Acute radiation syndrome (ARS) is an acute illness caused by exposure to a high dose of ionizi... more Acute radiation syndrome (ARS) is an acute illness caused by exposure to a high dose of ionizing radiation. ARS is the deterministic effect of radiation exposure of the whole body or a significant body volume (partial body irradiation) above a threshold dose of about 1 Gy (gray). Radiation accidents, such as those in Chernobyl (1986) and Fukushima (2011), or the possible use of nuclear weapons during the hostilities or terrorist attacks, can lead to the massive development of ARS in humans. The aim of the work is to introduce a new method of post-radiation treatment – the use of allogeneic mesenchymal stem cells (MSCs). Materials and methods. The information contained in specialized scientific journals that are freely available and accessible through the global Internet was studied. Discussion of the results. In the scenario of mass exposure of the population, when from several tens (hundreds) to millions of people can be irradiated, the transfusion of hematopoietic stem ce...
Journal of Cellular and Molecular Medicine, Apr 4, 2021
We have observed the spontaneous tumour regression in four patients (breast cancer, Hodgkin's dis... more We have observed the spontaneous tumour regression in four patients (breast cancer, Hodgkin's disease, non-Hodgkin's lymphoma and Ewing's sarcoma) who had relapsed/progressed after high-dose chemotherapy (HDC) and autologous haematopoietic stem cell transplantation (ASCT). 1 Patients' blood counts strongly resembled the blood counts in aplastic anaemia (aplastic anaemia (AA)-like syndrome). Moreover, some of these patients' morphology of the bone marrow trephine biopsies was identical to the AA picture. It should be noted LETTER TO THE EDITOR relapsed/progressed after HDC and ASCT and achieved spontaneous tumour regression (ie without any further treatment). The epitope 'alignment' in these cases is not only surprising, but it is also challenging. Will we go further, prepare monoclonal therapeutic antibodies, and possibly will be able to treat a wide variety of malignant tumours?
Acute radiation syndrome (ARS) is an acute illness caused by exposure to a high dose of ionizing ... more Acute radiation syndrome (ARS) is an acute illness caused by exposure to a high dose of ionizing radiation. ARS is the deterministic effect of radiation exposure of the whole body or a significant body volume (partial body irradiation) above a threshold dose of about 1 Gy (gray). Radiation accidents, such as those in Chernobyl (1986) and Fukushima (2011), or the possible use of nuclear weapons during the hostilities or terrorist attacks, can lead to the massive development of ARS in humans. The aim of the work is to introduce a new method of post-radiation treatment -the use of allogeneic mesenchymal stem cells (MSCs). Materials and methods. The information contained in specialized scientific journals that are freely available and accessible through the global Internet was studied. Discussion of the results. In the scenario of mass exposure of the population, when from several tens (hundreds) to millions of people can be irradiated, the transfusion of hematopoietic stem cells traditionally used in such cases would be impossible. MSCs can possibly differentiate into specialized cells, that is, turn into cells of various organs and tissues or induce such kind of regeneration. For practical use, there are two main sources of their isolation and reproduction ex vivo -bone marrow and adipose tissue. To date, it has been shown that MSCs derived from adipose tissue can be effective in mitigating the effects of acute radiation illness. Intravenously applied MSCs are migrating mainly to the bone marrow and are partially restoring its function. Deep anatomical structures are also involved in local radiation injuries: bone, muscles, nerves, blood and lymphatic vessels and skin. There is a strong body of evidence suggesting the «repair effect» of MSCs when used to treat such lesions. This is because MSCs can induce the repair and regeneration of the anatomical structures which they are locally applied, possibly by the paracrine effect. The main advantage of allogeneic MSCs over autologous ones is their logistical accessibility. They can be produced in advance in quantities and stored frozen. After thawing, the cells must be cultured for at least 48 hours in humidified incubators with the addition of 5% CO 2 . Findings. Treatment of MSCs should be started as soon as possible after radiation exposure. Rescue of damaged hematopoiesis in the bone marrow can be achieved by multiple intravenous administration of up to 1 million (10 6 ) freshly prepared allogeneic MSCs/kg body weight. Locally (around and in the irradiation area), the dose of MSCs may be lower -20 million cells. Repeated topical application should be carried out at intervals of two to four weeks. Subsequent surgical reconstruction should be performed by an experienced surgeon and in a specialized center with concomitant topical application of MSCs.
The specific poly(A) addition reaction catalyzed by crude nuclear extracts from HeLa cells can us... more The specific poly(A) addition reaction catalyzed by crude nuclear extracts from HeLa cells can use ADP as efficiently as ATP as the donor of AMP residues. Both the ADP-and ATP-supported reactions require an intact upstream polyadenylation signal sequence element (AAUAAA). The mutated signal sequence (AACAAA) supports neither reaction. The ADP-supported poly(A) addition reaction can be resolved by glycerol gradient centrifugation of the crude nuclear extract into two components which are active when recombined but are inactive individually. The ATP-supported poly(A) addition is reconstituted by recombining the same gradient fractions, but the activity is lower than that supported by ADP, suggesting that an ATP-specific factor has been removed. A 150 mM KCl fraction DEAE-Sepharose of the nuclear extract, also devoid of the ATP-supported poly(A) addition reaction, retains a normal ADP-supported reaction. Together, these data show that ADP is a substrate for polyadenylation, and suggest that different factors might be required to induce ADP-or ATP-specificity in the poly(A) addition reaction. Most eucaryotic mRNAs are 3'-polyadenylated. Polyadenylation of primary transcripts requires at least two steps : (a) a specific cleavage of the elongated transcript at a site downstream from the specific polyadenylation sequence element (AAUAAA) (Fitzgerald and Shenk, 1981 ; Gil and Proudfott, 1984;; and (b) subsequent 3' poly(A) addition . These reactions have been partially resolved and shown to require, in addition to a nonspecific poly(A) polymerase, a polymerase specificity factor (or factors) which recognizes the AAUAAA sequence element , and one or more factors responsible for the cleavage process. The total number of factors required for the entire cleavage/poly(A) addition reaction is not known. It is widely accepted that the specific (AAUAAA-requiring) poly(A) addition reaction utilizes ATP as the donor of AMP residues. However, the data showing ATP specificity for the reaction has been obtained only for the nonspecific poly(A) polymerase (Winters and Edmonds, 1973 a;. showed that adenylation of total HeLa cell RNA by a purified nonspecific polymerase is supported by ATP but not by GTP, CTP, UTP or ADP. Similarly, showed that adenylation of calf thymus RNA by a nonspecific calf
Journal of Cellular and Molecular Medicine, Mar 27, 2019
Exosomes are saucer-shaped microvesicles, 30-180 nm in diameter, enveloped in a lipid bilayer. Th... more Exosomes are saucer-shaped microvesicles, 30-180 nm in diameter, enveloped in a lipid bilayer. They contain various molecular constituents of their cell of origin, such as proteins, DNA, mRNA, as well as non-coding RNAs. It has been suggested that they play an influential role in cell-to-cell signalling, the exchange of genetic information and the reprogramming of the recipient cells. 1,2 Thus, exosomes derived from tumour cells may trigger tumour initiation, angiogenesis, growth, the progression of the disease, or the formation of metastases. They may also play an important role in tumour-stroma interactions, chemotherapy and drug resistance. These vesicles carry messages from tumour cells to immune or stromal cells which may result in the prevention of immune recognition and modification of their microenvironment. Tumour cells release an enormous amount of exosomes. Compared with healthy controls, their numbers are increased in the plasma of some cancer patients. A clear correlation between the total amount of tumour exosomes and the stage of tumour development was also reported in ovarian and prostate cancer patients. In this respect, some exosomal proteins and miRNAs have been suggested as diagnostic and prognostic indicators for lung cancer, esophageal squamous cell carcinoma, prostate cancer, breast cancer, glioblastoma, ovarian cancer and other cancer types. Interestingly,
Journal of Cellular and Molecular Medicine, Oct 5, 2016
Spontaneous tumour regression after high-dose therapy and autologous stem cell transplantation is... more Spontaneous tumour regression after high-dose therapy and autologous stem cell transplantation is associated with the aplastic anaemia-like syndrome and the presence of polyclonal autoantibodies against carbonic anhydrase I (CA I). When tumour cells were grown in vitro in the presence of patients' sera positive for anti-CA I autoantibodies, their morphological pattern was altered. These changes were accompanied by modifications in the gene expression profile. We observed downregulation of genes of the basal lamina assembly (collagen type IV alpha 4, the laminin subunit gamma 2), the extracellular matrix (collagen type I alpha 1), the cytoskeleton (keratin 14 type I), the collagen triple helix repeat containing 1 and the proto-oncogene WNT7B. On the other hand, the expression of the CA 1 gene was increased in the tumour cells. It was also noticed that the presence of anti-CA I autoantibodies did not impair tumour cell proliferation and cell viability in vitro. These findings were observed only in the presence of patients' sera positive for anti-CA I autoantibodies.
We describe the implementation, optimization, sensitivity determination and first clinical result... more We describe the implementation, optimization, sensitivity determination and first clinical results of polymerase chain reaction (PCR) amplification of polymorphic short tandem repeat (STR) markers and Amelogenin locus coupled with fluorescent detection and capillary electrophoresis in chimerism monitoring of patients transplanted at three different transplant centers using a commercially available multiplex microsatellite assay. The chimerism analysis was performed with genomic DNA extracted from unselected peripheral blood leukocytes of one hundred pediatric and adult patients, who underwent allogeneic stem cell transplantation (SCT) from human leukocyte antigen (HLA) matched or one antigen mismatched related or unrelated donors for malignant (70 patients) and non-malignant (30 patients) diseases. Tested were 79 donor recipient pairs for 15 STR systems and identified an informative marker in all but one of them (98,7%), using 6 selected systems out of these fifteen, that appeared h...
International Journal of Molecular Sciences, Jan 18, 2020
In our study, we performed retroviral transduction to overexpress codon-optimized variant of gene... more In our study, we performed retroviral transduction to overexpress codon-optimized variant of gene encoding human carbonic anhydrase I (optiCA1) in two tumor cell lines PC3 and MDA-MB-231, derived from human prostatic and breast carcinoma respectively. We achieved significantly enhanced and stable overexpression of exogenous optiCA1 gene. The expression of endogenous, wild CA1 gene was found to be normally low (C t 28.6 for PC3 cells) or below to the detection limit (C t 35.5 for MDA-MB-231 cells). No morphological changes and no decreasing viability of tumor cells were observed upon stable overexpression of the optiCA1 gene. In our study we have shown that the overexpression of the optimized human CA1 in engineered PC3 and MDA-MB-231 cells did not induce similar changes as we observed in tumor cells cultivated in the presence of human sera containing extensively high titers of anti-CA I autoantibodies from patients with complete remission of malignant disease. In both optiCA1transduced cell lines, the expression of selected genes responsible for basal lamina assembly, cytoskeleton, extracellular matrix proteins and proto-oncogenes (COL1A1, COL4A4, LAMC2, CTHRC1, and WNT7B) was not changed.
14593 Background: Prognosis of patients with metastatic renal carcinoma remains poor. We evaluate... more 14593 Background: Prognosis of patients with metastatic renal carcinoma remains poor. We evaluated the efficacy and toxicity of miniautologous transplantation of LAK in cytokine pretreated patients (pts) with metastatic RCC. Methods: Between May 1998 and July 2005, 29 pts (23M/6F) with metastatic RCC were included. All patients were pretreated with cytokine-based therapy (9 pts with interferon alfa, 9 pts with interferon alfa+5FU+IL-2, 10 pts with interferon alfa+5-FU and 1 patient with IL-2). Median age was 58 years (range 49–71). Patients were assigned into three prognostic groups according to MSKCC prognostic criteria for 2nd line treatment (Motzer et al., 2004). Six, seventeen and six pts had 0, 1 and 2–3 risk factors, respectively. Median number of metastatic sites was 2 (range 1–6). 9 pts had liver, 12 bone and 2 patients had cerebral metastases. Median time from cytokine treatment to LAK therapy was 9 months (range 0–41). Periferal blood stem cells (PBSC) were isolated. Part ...
Search by Subject Search using Medical Subject Headings (< b> MeSH</b>), a controlled... more Search by Subject Search using Medical Subject Headings (< b> MeSH</b>), a controlled vocabulary for indexing life sciences content.< br/> Note that some records do not have MeSH. These include Patents and the latest PubMed and PubMed Central records.
The recent development of reduced intensity conditioning and allotransplantation (RICT) has opene... more The recent development of reduced intensity conditioning and allotransplantation (RICT) has opened a new way to assure engraftment of donor cells while reducing early transplant-related mortality. We evaluated the combination of high-dose therapy and autologous peripheral blood stem cells transplantation (APBSCT) followed by RICT to extend the benefit of allografting procedures in de novo multiple myeloma (MM) patients. Fifteen subjects with stage III MM (median age 51 years, range 40-57) received high dose melphalan (200 mg/m(2)) followed by APBSCT previously collected after cyclophosphamide (4 g/m(2)) and granulocyte colony-stimulating factor (G-CSF). After 3-4 months from APBSCT, the patients underwent RICT, consisting of fludarabine 30 mg/m(2) + cyclophosphamide 300 mg/m(2) on days -4, -3, and -2. Acute graft-versus-host disease (GVHD) occurred in 2 patients; 6 patients developed chronic GVHD; 4 patients developed CMV antigenemia and were treated pre-emptively with ganciclovir. No transplant related mortality was shown. Response was simultaneously measured by both electrophoresis (EP) and immunofixation (IF); when IF was negative, patients were classified in complete remission (CR) and when it remained positive, near CR (nCR). After a median follow up of 44 months post APBSCT, 100 and 43% of patients are still alive and progression-free, respectively. Overall, the CR + nCR rate after dose-reduced allograft was enhanced from 26.7 to 73.3%. A correlation not statistically significant between GVHD and remission was found. In conclusion, an up-front tandem strategy with a very low reduced intensity-conditioning regimen for allografting following autografting is feasible and induces high CR/nCR rate in MM.
A single center, retrospective analysis evaluating the outcome of patients with poor-risk aggress... more A single center, retrospective analysis evaluating the outcome of patients with poor-risk aggressive non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy and autologous stem cell transplantation (ASCT) as a part of firstline therapy. Forty-seven patients younger than 65 years with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), peripheral T-cell lymphoma (PTCL) or alk-negative anaplastic large cell lymphoma (ALCL) underwent ASCT between July 1997 and November 2005. Patients with DLBCL and alk-negative ALCL had 2 or 3 age-adjusted International Prognostic Index risk factors. All patients were transplanted after MACOP-B induction therapy followed by 2 courses of DHAP and myeloablative chemotherapy BEM or CBV. The complete response rate to the high-dose therapy was 79% with an estimated 5-year progression-free survival of 66%. At a median follow-up of 35 months (range, 16 to 112 months) the estimated overall survival at five years was 59%. There were 4 treatment-related deaths. Twenty-nine of 47 patients remain in complete remission. Our results confirm the efficacy of high-dose therapy with ASCT during first-line treatment of patients with poor-prognosis aggressive lymphoma, with substantial number of patients cured by using this treatment approach.
Ribosomal RNA serves as the backbone in ribosomal assembly and also, at least to some degree, as ... more Ribosomal RNA serves as the backbone in ribosomal assembly and also, at least to some degree, as an active component of the mature ribosome. The introduction of nucleotide changes (e. g., by site-directed mutations) clearly offers the most promising tool for elucidating the function of ribosomal RNA.
Intermediate high dose VIP (etoposide, ifosfamide, cisplatin) achieved comparable efficacy and im... more Intermediate high dose VIP (etoposide, ifosfamide, cisplatin) achieved comparable efficacy and improved tolerance in comparison with high-dose chemotherapy plus PBSC in poor risk germ cell tumors. The aim of this study was to confirm the effectivity and tolerance of this regimen in clinical practice. Twenty-five consecutive patients, 9 previously untreated with poor prognosis and 16 relapsed, were treated with 1.6 VIP or 1.9 VIP+PBSC. A relative dose intensity of 1.6 VIP was used in 14 patients and 11 patients received the intensity of 1.9 VIP. Clinical response was achieved in 56% of patients. Fifty-eight percent of patients have survived more than 1 year and 44% more than 2 years. No significant difference was noted between previously treated and untreated patients, as well as between the patients on 1.6 VIP and 1.9 VIP, with the exception of improved 1-year survival of patients on 1.9 VIP. One of four cisplatin-refractory patients achieved durable partial remission with a normal ...
This is a clinical observation of a patient treated for metastatic head and neck cancer with mese... more This is a clinical observation of a patient treated for metastatic head and neck cancer with mesenchymal stem cells mediated prodrug gene therapy. The cells were applied intravenously. We did not observe any therapeutic effect. However, a temporal bicytopenia was observed.
Acute radiation syndrome (ARS) is an acute illness caused by exposure to a high dose of ionizi... more Acute radiation syndrome (ARS) is an acute illness caused by exposure to a high dose of ionizing radiation. ARS is the deterministic effect of radiation exposure of the whole body or a significant body volume (partial body irradiation) above a threshold dose of about 1 Gy (gray). Radiation accidents, such as those in Chernobyl (1986) and Fukushima (2011), or the possible use of nuclear weapons during the hostilities or terrorist attacks, can lead to the massive development of ARS in humans. The aim of the work is to introduce a new method of post-radiation treatment – the use of allogeneic mesenchymal stem cells (MSCs). Materials and methods. The information contained in specialized scientific journals that are freely available and accessible through the global Internet was studied. Discussion of the results. In the scenario of mass exposure of the population, when from several tens (hundreds) to millions of people can be irradiated, the transfusion of hematopoietic stem ce...
Journal of Cellular and Molecular Medicine, Apr 4, 2021
We have observed the spontaneous tumour regression in four patients (breast cancer, Hodgkin's dis... more We have observed the spontaneous tumour regression in four patients (breast cancer, Hodgkin's disease, non-Hodgkin's lymphoma and Ewing's sarcoma) who had relapsed/progressed after high-dose chemotherapy (HDC) and autologous haematopoietic stem cell transplantation (ASCT). 1 Patients' blood counts strongly resembled the blood counts in aplastic anaemia (aplastic anaemia (AA)-like syndrome). Moreover, some of these patients' morphology of the bone marrow trephine biopsies was identical to the AA picture. It should be noted LETTER TO THE EDITOR relapsed/progressed after HDC and ASCT and achieved spontaneous tumour regression (ie without any further treatment). The epitope 'alignment' in these cases is not only surprising, but it is also challenging. Will we go further, prepare monoclonal therapeutic antibodies, and possibly will be able to treat a wide variety of malignant tumours?
Acute radiation syndrome (ARS) is an acute illness caused by exposure to a high dose of ionizing ... more Acute radiation syndrome (ARS) is an acute illness caused by exposure to a high dose of ionizing radiation. ARS is the deterministic effect of radiation exposure of the whole body or a significant body volume (partial body irradiation) above a threshold dose of about 1 Gy (gray). Radiation accidents, such as those in Chernobyl (1986) and Fukushima (2011), or the possible use of nuclear weapons during the hostilities or terrorist attacks, can lead to the massive development of ARS in humans. The aim of the work is to introduce a new method of post-radiation treatment -the use of allogeneic mesenchymal stem cells (MSCs). Materials and methods. The information contained in specialized scientific journals that are freely available and accessible through the global Internet was studied. Discussion of the results. In the scenario of mass exposure of the population, when from several tens (hundreds) to millions of people can be irradiated, the transfusion of hematopoietic stem cells traditionally used in such cases would be impossible. MSCs can possibly differentiate into specialized cells, that is, turn into cells of various organs and tissues or induce such kind of regeneration. For practical use, there are two main sources of their isolation and reproduction ex vivo -bone marrow and adipose tissue. To date, it has been shown that MSCs derived from adipose tissue can be effective in mitigating the effects of acute radiation illness. Intravenously applied MSCs are migrating mainly to the bone marrow and are partially restoring its function. Deep anatomical structures are also involved in local radiation injuries: bone, muscles, nerves, blood and lymphatic vessels and skin. There is a strong body of evidence suggesting the «repair effect» of MSCs when used to treat such lesions. This is because MSCs can induce the repair and regeneration of the anatomical structures which they are locally applied, possibly by the paracrine effect. The main advantage of allogeneic MSCs over autologous ones is their logistical accessibility. They can be produced in advance in quantities and stored frozen. After thawing, the cells must be cultured for at least 48 hours in humidified incubators with the addition of 5% CO 2 . Findings. Treatment of MSCs should be started as soon as possible after radiation exposure. Rescue of damaged hematopoiesis in the bone marrow can be achieved by multiple intravenous administration of up to 1 million (10 6 ) freshly prepared allogeneic MSCs/kg body weight. Locally (around and in the irradiation area), the dose of MSCs may be lower -20 million cells. Repeated topical application should be carried out at intervals of two to four weeks. Subsequent surgical reconstruction should be performed by an experienced surgeon and in a specialized center with concomitant topical application of MSCs.
The specific poly(A) addition reaction catalyzed by crude nuclear extracts from HeLa cells can us... more The specific poly(A) addition reaction catalyzed by crude nuclear extracts from HeLa cells can use ADP as efficiently as ATP as the donor of AMP residues. Both the ADP-and ATP-supported reactions require an intact upstream polyadenylation signal sequence element (AAUAAA). The mutated signal sequence (AACAAA) supports neither reaction. The ADP-supported poly(A) addition reaction can be resolved by glycerol gradient centrifugation of the crude nuclear extract into two components which are active when recombined but are inactive individually. The ATP-supported poly(A) addition is reconstituted by recombining the same gradient fractions, but the activity is lower than that supported by ADP, suggesting that an ATP-specific factor has been removed. A 150 mM KCl fraction DEAE-Sepharose of the nuclear extract, also devoid of the ATP-supported poly(A) addition reaction, retains a normal ADP-supported reaction. Together, these data show that ADP is a substrate for polyadenylation, and suggest that different factors might be required to induce ADP-or ATP-specificity in the poly(A) addition reaction. Most eucaryotic mRNAs are 3'-polyadenylated. Polyadenylation of primary transcripts requires at least two steps : (a) a specific cleavage of the elongated transcript at a site downstream from the specific polyadenylation sequence element (AAUAAA) (Fitzgerald and Shenk, 1981 ; Gil and Proudfott, 1984;; and (b) subsequent 3' poly(A) addition . These reactions have been partially resolved and shown to require, in addition to a nonspecific poly(A) polymerase, a polymerase specificity factor (or factors) which recognizes the AAUAAA sequence element , and one or more factors responsible for the cleavage process. The total number of factors required for the entire cleavage/poly(A) addition reaction is not known. It is widely accepted that the specific (AAUAAA-requiring) poly(A) addition reaction utilizes ATP as the donor of AMP residues. However, the data showing ATP specificity for the reaction has been obtained only for the nonspecific poly(A) polymerase (Winters and Edmonds, 1973 a;. showed that adenylation of total HeLa cell RNA by a purified nonspecific polymerase is supported by ATP but not by GTP, CTP, UTP or ADP. Similarly, showed that adenylation of calf thymus RNA by a nonspecific calf
Journal of Cellular and Molecular Medicine, Mar 27, 2019
Exosomes are saucer-shaped microvesicles, 30-180 nm in diameter, enveloped in a lipid bilayer. Th... more Exosomes are saucer-shaped microvesicles, 30-180 nm in diameter, enveloped in a lipid bilayer. They contain various molecular constituents of their cell of origin, such as proteins, DNA, mRNA, as well as non-coding RNAs. It has been suggested that they play an influential role in cell-to-cell signalling, the exchange of genetic information and the reprogramming of the recipient cells. 1,2 Thus, exosomes derived from tumour cells may trigger tumour initiation, angiogenesis, growth, the progression of the disease, or the formation of metastases. They may also play an important role in tumour-stroma interactions, chemotherapy and drug resistance. These vesicles carry messages from tumour cells to immune or stromal cells which may result in the prevention of immune recognition and modification of their microenvironment. Tumour cells release an enormous amount of exosomes. Compared with healthy controls, their numbers are increased in the plasma of some cancer patients. A clear correlation between the total amount of tumour exosomes and the stage of tumour development was also reported in ovarian and prostate cancer patients. In this respect, some exosomal proteins and miRNAs have been suggested as diagnostic and prognostic indicators for lung cancer, esophageal squamous cell carcinoma, prostate cancer, breast cancer, glioblastoma, ovarian cancer and other cancer types. Interestingly,
Journal of Cellular and Molecular Medicine, Oct 5, 2016
Spontaneous tumour regression after high-dose therapy and autologous stem cell transplantation is... more Spontaneous tumour regression after high-dose therapy and autologous stem cell transplantation is associated with the aplastic anaemia-like syndrome and the presence of polyclonal autoantibodies against carbonic anhydrase I (CA I). When tumour cells were grown in vitro in the presence of patients' sera positive for anti-CA I autoantibodies, their morphological pattern was altered. These changes were accompanied by modifications in the gene expression profile. We observed downregulation of genes of the basal lamina assembly (collagen type IV alpha 4, the laminin subunit gamma 2), the extracellular matrix (collagen type I alpha 1), the cytoskeleton (keratin 14 type I), the collagen triple helix repeat containing 1 and the proto-oncogene WNT7B. On the other hand, the expression of the CA 1 gene was increased in the tumour cells. It was also noticed that the presence of anti-CA I autoantibodies did not impair tumour cell proliferation and cell viability in vitro. These findings were observed only in the presence of patients' sera positive for anti-CA I autoantibodies.
We describe the implementation, optimization, sensitivity determination and first clinical result... more We describe the implementation, optimization, sensitivity determination and first clinical results of polymerase chain reaction (PCR) amplification of polymorphic short tandem repeat (STR) markers and Amelogenin locus coupled with fluorescent detection and capillary electrophoresis in chimerism monitoring of patients transplanted at three different transplant centers using a commercially available multiplex microsatellite assay. The chimerism analysis was performed with genomic DNA extracted from unselected peripheral blood leukocytes of one hundred pediatric and adult patients, who underwent allogeneic stem cell transplantation (SCT) from human leukocyte antigen (HLA) matched or one antigen mismatched related or unrelated donors for malignant (70 patients) and non-malignant (30 patients) diseases. Tested were 79 donor recipient pairs for 15 STR systems and identified an informative marker in all but one of them (98,7%), using 6 selected systems out of these fifteen, that appeared h...
International Journal of Molecular Sciences, Jan 18, 2020
In our study, we performed retroviral transduction to overexpress codon-optimized variant of gene... more In our study, we performed retroviral transduction to overexpress codon-optimized variant of gene encoding human carbonic anhydrase I (optiCA1) in two tumor cell lines PC3 and MDA-MB-231, derived from human prostatic and breast carcinoma respectively. We achieved significantly enhanced and stable overexpression of exogenous optiCA1 gene. The expression of endogenous, wild CA1 gene was found to be normally low (C t 28.6 for PC3 cells) or below to the detection limit (C t 35.5 for MDA-MB-231 cells). No morphological changes and no decreasing viability of tumor cells were observed upon stable overexpression of the optiCA1 gene. In our study we have shown that the overexpression of the optimized human CA1 in engineered PC3 and MDA-MB-231 cells did not induce similar changes as we observed in tumor cells cultivated in the presence of human sera containing extensively high titers of anti-CA I autoantibodies from patients with complete remission of malignant disease. In both optiCA1transduced cell lines, the expression of selected genes responsible for basal lamina assembly, cytoskeleton, extracellular matrix proteins and proto-oncogenes (COL1A1, COL4A4, LAMC2, CTHRC1, and WNT7B) was not changed.
14593 Background: Prognosis of patients with metastatic renal carcinoma remains poor. We evaluate... more 14593 Background: Prognosis of patients with metastatic renal carcinoma remains poor. We evaluated the efficacy and toxicity of miniautologous transplantation of LAK in cytokine pretreated patients (pts) with metastatic RCC. Methods: Between May 1998 and July 2005, 29 pts (23M/6F) with metastatic RCC were included. All patients were pretreated with cytokine-based therapy (9 pts with interferon alfa, 9 pts with interferon alfa+5FU+IL-2, 10 pts with interferon alfa+5-FU and 1 patient with IL-2). Median age was 58 years (range 49–71). Patients were assigned into three prognostic groups according to MSKCC prognostic criteria for 2nd line treatment (Motzer et al., 2004). Six, seventeen and six pts had 0, 1 and 2–3 risk factors, respectively. Median number of metastatic sites was 2 (range 1–6). 9 pts had liver, 12 bone and 2 patients had cerebral metastases. Median time from cytokine treatment to LAK therapy was 9 months (range 0–41). Periferal blood stem cells (PBSC) were isolated. Part ...
Search by Subject Search using Medical Subject Headings (< b> MeSH</b>), a controlled... more Search by Subject Search using Medical Subject Headings (< b> MeSH</b>), a controlled vocabulary for indexing life sciences content.< br/> Note that some records do not have MeSH. These include Patents and the latest PubMed and PubMed Central records.
The recent development of reduced intensity conditioning and allotransplantation (RICT) has opene... more The recent development of reduced intensity conditioning and allotransplantation (RICT) has opened a new way to assure engraftment of donor cells while reducing early transplant-related mortality. We evaluated the combination of high-dose therapy and autologous peripheral blood stem cells transplantation (APBSCT) followed by RICT to extend the benefit of allografting procedures in de novo multiple myeloma (MM) patients. Fifteen subjects with stage III MM (median age 51 years, range 40-57) received high dose melphalan (200 mg/m(2)) followed by APBSCT previously collected after cyclophosphamide (4 g/m(2)) and granulocyte colony-stimulating factor (G-CSF). After 3-4 months from APBSCT, the patients underwent RICT, consisting of fludarabine 30 mg/m(2) + cyclophosphamide 300 mg/m(2) on days -4, -3, and -2. Acute graft-versus-host disease (GVHD) occurred in 2 patients; 6 patients developed chronic GVHD; 4 patients developed CMV antigenemia and were treated pre-emptively with ganciclovir. No transplant related mortality was shown. Response was simultaneously measured by both electrophoresis (EP) and immunofixation (IF); when IF was negative, patients were classified in complete remission (CR) and when it remained positive, near CR (nCR). After a median follow up of 44 months post APBSCT, 100 and 43% of patients are still alive and progression-free, respectively. Overall, the CR + nCR rate after dose-reduced allograft was enhanced from 26.7 to 73.3%. A correlation not statistically significant between GVHD and remission was found. In conclusion, an up-front tandem strategy with a very low reduced intensity-conditioning regimen for allografting following autografting is feasible and induces high CR/nCR rate in MM.
A single center, retrospective analysis evaluating the outcome of patients with poor-risk aggress... more A single center, retrospective analysis evaluating the outcome of patients with poor-risk aggressive non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy and autologous stem cell transplantation (ASCT) as a part of firstline therapy. Forty-seven patients younger than 65 years with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), peripheral T-cell lymphoma (PTCL) or alk-negative anaplastic large cell lymphoma (ALCL) underwent ASCT between July 1997 and November 2005. Patients with DLBCL and alk-negative ALCL had 2 or 3 age-adjusted International Prognostic Index risk factors. All patients were transplanted after MACOP-B induction therapy followed by 2 courses of DHAP and myeloablative chemotherapy BEM or CBV. The complete response rate to the high-dose therapy was 79% with an estimated 5-year progression-free survival of 66%. At a median follow-up of 35 months (range, 16 to 112 months) the estimated overall survival at five years was 59%. There were 4 treatment-related deaths. Twenty-nine of 47 patients remain in complete remission. Our results confirm the efficacy of high-dose therapy with ASCT during first-line treatment of patients with poor-prognosis aggressive lymphoma, with substantial number of patients cured by using this treatment approach.
Ribosomal RNA serves as the backbone in ribosomal assembly and also, at least to some degree, as ... more Ribosomal RNA serves as the backbone in ribosomal assembly and also, at least to some degree, as an active component of the mature ribosome. The introduction of nucleotide changes (e. g., by site-directed mutations) clearly offers the most promising tool for elucidating the function of ribosomal RNA.
Intermediate high dose VIP (etoposide, ifosfamide, cisplatin) achieved comparable efficacy and im... more Intermediate high dose VIP (etoposide, ifosfamide, cisplatin) achieved comparable efficacy and improved tolerance in comparison with high-dose chemotherapy plus PBSC in poor risk germ cell tumors. The aim of this study was to confirm the effectivity and tolerance of this regimen in clinical practice. Twenty-five consecutive patients, 9 previously untreated with poor prognosis and 16 relapsed, were treated with 1.6 VIP or 1.9 VIP+PBSC. A relative dose intensity of 1.6 VIP was used in 14 patients and 11 patients received the intensity of 1.9 VIP. Clinical response was achieved in 56% of patients. Fifty-eight percent of patients have survived more than 1 year and 44% more than 2 years. No significant difference was noted between previously treated and untreated patients, as well as between the patients on 1.6 VIP and 1.9 VIP, with the exception of improved 1-year survival of patients on 1.9 VIP. One of four cisplatin-refractory patients achieved durable partial remission with a normal ...
This is a clinical observation of a patient treated for metastatic head and neck cancer with mese... more This is a clinical observation of a patient treated for metastatic head and neck cancer with mesenchymal stem cells mediated prodrug gene therapy. The cells were applied intravenously. We did not observe any therapeutic effect. However, a temporal bicytopenia was observed.
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Papers by Jan Lakota