- Oncology, Cancer Biology, Cancer, Cancer Cell Biology, Gynaecology, Medical Sciences, and 23 moreBreast Cancer, Cell Cycle, Chemotherapy, Ovarian Cancer, Genetics, Cancer Research, Mitochondria, Endometrial Cancer, Mitochondrial DNA, Molecular Biology, Cell Biology, Pathology, Stem Cells, Cancer stem cells, Signal Transduction, Drug Resistance, kidney Cancer, Management, Metastasis, Renal cell Carcinoma, Clear Cell Renal Cell Carcinoma, Renal Progenitor Cells, and Renal Celledit
- Public Central Teaching Hospital Faculty Member - 2009/2010.edit
Sunitinib malate (Sutent™) is an inhibitor of multiple protein tyrosine kinases that shows antitumor and antiangiogenic activities. In a randomized Phase III trial of treatment-naive patients with metastatic renal cell carcinoma (mRCC),... more
Sunitinib malate (Sutent™) is an inhibitor of multiple protein tyrosine kinases that shows antitumor and antiangiogenic activities. In a randomized Phase III trial of treatment-naive patients with metastatic renal cell carcinoma (mRCC), patients treated with sunitinib showed a significant improvement in progression-free survival compared with those treated with IFN-α. Sunitinib also exhibited antitumor activity in unselected RCC patients, including those with who were refractory to treatment, had non-clear cell histology brain metastases, or an Eastern Cooperative Oncology Group performance status >1. Typical side effects of sunitinib malate are fatigue, asthenia, diarrhea, skin rash, stomatitis, hand-foot skin syndrome, hypothyroidism and hematological abnormalities. Hypertension, other toxicities may serve as biomarkers for improved clinical outcomes in sunitinib treatment. Currently, sunitinib remains the gold standard of care in the treatment of mRCC.
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Research Interests: Oncology, Epidemiology, Molecular Biology, Polymorphism, Molecular Medicine, and 21 moreCancer, Breast Cancer, Cell Biology, Cancer Cell Biology, Mitochondria, Biological Sciences, Clinical Practice, Mitochondrial DNA, Humans, Mutation, Biomedical science, Female, Male, Meta Analysis, Systematic review, Mitochondrial Diseases, Oxidative phosphorylation, Neoplasms, Cancer Patient, Clinical Application, and Adenosine Triphosphate
Research Interests: Dentistry, Oncology, Otolaryngology, Pediatrics, Radiology, and 18 moreSurgery, Cellular Biology, Cancer, Magnetic Resonance Imaging, Pediatric Oncology, Immunohistochemistry, Adolescent, Laryngology, Head and Neck, Humans, Male, Young Adult, Clinical Sciences, Aged, Middle Aged, Adult, Radiopharmaceuticals, and Angiofibroma
For osteoblastoma, with its predilection for the spinal column and appendicular skeleton, the skull is an unusual site, and paranasal sinus involvement is very rare. Herein, we report on a case in which the disease was located within the... more
For osteoblastoma, with its predilection for the spinal column and appendicular skeleton, the skull is an unusual site, and paranasal sinus involvement is very rare. Herein, we report on a case in which the disease was located within the sphenoid bone. To the best of our knowledge, this is the 4th reported case of osteoblastoma with a sphenoid origin (1). We report an osteoblastoma of the sphenoid sinus in a 12-year-old girl who presented with exophthalmos. Computed tomography (CT) demonstrated an expansile lesion of the sphenoid which caused the orbital contents to be compressed and deviated to the right. In the magnetic resonance imaging scan, the lesion was found to invade the cranial base in the frontal and temporal region, approximating to the cavernous sinus and internal carotid artery on the right. Bilateral fronto-orbital craniotomy was performed. Histologically, the lesion was composed of proliferating osteoblasts along with vascular stroma. The tumor was described as an ag...
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Metastasis is a complex process that propagates cells from the primary or initial site of the cancer occurrence to distant parts of the body. Cancer cells break from the cancer site and circulate through the bloodstream or lymph vessels,... more
Metastasis is a complex process that propagates cells from the primary or initial site of the cancer occurrence to distant parts of the body. Cancer cells break from the cancer site and circulate through the bloodstream or lymph vessels, allowing them to reach nearly all parts of the body. These circulating tumour cells (CTCs) contain specialized metastasis-initiating cells (MICs) that reside in the biological heterogeneous primary tumour. Researchers have hypothesized that metastasis of renal cell carcinoma is initiated by circulation of MICs in patients' blood and bone marrow. Based on the cancer stem/progenitor cell concept of carcinogenesis, understanding the molecular phenotypes of metastasis-initiating cells (MICs) in renal cancer could play a vital role in developing strategies for therapeutic interventions in renal cancer. Existence of MICs among CTCs in renal carcinoma has not been proven in large scale. However, some studies have reported that specialized markers are f...
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The problem of diagnosis in the field of head and neck region is still valid. Specific diagnosis and precise estimation of the tumor's size with the use of CT and MRI imaging is generally unsatisfactory. The Positron Emission... more
The problem of diagnosis in the field of head and neck region is still valid. Specific diagnosis and precise estimation of the tumor's size with the use of CT and MRI imaging is generally unsatisfactory. The Positron Emission Tomography (PET) supports this process with additional information about the tumor's metabolism. Numerous publications show that PET-CT has a great influence on the evaluation of the size of the tumor, presence of lymph node metastases, choice of treatment and the prognosis of the recurrence. Cancer cells represent a specific metabolic state. These cells intake large quantities of glucose and utilize it in the process of glycolysis. The oxidative phosphorylation is not efficient in the transformed cells and defects in mitochondrial functions are at the heart of malignant cell transformation. Disruption of the oxidative phosphorylation chain has been described in the neoplasms. As a consequence, in cancer the glycolysis is active even in the normoxic env...
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Sine efficiency of tyrosine kinase inhibitor (TKI) therapy in dialyzed patients is still unclear we aim to analyze the outcome of treatment in such cohort. We analyzed treatment outcomes of patients with clear cell renal cell carcinoma... more
Sine efficiency of tyrosine kinase inhibitor (TKI) therapy in dialyzed patients is still unclear we aim to analyze the outcome of treatment in such cohort. We analyzed treatment outcomes of patients with clear cell renal cell carcinoma (ccRCC) with special focus on those who were also treated with hemodialysis and described treatment safety and progression-free survival of eight patients treated with TKIs and hemodialysis. Our report supports statement that TKI treatment of dialyzed patients is safe and effective. ccRCC increases risk of developing renal insufficiency as well as end-stage renal disease that require dialysis. Introduction of multitargeted receptor kinase inhibitors (TKIs), including sunitinib, sorafenib and pazopanib significantly expanded life time expectancy of metastatic renal clear cell carcinoma. The advance also applies to patients with ccRCC and end-stage renal disease who undergo dialyses.
Our knowledge on the molecular basis of kidney cancer metastasisis still relatively low. About 25-30% of patients suffering from clear cell renal cell carcinoma (ccRCC)present metastatic disease at the time of primary diagnosis. Only 10%... more
Our knowledge on the molecular basis of kidney cancer metastasisis still relatively low. About 25-30% of patients suffering from clear cell renal cell carcinoma (ccRCC)present metastatic disease at the time of primary diagnosis. Only 10% of patients diagnosed with stage IV disease survive 5 years and 20-50% of patients diagnosed with localized tumor develop metastases within 3 years. High mortality of patients with this cancer is associated with a large potential for metastasis and resistance to oncologic treatments such as chemo- and radiotherapy. Literature data based on studies conducted on other types of cancers suggest that in metastatic ccRCC, the complex of interleukin-6 (IL-6) and its soluble receptor (sIL-6R; complex IL-6/sIL-6R) and the signal transduction pathway (gp130/STAT3) might play a key role in this process. Therefore, in this review we focus on the role of IL-6 and its signaling pathways as a factor for development and spread of RCC. Analyzing the molecular basis of cancer spreading will enable the development of prognostic tests, evaluate individual predisposition for metastasis, and produce drugs that target metastases. As the development of effective systemic treatments evolve from advancements in molecular biology, continued studies directed at understanding the genetic and molecular complexities of this disease are critical to improve RCC treatment options.
Tyrosine kinase inhibitors are novel therapies targeting specific cellular signalling pathways. Sunitinib and sorafenib primarily block tyrosine kinase receptors involved in the progression of many tumours, including clear cell renal cell... more
Tyrosine kinase inhibitors are novel therapies targeting specific cellular signalling pathways. Sunitinib and sorafenib primarily block tyrosine kinase receptors involved in the progression of many tumours, including clear cell renal cell cancer (ccRCC). Although developed to target selected receptors, it is becoming apparent that they inhibit other kinases; this may result in the development of unexpected side effects. This is potentially dangerous as kinases on noncancerous cells are also inhibited. TKI off-target effects contributing to cardiotoxicity, hypothyroidism, hypertension, fatigue, hair depigmentation, hand-foot syndrome and gastrointestinal perforation have been described. We report three patients (3/412) treated with sunitinib and sorafenib who developed chronic myeloid leukaemia (CML) during treatment for ccRCC, proposing a molecular mechanism of tyrosine kinase inhibitors action on bone marrow cells that might be co-responsible for CML development.
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Sunitinib malate (Sutent™) is an inhibitor of multiple protein tyrosine kinases that shows antitumor and antiangiogenic activities. In a randomized Phase III trial of treatment-naive patients with metastatic renal cell carcinoma (mRCC),... more
Sunitinib malate (Sutent™) is an inhibitor of multiple protein tyrosine kinases that shows antitumor and antiangiogenic activities. In a randomized Phase III trial of treatment-naive patients with metastatic renal cell carcinoma (mRCC), patients treated with sunitinib showed a significant improvement in progression-free survival compared with those treated with IFN-α. Sunitinib also exhibited antitumor activity in unselected RCC patients, including those with who were refractory to treatment, had non-clear cell histology brain metastases, or an Eastern Cooperative Oncology Group performance status >1. Typical side effects of sunitinib malate are fatigue, asthenia, diarrhea, skin rash, stomatitis, hand-foot skin syndrome, hypothyroidism and hematological abnormalities. Hypertension, other toxicities may serve as biomarkers for improved clinical outcomes in sunitinib treatment. Currently, sunitinib remains the gold standard of care in the treatment of mRCC.
Research Interests:
Research Interests:
Mammalian target of rapamycin (mTOR) is a kinase protein involved in PI3K/AKT signaling with a central role in the processes of cell growth, survival and angiogenesis. Frequent mutations of this pathway make upstream and downstream... more
Mammalian target of rapamycin (mTOR) is a kinase protein involved in PI3K/AKT signaling with a central role in the processes of cell growth, survival and angiogenesis. Frequent mutations of this pathway make upstream and downstream components novel targets for tailored therapy design. Two mTOR inhibitors - everolimus and temsirolimus - enable an increase in overall survival (OS) or progression-free survival (PFS) time in a treatment of renal cancer. Despite recent advances in renal cancer treatment, resistance to targeted therapy is common. Understanding of molecular mechanisms is the basis of drug resistance which can facilitate prediction of success or failure in combinational or sequential targeted therapy. The article provides current knowledge on the mTOR signaling network and gives insight into the mechanisms of resistance to mTOR inhibitors from the complex perspective of RCC biology. The mechanisms of resistance developed not only by cancer cells, but also by interactions wi...
The natural history of clear cell renal cell cancer is highly unpredictable with various progressors and with populations where small renal masses may be accompanied by metastatic disease. Currently, there is a critical need to determine... more
The natural history of clear cell renal cell cancer is highly unpredictable with various progressors and with populations where small renal masses may be accompanied by metastatic disease. Currently, there is a critical need to determine patient risk and optimize treatment regimes. For these patients, molecular markers may offer significant information in terms of prognostic and predictive values, as well as determination of valid therapeutic targets. Until now, only a few of the many identified clear cell renal cell cancer biomarkers have been clinically validated in large cohorts. And only several biomarkers are integrated in predictive or prognostic models. Therefore, a large cohesive effort is required to advance the field of clear cell renal cell cancer prognostic biomarkers through systematic discovery, verification, validation and clinical implementation.
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Everolimus is a mTOR inhibitor that demonstrates antitumor and antiangiogenic activities. In a randomized Phase III trial, patients with metastatic renal cell carcinoma who progressed on sunitinib/sorafenib were treated with everolimus... more
Everolimus is a mTOR inhibitor that demonstrates antitumor and antiangiogenic activities. In a randomized Phase III trial, patients with metastatic renal cell carcinoma who progressed on sunitinib/sorafenib were treated with everolimus and showed significant improvement in progression-free survival compared with best supportive care. Novel approaches in treatment are expected to ensure less toxic therapies and increase efficacy of everolimus. To provide a new perspective for mTOR inhibitor research and therapy, we discuss renal cell carcinoma cancer stem cells as a potential target for mTOR inhibitors and present new concepts on emerging antiangiogenic therapies. Finally, we point why systems biology approach with reverse molecular engineering may also contribute to the field of drug discovery in renal cell carcinoma.
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Rhabdomyosarcoma (RMS) is the most frequent soft tissue sarcoma in children. It is localized in the head and neck region in 40% of cases. Treatment of RMS is complex, including multi-drug chemotherapy, radiotherapy and surgery. The... more
Rhabdomyosarcoma (RMS) is the most frequent soft tissue sarcoma in children. It is localized in the head and neck region in 40% of cases. Treatment of RMS is complex, including multi-drug chemotherapy, radiotherapy and surgery. The progress that has been accomplished in oncology in recent decades significantly improved outcomes. The 5-year survival rate raised from 25% in 1970 to 73% in 2001, according to IRS-IV data. The outcome is influenced by primary tumor localization, clinical staging, histological tumor type and age at the moment of diagnosis. The relatively rare incidence of these tumors resulted in difficulties in creating more standardized therapeutic protocols. Comparison of outcomes in large patients groups led to an increase in the number of patients with complete remission. Although survival rates of RMS patients have improved, searching for new therapeutic modalities and substances is still essential to improve outcomes in cases of more advanced stages and unfavorable tumor localizations.
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Research Interests:
Cancer is a major health problem and cause of death worldwide that accounted for 7.6 million deaths in 2008, which is projected to continue rising with an estimated 13.1 million deaths in 2030 according to WHO. Breast cancer is the... more
Cancer is a major health problem and cause of death worldwide that accounted for 7.6 million deaths in 2008, which is projected to continue rising with an estimated 13.1 million deaths in 2030 according to WHO. Breast cancer is the leading cause of cancer-based death among women around the world and its incidence is increasing annually with a similar tendency. In contrast, renal cell carcinoma accounts for only 3% of total human malignancies but it is still the most common type of urological cancer with a high prevalence in elderly men (>60 years of age). There are several factors linked with the development of renal cell cancer only, while others are connected only with breast cancer. Genetic risk factors and smoking are the factors which contribute to carcinogenesis in general. Some evidence exists indicating that vitamin D receptor (VDR) gene polymorphisms are associated with both breast and renal cancer; therefore, we put forward the hypothesis that polymorphisms in the VDR g...
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Metastasis is a complex process that propagates cells from the primary or initial site of the cancer occurrence to distant parts of the body. Cancer cells break from the cancer site and circulate through the bloodstream or lymph vessels,... more
Metastasis is a complex process that propagates cells from the primary or initial site of the cancer occurrence to distant parts of the body. Cancer cells break from the cancer site and circulate through the bloodstream or lymph vessels, allowing them to reach nearly all parts of the body. These circulating tumour cells (CTCs) contain specialized metastasis-initiating cells (MICs) that reside in the biological heterogeneous primary tumour. Researchers have hypothesized that metastasis of renal cell carcinoma is initiated by circulation of MICs in patients' blood and bone marrow. Based on the cancer stem/progenitor cell concept of carcinogenesis, understanding the molecular phenotypes of metastasis-initiating cells (MICs) in renal cancer could play a vital role in developing strategies for therapeutic interventions in renal cancer. Existence of MICs among CTCs in renal carcinoma has not been proven in large scale. However, some studies have reported that specialized markers are f...
... czterech jonów wodorowych z macie-rzy mitochondrialnej (zostają zużyte do utworzenia dwóch cząsteczek wody) oraz jednoczesne przeniesienie czterech protonów w poprzek wewnętrznej błony mitochondrialnej [1]. Protony przenoszone są... more
... czterech jonów wodorowych z macie-rzy mitochondrialnej (zostają zużyte do utworzenia dwóch cząsteczek wody) oraz jednoczesne przeniesienie czterech protonów w poprzek wewnętrznej błony mitochondrialnej [1]. Protony przenoszone są poprzez trzy kanały (D, K i H ...
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Research Interests:
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Mitochondrial DNA mutations and polymorphisms have been the focus of intensive investigations for well over a decade in an attempt to understand how they affect fundamental processes such as cancer and aging. Initial interest in mutations... more
Mitochondrial DNA mutations and polymorphisms have been the focus of intensive investigations for well over a decade in an attempt to understand how they affect fundamental processes such as cancer and aging. Initial interest in mutations occurring in mitochondrial DNA of cancer cells diminished when most were found to be the same mutations which occurred during the evolution of human mitochondrial haplogroups. However, increasingly correlations are being found between various mitochondrial haplogroups and susceptibility to cancer or diseases in some cases and successful aging in others.
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Research Interests: Oncology, Epidemiology, Molecular Biology, Polymorphism, Molecular Medicine, and 18 moreCancer, Breast Cancer, Cell Biology, Cancer Cell Biology, Mitochondria, Poland, Mitochondrial DNA, Humans, Breast Cancer Early Detecion and Treatment, Female, Polymerase Chain Reaction, Statistical Significance, Risk factors, Single Nucleotide Polymorphism, Oxidative phosphorylation, Cancer Patient, Risk Factors, and Adenosine Triphosphate
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Data reported until today suggested a pivotal role of nuclear DNA mutations in the process of carcinogenesis. Recently more and more authors claim that disruption of mitochondrial DNA should not be excluded from this analysis. mtDNA have... more
Data reported until today suggested a pivotal role of nuclear DNA mutations in the process of carcinogenesis. Recently more and more authors claim that disruption of mitochondrial DNA should not be excluded from this analysis. mtDNA have been reported in many cancers of head and neck region. Mitochondrial D-loop has been proven to be mutation hot - spot with majority of mutations in the positions 303 to 315 of poly-C tract. Data show that 37% of patients with premalignant lesions and 62% with carcinoma in situ are positive for mtDNA mutations. Moreover mutations in genes encoding ND2, ND5, COIII, CYTB, and ATP6 were observed in 17% of patients. Mutations in mitochondrial rRNA genes occured in similar number of cases. Neoplastic cells undifferentiation and disease progression is accompanied by multiplication of mtDNA number and increased mtDNA content. mtDNA content corellates with the stage of the disease. mtDNA mutations faciliate cell proliferation and inhibit apoptosis by increas...
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Endometrial carcinoma is the most commonly diagnosed gynaecological cancer in developed countries. Although the molecular genetics of this disease has been in the focus of many research laboratories for the last 20 years, relevant... more
Endometrial carcinoma is the most commonly diagnosed gynaecological cancer in developed countries. Although the molecular genetics of this disease has been in the focus of many research laboratories for the last 20 years, relevant prognostic and diagnostic markers are still missing. At the same time mitochondrial DNA mutations have been reported in many types of cancer during the last two decades. It is therefore very likely that the mitochondrial genotype is one of the cancer susceptibility factors. To investigate the presence of mtDNA somatic mutations and distribution of inherited polymorphisms in endometrial adenocarcinoma patients we analyzed the D-loop sequence of cancer samples and their corresponding normal tissues and moreover performed mitochondrial haplogroup analysis. We detected 2 somatic mutation and increased incidence of mtDNA polymorphisms, in particular 16223C (80% patients, p = 0.005), 16126C (23%, p = 0.025) and 207A (19%, p = 0.027). Subsequent statistical analy...
Research Interests: Gynaecology, Oncology, Epidemiology, Cellular Biology, Molecular Biology, and 15 morePolymorphism, Molecular Medicine, Statistical Analysis, Cancer, Breast Cancer, Cell Biology, Cancer Cell Biology, Mitochondria, Molecular Genetics, Endometrial Cancer, Mitochondrial DNA, Developing Country, Risk factors, Endometrial carcinoma, and Risk Factors
Vulvar squamous cell carcinoma (VSCC) is a rare female genital neoplasm. Although numerous molecular changes have been reported in VSCC, biomarkers of clinical relevance are still lacking. On the other hand, there is emerging evidence on... more
Vulvar squamous cell carcinoma (VSCC) is a rare female genital neoplasm. Although numerous molecular changes have been reported in VSCC, biomarkers of clinical relevance are still lacking. On the other hand, there is emerging evidence on the use of mtDNA as a diagnostic tool in oncology. In order to investigate mtDNA status in VSCC patients, haplogroup distribution analysis and D-loop sequencing were performed. The results were compared with available data for the general Polish population, cancer free-centenarians as well as patients with endometrial and head and neck cancer. The obtained data were also compared with the current status of mitochondrial databases. Significant differences in haplogroup distribution between VSCC cohort, general Polish population and cancer-free centenarians cohort were found. Moreover, a correlation between the VSCC patients haplogroup and HPV status was observed. Finally, a specific pattern of mtDNA polymorphisms was found in VSCC. Our results sugges...
Research Interests: Gynaecology, Oncology, Epidemiology, Molecular Biology, Polymorphism, and 23 moreMolecular Medicine, Cancer, Breast Cancer, Cell Biology, Cancer Cell Biology, Poland, Gynaecological Cancer, Biological Sciences, Vulvar cancer, Mitochondrial DNA, Humans, Age, Mutation, Biomedical science, Haplotypes, Head and Neck Cancer, Female, Squamous Cell Carcinoma, Risk factors, Aged, Middle Aged, Risk Factors, and Base Sequence
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Research Interests: Genetics, Gynaecology, Oncology, Epidemiology, Cellular Biology, and 15 moreMolecular Biology, Molecular Medicine, Cancer, Breast Cancer, Cell Biology, Cancer Cell Biology, Cancer Biology, Mitochondria, Cancer Research, Mitochondrial DNA, Humans, Female, Risk factors, Risk Factors, and Cohort Studies
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Many models of tumour formation have been put forth so far. In general they involve mutations in at least three elements within the cell: oncogenes, tumour suppressors and regulators of telomere replication. Recently numerous mutations in... more
Many models of tumour formation have been put forth so far. In general they involve mutations in at least three elements within the cell: oncogenes, tumour suppressors and regulators of telomere replication. Recently numerous mutations in mitochondria have been found in many tumours, whereas they were absent in normal tissues from the same individual. The presence of mutations, of course, does not prove that they play a causative role in development of neoplastic lesions and progression; however, the key role played by mitochondria in both apoptosis and generation of DNA-damaging reactive oxygen species might indicate that the observed mutations contribute to tumour development. Recent experiments with nude mice have proven that mtDNA mutations are indeed responsible for tumour growth and exacerbated ROS production. This review describes mtDNA mutations in main types of human neoplasia.
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Research Interests:
This review addresses the significance of the expression of proliferating cell nuclear antigen (PCNA), p53 and some heat shock proteins (Hsps) in prostate carcinoma (PC). In fact, PCNA and p53 are two widely discussed tools in PC... more
This review addresses the significance of the expression of proliferating cell nuclear antigen (PCNA), p53 and some heat shock proteins (Hsps) in prostate carcinoma (PC). In fact, PCNA and p53 are two widely discussed tools in PC diagnosis, mainly because of the controversy regarding the significance of their expression during prostate cancer development and progression. At the same time, only few studies have shown the potential role of Hsps in carcinogenesis and their overexpression in pre-neoplastic and neoplastic ...
Research Interests:
Hsp60, a mitochondrial chaperonin highly conserved during evolution, has been found elevated in the cytosol of cancer cells, both in vivo and in vitro, but its role in determining apoptosis during oxidative stress (OS) has not yet been... more
Hsp60, a mitochondrial chaperonin highly conserved during evolution, has been found elevated in the cytosol of cancer cells, both in vivo and in vitro, but its role in determining apoptosis during oxidative stress (OS) has not yet been fully elucidated. The aim of the present work was to ...
Research Interests: Biochemistry, Oncology, Cellular Biology, Molecular Biology, Molecular Medicine, and 21 moreCancer, Immunohistochemistry, Cell Biology, Cancer Cell Biology, Oxidative Stress, Mitochondria, Mitochondrial Medicine, Cell Signaling, DNA damage, Apoptosis, Gene expression, Western blotting, DNA, Humans, Caspase, Hydrogen Peroxide, European, Comet Assay, Trypan Blue, Cell Survival, and Biochemistry and cell biology
There is growing evidence that molecular chaperones/heat shock proteins are involved in the pathogenesis of a number of human diseases, known as chaperonopathies. A better molecular understanding of the pathogenetic mechanisms is... more
There is growing evidence that molecular chaperones/heat shock proteins are involved in the pathogenesis of a number of human diseases, known as chaperonopathies. A better molecular understanding of the pathogenetic mechanisms is essential for addressing new strategies in diagnostics, therapeutics and clinical management of chaperonopathies, including those in which Hsp10 is involved. This chaperonin has been studied for a long time as a member of the mitochondrial protein-folding machine. However, although in normal cells Hsp10 is mainly localized in the mitochondrial matrix, it has also been found during and after stress in other subcellular compartments, such as cytosol, vesicles and secretory granules, alone or in combination with other proteins. In these extramitochondrial locales, Hsp10 plays an active role in cell signalling. For example, cancer cells often show altered levels of Hsp10, compared to normal cells. Hsp10 may also be found in the extracellular space and in the bl...
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Hsp60, a mitochondrial chaperonin highly conserved during evolution, has been found elevated in the cytosol of cancer cells, both in vivo and in vitro, but its role in determining apoptosis during oxidative stress (OS) has not yet been... more
Hsp60, a mitochondrial chaperonin highly conserved during evolution, has been found elevated in the cytosol of cancer cells, both in vivo and in vitro, but its role in determining apoptosis during oxidative stress (OS) has not yet been fully elucidated. The aim of the present work was to study the effects of OS on Hsp60 levels and its interactions with procaspase- 3 (p-C3) and p53 in tumor cells. NCI-H292 (mucoepidermoid carcinoma) cells were exposed to various concentrations of hydrogen peroxide (H2O2) for 24 hours. Cell viability was determined by Trypan blue and MTT assays. DNA damage was assessed by the Comet assay, and apoptosis was measured by the AnnexinV cytofluorimetric test. Exposure to increasing concentrations of H2O2 resulted in a reduction of cell viability, DNA damage, and early apoptotic phenomena. Hsp60, p-C3, p53, and p21 were assessed by Western blotting and immunocytochemistry before and after OS. Hsp60 and p-C3 were present before and after OS induction. Immunop...
Research Interests: Biochemistry, Oncology, Cellular Biology, Molecular Biology, Molecular Medicine, and 21 moreCancer, Immunohistochemistry, Cell Biology, Cancer Cell Biology, Oxidative Stress, Mitochondria, Mitochondrial Medicine, Cell Signaling, DNA damage, Apoptosis, Gene expression, Western blotting, DNA, Humans, Caspase, Hydrogen Peroxide, European, Comet Assay, Trypan Blue, Cell Survival, and Biochemistry and cell biology
Research Interests: Gynaecology, Oncology, Epidemiology, Cellular Biology, Molecular Biology, and 16 morePolymorphism, Molecular Medicine, Statistical Analysis, Cancer, Breast Cancer, Cell Biology, Cancer Cell Biology, Mitochondria, Molecular Genetics, Endometrial Cancer, Mitochondrial DNA, Developing Country, Risk factors, Endometrial carcinoma, Risk Factors, and Protective Factor
Mitochondria are subcellular organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As suggested over 70 years ago by Otto Warburg and recently confirmed with molecular techniques, alterations in... more
Mitochondria are subcellular organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As suggested over 70 years ago by Otto Warburg and recently confirmed with molecular techniques, alterations in respiratory activity and mitochondrial DNA (mtDNA) appear to be common features of malignant cells. Somatic mtDNA mutations have been reported in many types of cancer cells, but very few reports document the prevalence of inherited mitochondrial DNA polymorphisms in cancer patients compared to healthy control populations. Here we report the abundance of the 10398G polymorphism in a Polish breast cancer population and its frequency in controls. Amongst individuals with breast cancer the G single nucleotide polymorphism (SNP) is present in 23% of affected females compared to 3% of controls. This difference is highly statistically significant (P = 0.0008). It is therefore possible that the 10398G SNP constitutes an inherited predisposition factor for the development of breast cancer.
Research Interests: Oncology, Epidemiology, Molecular Biology, Polymorphism, Molecular Medicine, and 18 moreCancer, Breast Cancer, Cell Biology, Cancer Cell Biology, Mitochondria, Poland, Mitochondrial DNA, Humans, Breast Cancer Early Detecion and Treatment, Female, Polymerase Chain Reaction, Statistical Significance, Risk factors, Single Nucleotide Polymorphism, Oxidative phosphorylation, Cancer Patient, Risk Factors, and Adenosine Triphosphate
This review addresses the significance of the expression of proliferating cell nuclear antigen (PCNA), p53 and some heat shock proteins (Hsps) in prostate carcinoma (PC). In fact, PCNA and p53 are two widely discussed tools in PC... more
This review addresses the significance of the expression of
proliferating cell nuclear antigen (PCNA), p53 and some heat
shock proteins (Hsps) in prostate carcinoma (PC). In fact,
PCNA and p53 are two widely discussed tools in PC diagnosis,
mainly because of the controversy regarding the significance
of their expression during prostate cancer development
and progression. At the same time, only few studies have
shown the potential role of Hsps in carcinogenesis and their
overexpression in pre-neoplastic and neoplastic lesions of the
prostate.We briefly describe the physiological roles of Hsps in
normal cells, and the significance of their immunohistochemical
detection in PC as well as in pre-cancerous lesions of the
prostate.We will also discuss the possible functional interactions
of these molecules in both dysplastic and neoplastic
cells.
proliferating cell nuclear antigen (PCNA), p53 and some heat
shock proteins (Hsps) in prostate carcinoma (PC). In fact,
PCNA and p53 are two widely discussed tools in PC diagnosis,
mainly because of the controversy regarding the significance
of their expression during prostate cancer development
and progression. At the same time, only few studies have
shown the potential role of Hsps in carcinogenesis and their
overexpression in pre-neoplastic and neoplastic lesions of the
prostate.We briefly describe the physiological roles of Hsps in
normal cells, and the significance of their immunohistochemical
detection in PC as well as in pre-cancerous lesions of the
prostate.We will also discuss the possible functional interactions
of these molecules in both dysplastic and neoplastic
cells.
Research Interests:
Research Interests:
In human mitochondria, the characterization of multiple functional and structural interactions of mitochondrial chaperones is needed for the understanding of the cellular protein biogenesis as well as of the process of carcinogenesis. In... more
In human mitochondria, the characterization of multiple functional and structural interactions of mitochondrial chaperones is needed for the understanding of the cellular protein biogenesis as well as of the process of carcinogenesis. In light of current
available data, we propose that mitochondrial Hsp70, Hsp60/10, DnaJ-like proteins, GrpE-like proteins, Clp/Hsp100, and Hsp90 families should be analyzed as a part of multi-chaperones-interactors network, and that single protein-protein interaction
analysis does not constitute sufficient explanatory framework of carcinogenic potential of mitochondrial chaperones. We also believe that new chaperones and cell-cycle regulatory interactors are to be defined in the near future, but many technical and
methodological efforts are needed before any generalization of the data will be possible and a reliable map of multi-chaperones-interactors network will be constructed.
available data, we propose that mitochondrial Hsp70, Hsp60/10, DnaJ-like proteins, GrpE-like proteins, Clp/Hsp100, and Hsp90 families should be analyzed as a part of multi-chaperones-interactors network, and that single protein-protein interaction
analysis does not constitute sufficient explanatory framework of carcinogenic potential of mitochondrial chaperones. We also believe that new chaperones and cell-cycle regulatory interactors are to be defined in the near future, but many technical and
methodological efforts are needed before any generalization of the data will be possible and a reliable map of multi-chaperones-interactors network will be constructed.
Hsp60, a mitochondrial chaperonin highly conserved during evolution, has been found elevated in the cytosol of cancer cells, both in vivo and in vitro, but its role in determining apoptosis during oxidative stress (OS) has not yet been... more
Hsp60, a mitochondrial chaperonin highly conserved during evolution, has been found elevated in the cytosol of cancer cells, both in vivo and in vitro, but its role in determining apoptosis during oxidative stress (OS) has not yet been fully elucidated. The aim of the present work was to study the effects of OS on Hsp60 levels and its interactions with procaspase- 3 (p-C3) and p53 in tumor cells. NCI-H292 (mucoepidermoid carcinoma) cells were exposed to various concentrations of hydrogen peroxide (H2O2) for 24 hours. Cell viability was determined by Trypan blue and MTT assays. DNA damage was assessed by the Comet assay, and apoptosis was measured by the AnnexinV cytofluorimetric test. Exposure to increasing concentrations of H2O2 resulted in a reduction of cell viability, DNA damage, and early apoptotic phenomena. Hsp60, p-C3, p53, and p21 were assessed by Western blotting and immunocytochemistry before and after OS. Hsp60 and p-C3 were present before and after OS induction. Immunoprecipitation experiments showed an Hsp60/p-C3 complex before OS that persisted after it, while an Hsp60/p53 complex was not detected in either condition. The presence of wild type (wt) p53 was confirmed by RT-PCR, and p21 detection suggested p53 activation after OS. We postulate that, although OS may induce early apoptosis in NCI-H292 cells, Hsp60 exerts an anti-apoptotic effect in these cells and, by extension, it may do so in other cancer cells.
To date, little is known either about the physical interactions of heat shock protein 10 (Hsp10) with other proteins within the cell or its involvement in signal transduction pathways. Hsp10 has been considered mainly as a partner of... more
To date, little is known either about the physical interactions of heat shock protein 10 (Hsp10) with other proteins within the cell or its involvement in signal transduction pathways. Hsp10 has been considered mainly as a partner of Hsp60 in the Hsp60/10 protein folding machine. Only recently, Hsp10 was reported to interact with proteins involved in deoxyribonucleic acid checkpoint inactivation, termination of M-phase, messenger ribonucleic acid export, import of nuclear proteins, nucleocytoplasmic transport, and pheromone signaling pathways. At the same time, Hsp10 expression can be up-regulated in cancer cells, because it accumulates as the cell transformation progresses. Recent data suggest that Hsp10 may be not only a component of the folding machine but also an active player of the cell signaling network, influencing cell cycle, nucleocytoplasmic transport, and metabolism, with putative roles in the lack of cell differentiation and in the inhibition of apoptosis. In this review, we revise the involvement of Hsp10 in signal transduction pathways and its possible role in cancer etiology.
Mitochondria are cell organelles involved in processes of cell life and death, and therefore also in tumoral transformation. Indeed, mitochondria dysfunction is a prominent feature of cancer cells. Mitochondrial proteins and DNA have also... more
Mitochondria are cell organelles involved in processes of cell life and death, and therefore also in tumoral transformation. Indeed, mitochondria dysfunction is a prominent feature of cancer cells. Mitochondrial proteins and DNA have also been previously studied
as markers of tumorigenesis.
Heat shock proteins (HSPs) are ubiquitous evolutionary conserved proteins. HSPs enhance their expression in stressed cells and they are involved in gene expression regulation,
DNA replication, signal transduction, differentiation, apoptosis, cellular senescence or immortalization.
This review reflects recent views on the role of some mitochondrial molecular chaperones as prohibitin, mortalin and HSP60/HSP10 complex and their modifications leading to
cell transformation and cancer development. These molecules could represent modern molecular biomarkers for oncological management.
as markers of tumorigenesis.
Heat shock proteins (HSPs) are ubiquitous evolutionary conserved proteins. HSPs enhance their expression in stressed cells and they are involved in gene expression regulation,
DNA replication, signal transduction, differentiation, apoptosis, cellular senescence or immortalization.
This review reflects recent views on the role of some mitochondrial molecular chaperones as prohibitin, mortalin and HSP60/HSP10 complex and their modifications leading to
cell transformation and cancer development. These molecules could represent modern molecular biomarkers for oncological management.
Research Interests:
Research Interests: Psychology, Cardiology, Otolaryngology, Erythropoietin, Humans, and 14 moreObstructive sleep apnea, VEGF, Male, Follow-up studies, Myocardial Revascularization, Acute Myocardial Infarction, Clinical Sciences, Sleep breathing disorders, Polysomnography, Middle Aged, Percutaneous Coronary Intervention, Myocardial Infarction, Troponin I, and Statistics as Topic
For osteoblastoma, with its predilection for the spinal column and appendicular skeleton, the skull is an unusual site, and paranasal sinus involvement is very rare. Herein, we report on a case in which the disease was located within the... more
For osteoblastoma, with its predilection for the spinal column and appendicular skeleton, the skull is an unusual site, and paranasal sinus involvement is very rare. Herein, we report on a case in which the disease was located within the sphenoid bone. Tto the best of our knowledge, this is the 4th reported case of osteoblastoma with a sphenoid origin (1). We report an osteoblastoma of the sphenoid sinus in a 12-year-old girl who presented with exophthalmos. Ccomputed tomography (CTct) demonstrated an expansile lesion of the sphenoid which caused the orbital contents to be compressed and deviated to the right. In the magnetic resonance imaging scan, the lesion was found to invade the cranial base in the frontal and temporal region, approximating to the cavernous sinus and internal carotid artery on the right. Bilateral fronto-orbital craniotomy was performed. Histologically, the lesion was composed of proliferating osteoblasts along with vascular stroma. tumor was described as an aggressive osteoblastoma. In the follow-up CTct four months later, a pathological mass was observed in the area of the nasal septum, and a signal void was present on all sequences in the densely sclerotic areas. A second resection was performed. Tthe patient has been disease-free for 61 months. Herein, we present the diagnosis and management of this unusual lesion
Research Interests: Oncology, Otolaryngology, Surgery, Cancer, Electron Tomography, and 14 moreTreatment Outcome, Cancer Biology, Positron Emission Tomography, Head and Neck, Humans, Head and Neck Cancer, Male, Spectrum, Adult, Computerized tomography, Tracheostomy, X ray Computed Tomography, Antineoplastic Agents, and Surgical Treatment
Research Interests: Dentistry, Oncology, Otolaryngology, Pediatrics, Radiology, and 18 moreSurgery, Cellular Biology, Cancer, Magnetic Resonance Imaging, Pediatric Oncology, Immunohistochemistry, Adolescent, Laryngology, Head and Neck, Humans, Male, Young Adult, Clinical Sciences, Aged, Middle Aged, Adult, Radiopharmaceuticals, and Angiofibroma
Research Interests:
Endometrial carcinoma is the most frequently diagnosed cancer among gynecological malignancies in highly developed countries. Since 20 years research has been conducted to define the molecular pathology of this disease and much is already... more
Endometrial carcinoma is the most frequently diagnosed cancer among gynecological malignancies in highly developed countries. Since 20 years research has been conducted to define the molecular pathology of this disease and much is already known, but adequate prognostic, diagnostic and monitoring markers are still missing. Recently a new perspective has been opened by mitochondrial research. The role of abnormalities of those organelles and mutations of the mitochondrial genome has been defined in some types of cancer and is still under investigation. MtDNA mutations are also found in endometrial adenocarcinoma, although their impact on cell physiology has not been described so far. Some processes involving mitochondria are widely known and described by numerous papers. This includes electron transport and apoptosis, but other await further research. In a wide spectrum of projects a forward genetics approach has been used, as cancer tissue samples were collected from subjects with defined diagnosis and metabolic abnormalities and mtDNA mutations were checked. Thanks to this approach characteristic patterns of mitochondrial disruptions have been assigned to specific types of cancer. This review focuses on molecular characteristics of endometrial adenocarcinoma with special focus on mitochondrial abnormalities. Research on cancer molecular pathology in endometrial adenocarcinoma may lead to the development of specific screening and/or diagnostic markers.