Autoři prezentuji nove diagnosticke metody - použiti cytinetických, cytogenetických biomarkerů, t... more Autoři prezentuji nove diagnosticke metody - použiti cytinetických, cytogenetických biomarkerů, testovani chemoresistence a novějsi lecebne metody jako intersticialni brachyterapie a předoperacni intraarterialni chemoterapie u sarkomů měkkých tkani
Regional intrahepatic chemotherapy of inoperable primary and secondary liver tumours can achieve,... more Regional intrahepatic chemotherapy of inoperable primary and secondary liver tumours can achieve, as compared with the little effective systemic chemotherapy, a higher percentage of therapeutic responses. The objective of regional chemoimmunotherapy, i.e. the use of cytokines, in particular interferon alpha (IFN-a) and interleukin-2 (IL-2) in the therapeutic regimens is to improve the survival of patients with malignant liver tumours. One of the main prerequisites of the effect of locally administered cytokines is activation of hepatic lymphocytes (LAL)-liver associated lymphocytes, effectors with specific phenotype and potential anti-tumourous effect directly in the target area. Although in regional monotherapy the effectiveness of cytokines is low, regimens combining the administration of cytostatics with IL-2 achieve a 50-70% therapeutic response. The authors summarize basic data on the regional administration of cytokines and present an review of combined regimens of regional chemoimmunotherapy, including their own protocol of the Masaryk Oncological Institute in Brno.
The field of bispecific antibodies is an evolving field of research that has increasing clinical ... more The field of bispecific antibodies is an evolving field of research that has increasing clinical appeal. The fusion of two antibodies or antibody fragments introduced a new way to override natural specificity of T cell and induce effector responses against tumor targets in MHC-unrestricted manner. Initial experiences with bispecific antibodies demonstrate both the promise for and limitations of this anti-cancer strategy. Significant body of work has shown that bispecific antibodies have potential to induce T cell mediated anti-tumor responses in pre-clinical models. However, immunotherapy with bispecific antibodies in humans has yet to prove its value in clinical settings. In addition, the production of high-quality bispecific antibodies for clinical applications, the optimal size and avidity of bispecific antibodies, and in vivo T cell pre-activation remain critical issues. In this review, we summarize recent progress in bispecific antibody-based immunotherapy and address essential aspects of this anti-cancer strategy.
Modern surgery has become complex and technically sophisticated. This is particularly true for mi... more Modern surgery has become complex and technically sophisticated. This is particularly true for minimally invasive surgery, in which laparoscopy replaces laparotomy as the method of exposure for abdominal surgery. Adequate exposure of the region of interest remains one of the fundamental principles of surgery, and at the same time it represents one of the limiting factors in the development of laparoscopy. Currently available data suggest that adequate exposure can be achieved using a variety of approaches. As with all surgical procedures, understanding the advantages and disadvantages of different approaches that have been used for this purpose is essential for performing laparoscopy in a safe manner, allowing for better patient care. In this chapter, the current literature is reviewed and several different techniques for exposure of the operative field in laparoscopic surgery are discussed, including pneumoperitoneum and abdominal wall lifting.
Background/aims: In this study, we have compared the profiles of peripheral blood lymphocyte (PBL... more Background/aims: In this study, we have compared the profiles of peripheral blood lymphocyte (PBL) subsets and serum cytokine levels of healthy individuals with those of patients with unresectable liver metastases from colorectal carcinoma before starting regional chemoimmunotherapy. Since the therapeutic responses are limited only to a subset of patients, we hypothesize that the initial status of immunity and individual immune response to a tumor might be significant to the therapeutic outcome. Methodology: Cellular and humoral immunological parameters were compared between 10 patients with colorectal cancer metastases to the liver responding and non-responding to regional intra-arterial chemo-immunotherapy, and 5 healty individuals. Analyses included a flow cytometric immunophenotyping of peripheral blood mononuclear cells (CD3, CD4, CD8, CD19, CD25, CD28, CD56, CD57, CD80 and HLA.DR), estimation of serum cytokine levels of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and other immunological parameters are soluble IL-2 receptor (sIL-2), carcinoembryonic antigen (CEA), gastrointestinal cancer-associated antigen (CA 19-9), and C-reactive acute phase protein (CRP). A significantly lower proportion of CD8 lymphocytes and a trend for decreased CD19, CD28 and CD80 was detected among colorectal cancer patients before liver-directed chemotherapy compared to healthy controls. Results: The cancer patients showed a significantly increased population of peripheral NK cells as detected by both CD56+ and CD57+ phenotypes. Elevated serum levels of CRP, IL-4 and TNF-alpha, sIL-2R, but not IL-2, were also demonstrated in cancer patients as compared to controls. Activated CD25+ lymphocytes correlated negatively with CD28+ lymphocytes (r = -0.68, p < 0.01) and less significantly with CD4+ lymphocytes (r = -0.56, p < 0.05). The CD8+ cytotoxic cell subset might be negatively influenced by serum IL-4 (r = -0.57, p < 0.05). Positive correlation was found between sIL-2R and CRP (r = -0.78, p < 0.01), and between sIL-2R and TNF-alpha (r = 0.64, p < 0.05) serum levels in patients with progressive disease during the course of therapy, the initial proportions of CD4+, CD19+ and CD28+ lymphocytes were significantly lower than those among responders. Among humoral parameters, only sIL-2R showed a marginal correlation with therapeutic response, being more elevated among non-responding patients. Pre-treatment serum levels of CEA and CA 19-9 showed correlation with neither therapeutic response nor with any of the cellular or humoral immunological parameters analyzed. Conclusions: The results may serve as an initial guideline to open a discussion on the rationale of such a panel of tests, hopefully leading to standardized laboratory pre-selection and monitoring of patients treated with regional chemoimmunotherapy.
Uvodni prace monotematickeho cisla casopisu Klinicka onkologice věnovane testovani chemoresistenc... more Uvodni prace monotematickeho cisla casopisu Klinicka onkologice věnovane testovani chemoresistence nadorů, ktera uvadi do souvislosti klinicke potřeby a otazky s laboratornimi možnostmi predikce nadorove chemoresistence.
Proceedings of the International Conference on Prevention and#N#Early Diagnosis of Lung Cancer .University of Insubria, Varese,#N#I & University of Massachusetts Medical School, Boston, MA.Vol#N#1,180; 1998., 1998
Clinical Orthopaedics and Related Research, Apr 1, 2002
The combination of improved resection, stabilization, and fusion techniques allows for more aggre... more The combination of improved resection, stabilization, and fusion techniques allows for more aggressive removal of malignant spinal tumors with acceptable mortality and morbidity. Thirty consecutive patients with primary sarcomas of the mobile spine, who were operated on at the authors&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; institution from January 1970 to December 2000, were included in the current study. Demographic information, tumor location, type of resection, resection margins, local recurrence, and overall survival data were retrieved and analyzed. Treatment consisted of en bloc resection in 12 patients (40%) and piecemeal resections in 18 patients (60%). The resection was classified as wide in seven patients (23.3%), marginal in three patients (10%), and intralesional in 20 patients (66.7%). Pathology reports showed tumor-free resection margins in 12 patients (40%). In the remaining 18 patients (60%), resection margins were positive and resulted in a fivefold increase in the risk of a local recurrence. Ninety-two percent of the patients with local recurrence died of sequelae associated with the local recurrence. Primary sarcomas of the mobile spine in certain cases, can be removed completely with tumor-free resection margins. En bloc resection with tumor-free margins provides substantial improvement in overall survival.
Clinical Orthopaedics and Related Research, Oct 1, 2003
Treatment of patients with metastatic disease of the spine continues to be a challenging problem.... more Treatment of patients with metastatic disease of the spine continues to be a challenging problem. Advances in imaging studies and surgical techniques have improved patient outcomes with operative intervention. However, the lack of a validated set of criteria to determine spinal instability makes patient selection for surgical intervention difficult. Multiple classification systems that assist surgeons in determining appropriate operative candidates have been proposed. We will review current information on the evaluation and treatment of metastatic disease of the spine and discuss classification systems that assist in determining appropriate operative candidates.
Autoři prezentuji nove diagnosticke metody - použiti cytinetických, cytogenetických biomarkerů, t... more Autoři prezentuji nove diagnosticke metody - použiti cytinetických, cytogenetických biomarkerů, testovani chemoresistence a novějsi lecebne metody jako intersticialni brachyterapie a předoperacni intraarterialni chemoterapie u sarkomů měkkých tkani
Regional intrahepatic chemotherapy of inoperable primary and secondary liver tumours can achieve,... more Regional intrahepatic chemotherapy of inoperable primary and secondary liver tumours can achieve, as compared with the little effective systemic chemotherapy, a higher percentage of therapeutic responses. The objective of regional chemoimmunotherapy, i.e. the use of cytokines, in particular interferon alpha (IFN-a) and interleukin-2 (IL-2) in the therapeutic regimens is to improve the survival of patients with malignant liver tumours. One of the main prerequisites of the effect of locally administered cytokines is activation of hepatic lymphocytes (LAL)-liver associated lymphocytes, effectors with specific phenotype and potential anti-tumourous effect directly in the target area. Although in regional monotherapy the effectiveness of cytokines is low, regimens combining the administration of cytostatics with IL-2 achieve a 50-70% therapeutic response. The authors summarize basic data on the regional administration of cytokines and present an review of combined regimens of regional chemoimmunotherapy, including their own protocol of the Masaryk Oncological Institute in Brno.
The field of bispecific antibodies is an evolving field of research that has increasing clinical ... more The field of bispecific antibodies is an evolving field of research that has increasing clinical appeal. The fusion of two antibodies or antibody fragments introduced a new way to override natural specificity of T cell and induce effector responses against tumor targets in MHC-unrestricted manner. Initial experiences with bispecific antibodies demonstrate both the promise for and limitations of this anti-cancer strategy. Significant body of work has shown that bispecific antibodies have potential to induce T cell mediated anti-tumor responses in pre-clinical models. However, immunotherapy with bispecific antibodies in humans has yet to prove its value in clinical settings. In addition, the production of high-quality bispecific antibodies for clinical applications, the optimal size and avidity of bispecific antibodies, and in vivo T cell pre-activation remain critical issues. In this review, we summarize recent progress in bispecific antibody-based immunotherapy and address essential aspects of this anti-cancer strategy.
Modern surgery has become complex and technically sophisticated. This is particularly true for mi... more Modern surgery has become complex and technically sophisticated. This is particularly true for minimally invasive surgery, in which laparoscopy replaces laparotomy as the method of exposure for abdominal surgery. Adequate exposure of the region of interest remains one of the fundamental principles of surgery, and at the same time it represents one of the limiting factors in the development of laparoscopy. Currently available data suggest that adequate exposure can be achieved using a variety of approaches. As with all surgical procedures, understanding the advantages and disadvantages of different approaches that have been used for this purpose is essential for performing laparoscopy in a safe manner, allowing for better patient care. In this chapter, the current literature is reviewed and several different techniques for exposure of the operative field in laparoscopic surgery are discussed, including pneumoperitoneum and abdominal wall lifting.
Background/aims: In this study, we have compared the profiles of peripheral blood lymphocyte (PBL... more Background/aims: In this study, we have compared the profiles of peripheral blood lymphocyte (PBL) subsets and serum cytokine levels of healthy individuals with those of patients with unresectable liver metastases from colorectal carcinoma before starting regional chemoimmunotherapy. Since the therapeutic responses are limited only to a subset of patients, we hypothesize that the initial status of immunity and individual immune response to a tumor might be significant to the therapeutic outcome. Methodology: Cellular and humoral immunological parameters were compared between 10 patients with colorectal cancer metastases to the liver responding and non-responding to regional intra-arterial chemo-immunotherapy, and 5 healty individuals. Analyses included a flow cytometric immunophenotyping of peripheral blood mononuclear cells (CD3, CD4, CD8, CD19, CD25, CD28, CD56, CD57, CD80 and HLA.DR), estimation of serum cytokine levels of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and other immunological parameters are soluble IL-2 receptor (sIL-2), carcinoembryonic antigen (CEA), gastrointestinal cancer-associated antigen (CA 19-9), and C-reactive acute phase protein (CRP). A significantly lower proportion of CD8 lymphocytes and a trend for decreased CD19, CD28 and CD80 was detected among colorectal cancer patients before liver-directed chemotherapy compared to healthy controls. Results: The cancer patients showed a significantly increased population of peripheral NK cells as detected by both CD56+ and CD57+ phenotypes. Elevated serum levels of CRP, IL-4 and TNF-alpha, sIL-2R, but not IL-2, were also demonstrated in cancer patients as compared to controls. Activated CD25+ lymphocytes correlated negatively with CD28+ lymphocytes (r = -0.68, p < 0.01) and less significantly with CD4+ lymphocytes (r = -0.56, p < 0.05). The CD8+ cytotoxic cell subset might be negatively influenced by serum IL-4 (r = -0.57, p < 0.05). Positive correlation was found between sIL-2R and CRP (r = -0.78, p < 0.01), and between sIL-2R and TNF-alpha (r = 0.64, p < 0.05) serum levels in patients with progressive disease during the course of therapy, the initial proportions of CD4+, CD19+ and CD28+ lymphocytes were significantly lower than those among responders. Among humoral parameters, only sIL-2R showed a marginal correlation with therapeutic response, being more elevated among non-responding patients. Pre-treatment serum levels of CEA and CA 19-9 showed correlation with neither therapeutic response nor with any of the cellular or humoral immunological parameters analyzed. Conclusions: The results may serve as an initial guideline to open a discussion on the rationale of such a panel of tests, hopefully leading to standardized laboratory pre-selection and monitoring of patients treated with regional chemoimmunotherapy.
Uvodni prace monotematickeho cisla casopisu Klinicka onkologice věnovane testovani chemoresistenc... more Uvodni prace monotematickeho cisla casopisu Klinicka onkologice věnovane testovani chemoresistence nadorů, ktera uvadi do souvislosti klinicke potřeby a otazky s laboratornimi možnostmi predikce nadorove chemoresistence.
Proceedings of the International Conference on Prevention and#N#Early Diagnosis of Lung Cancer .University of Insubria, Varese,#N#I & University of Massachusetts Medical School, Boston, MA.Vol#N#1,180; 1998., 1998
Clinical Orthopaedics and Related Research, Apr 1, 2002
The combination of improved resection, stabilization, and fusion techniques allows for more aggre... more The combination of improved resection, stabilization, and fusion techniques allows for more aggressive removal of malignant spinal tumors with acceptable mortality and morbidity. Thirty consecutive patients with primary sarcomas of the mobile spine, who were operated on at the authors&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; institution from January 1970 to December 2000, were included in the current study. Demographic information, tumor location, type of resection, resection margins, local recurrence, and overall survival data were retrieved and analyzed. Treatment consisted of en bloc resection in 12 patients (40%) and piecemeal resections in 18 patients (60%). The resection was classified as wide in seven patients (23.3%), marginal in three patients (10%), and intralesional in 20 patients (66.7%). Pathology reports showed tumor-free resection margins in 12 patients (40%). In the remaining 18 patients (60%), resection margins were positive and resulted in a fivefold increase in the risk of a local recurrence. Ninety-two percent of the patients with local recurrence died of sequelae associated with the local recurrence. Primary sarcomas of the mobile spine in certain cases, can be removed completely with tumor-free resection margins. En bloc resection with tumor-free margins provides substantial improvement in overall survival.
Clinical Orthopaedics and Related Research, Oct 1, 2003
Treatment of patients with metastatic disease of the spine continues to be a challenging problem.... more Treatment of patients with metastatic disease of the spine continues to be a challenging problem. Advances in imaging studies and surgical techniques have improved patient outcomes with operative intervention. However, the lack of a validated set of criteria to determine spinal instability makes patient selection for surgical intervention difficult. Multiple classification systems that assist surgeons in determining appropriate operative candidates have been proposed. We will review current information on the evaluation and treatment of metastatic disease of the spine and discuss classification systems that assist in determining appropriate operative candidates.
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Papers by Robert Talac