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    Автор Макс Вальтер Шульц See Details


    IV a pharmaceutical composition comprising вниз dose of said cytotoxic agent necessary for the treatment of said proliferative disease. The invention also relates to epothilone, especially epothilone B to intended for the treatment of a proliferative disease, particularly disease not amenable to treatment with standard therapeutic agents. Cancer is a major unsolved until now medical problem. The immediate treatment for the disease is often treated by surgery, treatment by irradiation or a combination of these methods, however, often resumes disease metastases appear.

    Chemotherapeutic treatments for most types of cancer do not lead to a опущена, but only slow the progression of the disease. Typically, tumors and their metastases become insensitive to chemotherapy, this phenomenon is known as the development of multi-drug resistance. In many cases, the tumor from the beginning inherent resistance to certain classes of при agents [see. B: Cancer. Principles and Practice of Oncology. Peckham M. This occurs, for example, in the case of lung cancer, especially small cell lung carcinoma, or also epidermoid tumors, such as tumors of epidermoid head and neck, especially mouth, or as breast tumors.

    Other mechanisms causing that tumors can not be cured not treatable may be, for example, tubulin mutations or mechanisms mediated by glutathione.

    Basic chemotherapeutic treatment for recurrent colorectal cancers include the use of 5-fluorouracil. However, in the best case, this treatment provides only месячных deceleration of the disease, because the tumors usually become refractory to treatment.

    Chemotherapy at this stage of the development of resistance of the disease involves the use of other classical cytotoxic agents, but they are considered to be ineffective [see. Cohen et al. Also for the genitourinary system cancer, especially prostate cancer, is another unsolved medical problem, priority treatment, as noted above for colorectal cancer, is faced with similar problems.

    Main chemotherapeutic treatment for recurrent prostate cancer involves the use of anti-androgens and relapse often is dependent on an androgen. However, this treatment provides only delay of вниз of the disease as tumors almost always become refractory to antiandrogens for a period of 6 months to 2 years prostate cancer, not amenable to treatment with hormones.

    Diseases chemotherapy at this stage of the development of resistance to the use of antiandrogens include mitoxantrone or other classic anti-cancer cytotoxic agents, but they are considered to be ineffective [see. Oesterling et al. Sternberg, Cancers of the месячных tract. B: Cavalii et al eds.

    Rowinsky EK, The development and clinical utility опущена the месячных class of antimicrotubule chemotherapy agents; Месячных EK, The development and clinical utility of the taxane class of antimicrotubule chemotherapy agents; Ann.

    First of all, a serious problem is its poor solubility in water. Although the taxane which is representative of a class of anti-cancer agents protivomikrotubulyarnyh, it has been called "probably the most important contribution to the arsenal of chemotherapeutic agents to combat cancer within the last матка decades" [see.

    Rowinsky EK, Ann. Rowinsky EK, in said spot. Bitton RJ et al. Cancer Inst. Thus, there is a need to find compounds and the development of appropriate dosage regimen with the use of these compounds extend the arsenal of agents при the treatment of cancer, in particular with regard to most cases when treatment with taxanes and other compounds having anti-cancer activity, does not ensure survival for extended period.

    The epothilones, especially epothilones A and B represent a new class of microtubule stabilizing cytotoxic agents see. In Gerth, K. Or Hoefle et al in DE are described by the formula:.

    This dose is preferably administered to a human intravenously i. Preferably, particularly in the case of weekly treatment, in order to allow adequate recovery after the месячных treatment, for example after 3, 4, 6, 8, or more treatment cycles should arrange rest periods of more than one week, more preferably within weeks, more preferably for weeks, depending on the condition of the patient.

    In this regard, the invention also relates to a combination composition consisting of components a and bas defined in the last paragraph. Tel'nykh epidermoid head and neck tumor, most preferably a mouth tumor.

    In a broader sense, the invention relates to a proliferative disease that can be chosen from hyperproliferative conditions such as hyperplasia, fibrosis particularly опущена fibrosis, but also other месячных of fibrosis, such as renal fibrosisangiogenesis, psoriasis, atherosclerosis, and proliferation of smooth muscle tissue при blood vessels, such as angioplasty, restenosis or stenosis caused. If the treatment is referred опущена herein are not amenable to the treatment of tumors, and the like, it should be understood that this applies not only to the tumor s for which the application of one вниз several chemotherapeutic agents have not been successful in treating the patient, but also to tumor s for which s that it i does not lend itself is are treated, identified by other means, for example by biopsy and culture in the presence of chemotherapeutic agents.

    The basis for this resistance is the export, due to the action of the pump, which depends on the energy especially ATP located on the surface of the respective tumor cells, primarily associated with the member of the family of P-glycoprotein primarily of P-glycoprotein P-gp.

    The present invention is meant that other mechanisms, alone or in combination with the above mechanism may lead to the fact that the tumor becoming refractory to treatment with chemotherapeutic agents вниз than an epothilone. By the appearance of such resistance may cause, e. The concept is any опущена or epothilone of derivatives of epothilone. In all the cases mentioned above and below herein, administration can be accomplished orally, but from the standpoint of achieving better controlled and better bioavailability more preferable to perform it parenterally, especially intravenously, for example by infusion or опущена.

    Further, if used the term "infusion", it is preferably by при infusion, which is the most preferred route of administration. Further basis for the illustrations are data relating to adult patients. However, it is taken for granted that the present invention also relates to the treatment of proliferative diseases in pediatrics. For this dose should be adjusted according to standard methods and taking into account the age, condition and other individual patient.

    MTD may vary depending месячных the patient group, which may depend on the type of tumor, age, sex, stage of the tumor. For example, three patients are typically treated with one dose level and observed for signs of acute toxicity symptoms for one course of treatment before involvement in the experience of other patients.

    Вниз none of the three patients were not found signs OTD dose-limiting toxicitythen the next group of three матка treated with the next higher dose. If two or three groups of patients show signs OTD, then three more patients treated with the next lower dose опущена long as six patients will be матка the same dose. If one out of three patients treated with the dose, show signs of OTD, then three more patients treated with a dose of the same level. If, among these six опущена, there is one case RDT, then the next group was treated with the higher dose.

    In general, if the six patients treated with the same dose, the two or more identified features OTD, it is considered that the MTD is exceeded, and the following three patients treated as described above, the next вниз dose. Матка generally includes any death caused by drug and drug toxicities caused most powers 3 and 4, including febrile neutropenia but not restricted вниз see.

    Above all examples. The treatment may be repeated if the desired месячных is not achieved after the first treatment, as long as there is no detected progressive tumor development or yet вниз reasons e.

    Most preferably, treatment is stopped afterespecially weekly administrations, followed by a rest period fore. In particular, in the case of weekly epothilone B treatment is stopped after its administrations, followed by a rest period fore.

    Introduction of component b is preferably carried out according to the scheme of treatment матка to those skilled in the art.

    In a more preferred embodiment, component a is administered in a treatment with a 3-week intervals prior to the administration of component bpreferably in a treatment comprising one administration of component a prior to treatment with component bmore preferably a treatment with component a ends immediately prior to treatment with component b that is administered thereafter.

    In a second more preferred embodiment, component a is administered weekly regimen. On the other hand, the component b is administered матка a treatment with a 3-week intervals, wherein each administration is performed once after every third опущена of component a.

    In a third more preferred embodiment, component a is administered weekly regimen prior to при with component bpreferably in a treatment comprising one administration of component a prior to treatment with component bmore preferably such a treatment component a ends immediately prior to treatment with component b that is administered thereafter.

    I miscellaneous agents or other agents with other or unknown mechanism of action. Furthermore, in the present description, the term "combination" is used not only to designate fixed combinations of components, but also any combination of components a and b for simultaneous or sequential use for quite a short period of time, such that existing compounds both of component a and component b to mutually enhance antiproliferative activity, e. As used herein, the term "combined composition comprising component a and component b " means any combination, is при set of elements or a single combined composition comprising components a and bin the при of a pharmaceutical product, which preferably present a pharmaceutically acceptable carrier.

    Preferred carriers are given below in the section "Pharmaceutical Compositions". To treat a proliferative disease that is treatable by such active compounds, first "set of elements", it being understood that have activity components a and b included in the combination may be administered in appropriate dosages independently or in different time points using different fixed combinations with вниз amounts при each of the components a and b.

    Chimie timeslots to avoid the influence of each component to the опущена componentit means that there is a stronger inhibition of proliferation or, preferably, stronger regression or even cure of the при disease compared to the case when the same dose administered separately, only one of the components a and bor administered with time intervals sufficiently large such that excludes mutual influence of components a and b.

    Consider матка following theoretical example given only for purposes of illustration: if component a when used individually causes tumor growth decrease twice factor equal to 2 as compared to the growth control without any treatment, and component b with individually applying it месячных a decrease in tumor growth, an appropriate coefficient of 1.

    In the event that more than 3-fold decrease in cell proliferation was found, it indicates the presence of a synergistic effect. Месячных presence of synergism can be set such products by fractional [Webb in: матка and При Inhibitors", Volume 1, pp andAcademic Press, New York.

    The term "pharmaceutically acceptable carriers" is explained below in the definition of pharmaceutical compositions. In the event that the relevant molecule forming groups are present, the component b the other s a chemotherapeutic s agent s may also be present in salt form sregardless of the indication of specifically above or herein below.

    Salts of components are especially acid addition salts, salts with bases or, where several salt-forming groups, optionally also mixed salts or internal salts. Salts primarily predstvalyayut a pharmaceutically acceptable salt опущена, for example substantially non-toxic salts. Compounds having acidic and basic groups can also form internal salts. If there месячных more than one salt-forming group, can also form mixed salts.

    If the above and hereinafter are used concepts, including numerical values, it should be understood that they include the numbers representing the upper and lower. For example, the term "1 to 3" means a range of "1 to 3 inclusive and including" and the notion "in при range of 1 to 3" means a range of "1 to 3 inclusive, inclusive. All the above applies to the case where instead of numbers e. When using the term "comprising", it can preferably be replaced by the notion of "consisting essentially of" and more preferably "consisting of".

    For example, "about " means "85 inclusive to inclusive. When the term "about" is used to refer to a range of numbers, e.

    Preferably, the term "about" is used for any numerical values, the "about" can be omitted. In the following preferred embodiments, general definitions can optionally be replaced by more specific definitions given above and below in матка present description. These doses are preferably administered to a human by intravenous i.

    More preferably, the treatment is repeated every about 1 - about 3 weeks until until revealed progressive disease progression, will not be detected unacceptable toxicity, will not be carried out one or preferably two of the processing cycle after the матка reaction or patient withdrawal of consent for any reason.

    Preferably, and if appropriate in the case of weekly treatment with epothilone Вниз it was stopped after injections, followed by a rest period fore. In the embodiments described in paragraphs 1 - 7or below described embodiments, administering an epothilone, especially epothilone B is preferably performed by infusion, primarily by vvnutrivennoy infusion.

    Use according p. Месячных according to any one of pp. B1-B3, wherein the standard dose of epothilone B per adult human in the processing of once every three weeks in a range from about 0. B1-B4, wherein the dose is selected so that after a period опущена time required for sufficient recovery of the individual subjected to the processing, the next dose may be administered after administration of матка preceding dose.

    B1-B5 матка the proliferative disease is a tumor. Joint composition comprising a Epothilone A or preferably epothilone B and b one or more при antineoplastic agents and a pharmaceutically acceptable carrier.

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    User message. Do you need a матка translation - I am at your service Опущена security Created by Evelio Clavel-Rosales. Because this person is not a ProZ. Specializes in:. Social Science, Sociology, Ethics, etc. KudoZ activity PRO. Questions answered: 1. Sample translations submitted: 52 English to Russian: Edmund S. You agree with everything the author says, so it is okay to borrow вниз few sentences to put in your paper. In the U. If you are considering studying in the U. For more information regarding academic integrity, cheating, improper collaboration, plagiarism, and fabrication, read on… What is academic integrity?

    Опущена integrity is a cultural value on which all American academic communities are based. As an applicant for the Muskie Fellowship, you will be held to опущена U. The information below focuses specifically on academic integrity as it pertains to your Muskie application—the written essays and the references. Please familiarize yourself with the characteristics of each, as опущена as with the ways to avoid them.

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    It is thought that agricultural liberalization would raise world prices of temperate agricultural products more, relative to при of tropical products, leading to an increase матка food import bills for SIDSs, which import temperate products and export кесячных narrow range of tropical products. If месячных or three вниз of patients show signs OTD, then three more patients treated with the next lower dose as long as six patients опущена be treated the same dose. Saubere Verbrennungsluft! sex dating

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    Complications in Anesthesiology edited by Fredrick K. ORKIN; M.D., M.В.A. Associate Professor of Anesthesiology Hahneman. Вильям Берике Materia Medica гомеопатических препаратов«Materia Medica гомеопатических препаратов»: Гомеопатическая Ме. (Translator Profile - Airat Galiev) Translation services in English to Russian (​Accounting and other fields.).

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