| 1. |
- Ceelen, Wim P., et al.
(author)
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Pharmacodynamic aspects of intraperitoneal cytotoxic therapy
- 2007
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In: Cancer treatment and research. - 0927-3042. ; 134, s. 195-214
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Journal article (peer-reviewed)abstract
- The rationale for ip administration as an adjunct to surgery is firmly based on theoretical and pharmacokinetic grounds. The superiority of combined ip and intravenous chemotherapy over intravenous chemotherapy alone has been established in randomized trials in stage IIIc ovarian cancer patients. Intraoperative ip cytotoxic therapy results in a definite pharmacological advantage, since high peritoneal concentrations are achieved with limited systemic absorption. At present, however, it is not clearly established to what extent this PK advantage will result in enhanced anticancer activity and, ultimately, in a survival benefit. Preclinical models show that direct penetration into tumour tissue is limited to a few millimeters. Furthermore, the limited exposure time of intraoperative chemoperfusion could limit cytotoxic activity despite high local concentrations. Among the cytotoxic agents currently used, the pharmacodynamic aspects of the platinum compounds are the best studied both with and without associated hyperthermia. Newer agents such as the taxanes and the camptothecins appear promising for ip chemoperfusion during or immediately after surgery. Pharmacodynamic aspects of HIPEC needing further preclinical study-including mathematical modeling - are the establishment of tumour tissue penetration of the newer agents and its relation to hyperthermia, the definition of the relative contribution of direct penetration versus vascular supply by absorbed drug, and the efficacy of combined ip and intravenous regimens. Ultimately, however, randomised trials of ip chemotherapy with surgery will have to provide the evidence base to further build upon.
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| 2. |
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| 3. |
- Gullberg, U, et al.
(author)
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Receptors for hematopoietic regulatory cytokines : overview of structure and function
- 1995. - 1
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In: Cytokines: : Interleukins and Their Receptors - Interleukins and Their Receptors. - Boston, MA : Springer US. - 0927-3042. - 9780792336365 - 9781461312413 ; 80, s. 1-24
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Book chapter (peer-reviewed)abstract
- The production of blood cells is regulated by the action of external factors, cytokines, that can be released by many cell types. In the first place, a population of multipotent stem cells, mostly in the resting Go phase of the cell cycle, but with self-renewal capacity, gives rise to progenitor cells that are predetermined for differentiation into all kinds of blood cells. Expression of genes for cytokine receptors leads to external regulation of hematopoiesis by cytokines which bind to the receptors, resulting in modifications of proliferation and differentiation, as cytokines are not only growth factors, but are also maturation factors capable of directing hematopoiesis towards functionally competent cells. What is more, they are survival factors capable of suppressing programmed cell death (apoptosis). This is of particular importance for the viability of stem cells which must be preserved. Thus cytokines can act at all positions of the hematopoietic family tree, and the response can differ from proliferation and differentiation of progenitor cells to functional activation of mature cells. Under physiological conditions, during constitutive hematopoiesis, the regulatory cytokines are produced locally, for instance by stromal ceils of the microenvironment, and act locally in a paracrine manner [2].
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| 4. |
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| 5. |
- Lilja, Hans, et al.
(author)
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Successful separation between benign prostatic hyperplasia and prostate cancer by measurement of free and complexed PSA
- 1996
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In: Diagnosis and Treatment of Genitourinary Malignancies. - Boston, MA : Springer US. - 0927-3042. - 9781461379133 - 9781461563433 ; 88, s. 93-101
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Book chapter (peer-reviewed)abstract
- Prostate-specific antigen (PSA) is a serine protease belonging to the human glandular kallikrein gene family [1–3]. The expression of PSA is mainly androgen dependent, and the detection of very high expression levels is restricted to the prostate tissue, but extraprostatic production at much lower levels has been demonstrated in several other tissues such as normal and malignant breast epithelium, endometrium, and bulbourethral glands [4–10]. PSA is synthesized by the columnar epithelium in the glandular ducts and acini of the prostate, but not by any other cells in prostate tissue. It is secreted at high concentrations (0.2-5mg/mL) into seminal fluid [4–6,11]. PSA is synthesized as an inactive precursor [2,3,12]. Like other glandular kallikreins, the PSA-precursor is processed stepwise by release of a leader peptide followed by liberation of an activation peptide that results in conversion of the zymogen into enzymatically active PSA [12]. This process may occur in parallel with the secretory release from the prostate epithelium and most probably occurs prior to the ejaculatory mixing of secretions from the prostate, seminal vesicles, and epididymis, since PSA is active in ejaculates collected from subjects with defective seminal vesicles and deferent ducts [1]. The protease(s) responsible for processing of the PSA precursor have not been identified. The mature 237-amino-acid form of PSA is a single-chain serine protease with extensive structural similarity to the glandular kallikreins [1,12–14]. However, the substrate specificity is uniquely different from that of the trypsin-like glandular kallikreins and resembles that of chymotrypsin, since PSA catalyzes the hydrolysis of peptide bonds’ carboxy-terminal to residues of tyrosine and leucine [15–17]. Synthetic peptide substrates for chymotrypsin can be used to measure PSA activity, but they are hydrolyzed much less efficiently by PSA than by chymotrypsin and are therefore both nonspecific and insensitive in detecting PSA activity [16].
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| 6. |
- Sandelin, K
(author)
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Parathyroid carcinoma
- 1997
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In: Cancer treatment and research. - Boston, MA : Springer US. - 0927-3042. ; 89, s. 183-92
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Journal article (peer-reviewed)
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