts
1) Avoid fried and spicy food.
2) Reduce the consumption of beans, pulses, lady's finger and tomatoes.
3) Avoid suppression of natural urge of urination.
4) Avoid sedentary life style.


http://bodycare-reviews.info/wp-content/uploads/2010/03/Ayurveda.jpg


== Calcury Tablets ==
http://www.ayurvedaforall.com/291/calcury-tablets.html 7.63 euro
by Charak Pharmaceuticals 75 gramme  40 tablets
The natural Lithotriptic and diuretic
httpwww.herbalcureindia.com/products/kidney-support.htm
Calcury is a very special herb mineral formulation to take care of and prevent for a lot of urinary tract infection and stone formation. Calcury perceptibly encourage a healthy urinary tract and helps to keep up a normal urine composition and mucosal integrity. It is a conventional aid in maintaining healthy water organization and a diuretic that greatly relieves temporary water - weight gain. As a dietary supplement Calcury assists too a lot of kidneys and urinary tract in usual functions
Calcury averts the high saturation of lithogenic materials. It is also very supportive in regulating the absorption of oxamide absorption from the extra intestine and thereby regulates the crystalloid-colloid inequality. Calcury helps in inhibiting calculogenesis by lowering the stone forming materials like oxalic acid, calcium hydroxyproline and leads to eviction by micro pulverization.

Herbal Calcury leads to the crashing of the calculi and the crystals by performing on the mucin that combines the element in gig. Calcury 's antimicrobial actions are further beneficial in the avoidance of chronic urinary tract infections (UTI) that are linked with urinary stones and crystalluria. herbal Calcury possesses antispasmodic as well as anti inflammatory actions both reduce ureteric colic and ease the condition of sore and burning micturition.
Dosage: 1 to 2 tablets three times a day for 6-8 weeks.

http://www.herbalcureindia.com/images/cystone_pic001.jpg

== CYSTONE tablets ==
http://www.ayurvedaforall.com/1554/cystone-tablets-special-offer.html 21.57 euro
Himalaya Healthcare Ltd

Cystone prevents supersaturation of lithogenic substances, controls oxamide (a substance that precipitates stone formation) absorption from the intestine and corrects the crystalloid-colloid imbalance. Cystone inhibits calculogenesis by reducing stone-forming substances like oxalic acid, calcium hydroxyproline, etc., and causes their expulsion by micropulverization.

Cystone causes disintegration of the calculi and the crystals by acting on the mucin, which binds the particles together. Cystone's antimicrobial activity is beneficial in the prevention of urinary tract infections associated with urinary stones and crystalluria. Cystone's antispasmodic and anti-inflammatory activities relieve ureteric colic and alleviate symptoms of painful and burning micturition.
Indications
Cystone tablets is useful:
   1. Effective in both prophylaxis and treatment of adult and pediatric urolithiasis:
         1. Oxalate stones
         2. Phosphate stones
         3. Uric acid and urate stones
         4. Infection stones
   2. Crystalluria
   3. Prevention of post-lithotripsy recurrence
   4. As an adjuvant in:
         1. Chronic urinary tract infections
         2. Non-specific urethritis including dysuria
         3. Burning micturition
         4. Hyperuricemia
Composition     
Each Cystone tablet contains:
Exts.     Shilapuspha (Didymocarpus pedicellata)     130mg
    Pasanabheda (Saxifraga ligulata Syn. Bergenia ligulata / ciliata)     98mg
    Manjishtha (Rubia cordifolia)     32mg
    Nagarmusta (Cyperus scariosus)     32mg
    Apamarga (Achyranthes aspera)     32mg
    Gojiha (Onosma bracteatum)     32mg
    Sahadevi (Vernonia cinerea)     32mg
Pdrs.     Shilajeet (Purified)     26mg
    Hajrul yahood bhasma     32mg


ATTENTION:  other ingredients on another webpage

Prevents stone formation in the urinary tract.
Normalizes acidic urine and relieves burning urination.
Reduces pain and inflammation.
Has antibacterial action.
Cystone treats stones in the urinary tract, and recurrent urinary tract infections. Cystone inhibits stone formation by
Reducing the concentration of stone forming substances in the blood and expelling them from the body.
Breaking up stones by acting on mucin, a gummy substance which binds particles together.
Normalizing acidic urine.
Reducing oxidative stress, which is implicated in urinary stone
formation.
Cystone's antibacterial action along with its antibacterial, anti-inflammatory, pain relieving and urine pH normalizing actions prevent stone formation in the urinary tract and provide relief from pain and burning urination associated with urinary stones and urinary tract infections.
Indications:
Prevent and treat urinary stones.
Prevent recurrence of stones after surgery.
As an aid in preventing recurrence of urinary tract infections.
Aid in treating burning urination.
Ingredients Include:
Ginger (Zingiber officinale)
Shilapuspha (Didymocarpus pedicellata)
Pasanabheda (Saxifraga ligulata)
Indian madder (Rubia cordifolia)
Umbrella's edge (Cyperus scariosus)
Prickly chaff flower (Achyranthes aspera)
Sedge (Onosma bracteatum)
Purple fleabane (Sahadevi)
Lime silicate calx (Badrashma bhasma)
Mineral pitch (Shilajeet)
Use Directions:
One tablet twice daily.
Safety, Contraindications and Drug intractions:
Contraindications
There are no contraindications for the use of Cystone
Special precautions
Special precautions are to be exercised in patients with kidney, liver and heart impairment.
Side effects
Cystone does not produce any side effects, if taken as per the prescribed dosage.
Drug intractions
No clinically or biochemically significant drug intractions have been reported with the use of Cystone.
Presentation
Sealed packs of 60 tablets.




== Dihcap Capsule by  Capro Labs 100.00 Gram(s)  22.34 euro
Diucap is an exceptionally safe, Ayurvedic remedy for Urinary disorders. Diucap increases Urine output without any strain on the kidneys.


== Alka 5 syrup ==
httpwww.ayurvedaforall.com/1333/alka-5-syrup.html  euro 11.56 
 by Charak Pharmaceuticals
200.00 Gram(s)  Syrup: 100ml
Indications  1) Dysuria  2) Urinary tract infections  3) Urinary calculi

Dosage Syrup  Adult: Adults: 10 to 15 ml thrice a day for 1-2 weeks
Children: Children: 5 ml thrice a day for 1-2 weeks

Benefits

1) Soothes burning micturation.
2) Reduce inflammation & pain.
3) Exhibits antibacterial activity.
4) Induces diuresis and reduce urgency and frequency.
5) Safe and potentiates the action of antibacterial.


KIDNEY DO'S AND DON'TS

Do's
1) Drink plenty of water throughout the day.
2) Consume white variety of pumpkin and gourd.
3) Mung, wheat, barley and ginger juice is recommended.
4) Stay indoors in summer/ hot days.

Don'ts
1) Avoid fried and spicy food.
2) Reduce the consumption of beans, pulses, lady's finger and tomatoes.
3) Avoid suppression of natural urge of urination.
4) Avoid sedentary life style.


=== Gokshuradi guggulu tablet ===
httpwww.ayurvedaforall.com/1426/gokshuradi-guggulu-tablet.html 13.87 euro
Manufacturer: Arya Vaidya Nilayam, Madurai
100 grammes  90 tablets
Supports proper function of the genitourinary tract
Strengthens and rejuvenates the kidneys and prostate
Detoxifies the urinary tract
Decreases risk factors that cause stone formation
Maintains proper prostate size and function
Enhances sexual vigor and control
Ayurvedic Energetics:
Rasa (taste): sour, sweet, pungent, bitter, astringent
Virya (action): cooling
Vipaka (post-digestive effect): sweet
Doshas (constitutions): Balancing for all doshas, especially pitta
Herbal Actions:
alterative, antibilious, antiemetic, anti-inflammatory, antipyretic, antiviral, appetizer, astringent, carminative, demulcent, depurative, digestant, diuretic, laxative, nutritive, opthalmic, purgative, refrigerant, rejuvenative, stomachic, tonic, vulnerary
Traditional Uses:
arthritis (kapha-type), cysts, edema, fibrocystic breasts, excess body weight, swollen joints, urinary stones, water retention
Possible Contraindications:
Dehydration
Commentary:
Gokshuradi Guggulu is a traditional Ayurvedic compound used to support the proper function of the genitourinary tract. It strengthens and tones the kidneys, bladder and urethra as well as the reproductive organs. The main ingredient, gokshura, is renowned for its rejuvenating action on the kidneys and prostate. Combined with guggulu, triphala and trikatu, it detoxifies the urinary system and maintains healthy urinary composition, thus reducing the risk factors that may lead to stone formation. Balancing to all doshas, Gokshuradi Guggulu revitalizes kidneys weakened by vata, calms pitta inflammations, and reduces stones and swelling due to excess kapha


=== RENALKA ===

httpwww.ayurvedicherbalcure.com/renalka-syrup.html  10 euro
httpwww.himalayahealthcare.com/products/renalka.htm ???
httpwww.ayurvedaforall.com/607/renalka.html  6.93 euro
Renalka syrup is useful when the following symptoms are displayed:
Burning micturition Cystitis Recurrent UTI  Dysuria  Hematuria   As an adjuvant to antibiotics in UTI
by Himalaya Healthcare Ltd  6.93 euro

Each teaspoonful (5ml) of Renalka syrup contains:
Exts. Gokshura (Tribulus terrestris) 50mg
 Varuna (Crataeva magna Syn. C.nurvala) 50mg
 Sariva (Hemidesmus indicus) 50mg
 Musta (Cyperus rotundus) 50mg
 Ushira (Vetiveria zizanioides) 50mg
 Shatavari (Asparagus racemosus) 50mg
 Trikatu 16.50mg
 Ela (Elettaria cardamomum) 16.50mg
Pdrs. Kshara parpati 75mg


=== Gokshurapunarnavadi Tablet ===
httpwww.ayurvedaforall.com/238/gokshurapunarnavadi-tablet.html 16.95 euro
by Bipha Drugs ajaygv@gmail.com  +91 481 2563797





== Gokshuradi Guggulu DS ==
httpwww.ayurvedaforall.com/1432/gokshuradi-guggulu-ds.html 20.03euro
manufactured by Arya Vaidya Nilayam, Madurai
100.00 Gram(s) 90 tablets

Supports proper function of the genitourinary tract
Strengthens and rejuvenates the kidneys and prostate
Detoxifies the urinary tract
Decreases risk factors that cause stone formation
Maintains proper prostate size and function
Enhances sexual vigor and control
Ayurvedic Energetics:
Rasa (taste): sour, sweet, pungent, bitter, astringent
Virya (action): cooling
Vipaka (post-digestive effect): sweet
Doshas (constitutions): Balancing for all doshas, especially pitta
Herbal Actions:
alterative, antibilious, antiemetic, anti-inflammatory, antipyretic, antiviral, appetizer, astringent, carminative, demulcent, depurative, digestant, diuretic, laxative, nutritive, opthalmic, purgative, refrigerant, rejuvenative, stomachic, tonic, vulnerary
Traditional Uses:
arthritis (kapha-type), cysts, edema, fibrocystic breasts, excess body weight, swollen joints, urinary stones, water retention
Possible Contraindications:
Dehydration

Gokshuradi Guggulu is a traditional Ayurvedic compound used to support the proper function of the genitourinary tract. It strengthens and tones the kidneys, bladder and urethra as well as the reproductive organs. The main ingredient, gokshura, is renowned for its rejuvenating action on the kidneys and prostate. Combined with guggulu, triphala and trikatu, it detoxifies the urinary system and maintains healthy urinary composition, thus reducing the risk factors that may lead to stone formation. Balancing to all doshas, Gokshuradi Guggulu revitalizes kidneys weakened by vata, calms pitta inflammations, and reduces stones and swelling due to excess kapha


Himplasia PROSTATE
httpwww.ayurvedaforall.com/585/himplasia.html

Shilajit Gold  REJUVINATE



== Uramarunnu Tablet ==
httpwww.ayurvedaforall.com/198/uramarunnu-tablet.html 9.24  only
by Bipha Drugs 30 grammes 50 tablets
Specially formulated tablet for infants.
Uramarunnu BIPHA  digestive disorders in children
http://www.dsir.gov.in/reports/ExpTechTNKL/Abs%20new/BIPHA.htm
http://www.dsir.gov.in/reports/ExpTechTNKL/Abs%20new/Ayurveda.htm


Wednesday, August 11, 2010

RADIO PROGRAMME

751 Coley's Toxin, Cancer and Immunology Archive

August 7, 2010


http://www.peoplespharmacy.com/siteassets/PP-751B.mp3
 http://www.peoplespharmacy.com/siteassets/MatzingerFull.mp3


Dr. William Coley was a cancer surgeon at the turn of the 20th century. In an effort to improve the treatment he could offer his patients, he created a toxin that made them really sick. If they recovered from their fever, however, they were often cured of their sarcomas.

A century later, cancer researchers are taking a new look at Coley's toxin and how it might help us understand spontaneous remissions and the role of the immune system. In exploring this topic, we encounter an innovative immunologist who has developed a new paradigm for how the immune system works.

Guest: Uwe Hobohm, PhD, is a cell biologist and Professor of Bioinformatics at the University of Applied Sciences in Giessen, Germany. He has worked at the European Molecular Biology Laboratory in Heidelberg and at F. Hoffmann-La Roche in Basel. He is the author of Healing Heat: An Essay on Cancer Immune Defence.
http://bioinfo.tg.fh-giessen.de/pamp-cancer/

Polly Matzinger, PhD, is an ex-Playboy bunny turned scientist. At the National Institute of Allergy and Infectious Diseases, she is section head of the Ghost Lab, more formally known as the section on T cell tolerance and memory of the Laboratory of Cellular and Molecular Immunology. In her private life, she trains award-winning sheep dogs. The photo is of Polly and her dog Annie.

This is the first in a 3-part series on cancer and the immune system.

Truly fascinating and engaging. As an analytical LC-MS chemist, i too struggle with making useful analogies to convey science to laypeople whose eyes glaze with things they don't [wish to?] comprehend. Ms. Matzinger perceptively and intuiitively nails this. Dendritic cells as the Pacmen/sheepdogs of immune response. what a concept!! at any level 6th grade or otherwise. i wish her and colleagues in this arena well, for all to benefit.



Monday, August 2, 2010

BCG strain variations




http://www.iayork.com/Images/2009/6-19-09/BCG_MaxPlanck.jpg

Macrophage engulfing Bacillus Calmette-Guérin


  Tb family trees
By iayork  BCG (Max Planck)


The oldest vaccine, as everyone knows, is the smallpox vaccine. 1 Another  old vaccine (though not in the same class as smallpox vaccine) is the tuberculosis vaccine, Bacillus Calmette-Guérin (BCG), developed in 1921.

There's all kinds of interesting stuff about BCG. It's a live vaccine, meaning that the vaccine is live Mycobacterium bovis (the bovine tuberculosis bacterium). Albert Calmette and his assistant/colleague Camille Guérin, at the Institut Pasteur, repeatedly passaged a virulent isolate of M. bovis on a particular type of medium, noticed that some colonies looked different, and determined that these were less virulent for lab animals; after further passages, they announced that the variant was "inoffensif" in humans,2 and by the late 1920s BCG was being used around the world as a vaccine against tuberculosis. Overall, it's probably around 50% effective as a vaccine, with geographical location accounting for most of the variability. 3 That's very low as vaccine efficacy goes, and it means that vaccination is really only useful where there's lots of disease, not so much where there's a moderate incidence; which pretty much matches how BCG has been used worldwide.  On the other hand, the vaccine seems to be pretty innocuous, with a low complication rate.

BCG Genealogy


This much, I was more or less aware of,5 but there's much more to the story than that, as I've recently learned. 4,6 One fascinating question is, exactly what is the vaccine? This is an old vaccine, it was never homogenous (that is, it was basically a crude culture consisting of a wide range of minor variants around a central genome), and it's been passaged independently all over the world for 85 years. There's no such thing as "the" BCG any more; there are dozens of different BCGs, some of which can be traced directly back to the original Pasteur stock, others of which have bounced around and been sub-cultured from sub-cultures. There are at least 6 widely-used vaccine strains of BCG,7 not to mention older strains,  trial strains, and so on; and most of them behave differently in more or less subtle ways.  (See the genealogy of some of the more prominent strains, to the right.)


http://www.iayork.com/Images/2009/6-19-09/BCGGenealogy.gif

  Even the "same" strains have clearly changed over time; for example, somewhere between 1926 and 1934, the Pasteur strain of BCG became drastically less virulent:8

    Watson also stated that the strains he had received from Calmette between 1924 and 1927 were potentially virulent for animals, whereas the BCG strains he received and tested between 1929 and 1932 were no longer virulent.9

We don't have the original BCG strain any more, let alone the virulent M. bovis isolate from which it was derived, but some of the history can be inferred from genome analysis. Unsurprisingly, the different sub-strains have slight variants in their DNA sequences:

    These results are best understood from an evolutionary perspective and indicate that BCG has continued to change with in-vitro passage. All BCG strains are lacking deletion region 1, a genetic deletion that may correspond with the altered morphotype observed by Calmette and Guérin. Subsequently, strains obtained before 1926 and maintained on different continents have the 2-IS6110/mpt64+ genotype, which was likely the genetic composition of early BCG. … With such documented genetic change it would be surprising if there has not been phenotypic change over 1173 passages in-vitro, a notion supported in numerous reports describing ongoing attenuation after 1921. … In conclusion, we have demonstrated that through DNA fingerprinting, it is possible to verify the micro-evolution of attenuated Mycobacterium bovis over about one thousand passages. 4

So: We have an old, widely-used vaccine strain, that has a long history of variation. (This is similar, by the way, to smallpox vaccine — vaccinia virus was also widely distributed and showed extensive variation in its characteristics.) The BCG strains used today have all been more or less selected — either deliberately, or empirically — to be safe and effective vaccines; they've also been selected for a wide range of other factors (stability, ease of processing, rapid growth, and so on), some of which we know about, some of which we don't.

Could strain variability account for the wild variation in tested vaccine efficacy? Well. historically, perhaps not — different strains of BCG haven't correlated with the differences in efficacy that have been seen, most of which (as I said) follow geography.

But I'll leave you with this: It seems that the BCG vaccines used today are generally less effective than they were back in the 1920s.10 Could that be linked to some of these genomic variations?

    In early clinical studies, the live tuberculosis vaccine Mycobacterium bovis BCG exhibited 80% protective efficacy against pulmonary tuberculosis (TB). Although BCG still exhibits reliable protection against TB meningitis and miliary TB in early childhood it has become less reliable in protecting against pulmonary TB.11


   1. Even if we take into account the mysterious shift from cowpox to vaccinia virus as the vaccine strain[?]
   2. A. Calmette and C. Guérin, Nouvelles recherches expérimentales sur la vaccination des bovidés contre la tuberculose. Ann. Inst. Pasteur. 34 (1920), pp. 553–560.[?]
   3. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature.
      JAMA. 1994 Mar 2;271(9):698-702
      Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV, Mosteller F.[?]
   4. Behr, M. (1999). A historical and molecular phylogeny of BCG strains Vaccine, 17 (7-8), 915-922 DOI: 10.1016/S0264-410X(98)00277-1[?][?][?]
   5. As I've pointed out before, I'm not a bacteriologist, so I mainly picked up this much by osmosis[?]
   6. Development of the Mycobacterium bovis BCG vaccine: review of the historical and biochemical evidence for a genealogical tree.
      Tubercle and Lung Disease(1999) 79(4), 243–250
      T. Oettinger, M. Jørgensen, A. Ladefoged, K. Hasløv, P. Andersen[?]
   7. Connaught, Danish, Glaxo, Moreau, Pasteur, and Tokyo[?]
   8. Watson E A. Studies on bacillus Calmette-Guérin (BCG) and vaccination against tuberculosis. Can J Med Res 1933;9:128.[?]
   9. Development of the Mycobacterium bovis BCG vaccine: review of the historical and biochemical evidence for a genealogical tree.
      T. Oettinger, M. Jørgensen, A. Ladefoged, K. Hasløv, P. Andersen
      Tubercle and Lung Disease(1999) 79(4), 243–250  [?]
  10. Correlation between BCG genomics and protective efficacy.
      Scand J Infect Dis. 2001;33(4):249-52.
      Behr MA      and Has BCG attenuated to impotence?
      Marcel A. Behr1 & Peter M. Small
      Nature 389, 133-134 (11 September 1997) doi:10.1038/38151[?]
  11. Reducing the Activity and Secretion of Microbial Antioxidants Enhances the Immunogenicity of BCG
      Sadagopal et al
      PLoS ONE 4(5): e5531. doi:10.1371/journal.pone.0005531[?]

School medicine since 1976 - Bacteria against Cancer!!!


http://www.isracast.com/images/TechImages/260809cancer1.jpg

Th1 Th2 Autoimmune Disease Cancer Immunomodulation


http://medicineworld.org/images/blogs/11-2006/vaccine-89110.jpg

Dr. O'Donnell started by citing the some history relating to immunotherapy and cancer. He stated that in 1891 Coley first injected cancers with bacterial toxins and saw tumor shrinkage. In 1929 Pearl noted that lower cancer rates in tuberculosis  patients by autopsy series. In 1976 Morales used intravesical BCG in bladder cancer patients. Use of BGC resulted in decreased tumor cells in cytology specimens, but more neutrophils, suggesting an immune response.

Cytokine production of interleukins is central to the immune response. T cells are stimulated to the bladder after BCG therapy and are present for months thereafter. Interferon-gamma (IFN-gamma) is upregulated and participates in cellular immunity. IFN-gamma is always the last cytokine to come up and may be influenced by more proximal cytokines in the pathway. IL-10 knockout experiments showed that IFN-gamma is critical to the response.

http://edoc.hu-berlin.de/dissertationen/roese-lars-2004-06-09/HTML/Roese_html_4d987cfe.gif

IFN-gamma production is from BCG-stimulated human peripheral blood mononuclearcytes. Cox-2 inhibitors or indocin also inhibit IFN-gamma expression. BCG + IFN-gamma accentuates a type I cytokine response, suggesting that IFN-gamma may suppress IL-10. Response to BCG was increased if IFN-gamma was added. In fact, adding IFN-gamma and decreasing BCG maintains effectiveness.

TRAIL, an apoptosis inducing ligand was found to have higher urine levels in BCG responders vs. non-responders. TRAIL is strongly associated with neutrophils and is increased by IFN-gamma and alpha. BCG promoted cleavage of soluble TRAIL: from neutrophils and a Phase II trial using BCG + IFN-alpha. However, for those who have failed BCG twice, there does not seem to be benefit using the BCG-IFN-alpha. Other trials underway include adenoviral cytokine gene therapy and new gene polymorphisms that affect BCG anti-tumor response are being identified. Useful markers of BCG response are needed to help stratify patients and the basis for BCG failure needs to be better identified. This is an exciting area of research that will improve outcomes for patients in the future.

http://www.eyegene.co.kr/Eyegene/images/p_b04_001.gif


BCG: The Current Treatment of Choice for Bladder Cancer

Max Sherman, BSPharm

Published Online: September 1, 2007 - 12:00:00 AM (CDT)

After a recent physical examination, my wife learned that red and white blood cells were detected in her urine. The doctor ordered an intravenous pyelogram to determine the cause. In this test, an iodine-containing contrast material is injected into the bloodstream, and a series of x-rays is then taken at timed intervals. The resulting films allow the radiologist to view the entire urinary tract. Unfortunately, the diagnosis revealed that my wife had bladder cancer, a well-differentiated papillary tumor, which fortunately could be completely removed by transurethral resection and fulguration.

The urologist told us that a high-grade transitional type of tumor would require the instillation of chemotherapeutic drugs such as mitomycin C or doxorubicin. Another option would be to use Bacille Calmette-Gu?rin (BCG) vaccine instillations?-a treatment that controls superficial bladder cancer, particularly carcinoma in situ. I was surprised to learn that an ancient vaccine, originally designed to prevent tuberculosis (TB), is employed for a completely unrelated indication and is the current treatment of choice for bladder cancer. I thought that other pharmacists might be as curious as I was to learn more about the drug, its discovery, and its alternative use.


http://image.absoluteastronomy.com/images/encyclopediaimages/b/bc/bcg_apparatus_ja2.jpg

History Tuberculosis

Live attenuated BCG vaccine is indicated for the prevention of disease associated with Mycobacterium tuberculosis. In 1904, the organism destined to be used for the vaccine was isolated from a case of TB in cattle. The culture was highly virulent for many types of animals, and probably for humans, but it became progressively weakened while being cultivated in the test tube by French bacteriologists Albert Calmette and Camille Gu?rin.1

This cultivation required 231 passages through the laboratory over a period of 13 years. Because of the inability to preserve viable bacteria (by freezing), this live vaccine required continued passage, eventually resulting in a profusion of phenotypically different daughter strains.2 This special Mycobacterium bovis strain was named in honor of the researchers.3

Once they were convinced of the safety and immunizing power of BCG in animals, Calmette and his collaborators conducted a large program of vaccination of children born into tuberculous families.4 At first, the vaccine was administered by mouth and only to newborn infants.1 Now, the method most commonly used consists of injecting the vaccine into the superficial layers of the skin or depositing a drop of it on the skin and pricking with a sharp needle, as is done in smallpox vaccinations.

At best, the vaccine is 80% effective in preventing TB for a duration of 15 years. One third of clinical trials have shown no protective effect, however.5

Despite the questions about its efficacy, only a few countries do not use BCG for routine vaccination. This situation may change in the future, however, with recent evidence that older versions of the vaccine may be more effective than some of the more recent strains.6 In the United States, BCG generally is not administered to adults, because it is felt that having a reliable Mantoux test, and being able to accurately detect active disease, is more beneficial to society than vaccinating against a relatively rare condition.5

http://www.iayork.com/Images/2007/12-10-07/HIV_Wellcome.jpg

History Bladder Cancer

At the beginning of the 20th century, it became known that TB patients were less likely to contract cancer. Apparently the disease had an antitumor effect. An autopsy series by Raymond Pearl at Johns Hopkins Hospital in 1929 was one of the first reports that documented a lower frequency of cancer in patients with TB.3 The mechanism is unclear.

In the 1930s, the use of BCG as a cancer therapy was first raised, but there was little attention or enthusiasm during the 1950s and 1960s. Further research by Coe and Feldman rekindled interest, with the demonstration of a strong delayed hypersensitivity reaction to BCG in the guinea pig bladder.7

In 1976, Morales, Eidinger, and Bruce were the first to report on successful treatment of superficial bladder cancer with intravesical (within the bladder) BCG.8 They were able to demonstrate a remarkable decrease in the rates of recurrence in 9 patients. A randomized prospective trial by Donald Lamm and associates in 1980 confirmed these earlier observations.9

BCG is now regarded as the most successful urologic immunotherapy for treating cancer. It has become the treatment of choice for high-risk superficial bladder cancer in most countries, and it is given at an increasing annual rate of approximately 1 million doses.2


http://www.healthjockey.com/img/aids-infected-cell.jpg

Mechanism of Action

The initial crucial step in BCG therapy seems to be the binding of mycobacteria to the urothelial lining?which depends on the interaction of a fibronectin attachment protein on the bacterial surface with the fibronectin in the bladder wall. The presence of BCG then leads to the activation of urothelial and antigen-presenting cells.2 This action results in a massive local immune response (immunotherapy) characterized by induced expression of cytokines in the urine and bladder tissue, and an influx of granulocytes as well as mononuclear cells into the bladder wall. After these events, a massive cellular infiltration is seen, and this local inflammatory reaction in the bladder mucosa is characterized by large numbers of T cells, both CD4 and CD8, as well as macrophages.3

The contribution of CD4 T cells also is marked by the secretion of cytokines, leading to the maturation of cytotoxic T cells or possibly specific BCG-activated killer cells. The latter are capable of differentiating between normal and tumor cells. Only viable BCG organisms can induce the activity of the killer cells. This fact may explain why live attenuated BCG is necessary for successful intravesical BCG therapy.3

It is important to note that this activity in patients? bladders can persist for more than 1 year after the initial 6-week therapeutic induction course, but it commonly begins to wane after 3 to 6 months. This result provides the rationale for maintenance therapy.



Treatment Regimen

Standard treatment consists of a once-weekly instillation of BCG for 6 weeks. Patients are given live attenuated BCG mixed in 50 mL of normal saline, instilled into the bladder via a urethral catheter. The patient retains the fluid within the bladder for an hour, and during this period the patient lies prone for 15 minutes, supine for 15 minutes, and on each side for 15 minutes. Alternatively, some urologists recommend that the instillation be retained in the bladder for 2 hours. This duration ensures that all of the bladder mucosa comes into contact with the BCG.

Caution is suggested in handling the BCG because of a small risk of TB infection. The staff administering the BCG should be suitably protected with masks, goggles, gloves, and gowns to avoid inhalation and contact of BCG with broken skin. All equipment, supplies, and receptacles in contact with BCG should be handled and disposed of as biohazardous materials.

Patients should be advised to pour 2 cups of household bleach into their toilets after urinating to neutralize any BCG that may be found in the urine. The medication and bleach should remain in the toilet for 15 to 20 minutes before flushing. Patients should be advised to wash their hands and genital areas thoroughly after urinating and to drink plenty of fluids after each instillation to flush the bladder.

At the conclusion of the 6-week course, the patient undergoes a cystoscopy. If the bladder is free of tumor recurrence, then the patient is entered into a program of regular cystoscopic follow- up. If the tumor recurs, then the patient can, after resection, have a further course of BCG.3


Side Effects and Contraindications

Specific side effects are common. The most frequent are abacterial cystitis and dysuria, hematuria, and a low-grade pyrexia. These side effects usually subside within a 48-hour period and require little more than an analgesic for treatment. In these cases, BCG treatment can continue, but if the side effects are troublesome, increasing the time between treatments or reducing the dose should be considered.

Contraindications include an impaired immune response caused by disease, drugs, or other therapy; pregnancy and lactation; and positive HIV serology.


References

1. Dubos R, Dubos J. The White Plague. New Brunswick, NJ: Rutgers University Press; 1952.

2. Bohle A, Sven B. Immune mechanisms in Bacillus Calmette Guerin immunotherapy for superficial bladder cancer. J Urol. 2003;170:964-969.

3. Meyer JP, Persad R, Gillatt DA. Use of bacille Calmette-Guerin in superficial bladder cancer. Postgrad Med J. 2002;78:449-454.

4. Fine PEM, Carneiro IAM, Milstien JB, Clements CJ. Issues relating to the use of BCG in immunization programmes. Geneva, Switzerland: World Health Organization; 1999.

5. http://en.wikipedia.org. Accessed January 18, 2007.

6. Brosch R, Gordon SV, Garnier T, et al. Genome plasticity of BCG and impact on vaccine efficacy. Proc Natl Acad Sci USA. 2007;104:5596-5601.

7. Coe JE, Feldman JD. Extracutaneous delayed hypersensitivity, particularly in guinea pig bladder. Immunology. 1966;10:127-136.

8. Morales A, Eidinger D, Bruce AW. Intracavity Bacille Calmette-Guerin in the treatment of superficial bladder tumors. J Urol.1976; 116:180-183.

9. Lamm DL, Thor DE, Harris SC, Reyna JA, Stogdill VD, Radwin HM. Bacille Calmette-Guerin immunotherapy of superficial bladder cancer. J Urol. 1980;124:38-40.