Posted by rob on October 27, 2004 under Uncategorized | 
Herbal Supplement Cuts Effectiveness of Cancer-Fighting Drug Gleevec
Oct. 26, 2004 — The herbal supplement St. John’s Wort reduces the effectiveness of the cancer-fighting drug Gleevec, according to researchers from the University of Buffalo.
“Based on the results of this study, St. John’s Wort should be avoided in patients treated with [Gleevec], if possible,” write the researchers, who included Patrick Smith, PharmD.
Gleevec is used to treat a type of cancer called chronic myeloid leukemia (CML). As the first drug to specifically target cancer cells, it was considered a breakthrough medication and was quickly approved by the U.S. Food and Drug Administration (FDA) in 2001.
Currently, Gleevec is only approved to treat CML. However, other studies have suggested that it might have potential in combating other kinds of cancer.
Gleevec differs from chemotherapy in several respects. First, it’s taken orally, rather than intravenously. Second, the pills are spread over years, whereas chemotherapy is typically conducted in concentrated time periods. In addition, it zeroes in on cancer cells only, rather than killing all the cells in an affected area.
St. John’s Wort, on the other hand, is not a cancer treatment. Instead, it’s a popular supplement that has been used for years for medicinal purposes including mood elevation and mild-to-moderate depression.
While there is some evidence that St. John’s Wort works to treat mild and moderate depression, it lacks effect in treating major depression. However, St. John’s wort can interact with certain drugs, and these interactions can be dangerous.
Previous Cautions
Many of the so-called “natural substances” can have harmful effects. If taken in large quantities or if taken with another drug that interferes with its availability, these natural substances can have negative health consequences.
Several studies have shown that St. John’s Wort conflicts with prescription medications. In 2002, a Dutch study showed that St. John’s Wort interfered with and limited the effectiveness of the cancer-fighting medication irinotecan.
The FDA has warned in the past that St. John’s Wort could interact with a host of medications reducing their effectiveness, including those taken for HIV infection (indinavar), heart disease (high blood pressure calcium channel blockers such as diltiazam), seizure, cancer, organ transplant rejection (cyclosporine), and pregnancy (birth control pills).
Next: Latest Findings With St. John’s Wort
Latest Findings
Smith’s study, which is scheduled to appear in the November issue of the journal Pharmacotherapy, tested St. John’s Wort’s effects on Gleevec in 10 healthy adults.
The 18-day study was conducted in two phases. First, participants took 400 milligrams of Gleevec with a light meal after an overnight fast, then provided periodic blood samples for the next 48 hours.
Next, participants kept taking Gleevec in the same manner, along with 300 milligrams of St. John’s Wort three times daily for 15 days.
Gleevec’s effects were “significantly altered” by St. John’s Wort, say the researchers. Gleevec’s blood levels were diminished by 32%-42%.
“A drug interaction of this magnitude might contribute to the development of [Gleevec] resistance and treatment failures,” write the researchers.
“Clinicians should be aware that St. John’s Wort may reduce [Gleevec] exposure by 30%-40%, and take appropriate actions to educate patients receiving [Gleevec] treatment.”
St. John’s Wort appears to speed up metabolism of Gleevec, ushering it out of the body before it has the chance to fully exert its effects. As a result, the body could stop responding to Gleevec, since it’s not present at appropriate blood levels.
St. John’s Wort is unregulated in the U.S., so it’s impossible to know the exact dose of each bottle sold in America. For that reason, St. John’s Wort’s interaction with Gleevec may be even greater in some cases, as well as in certain people who may be more sensitive to such effects, say the researchers.
A Call for Full Disclosure
Patients taking herbal supplements need to tell their health care providers about it, say Smith and colleagues, who cite studies that say about a third to one-half of all cancer patients use some type of alternative medicine, such as vitamins and herbal supplements.
Too often, the public is unaware that such preparations can interact with and even undermine their prescription medications.
That’s not to say that depression and mood concerns, which are the main reasons why people take St. John’s Wort, aren’t important. The best approach may be discussing all supplements and remedies with a doctor, along with the problems that prompted interest in those preparations in the first place.
SOURCES: Smith, P. “The Influence of St. John’s Wort on the Pharmacokinetics and Protein Binding of Imatinib Mesylate.” News release, University of Buffalo. WebMD Medical News: “Gleevec New CML Gold Standard.” WebMD Medical News: “FDA Approves ‘Breakthrough’ Leukemia Drug.” WebMD Medical News: “St. John’s Wort Reduces Chemotherapy Effects.”
http://my.webmd.com/content/article/95/103536.htm
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Src kinase is an enzyme that may contribute to the ability of pancreatic cancer cells to metastasize or spread. BMS-354825 is an experimental compound that inhibits Src kinase.
Dr. Hong’s preliminary research shows that BMS-354825 inhibits Src kinase in pancreatic cancer cells in the laboratory. The inhibition of Src kinase then inhibits vascular endothelial growth factor (VEGF) in these cells. VEGF contributes to the ability of cancer cells to form new blood vessels and create a blood supply for the tumor. Dr. Hong hypothesizes that BMS-354825 may be an effective treatment for pancreatic cancer.
He will test his hypothesis first by determining if BMS-354825 kills isolated pancreatic cancer cells in the lab. Then, he will combine BMS-354825 with gemcitibine to determine if the two compounds together kill the isolated pancreatic cancer cells. Lastly, he will evaluate the antitumor activity of BMS-354825 alone and with gemcitibine in mouse models of pancreatic cancer.
http://www.pancan.org/Research/davidhong.htm
Posted by rob on October 26, 2004 under Uncategorized |
Some of the participants in an Underwater Pumpkin Carving contest show their creations on October 23, 2004, some 25 feet beneath the sea’s surface in the Florida Keys National Marine Sanctuary, about eight miles off Key Largo. The wacky event was the brainchild of Amoray Dive Resort in Key Largo. Participants were judged on design originality, steadiness of carving hand and scuba skills.
Posted by rob on October 25, 2004 under Uncategorized |
A pedestrian runs for cover as she emerges from Taipei train station during Typhoon Nock-Ten, October 25, 2004. Strong winds and heavy rain lashed Taiwan on Monday as the typhoon bore down on the island’s eastern shore, forcing schools and businesses in the capital Taipei and other regions to close.
Posted by rob on October 24, 2004 under Uncategorized |
Sumatran tiger Assiqua top grooms her son Dumai at Taronga Zoo in Sydney, Australia, Friday, Oct.22, 2004. Tiger cubs Jumilah, Sendiri and Dumai turn one year old this week and are a valuable addition to breeding programs as Sumatrans in the wild only number about 400.
Posted by rob on October 23, 2004 under Uncategorized |
Pediatr Blood Cancer. 2004 Oct; 43(5): 523-33
Pulsipher MA
BACKGROUND: Long-term survival of pediatric patients with chronic myelogenous leukemia (CML) receiving myeloablative hematopoietic stem cell transplantation from fully-matched related and unrelated donors has been reported between 60 and 75%, but is associated with significant morbidity. Imatinib mesylate (STI-571, Gleevec) and reduced intensity conditioning stem cell transplantation (RIC) are two promising new tools that offer potential for decreasing therapy associated morbidity for patients with CML. RESULTS: Large trials have shown significant responses in chronic phase patients treated with imatinib and reasonable but short-lived responses in advanced phase CML. Data from adult studies is beginning to define populations likely to progress or have prolonged responses to imatinib, and some adult treatment paradigms are moving toward reserving transplantation until patients are at risk of failure with imatinib. Early trials of RIC transplantation in CML show decreased transplant related morbidity with efficacy similar to conventional transplantation, but the approach has yet to be verified in phase III studies. Data in pediatric patients with imatinib and RIC transplantation is limited. CONCLUSIONS: Studies with imatinib are underway in pediatrics, but whether pediatric dosing schemes will lead to outcomes similar to adults is unknown. Because HLA-matched myeloablative transplantation offers a high rate of cure in the pediatric population, clinical studies assessing the role of imatinib mesylate and RIC transplantation should be planned carefully in order to avoid sub-optimal outcomes.
http://www.hubmed.org/display.cgi?issn=15455009&uids=15382266
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Best Pract Res Clin Haematol. 2004 Sep; 17(3): 439-51
Kolb HJ, Rank A, Chen X, Woiciechowsky A, Roskrow M, Schmid C, Tischer J, Ledderose G
Adoptive immunotherapy with transfusion of donor lymphocytes in allogeneic stem cell chimeras has been successful in the treatment of recurrent chronic myelogenous leukaemia (CML) and some patients with acute myeloid leukaemia (AML). The hypothesis that the graft-vs-leukaemia effect (GVL) is promoted by leukaemia-derived dendritic cells has been supported by the concurrent treatment of patients with cytokines that are known to induce differentiation of leukaemia cells towards dendritic cells. In combination with donor lymphocyte transfusions, treatment with interferon-alpha and granulocyte-macrophage colony-stimulating factor has been studied in patients with recurrent CML and AML, and pre-emptively in patients with high-risk AML. Long-term remissions have been observed in cytokine-treated patients, indicating the beneficial effect of cytokine stimulation of GVL reactions. This is likely to be due to differentiation of leukaemia progenitor cells towards dendritic cells in vivo.
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http://www.hubmed.org/display.cgi?issn=15216926&uids=15498715
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Bayern Munich fans burn flares during the Juventus vs Bayern Munich Champions League group C football match at Delle Alpi stadium in Turin.
Posted by rob on October 22, 2004 under Uncategorized |
Cancer Genet Cytogenet. 2004 Oct 1; 154(1): 52-6
Kwon HC, Kim SH, Kim JS, Han H, Roh MS, Han JY, Seo SY, Lee YH, Kim HJ
The tyrosine kinase inhibitor STI571 is an effective agent for the treatment of chronic myelogenous leukemia (CML). However, a lack of response to STI571 or the recurrence of the disease after a transient initial response is usually seen in patients with advanced stage CML. We have established a novel STI571 (Gleevec/Glivec, imatinib mesylate)-resistant acute myelocytic leukemia cell line (SR-1) from an STI571-resistant blast crisis patient. By flow cytometry, the immunophenotype of SR-1 was found to be compatible with a myeloid lineage (CD13+, CD33+, HLA-DR+, anti-MPO+). Conventional cytogenetics showed a three-way reciprocal translocation involving 7p22, 9q34, and 22q11.2, i.e., a variant Philadelphia chromosome translocation. The BCR/ABL rearrangement was detected by fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction. To determine the tumorigenicity of the SR-1 cell line in vivo, cells were injected subcutaneously into severe combined immunodeficiency mice. Four weeks later, tumors had grown and showed the same laboratory findings as in SR-1. Although STI571 resistance is a known treatment complication, in vivo STI571-resistant cell lines have not been fully established. We hope that our SR-1 cell line may be useful in molecular pathogenetic investigations of STI571-resistant CML.
http://www.hubmed.org/display.cgi?issn=01654608&uids=15381372
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Clin Cancer Res. 2004 Oct 1; 10(19): 6661-8
Gottschalk S, Anderson N, Hainz C, Eckhardt SG, Serkova NJ
The therapeutic efficacy of imatinib mesylate (Gleevec) is based on its specific inhibition of the BCR-ABL oncogene protein, a widely expressed tyrosine kinase in chronic myelogenous leukemia (CML) cells. The goal of this study was to evaluate glucose metabolism in BCR-ABL-positive cells that are sensitive to imatinib exposure. Two human BCR-ABL-positive cell lines (CML-T1 and K562) and one BCR-ABL-negative cell line (HC-1) were incubated with different imatinib concentrations for 96 hours. Magnetic resonance spectroscopy on cell acid extracts was performed to evaluate [1-13C]glucose metabolism, energy state, and changes in endogenous metabolites after incubation with imatinib. Imatinib induced a concentration-dependent inhibition of cell proliferation in CML-T1 (IC50, 0.69 +/- 0.06 micromol/L) and K562 cells (IC50, 0.47 +/- 0.04 micromol/L), but not in HC-1 cells. There were no metabolic changes in imatinib-treated HC-1 cells. In BCR-ABL-positive cells, the relevant therapeutic concentrations of imatinib (0.1-1.0 micromol/L) decreased glucose uptake from the media by suppressing glycolytic cell activity (C3-lactate at 0.25 mmol/L, 65% for K562 and 77% for CML-T1 versus control). Additionally, the activity of the mitochondrial Krebs cycle was increased (C4-glutamate at 0.25 micromol/L, 147% for K562 and 170% for CML-T1). The improvement in mitochondrial glucose metabolism resulted in an increased energy state (nucleoside triphosphate/nucleoside diphosphate at 0.25 micromol/L, 130% for K562 and 125% for CML-T1). Apoptosis was observed at higher concentrations. Unlike standard chemotherapeutics, imatinib, without cytocidal activity, reverses the Warburg effect in BCR-ABL-positive cells by switching from glycolysis to mitochondrial glucose metabolism, resulting in decreased glucose uptake and higher energy state.
http://www.hubmed.org/display.cgi?issn=10780432&uids=15475456
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Leukemia. 2004 10 21;
Weisberg E, Catley L, Kujawa J, Atadja P, Remiszewski S, Fuerst P, Cavazza C, Anderson K, Griffin JD
NVP-LAQ824 is a novel potent hydroxamic acid-derived histone deacetylase inhibitor that induces apoptosis in nanomolar concentrations in myeloid leukemia cell lines and patient samples. Here we show the activity of NVP-LAQ824 in acute myeloid leukemia cells and BCR/ABL-expressing cells of mouse and human origin, both sensitive and resistant to imatinib mesylate (Gleevec, STI-571). Whereas imatinib inhibited overall cellular tyrosine phosphorylation in Ba/F3.p210 cells, NVP-LAQ824 did not inhibit tyrosine phosphorylation, and did not affect BCR/ABL or ABL protein expression. Neither compound was able to inhibit cellular tyrosine phosphorylation in the imatinib-resistant Ba/F3.p210-T315I cell line. These data taken together suggest that BCR/ABL kinase activity is not a direct target of NVP-LAQ824. Synergy between NVP-LAQ824 and imatinib was demonstrated against BCR/ABL-expressing K562 myeloid leukemia cell lines. In addition, we show that NVP-LAQ824 was well tolerated in vivo in a pre-clinical murine leukemia model, with antileukemia activity resulting in significant prolongation of the survival of mice when treated with NVP-LAQ824 compared to control mice. Taken together, these findings provide the framework for NVP-LAQ824 as a novel therapeutic in myeloid malignancies.Leukemia advance online publication, 21 October 2004; doi:10.1038/sj.leu.2403519.
http://www.hubmed.org/display.cgi?issn=08876924&uids=15496979
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Br J Cancer. 2004 10 19;
Deutsch E, Maggiorella L, Wen B, Bonnet ML, Khanfir K, Frascogna V, Turhan AG, Bourhis J
Chronic myelogenous leukaemia (CML) is a clonal malignancy of the pluripotent haematopoietic stem cell, characterised by an uncontrolled proliferation and expansion of myeloid progenitors expressing a fusion oncogene, BCR-ABL, the molecular counterpart of the Ph1 chromosome. The tyrosine kinase (TK) activity of BCR-ABL is known to activate several major signalling pathways in malignant cells, including Ras, JAK/STAT and PI3K/Akt with evidence of proteasome-mediated degradation of other targets such as the DNA repair protein DNA-PKcs and cyclin-dependent kinases inhibitor p27. Targeting these abnormalities by blocking TK of BCR-ABL with STI571 provided a promising approach for the therapy of CML. The recent development of resistance to STI571 illustrates, however, that the use of other TK inhibitors could be of major interest for therapeutic purposes. To this end, the TK inhibitor Tyrphostin AG1024 was used to evaluate effect on regulation of BCR-ABL expression, inhibition of cell proliferation and tumour formation in vivo in human and murine BCR-ABL expressing cell lines. Tyrphostin AG1024 was shown to downregulate expression of BCR-ABL and P-Akt, and to upregulate DNA-PKcs expression. In addition, Tyrphostin AG1024 was able to inhibit cell proliferation, and delay tumour growth in vivo. Thus, AG1024 is able to interfere with three major targets of BCR-ABL in leukaemic cells. Interestingly, Tyrphostin AG1024 was also effective against cells resistant to STI571 by distinct mechanisms including Bcr-Abl mutation. Therefore, these data suggest that Tyrphostin AG1024 could represent the basis of a novel therapy for STI571 refractory CML.British Journal of Cancer advance online publication, 19 October 2004; doi:10.1038/sj.bjc.6602190 www.bjcancer.com.
http://www.hubmed.org/display.cgi?issn=00070920&uids=15494718
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J Cell Sci. 2004 10 19;
Malmberg EK, Andersson CX, Gentzsch M, Chen JH, Mengos A, Cui L, Hansson GC, Riordan JR
The breakpoint cluster region protein (Bcr) is a large soluble oligomeric multidomain protein best known because of its involvement in chronic myelogenous leukemia (CML). A chromosomal translocation between its gene and that of the c-abl kinase (‘Philadelphia chromosome’) plays a major causative role in that malignancy. Thus most attention has been paid to the role of the protein in hemopoietic cells. However, Bcr is also expressed in other cell types including epithelia. Bcr is generally considered to be a cytoplasmic protein but in addition to its kinase and GTPase exchange and activating domains it contains potentially membrane-interacting pleckstrin homology and C2 domains as well as a PDZ-binding C terminus mediating an interaction with a PDZ-domain protein at intercellular junctions of epithelial cells. We have examined the ability of Bcr to interact with other epithelial PDZ proteins and found specific binding to both the apical PDZK1 protein and the Golgi-localized Mint3. The former is important in the organization of several apical functions and the latter in vesicular trafficking in the secretory pathway. Hence these findings extend the interactions and likely signaling impact of Bcr in epithelia from the cytosol to at least these two membrane compartments.
http://www.hubmed.org/display.cgi?issn=00219533&uids=15494376
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11th October 2004
Justice A S Anand
The Chairperson
National Human Rights Commission (NHRC)
Sardar Patel Bhavan, Sansad Marg
New Delhi 110001
Sub: (Third Amendment to Patents Act 2004)
Dear Justice Anand:
I am writing this letter on behalf of Affordable Medicines and Treatment Campaign (AMTC). The AMTC is a national campaign aimed at creating an environment that will ensure sustained accessibility and affordability of medicines and treatment for every individual in India, including access to affordable Anti-Retroviral Therapy for persons living with HIV/AIDS. It consists of civil society organisations, NGOs, patients groups, healthcare providers and concerned individuals. The campaign was initiated in 2001 with the following mission statement:
The right to life and health is a fundamental right guaranteed to every person living in India and is non-negotiable. This campaign aims to demand and create an environment that will ensure sustained accessibility and affordability of medicines and treatment for every individual in India, including access to affordable Anti-Retroviral Therapy for persons living with HIV/AIDS. This campaign shall be democratic and participatory. It will seek the mobilization of communities and civil society to make state, national and international agencies and industry accountable for securing health for all.
AMTC attempts to encourage action on a wide spectrum of issues relating to the right to treatment. These include WTO negotiations relating to the TRIPS agreement (TRIPS), the impending amendment to Patents Act 1970, law and regulation of drug pricing, national and state level governmental policies relating to health including vertical disease programmes, health needs of the population, transparency and accountability in the pharmaceutical sector, treatment literacy and health care infrastructure etc.
As you are aware the Government of India has initiated to amend the Patents Act 1970 to introduce product patent protection to drug, medicine or food. A Patent Amendment Bill (Bill) was introduced to this effect in the 13th Lok Sabha in December 2003. The Bill lapsed due to the dissolution of Lok Sabha. In the last week of August 2004 the Cabinet has decided to refer the Bill to a Group of Ministers (GOM) to study the implications of contentious issues in the Bill. The GOM consists of Minister of Defense, Minister of Health, Minister of Human Resources Development and Minister of Commerce and Industry. We have learned from news reports that provisions of the referred Bill are identical to the lapsed Bill. This is a matter of concern because the Bill in its present form seriously compromises the accessibility and availability of medicines, two important components of right to health.
Introduction of product patent protection for medicines and agro-chemicals is part of India’s obligation under (TRIPS). TRIPS obligates member countries to provide a universal minimum standard of protection for various types intellectual property rights viz. trade mark, copyrights, geographical indications, patents, industrial designs, plant varieties, topography of integrated circuits and trade secrets. India has amended the
Patents Act in 1999 and 2002 to comply with the obligations of TRIPS. The only pending obligation with regard to TRIPS is the introduction of product patents to medicines and agro-chemicals. India is to carry out this obligation by, before 1st January 2005.
As you know, the Patents Act 1970 does not provide product patent protection for medicines and food. The Patents Act 1970 was enacted to scrap the Patents Act 1911, which provided product patent protection for medicines and food. The Patents Act 1970 provides only process patent protection to medicines and food. Process patent does not prevent others from making the product per se but prevents others from using the patented process as well as using, offering for sale, selling or importing the product obtained from the patented process. On the other hand, product patent prohibits others from making, using, offering for sale, selling or importing the patented product. As a result the product patent gives a monopoly to the patent owner for the production of patented article during the term of the patent (20 years). Therefore product patent protection for medicines and agro-chemicals creates monopoly and eliminates competition in the pharmaceutical market. Drug companies often abuse the patent monopoly and fix exorbitant prices for the patented medicines. The introduction of product patent thus reduces accessibility and affordability of drugs.
The impact of product patent on the accessibility and availability of drugs are well documented. The most striking incident is the impact of product patent on access to HIV/AIDS drugs. Till 2000, antiretroviral (ARV) drugs were not accessible to the vast majority of people living with HIV/AIDS (PLHA) all over the world because of the high price. Multinational drug companies priced ARV drugs between US$12-13,000 annually per person. The price started falling in 2000 when manufacturers from India introduced generic versions of ARV drugs. Now these generic drugs are given as low as US$ 140 annually per person to certain international organisations like the Clinton Foundation. This is possible because of the absence of a product patent regime in India. Further, the absence of product patent protection has also facilitated the introduction of fixed dose combination (FDC) of ARV drugs. A three-in-one cocktail pill introduced by the generic manufacturers substituted two pills for six pills per day. Thus the FDCs increased the accessibility as well as availability of ARV drugs. The introduction of FDCs became possible only because of the absence of product patent protection in India. The introduction of a product patent regime would prevent generic companies in India from repeating this miracle.
The impact of monopoly on access to medicines is already felt in India. The Controller of Patents has granted an Exclusive Marketing Right (EMR) to Novartis AG, for the drug called Gleevec used for the treatment of patients suffering from Chronic Myeloid Leukaemia (CML), a life threatening form of cancer. EMR is granted as a transitional arrangement before providing product patent protection. Gleevec is sold by Novartis AG at Rs. 1,20,000 per month.. The generic version of the drug was otherwise available to CML patients at Rs 9,000- 12,000 per month. The EMR, if enforced will result in the withdrawal of generic version of Gleevec from the market. Consequently, the overwhelming majority of patients that suffer from CML every year in India will be denied access to this life saving drug. Both the industry and the civil society have approached the Supreme Court of India to challenge the decision of granting EMR on Gleevec.
Thus it shows that introduction of product patent in India will reduce the accessibility and availability of medicines. Therefore, we feel that utmost care is required to introduce the product patent regime. Certain flexibility available under the TRIPS should be used to its full extent to safeguard accessibility and availability of drugs and medicines. The Bill, however, fails to make use of this flexibility at its optimum level. Main criticisms against the bill are as follows.
Firstly, the Bill proposes to extend the scope of patentability beyond the TRIPS requirements by amending Section 3 (d) to allow patent protection for new use of known drugs. Patent for new use would help pharmaceutical companies to extend the monopoly over the drug even after the expiry of original patent. There is no obligation under TRIPS to provide patent protection to new use of known drugs. Earlier, the Mashelkar Committee recommended to limit the patent protection only to new chemical molecules.
Secondly, the Bill proposes to do away with the pre-grant opposition procedure. Currently, there are approximately 6,000 applications pending in the mailbox. In the absence of pre-grant opposition, these 6,000 applications would escape much needed public scrutiny. Public scrutiny is crucial in light of the fact that less than 500 drugs have been granted marketing approvals in India between 1995-2004.
Thirdly, the Bill has not properly incorporated the “August 30th Decision”, which permits the grant of compulsory license for export purposes. The Bill proposes to permit compulsory licensing for export purpose if there is a compulsory license in the importing country having no or insufficient manufacturing capacity in the pharmaceutical sector. This ignores the fact that Least Developing Countries (LDCs) need not provide product patent till 2016. In the absence of patent protection, issuance of compulsory license is impossible. In that event, the Indian drug companies would not be able to export to LDCs.
Lastly, the Bill fails to revamp the compulsory licensing mechanism. Even though the Chapter on compulsory licenses in the Patents Act 1970 states the need for protecting the public interest, the same spirit is not reflected in the substantial provisions. Cumbersome procedures without any time line for the final disposal of application makes the compulsory license mechanism an impractical option to curb abuse of patent monopoly.
India as a party to the International Covenant on Economic Social and Cultural Rights (ICESCR) has an international obligation to protect peoples’ right to health. According to Article 12 of ICESCR “The States Parties to the present Covenant recognize the right of everyone to the enjoyment of the highest attainable standard of physical and mental health”. As you know, accessibility to and availability of drugs are recognized as important components of right to health. The introduction of product patent in the current form will further reduce the access to drugs. The Supreme Court of India recognized the enforceability of right to health within the scope of Article 21 of the Indian Constitution (Vincent Panikurlangara v Union of India 1987 (2) SCC 165). Further, Article 15(1)(b) of the ICESCR recognises “right of everyone to enjoy the benefits of scientific progress and its applications”. The Supreme Court often interpreted fundamental rights in consonance with international treaties. Hence, the implementation of product patent should not result in the denial of rights guaranteed under the Constitution of India and the ICESCR. According to Section 2 (d) & (f) of Protection of Human Rights Act, 1993 rights under the ICESCR are the rights that the National Human Rights Commission (NHRC) has to protect.
We therefore request your urgent intervention to safeguard peoples’ right to health guaranteed under the Constitution of India and ICESCR by using the mandate under Section 12 (d), (f) and (j) of the Protection of Human Rights Act, 1993. In the context, we request NHRC:
- To seek information from the Government of India regarding the steps which are already taken or under consideration to safeguard the right to health under the product patent regime.
- To study and recommend to the Government of India on the steps to be taken to ensure the enjoyment of benefits of scientific progress and its application, an obligation under Article 15(1) (b) of ICESCR.
- To study and recommend to the Government of India on the options available within the TRIPS Agreement to safeguard right to health.
- To hold a national level consultation with concerned individuals and groups on the implications of intellectual property rights on peoples’ right to health.
With warm regards,
For AMTC
Anand Grover
Project Director, Lawyers collective HIV/AIDS Unit
Cc: Justice Y. Bhaskar Rao , Member, NHRC
Cc: Mr. R.S. Kalha, Member, NHRC
Cc: Mr. P.C.Sharma, Member, NHRC
Cc: Mr. Tarlochan Singh, Member, NHRC
http://hrw.org/english/docs/2004/10/22/india9556.htm
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The all-new Jeep Grand Cherokee moves up the side of a 30-story skyscraper in New York, Thursday, Oct. 21, 2004, to promote its performance, style and off-road capability. The event, staged by mounting the jeep on a track on the building, kicked-off the arrival of the 2005 Jeep Grand Cherokee at dealerships nationwide this weekend.
Posted by rob on October 21, 2004 under Uncategorized |
Roiling clouds, whipped up by high winds, obscure much of Mount St. Helens, showing only its’ snow-covered northwestern flank while water flows through the drainage area feeding the North Toutle River as seen from Castle Lake Viewpoint in southwest Washington.
Posted by rob on October 20, 2004 under Uncategorized |
Int J Mol Med. 2004 Nov; 14(5): 925-9
Chui CH, Cheng GY, Ke B, Lau FY, Wong RS, Kok SH, Fatima S, Cheung F, Cheng CH, Chan AS, Tang JC
The effective microorganism (EM-X) fermentation extract is derived from rice bran and seaweed extract. It has been shown to possess anti-oxidation activity both in vitro and in vivo. To our knowledge, the possible in vitro anti-cancer potential of EM-X has not been demonstrated. Here we showed that the double concentrate of EM-X (EM-X2) at concentrations of 20-30% by volume, had growth inhibitory activity on MDA-MB231 breast cancer cell line and K-562 chronic myelogenous leukaemia cell lines by [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2-H-tetrazolium, inner salt] (MTS) assay. No characteristic features of apoptosis could be observed morphologically. Colony formation assay illustrated that both MDA-MB231 breast cancer and K-562 CML cells lost part of their regeneration potential after treatment with EM-X2 at 30% concentration by volume for 24 h. At these concentrations, only slight growth inhibitory effect was observed in 293 human kidney fibroblast cells and in three non-malignant bone marrows. Intracellular nitro blue tetrazolium (NBT) reduction assay showed that both MDA-MB231 breast cancer and K-562 CML cells had about 30% reduction of intracellular NBT after incubation with 30% of EM-X2. Increased activity of superoxide dismutase (SOD) could be detected from both MDA-MB231 and K-562 cell lines after incubating with 30% of EM-X2. Taken together, our data suggested that EM-X could inhibit growth and reduce the regeneration potential of cancer cells, possibly through its antioxidation activity.
http://www.hubmed.org/display.cgi?issn=11073756&uids=15492867
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Scott Med J. 2004 Aug; 49(3): 87-90
Harrison SJ, Johnson PR, Holyoake TL
The management of CML has recently become increasingly complex. The Scotland Leukaemia Registry (SLR) sent questionnaires to all 26 Scottish haematology units, of which 18 (69%) responded. From January 1999 to December 2000, 64 new cases of CML were identified by the audit (incidence 0.64/100,00/yr), of which 46 were registered with the SLR. At diagnosis, all 18 units combined bone marrow examination with cytogenetics/FISH, but only 13 performed RT-PCR. Of four units that calculated the Hasford Score, only two used it to inform clinical decisions. 52% of patients entered clinical trials, 57% involving imatinib mesylate (IM). Of the 23 patients who were tissue typed, suitable donors were found for 18, 11 sibling, and 7 unrelated, representing 28% of the total patient population. Only 13/64 patients (20%) did not have a BMT donor identified or enter a clinical trial. Although 38% of units would consider reduced intensity allografting in patients > 60 years, no centres currently routinely tissue-type such patients. For first line therapy 56% of patients received hydroxyurea +/- interferon. Of the newer agents, 83% of units believed imatinib mesylate should be reserved for clinical trials, 83% would consider using oral ara-C and 89% pegylated-interferon.
http://www.hubmed.org/display.cgi?issn=00369330&uids=15462221
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OBJECTIVE: Imatinib is a potent inhibitor of the Bcr-Abl and c- kit tyrosine kinases and is approved for the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia and gastrointestinal stromal tumors. Because imatinib is predominantly metabolized by cytochrome P450 (CYP) 3A4, its pharmacokinetics may be altered when it is coadministered with drugs or herbs (eg, St John’s wort) that modulate CYP3A4 activity.Thus we examined the effects of St John’s wort on imatinib pharmacokinetics. METHODS: This 2-period, open-label, fixed-sequence study was completed by 12 healthy subjects (6 men and 6 women) aged between 20 and 51 years. Each subject received 400 mg imatinib orally on study day 1, St John’s wort (300 mg 3 times daily) on days 4 to 17, and 400 mg imatinib again on day 15. Serial blood samples were obtained over a 72-hour period after each imatinib dose. Imatinib and N -desmethyl-imatinib (CGP 74588) were quantified in plasma by liquid chromatography-mass spectrometry. RESULTS: St John’s wort administration increased imatinib clearance by 43% ( P < .001), from 12.5 +/- 3.6 L/h to 17.9 +/- 5.6 L/h; imatinib area under the concentration versus time curve (AUC) extrapolated to infinity was decreased by 30%, from 34.5 +/- 9.5 microg . h/mL to 24.2 +/- 7.0 microg . h/mL ( P < .001). Imatinib half-life (12.8 hours versus 9.0 hours) and maximum concentration (C max ) (2.2 microg/mL versus 1.8 microg/mL) were also significantly decreased ( P < .005). N -desmethyl-imatinib C max was increased from 285 +/- 95 ng/mL to 318 +/- 95 ng/mL during St John’s wort dosing, but the AUC from 0 to 72 hours was not altered. CONCLUSIONS: These data indicate that St John’s wort increases imatinib clearance. Thus patients taking imatinib should avoid taking St John’s wort. Concomitant use of enzyme inducers, including St John’s wort, may necessitate an increase in the imatinib dose to maintain clinical effectiveness.
http://www.hubmed.org/display.cgi?issn=00099236&uids=15470331
Posted by rob on under Uncategorized |
Am J Clin Pathol. 2004 Oct; 122(4): 598-609
Ross JS, Schenkein DP, Pietrusko R, Rolfe M, Linette GP, Stec J, Stagliano NE, Ginsburg GS, Symmans WF, Pusztai L, Hortobagyi GN
The regulatory agency approvals in the United States and Europe of imatinib mesylate (Gleevec) for patients with bcr/abl-positive chronic myelogenous leukemia, cetuximab (Erbitux) for patients with epidermal growth factor receptor overexpressing metastatic colorectal cancer, the antiangiogenesis agent bevacizumab (Avastin), and the proteasome inhibitor bortezomib (Velcade)–and the considerable public interest in new anticancer drugs that take advantage of specific genetic defects that render the malignant cells more likely to respond to specific treatment–are driving a new era of integrated diagnostics and therapeutics. The recent discovery of a drug response predicting activating mutation in the epidermal growth factor receptor gene for patients with non-small cell lung cancer treated with gefitinib (Iressa) has intensified this interest. In this review, the history of targeted anticancer therapies is highlighted, with focus on the development of molecular diagnostics for hematologic malignancies and the emergence of trastuzumab (Herceptin), an antibody-based targeted therapy for HER-2/neu overexpressing metastatic breast cancer: The potential of pharmacogenomic strategies and the use of high-density genomic microarrays to classify and select therapy for cancer are briefly considered. This review also considers the widely held view that, in the next 5 to 10 years, the clinical application of molecular diagnostics will further revolutionize the drug discovery and development process; customize the selection, dosing, route of administration of existing and new therapeutic agents; and truly personalize medical care for cancer patients.
http://www.hubmed.org/display.cgi?issn=00029173&uids=15487459
