Location via proxy:   [ UP ]  
[Report a bug]   [Manage cookies]                
Skip to main content
Goran Brajuskovic
  • Faculty of Biology
    University of Belgrade
    Studentski trg 16
    11000 Belgrade
    Serbia

Goran Brajuskovic

The efficiency of Chlorambucil in the induction of apoptosis was investigated in the study, and measurable apoptosis parameters were compared to the other prognostic factors with the aim of possible prediction of clinical response to the... more
The efficiency of Chlorambucil in the induction of apoptosis was investigated in the study, and measurable apoptosis parameters were compared to the other prognostic factors with the aim of possible prediction of clinical response to the therapy in the patients with CD5 + B-cell chronic lymphocytic leukemia (B-CLL). Seven newly diagnosed patients, initially treated with daily high-doses of Chlorambucil (HD-CLB) were analyzed. Quantitative analysis of apoptosis parameters on semi-fine sections obtained from peripheral blood was performed prior and during the first five days of therapy. The level of spontaneous apoptosis (SA) was determined, as well as the maximal response by apoptosis (MAR), and the time needed to establish maximal response by apoptosis (TMAR), respectively. The results revealed that the level of SA in the studied group of patients was 11.39%-20.50%. In three patients with achieved criteria for complete remission (CR) was observed high level of SA, TMAR 2-4 days and MAR 23.42-26.36%, respectively. All patients with CR were with negative LDT, non-diffuse involvement of bone marrow and clinical stage B. Criteria for partial remission (PR) were achieved in 4 patients. Within this group, all three measurable parameters of apoptosis could have been determined in only one patient, while in the rest was noticed the increased percentage of apoptotic cells on the last day of follow-up. In all patients was observed negative LDT, diffuse bone marrow involvement, and 2 out of 4 patients had CLPL of cytomorphological type and clinical stage B. By comparing the obtained values of measurable apoptotic parameters with the clinical response to the applied therapy with HD-CLB, it is possible to divide our patients into two groups: patients who have achieved CR have the highest percentage of cells dying due to the therapy-induced apoptosis, as well as the higher values of measurable parameters compared to the certain parameters of the patients with the criteria for PR. Our preliminary results of therapeutic response to the apoptosis might be useful for the timely decision upon the duration of therapy and change of modality of treatment for every patient during the follow-up period.
MiRNA-associated genetic variants occurring in regulatory regions can affect the efficiency of transcription and potentially modify pri-miRNA or pre-miRNA processing. Since miRNA-based mechanisms are shown to be involved in the... more
MiRNA-associated genetic variants occurring in regulatory regions can affect the efficiency of transcription and potentially modify pri-miRNA or pre-miRNA processing. Since miRNA-based mechanisms are shown to be involved in the pathogenesis of prostate cancer (PCa), the aim of the present study was to evaluate the effect of rs4938723, rs1076064 and rs4705343 occurring in regulatory regions of miR-34b/c, miR-143/145 and miR-378, respectively, on PCa risk and progression in Serbian population. We examined a total of 1060 subjects, of which 350 were patients with PCa, 354 were patients with benign prostatic hyperplasia (BPH), while 356 healthy volunteers were included in the control group. Genotyping of rs4938723, rs1076064 and rs4705343 was performed by using Taqman® SNP Genotyping Assays. Allele C of rs4705342 was found to increase the risk of PCa (P=0.031 for codominant model, P=0.0088 for recessive model). Rs1076064 minor allele G was found to associate with serum PSA score, as well as with PCa T category and disease aggressiveness. For rs4938723 minor allele C was shown to be associated with the lower PCa T category (Pdom=0.0046; OR=0.36, 95 % CI 0.17-0.76) in T2 vs. T1 comparison. Rs4705342 was identified as PCa susceptibility variant in Serbian population, while for rs1076064 and rs4938723 association with PCa progression parameters was found.
Previous studies conducted in Asian and European populations have provided evidence of the association between microRNA-related genetic variants and prostate cancer (PCa) risk and/or progression. Nevertheless, the results obtained in... more
Previous studies conducted in Asian and European populations have provided evidence of the association between microRNA-related genetic variants and prostate cancer (PCa) risk and/or progression. Nevertheless, the results obtained in these studies are inconsistent, which could be explained by the limitations of single-locus main effect evaluations to detect joint effects of multiple genetic variants, reflected in statistical epistases. Therefore, we conducted the analysis of potential epistatic interactions between variants located in microRNA genes and in genes encoding the components of RNA-induced silencing complex (RISC) in relation with PCa risk/aggressiveness. Raw data on genotyping results from our previous studies involving four microRNA polymorphisms and five variants in RISC genes were subjected to the exclusion of samples based on missing data criterion, followed by the re-evaluation of Hardy-Weinberg equilibrium. Afterwards, these genotyping results were included in the ...
MiR-21 and miR-375 have been reported as dysregulated in prostate cancer (PCa) in multiple previous studies. Still, variable or even opposing data for the expression of these microRNAs in PCa were found, and their potential biomarker... more
MiR-21 and miR-375 have been reported as dysregulated in prostate cancer (PCa) in multiple previous studies. Still, variable or even opposing data for the expression of these microRNAs in PCa were found, and their potential biomarker properties remain elusive. In an attempt to clarify their significance as PCa biomarkers, as well as to compare different types of specimens as a source of relevant microRNAs, we used plasma and matching plasma-derived exosomes from patients with PCa and patients with benign prostatic hyperplasia (BPH). Plasma and exosomes were obtained from 34 patients with PCa and 34 patients with BPH, and their levels of expression of miR-21 and miR-375 were determined by RT-qPCR. We found no significant difference in the level of expression of these microRNAs in plasma and exosomes between patients with PCa and BPH. The level of exosomal miR-21 was elevated in PCa patients with high serum PSA values, as well as in patients with aggressive PCa, while for plasma sampl...
Results of numerous studies gave contradictory conclusions when analysing associations between copy number variants (CNVs) within the azoospermia factor (AZF) locus of the Y chromosome and idiopathic male infertility. The aim of this... more
Results of numerous studies gave contradictory conclusions when analysing associations between copy number variants (CNVs) within the azoospermia factor (AZF) locus of the Y chromosome and idiopathic male infertility. The aim of this study was to identify the presence and possible association of CNVs in the AZF region of Y chromosome with idiopathic male infertility in the Serbian population. Using the multiplex ligation-dependent probe amplification technique, we were able to detect CNVs in 24 of 105 (22.86%) infertile men and in 11 of 112 (9.82%) fertile controls. The results of Fisher's exact test showed a statistically significant difference between cases and controls after merging g(reen)-r(ed)/g(reen)-r(ed) and b(lue)2/b(lue)3 partial deletions identified in the AZFc region (p = 0.024). At the same time, we observed a trend towards statistical significance for a deletion among gr/gr amplicons (p = 0.053). In addition to these, we identified a novel complex CNV involving inversion of r2/r3 amplicons, followed by b2/b3 duplication and b3/b4 deletion, respectively. Additional analyses on a larger study group would be necessary to draw meaningful conclusions about associations among CNVs that presented with higher frequency in the infertile men than the fertile controls.
PurposeThe purpose of this study is to evaluate the potential association between genetic variants in genes encoding the components of RNA-induced silencing complex and prostate cancer (PCa) risk. Genetic variants chosen for this study... more
PurposeThe purpose of this study is to evaluate the potential association between genetic variants in genes encoding the components of RNA-induced silencing complex and prostate cancer (PCa) risk. Genetic variants chosen for this study are rs3742330 in DICER1, rs4961280 in AGO2, rs784567 in TARBP2, rs7813 in GEMIN4 and rs197414 in GEMIN3.MethodsThe study involved 355 PCa patients, 360 patients with benign prostatic hyperplasia and 318 healthy controls. For individuals diagnosed with PCa, clinicopathological characteristics including serum prostate-specific antigen level at diagnosis, Gleason score (GS) and clinical stage were determined. Genotyping was performed using high-resolution melting analysis, PCR–RFLP, TaqMan SNP Genotyping Assay and real-time PCR-based genotyping assay using specific probes. Allelic and genotypic associations were evaluated by unconditional linear and logistic regression methods.ResultsThe study provided no evidence of association between the analyzed genetic variants and PCa risk. Nevertheless, allele A of rs784567 was found to confer the reduced risk of higher serum PSA level at diagnosis (P = 0.046; Difference = −66.64, 95 % CI −131.93 to 1.35, for log-additive model). Furthermore, rs4961280, as well as rs3742330, were shown to be associated with GS. These variants, together with rs7813, were found to be associated with the lower clinical stage of PCa. Also, rs3742330 minor allele G was found to be associated with lower PCa aggressiveness (P = 0.036; OR 0.14, 95 % CI 0.023–1.22, for recessive model).ConclusionsAccording to our data, rs3742330, rs4961280 and rs7813 qualify for potentially protective genetic variants against PCa progression. These variants were not shown to be associated with PCa risk.
Due to their potentially functional significance, genetic variants within microRNA genes have been recognized as candidates for cancer-related genetic biomarkers. Among the most extensively studied so far are rs3746444, rs11614913 and... more
Due to their potentially functional significance, genetic variants within microRNA genes have been recognized as candidates for cancer-related genetic biomarkers. Among the most extensively studied so far are rs3746444, rs11614913 and rs895819. Nevertheless, only few previous studies in Asian population analyzed the association of rs3746444 and rs11614913 with prostate cancer (PCa) risk, while rs895819 was not evaluated in relation to this issue. The aim of this study was to assess the possible association between these genetic variants and PCa risk and progression in Serbian population. 355 samples of peripheral blood were obtained from the patients with PCa and 353 samples from patients with benign prostatic hyperplasia (BPH). 312 volunteers derived from general population who gave samples of buccal swabs were included in the control group. Genotyping of rs3746444, rs11614913 and rs895819 was performed by using PCR-RFLP method, HRM analysis and allele-specific PCR, respectively. A...
MiRNA-associated genetic variants occurring in regulatory regions can affect the efficiency of transcription and potentially modify pri-miRNA or pre-miRNA processing. Since miRNA-based mechanisms are shown to be involved in the... more
MiRNA-associated genetic variants occurring in regulatory regions can affect the efficiency of transcription and potentially modify pri-miRNA or pre-miRNA processing. Since miRNA-based mechanisms are shown to be involved in the pathogenesis of prostate cancer (PCa), the aim of the present study was to evaluate the effect of rs4938723, rs1076064 and rs4705343 occurring in regulatory regions of miR-34b/c, miR-143/145 and miR-378, respectively, on PCa risk and progression in Serbian population. We examined a total of 1060 subjects, of which 350 were patients with PCa, 354 were patients with benign prostatic hyperplasia (BPH), while 356 healthy volunteers were included in the control group. Genotyping of rs4938723, rs1076064 and rs4705343 was performed by using Taqman® SNP Genotyping Assays. Allele C of rs4705342 was found to increase the risk of PCa (P=0.031 for codominant model, P=0.0088 for recessive model). Rs1076064 minor allele G was found to associate with serum PSA score, as wel...
Introduction/Objective. Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease. The majority of cases are apparently sporadic ALS (SALS) with variants in susceptibility genes or sometimes in high-risk ALS genes. Two ALS... more
Introduction/Objective. Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease. The majority of cases are apparently sporadic ALS (SALS) with variants in susceptibility genes or sometimes in high-risk ALS genes. Two ALS susceptibility genes are SMN1, whose functional loss causes spinal muscular atrophy (SMA), and a nearly identical SMN2 gene, which modulates SMA severity. In this study we examined the association of copy number variations (CNVs) of SMN1 and SMN2 genes and two additional genes, SERF1 and NAIP, residing in the same genomic region (i.e. 5q13.2 segmental duplication), with SALS in patients from Serbia. Methods. Multiplex ligation-dependent probe amplification was used to determine CNVs of each gene in a clinically well-characterised group of 153 Serbian SALS patients and 153 controls. Results. Individual association between SMN1, SMN2, SERF1 or NAIP CNVs and SALS susceptibility or survival was not found. Survival curves based on the multivariable Cox ...
Introduction: Suicide attempt (SA) is in the middle of continuum of complex suicidal behavior phenotype. Psychiatric disorders and acute stressful life events (SLEs) are triggers for suicidal behavior. Serotonin system genes are often... more
Introduction: Suicide attempt (SA) is in the middle of continuum of complex suicidal behavior phenotype. Psychiatric disorders and acute stressful life events (SLEs) are triggers for suicidal behavior. Serotonin system genes are often implicated in suicidal behavior. Tryptophan hydroxylase 2 (TPH2), exclusively expressed in the brain, is the rate-limiting enzyme for serotonin biosynthesis. TPH2 may be enrolled in stress-response mechanisms via hypothalamic–pituitary–adrenal axis, while TPH2 variant rs7305115 has been reported to affect gene expression in postmortem human pons. To date, only poor examination of this variant in etiology of suicidal behavior has reported conflicting results. The aim of the present study was to assess rs7305115 main effect and its interaction with acute SLEs in SA pathology among Serbian psychiatric patients. Methods: 165 suicide attempters and 188 suicide non-attempters, suffering from major psychiatric disorders, participated in the study. Acute SLEs score was assessed using the List of Threatening Experiences Questionnaire. Variant rs7305115 was genotyped using TaqMan-based allelic discrimination assay. Statistical analyses were done in SNPstats by applying logistic regression adjusted by psychiatric diagnoses. Results: Variant rs7305115 was not associated with SA in Serbian psychiatric patients, neither alone, nor in combination with acute SLEs, for all five models of inheritance tested (P>0.05). Discussion: Our finding does not support the main and moderating implication of TPH2 variant rs7305115 in SA liability among Serbian psychiatric patients. Further examination in larger samples of this variant in SA patology is necessary due to its functional relevance.
Adrenal incidentalomas are a heterogeneous group of pathological entities, including benign or malignant adrenocortical or medullary tumors, hormonally active or inactive lesions, which are identified incidentally during the examination... more
Adrenal incidentalomas are a heterogeneous group of pathological entities, including benign or malignant adrenocortical or medullary tumors, hormonally active or inactive lesions, which are identified incidentally during the examination of nonadrenal-related abdominal complaints. About 1.5% to 23% of adrenal incidentalomas are pheochromocytomas. Composite pheochromocytoma is a rare tumour of adrenal medulla with divergente clinical course. This type of pheochromocytoma is designated "composite" or "mixed," depending on whether pheochromocytoma and nonpheochromocytoma components show the same embryologic origin. Nonpheochromocytoma components found in the composite pheochromocytoma include ganglioneuroma, ganglioneuroblastoma, neuroblastoma, and malignant schwannoma. The biologic behavior of composite pheochromocytomas may be as difficult to predict as more traditional pheochromocytomas; based on the number of cases reported to date the presence of areas resemblin...
Objectives. Adenosine to inosine RNA editing, serotonin 2C receptor (HTR2C), and stressful life events (SLEs) have all been implicated in suicidal behaviour. We examined the main and moderating effects of RNA editing (ADAR, ADARB1) and... more
Objectives. Adenosine to inosine RNA editing, serotonin 2C receptor (HTR2C), and stressful life events (SLEs) have all been implicated in suicidal behaviour. We examined the main and moderating effects of RNA editing (ADAR, ADARB1) and HTR2C genes, childhood trauma (CT), recent SLEs and psychiatric disorders as contributors to suicide attempt (SA) vulnerability. Methods. Study included 165 suicide attempters and 188 suicide non-attempters, all diagnosed with one of major psychiatric disorders. CT and recent SLEs were assessed using Early Trauma Inventory-Self Report and List of Threatening Experiences Questionnaire, respectively. Selected ADAR and ADARB1 tag-variants, and HTR2C rs6318 were pre-screened for association with SA, while generalized linear models and backward selection were applied to identify individual and interacting SA risk factors. Results. ADARB1 rs9983925 and rs4819035 and HTR2C rs6318 were associated with SA. The best minimal model found emotional abuse, recent SLEs, rs9983925 and rs6318 as independent SA risk factors, and general traumas as a factor moderating the effect of psychiatric disorders and emotional abuse. Conclusions. SA vulnerability in psychiatric patients is related to the joint effect of ADARB1 and HTR2C variants, the existing mood disorder and the cumulative exposures to a various childhood and recent stressful experiences.
Lupus nephritis (LN) is one of the most significant manifestations in systemic lupus erythematosus (SLE), although in some cases there is no direct correlation among clinical, serologic and histologic findings. Therefore, renal biopsy and... more
Lupus nephritis (LN) is one of the most significant manifestations in systemic lupus erythematosus (SLE), although in some cases there is no direct correlation among clinical, serologic and histologic findings. Therefore, renal biopsy and histopathologic classification by the activity and chronicity assessment of LN are considered necessary before the initiation of the treatment. In this paper 311 renal biopsies in patients with LN were analyzed and classified according to the WHO Classification published in 1974. Renal biopsy specimens were routinely processed for standard analysis by light microscopy (LM), immunofluorescent (IF), and electron microscopy (EM). Biopsy findings were compared with the common clinical symptoms. It is important to recognize that histopathologic lesions in the analyzed tissue might precede the symptoms and clinical manifestations, and therefore are an important factor in the appropriate therapeutic approach. Histopathological assessment of the class of L...
Background. High-dose chemotherapy followed by hematopoietic stem cell support can be used as a first-line treatment in patients with germ-cell tumor (GCT) with poor prognosis. Long-term survival rate is attained in 50% of these patients.... more
Background. High-dose chemotherapy followed by hematopoietic stem cell support can be used as a first-line treatment in patients with germ-cell tumor (GCT) with poor prognosis. Long-term survival rate is attained in 50% of these patients. The aim of this paper was to present the experience at the Department of Hematology, Military Medical Academy, with high-dose cytostatic therapy as first-line chemotherapy in GCT patients with poor prognosis. Methods. Between 1997 and 2003, five patients with high-risk germ-cell tumors were treated with high-dosage chemotherapy followed by an autologous stem cell transplantation. All the patients were with non-seminomatous germ-cell tumors with mixed histology, and one was with extragonadal retroperitoneal germ-cell tumor. Results. The follow-up period ranged from 8 to 33 months. Three patients achieved complete remision, two patients only partial remision, and one was not followed-up. One patient was with residual tumor resection, using retroperit...
Chronic lymphocytic leukemia (CLL) is a neoplastic disease characterized by the accumulation of morphologically mature monoclonal CD 5+ B cells in the early phase (G0/G1) of the cell cycle. It is considered that the accumulation of... more
Chronic lymphocytic leukemia (CLL) is a neoplastic disease characterized by the accumulation of morphologically mature monoclonal CD 5+ B cells in the early phase (G0/G1) of the cell cycle. It is considered that the accumulation of neoplastically transformed lymphocytes B (CLL cells) is primarily the consequence of the disturbance, i.e., blockade of these cells' apoptosis process. Apoptosis is the specific process of programmed cell death regulated by numerous extracellular and intracellular mechanisms. The Bcl-2 proteins are well-known modulators of this process. Some of these proteins (such as Bcl-2, and Bcl-Xl) are anti-apoptotic, while others (such as Bad or Bax) are pro-apoptotic. Our study included the analysis of 20 peripheral blood specimens from 20 patients with CLL, and 20 peripheral blood specimens of healthy persons who represented the control group. Using Western blotting analysis, we quantitatively examined the protein expression of Bcl-2 family (Bcl-2, Bax, Bad, a...
B type Chronic Lymphocytic Leukemia (B-CLL) is a malignant disease characterized by the progressive accumulation of morphologically mature, but immunologically dysphunctional CD 5+ lymphocytes in the blood, bone marrow and lymphatic... more
B type Chronic Lymphocytic Leukemia (B-CLL) is a malignant disease characterized by the progressive accumulation of morphologically mature, but immunologically dysphunctional CD 5+ lymphocytes in the blood, bone marrow and lymphatic organs in the early phase of the cell cycle. B-CLL is an example of human malignancy caused by alternations in the pathways of programmed cell death - apoptosis. Recent investigations showed a probable role of apoptosis as a prognostic parameter in B-CLL patients. Since the introduction of chlorambucil in the therapy in 1952, besides all the achievements in modern oncology, chlorambucil remained the most common antineoplastic agent in the treatment of CLL. Numerous experimental studies both in vitro and in vivo, showed the capability of antineoplastic agents to induce the process of apoptosis of neoplastically transformed cells. In this study the effect of chlorambucil on B lymphocites was monitored in 16 samples of peripheral blood tarlen from B-CLL dia...
Several variants within gene-encoding endothelial isoform of nitric oxide synthase have been reported to confer prostate cancer (PCa) susceptibility and/or progression. Nevertheless, studies referring to this issue have yielded... more
Several variants within gene-encoding endothelial isoform of nitric oxide synthase have been reported to confer prostate cancer (PCa) susceptibility and/or progression. Nevertheless, studies referring to this issue have yielded inconsistent results. In order to elucidate the involvement of these variants in prostate carcinogenesis, we have conducted a meta-analysis of previously published case-control and relevant case-only studies. Eleven studies comprising in total 3,806 cases and 4,466 controls were included in the meta-analysis which yielded evidence of association of rs2070744 (ORCC = 1.43, 95% CI 1.04-1.97; p = 0.03) and intron 4a/b variant (ORab+aa = 1.47, 95% CI 1.00-2.14; p = 0.05) with PCa risk under recessive and dominant model, respectively. Furthermore, PCa patients carrying 4a/b a allele were found to have an increased risk of cancer progression to a less differentiated form, characterized by a high Gleason score (OR = 2.29, 95% CI 1.51-3.49; p < 0.01) and to higher TNM stage (OR = 2.55, 95% CI 1.71-3.81; p < 0.01). These results support the involvement of NOS3 variants in molecular pathogenesis of PCa.
Myotonic dystrophy type 1 (DM1) is the most common adult onset muscular dystrophy, presenting as a multisystemic disorder with extremely variable clinical manifestation, from asymptomatic adults to severely affected neonates. A striking... more
Myotonic dystrophy type 1 (DM1) is the most common adult onset muscular dystrophy, presenting as a multisystemic disorder with extremely variable clinical manifestation, from asymptomatic adults to severely affected neonates. A striking anticipation and parental-gender effect upon transmission are distinguishing genetic features in DM1 pedigrees. It is an autosomal dominant hereditary disease associated with an unstable expansion of CTG repeats in the 3′-UTR of theDMPKgene, with the number of repeats ranging from 50 to several thousand. The number of CTG repeats broadly correlates with both the age-at-onset and overall severity of the disease. Expanded DM1 alleles are characterized by a remarkable expansion-biased and gender-specific germline instability, and tissue-specific, expansion-biased, age-dependent, and individual-specific somatic instability. Mutational dynamics in male and female germline account for observed anticipation and parental-gender effect in DM1 pedigrees, while...
Prion diseases are a group of etiologically heterogeneous neurodegenerative disorders. We have analyzed the coding region of PRNP gene in 121 healthy citizens of Serbia to determine whether the frequencies of M129V, E219K, and octapeptide... more
Prion diseases are a group of etiologically heterogeneous neurodegenerative disorders. We have analyzed the coding region of PRNP gene in 121 healthy citizens of Serbia to determine whether the frequencies of M129V, E219K, and octapeptide repeat number polymorphism. For Serbian population, polymorphism of PRNP gene at codon 129 does not differ from healthy European populations. Also codon 219 is monomorphic for the Glu allele both in Serbian population and other European populations. On the contrary, in Serbian population we did not detect any deletions or insertions in octapeptide repeat region, whereas deletions were detected in other European populations.
Genetic variability of sessile oak (Quercus petraea agg. Ehrendorfer, 1967) in Serbia is estimated applying cpDNA universal primer pairs that were characterized by a high informative level for chloroplast genome variability assessment in... more
Genetic variability of sessile oak (Quercus petraea agg. Ehrendorfer, 1967) in Serbia is estimated applying cpDNA universal primer pairs that were characterized by a high informative level for chloroplast genome variability assessment in previous investigations. Five different haplotypes were detected in the analyzed sample material from populations in Serbia.
BACKGROUND: The level of spontaneous apoptosis, the maximal response by apoptosis and the time when maximal apoptotic response is established are significant prognostic parameters that correlate with the therapeutic response of patients... more
BACKGROUND: The level of spontaneous apoptosis, the maximal response by apoptosis and the time when maximal apoptotic response is established are significant prognostic parameters that correlate with the therapeutic response of patients with malignant diseases. METHODS: Our study included 12 patients with B-CLL (I group of 7 patients) and ANLL (II group of 5 patients). Detection of apoptotic parameters on semifine section of peripheral blood was performed. Bcl 2 and mutated p53 expression were analyzed using the monoclonal antibodies by APAAP techniques. RESULTS: In our work, the established levels of spontaneous and therapy induced apoptosis correlate with clinical response of patients. All patients were bcl 2 strongly positive. Expression of p53 protein was not detected in these patients. The ultra structural analysis of the malignant cells has shown that a great number of cells react to antineoplastic agents? effect either by activating the cell response to stress or by apoptosis...

And 64 more