George Sourvinos - Academia.edu (original) (raw)
Papers by George Sourvinos
The International journal of biological markers
British journal of biomedical science
Cardiovascular Research
Objective: Microsatellite instability (MIN) is an early event in DNA repair-deficient associated ... more Objective: Microsatellite instability (MIN) is an early event in DNA repair-deficient associated diseases and reflects an elevated mutation rate in the genome of neoplastic cells. Sporadic cardiac myxomas are the most common primary heart tumours and their aetiopathology remains obscure. This study investigates the incidence of MIN in sporadic cardiac myxomas as a possible genetic mechanism of tumour pathogenesis. Methods: Eleven surgically excised sporadic cardiac myxomas were assessed for MI using twenty-two highly polymorphic microsatellite markers, located on a wide range of chromosomal arms. DNA was extracted from myxoma tissue specimens as well as the respective normal tissue and subjected to polymerase chain reaction. Results: The microsatellite analysis revealed that seven myxoma specimens (64%) exhibited MIN in at least one marker. One tumour specimen exhibited evidence of MIN in four microsatellite markers, while the most frequently affected marker was D17S855 (27%), located on chromosome 17q. Discussion: We have detected a considerable incidence of MIN in sporadic cardiac myxomas indicating that decreased fidelity in DNA replication and repair is common in these tumours. To the best of our knowledge this is the first report describing MIN in sporadic cardiac myxomas, as a possible pathogenetic mechanism of these rare neoplasms.
European Respiratory Review, 2015
The prevalence of obstructive sleep apnoea (OSA) is continuously increasing in patients with idio... more The prevalence of obstructive sleep apnoea (OSA) is continuously increasing in patients with idiopathic pulmonary fibrosis (IPF) and, for the first time, the recent IPF guidelines recognise OSA as an important associated comorbidity that can affect patient's survival. Thus, it becomes conceivable that clinicians should refer patients with newly diagnosed IPF to sleep centres for the diagnosis and treatment of OSA as well as for addressing issues regarding the reduced compliance of patients with continuous positive airway pressure therapy. The discovery of biomarkers common to both disorders may help early diagnosis, institution of the most appropriate treatment and follow-up of patients. Better understanding of epigenetic changes may provide useful information about pathogenesis and, possibly, development of new drugs for a dismal disease like IPF.
The Pediatric infectious disease journal, 2015
Cellular signalling, 2015
The interaction between CD40 and its ligand, CD40L/CD154, is crucial for the efficient initiation... more The interaction between CD40 and its ligand, CD40L/CD154, is crucial for the efficient initiation and regulation of immune responses against viruses. Herpes Simplex Virus type-1 (HSV-1) is a neurotropic virus capable of manipulating host responses and exploiting host proteins to establish productive infection. Herein we have examined the impact of CD40L-mediated CD40 activation on HSV-1 replication in U2OS cells stably expressing the CD40 receptor. Treatment of these cells with CD40L significantly reduced the HSV-1 progeny virus compared to non-treated cells. The activation of CD40 signaling did not affect the binding of HSV-1 virions on the cell surface but rather delayed the translocation of VP16 to the nucleus, affecting all stages of viral life cycle. Using pharmacological inhibitors and RNAi we show that inhibition of PI3 kinase but not autophagy reverses the effects of CD40L on HSV-1 replication. Collectively, these data demonstrate that CD40 activation exerts a direct inhibit...
Journal of B.U.ON. : official journal of the Balkan Union of Oncology
Direct comparisons between different vaccination programmes can reveal new targets and solve chal... more Direct comparisons between different vaccination programmes can reveal new targets and solve challenges that have been faced and managed in the past during similar health interventions. In the rubella vaccination programme both boys and girls were included in order to ensure that women of childbearing age are effectively protected. For human papillomavirus (HPV) vaccination, at the moment only girls have been included into the scheme. The aspect of vaccinating both boys and girls against HPV, similarly to the rubella paradigm, would interrupt "high-risk" HPVs transmission from males to females and vice versa ensuring further elimination of HPV. The new generation of HPV vaccines is expected to cost less and this will contribute to the possible introduction of HPV vaccine in both males and females.
British journal of biomedical science, 2010
Journal of B.U.ON. : official journal of the Balkan Union of Oncology
Retroviruses have been found in many bird and animal species where they often cause various types... more Retroviruses have been found in many bird and animal species where they often cause various types of cancer. Dr. Robert Gallo's contribution to the field of retrovirology and the link he established between RNA viruses and cancer has been significant. Historical aspects of his discoveries in the area of human retroviruses are presented and an attempt is made to focus attention on his outstanding role.
The International journal of biological markers
Human papillomavirus (HPV) testing can identify women at risk of cervical cancer. Currently, mole... more Human papillomavirus (HPV) testing can identify women at risk of cervical cancer. Currently, molecular detection methods are the gold standard for identification of HPV. The three categories of molecular assays that are available are based on the detection of HPV DNA and include (1) non-amplified hybridization assays, such as Southern transfer hybridization (STH), dot blot hybridization (DB) and in situ hybridization (ISH); (2) signal amplified hybridization assays, such as hybrid capture assays (HC2); (3) target amplification assays, such as polymerase chain reaction (PCR) and in situ PCR. STH requires large amounts of DNA, is laborious and not reproducible, while ISH has only moderate sensitivity for HPV. The sensitivity of the HC2 assay is similar to that of PCR-based assays, with high sensitivity being achieved by signal rather than target amplification. PCR-based detection is both highly sensitive and specific. Since PCR can be performed on very small amounts of DNA, it is idea...
Journal of virology, 2007
The human cytomegalovirus (HCMV) immediate-early 2 (IE2) transactivator has previously been shown... more The human cytomegalovirus (HCMV) immediate-early 2 (IE2) transactivator has previously been shown to form intranuclear, dot-like accumulations in association with subnuclear structures known as promyelocytic leukemia protein (PML) nuclear bodies or ND10. We recently observed that IE2 can form dot-like structures even after infection of PML knockdown cells, which lack genuine ND10. To further analyze the determinants of IE2 subnuclear localization, a recombinant HCMV expressing IE2 fused to the enhanced green fluorescent protein was constructed. We infected primary human fibroblasts expressing Sp100 fused to the autofluorescent protein mCherry while performing live-cell imaging experiments. These experiments revealed a very dynamic association of IE2 dots with ND10 structures during the first hours postinfection: juxtaposed structures rapidly fused to precise co-localizations, followed by segregation, and finally, the dispersal of ND10 accumulations. Furthermore, by infecting PML kno...
The European respiratory journal. Supplement, 2001
Understanding of the cellular and cytokine interactions associated with inflammation and fibrosis... more Understanding of the cellular and cytokine interactions associated with inflammation and fibrosis in interstitial lung diseases (ILDs) has increased substantially during the past few years. Presently, many agents are known to have the ability to induce ILDs, although only a small percentage of exposed individuals will develop the disease. In addition, the majority of ILDs are of unknown origin and many are labelled "idiopathic". Therefore, host susceptibility, genetic factors and, possibly, environmental cofactors may be important for the clinical expression of ILDs. The present review reports evidence of the genetic predisposition to develop ILDs of unknown origin, more specifically sarcoidosis, idiopathic pulmonary fibrosis (IPF), lymphangioleio-myomatosis and ILDs, in systemic sclerosis. For instance, for sarcoidosis and IPF several histocompatibility antigens have been associated with the development and/or the clinical presentation of the disease. Furthermore, there a...
Folia biologica, 2000
Retroviruses are implicated in a series of human and animal tumours such as leukaemias, mammary t... more Retroviruses are implicated in a series of human and animal tumours such as leukaemias, mammary tumours or skin cancer. The mechanism that they use to induce tumour formation varies. Insertional mutagenesis is a common mechanism in rodent, feline and avian retroviruses, where the retrovirus integrates into the host genome and affects the transcription of the neighbouring genes. Cloning of these affected genes led to identification of a series of oncogenes that play a significant role in the induction of human neoplasms. Retrovirus insertion also serves as a model to identify collaborating oncogenes. Human retroviruses use different, more complex mechanisms contributing to oncogenesis. Studies of the propagation and induction mechanisms used by retroviruses have given insight to the understanding of oncogenesis.
Gene expression, 2000
The level of RNA polymerase (pol) III transcription is tightly linked to the rate of growth; it i... more The level of RNA polymerase (pol) III transcription is tightly linked to the rate of growth; it is low in resting cells and increases following mitogenic stimulation. When mammalian cells begin to proliferate, maximal pol III activity is reached shortly before the G1/S transition; it then remains high throughout S and G2 phases. Recent data suggest that the retinoblastoma protein RB and its relatives p107 and p130 may be largely responsible for this pattern of expression. During G0 and early G1 phase, RB and p130 bind and repress the pol III-specific factor TFIIIB; shortly before S phase they dissociate from TFIIIB, allowing transcription to increase. At the end of interphase, when cells enter mitosis, pol III transcription is again suppressed; this mitotic repression is achieved through direct phosphorylation of TFIIIB. Thus, pol III transcription levels fluctuate as mammalian cells cycle, being high in S and G2 phases and low during mitosis and early G1. In addition to this cyclic...
Archives of Virology, 2015
Merkel cell polyomavirus (MCPyV) is a newly discovered human small, non-enveloped, double-strande... more Merkel cell polyomavirus (MCPyV) is a newly discovered human small, non-enveloped, double-stranded DNA virus, which was classified into the Polyomaviridae family. MCPyV is acquired in early childhood through close contact involving respiratory tract secretions and causes a widespread, previously unrecognised, asymptomatic infection in both immunocompetent children and adults. To date, several researchers have established that MCPyV is the potential causative agent of Merkel cell carcinoma, a relatively rare but life-threatening skin cancer of neuroendocrine origin. In our review, we present current data on the presence of MCPyV DNA in children and address the possible role that the respiratory tract plays in the route of viral transmission. Future studies are required to fully elucidate the potential implications of MCPyV infection in children.
Archives of Disease in Childhood, 2012
Pathology & Oncology Research, 2008
Viral-induced carcinogenesis has been attributed to the ability of viral oncoproteins to target a... more Viral-induced carcinogenesis has been attributed to the ability of viral oncoproteins to target and interact with the host cellular proteins. It is generally accepted that Human papilloma virus (HPV) E6 and E7 function as the dominant oncoproteins of 'high-risk' HPVs by altering the function of critical cellular proteins. Initially it was shown that HPV E6 enhances the degradation of p53, while HPV E7 inactivates the function of the retinoblastoma tumor suppressor protein Rb. However, recent studies during the last decade have identified a number of additional host cellular targets of both HPV E6 and E7 that may also play an important role in malignant cellular transformation. In this review we present the interactions of HPV E6 and E7 with the host cellular target proteins. We also present the role of DNA integration in the malignant transformation of the epithelial cell.
International Journal of Oncology, 2002
Oncology Letters, 2014
Human papillomavirus (HPV) is composed of a particularly heterogeneous family of DNA viruses, whi... more Human papillomavirus (HPV) is composed of a particularly heterogeneous family of DNA viruses, which has gained much attention in recent years due to the discoveries of Professor Harald zur Hausen, who first identified a connection between HPV and cervical cancer. Professor Harald zur Hausen, the 'Father of HPV Virology', was the recipient of the 2008 Nobel Prize. HPV can be transmitted through physical contact via autoinoculation or fomites, sexual contact, as well as vertically from the HPV-positive mother to her newborn, causing subclinical or clinical infections. In infancy and childhood, HPV-associated clinical infections include skin warts, genital warts and juvenile recurrent respiratory papillomatosis, while cervical squamous intraepithelial lesions have also been reported among adolescent girls. To date, several research teams, worldwide, have extensively investigated HPV from the paediatric point of view. This primitive effort has been performed before the recent great expansion of paediatric HPV research due to the vaccination programmes against HPV, which were introduced into clinical practice in 2006. In this review article, we present a brief overview of paediatric HPV research after the first report in 1978 involving children in the research of HPV until the time point of this great expansion. In the future, it is expected that further unresolved issues will be addressed and clarified, as the paediatric story of HPV remains a challenging research target.
International Journal of Oncology, 2007
Although it is well established that ras genes contribute to tumourigenesis either through the ac... more Although it is well established that ras genes contribute to tumourigenesis either through the accumulation of mutations or by aberrant expression in a wide range of human cancers, little is known regarding their involvement in human nasal polyps (NPs). In the present study, the occurrence of mutations in codons 11 and 12 of the ras family genes was examined by PCR/RFLP and direct sequencing in 23 human NPs and their adjacent turbinates, as well as in turbinates from 13 control subjects. Moreover, the expression pattern of ras mRNA levels was assessed in NP specimens and compared to adjacent and control tissues. K-ras codon 11 and 12 mutations were detected in 17 and 35% of NPs, respectively, and were found in the adjacent inferior turbinate (AIT) (22 and 16%, respectively) and adjacent middle turbinates (AMT) (16 and 26%, respectively). K-and H-ras expression levels were elevated, whereas N-ras mRNA levels were lower in NPs and adjacent turbinates as compared to the control tissues. K-ras mRNA levels were up-regulated in advanced-stage polyps (P=0.037), while N-ras levels were found elevated in small polyps (P=0.046). Statistically significant negative correlations between K-and N-ras expression profiles arose in NPs and AITs (P=0.009 and 0.003, respectively). This, to our knowledge, is the first report on ras mutations and expression analysis in NPs. Our findings suggest a potential key role for activated members of ras family genes in terms of their contribution to the development of NPs as well as to the hypertrophy of adjacent turbinates.
The International journal of biological markers
British journal of biomedical science
Cardiovascular Research
Objective: Microsatellite instability (MIN) is an early event in DNA repair-deficient associated ... more Objective: Microsatellite instability (MIN) is an early event in DNA repair-deficient associated diseases and reflects an elevated mutation rate in the genome of neoplastic cells. Sporadic cardiac myxomas are the most common primary heart tumours and their aetiopathology remains obscure. This study investigates the incidence of MIN in sporadic cardiac myxomas as a possible genetic mechanism of tumour pathogenesis. Methods: Eleven surgically excised sporadic cardiac myxomas were assessed for MI using twenty-two highly polymorphic microsatellite markers, located on a wide range of chromosomal arms. DNA was extracted from myxoma tissue specimens as well as the respective normal tissue and subjected to polymerase chain reaction. Results: The microsatellite analysis revealed that seven myxoma specimens (64%) exhibited MIN in at least one marker. One tumour specimen exhibited evidence of MIN in four microsatellite markers, while the most frequently affected marker was D17S855 (27%), located on chromosome 17q. Discussion: We have detected a considerable incidence of MIN in sporadic cardiac myxomas indicating that decreased fidelity in DNA replication and repair is common in these tumours. To the best of our knowledge this is the first report describing MIN in sporadic cardiac myxomas, as a possible pathogenetic mechanism of these rare neoplasms.
European Respiratory Review, 2015
The prevalence of obstructive sleep apnoea (OSA) is continuously increasing in patients with idio... more The prevalence of obstructive sleep apnoea (OSA) is continuously increasing in patients with idiopathic pulmonary fibrosis (IPF) and, for the first time, the recent IPF guidelines recognise OSA as an important associated comorbidity that can affect patient's survival. Thus, it becomes conceivable that clinicians should refer patients with newly diagnosed IPF to sleep centres for the diagnosis and treatment of OSA as well as for addressing issues regarding the reduced compliance of patients with continuous positive airway pressure therapy. The discovery of biomarkers common to both disorders may help early diagnosis, institution of the most appropriate treatment and follow-up of patients. Better understanding of epigenetic changes may provide useful information about pathogenesis and, possibly, development of new drugs for a dismal disease like IPF.
The Pediatric infectious disease journal, 2015
Cellular signalling, 2015
The interaction between CD40 and its ligand, CD40L/CD154, is crucial for the efficient initiation... more The interaction between CD40 and its ligand, CD40L/CD154, is crucial for the efficient initiation and regulation of immune responses against viruses. Herpes Simplex Virus type-1 (HSV-1) is a neurotropic virus capable of manipulating host responses and exploiting host proteins to establish productive infection. Herein we have examined the impact of CD40L-mediated CD40 activation on HSV-1 replication in U2OS cells stably expressing the CD40 receptor. Treatment of these cells with CD40L significantly reduced the HSV-1 progeny virus compared to non-treated cells. The activation of CD40 signaling did not affect the binding of HSV-1 virions on the cell surface but rather delayed the translocation of VP16 to the nucleus, affecting all stages of viral life cycle. Using pharmacological inhibitors and RNAi we show that inhibition of PI3 kinase but not autophagy reverses the effects of CD40L on HSV-1 replication. Collectively, these data demonstrate that CD40 activation exerts a direct inhibit...
Journal of B.U.ON. : official journal of the Balkan Union of Oncology
Direct comparisons between different vaccination programmes can reveal new targets and solve chal... more Direct comparisons between different vaccination programmes can reveal new targets and solve challenges that have been faced and managed in the past during similar health interventions. In the rubella vaccination programme both boys and girls were included in order to ensure that women of childbearing age are effectively protected. For human papillomavirus (HPV) vaccination, at the moment only girls have been included into the scheme. The aspect of vaccinating both boys and girls against HPV, similarly to the rubella paradigm, would interrupt "high-risk" HPVs transmission from males to females and vice versa ensuring further elimination of HPV. The new generation of HPV vaccines is expected to cost less and this will contribute to the possible introduction of HPV vaccine in both males and females.
British journal of biomedical science, 2010
Journal of B.U.ON. : official journal of the Balkan Union of Oncology
Retroviruses have been found in many bird and animal species where they often cause various types... more Retroviruses have been found in many bird and animal species where they often cause various types of cancer. Dr. Robert Gallo's contribution to the field of retrovirology and the link he established between RNA viruses and cancer has been significant. Historical aspects of his discoveries in the area of human retroviruses are presented and an attempt is made to focus attention on his outstanding role.
The International journal of biological markers
Human papillomavirus (HPV) testing can identify women at risk of cervical cancer. Currently, mole... more Human papillomavirus (HPV) testing can identify women at risk of cervical cancer. Currently, molecular detection methods are the gold standard for identification of HPV. The three categories of molecular assays that are available are based on the detection of HPV DNA and include (1) non-amplified hybridization assays, such as Southern transfer hybridization (STH), dot blot hybridization (DB) and in situ hybridization (ISH); (2) signal amplified hybridization assays, such as hybrid capture assays (HC2); (3) target amplification assays, such as polymerase chain reaction (PCR) and in situ PCR. STH requires large amounts of DNA, is laborious and not reproducible, while ISH has only moderate sensitivity for HPV. The sensitivity of the HC2 assay is similar to that of PCR-based assays, with high sensitivity being achieved by signal rather than target amplification. PCR-based detection is both highly sensitive and specific. Since PCR can be performed on very small amounts of DNA, it is idea...
Journal of virology, 2007
The human cytomegalovirus (HCMV) immediate-early 2 (IE2) transactivator has previously been shown... more The human cytomegalovirus (HCMV) immediate-early 2 (IE2) transactivator has previously been shown to form intranuclear, dot-like accumulations in association with subnuclear structures known as promyelocytic leukemia protein (PML) nuclear bodies or ND10. We recently observed that IE2 can form dot-like structures even after infection of PML knockdown cells, which lack genuine ND10. To further analyze the determinants of IE2 subnuclear localization, a recombinant HCMV expressing IE2 fused to the enhanced green fluorescent protein was constructed. We infected primary human fibroblasts expressing Sp100 fused to the autofluorescent protein mCherry while performing live-cell imaging experiments. These experiments revealed a very dynamic association of IE2 dots with ND10 structures during the first hours postinfection: juxtaposed structures rapidly fused to precise co-localizations, followed by segregation, and finally, the dispersal of ND10 accumulations. Furthermore, by infecting PML kno...
The European respiratory journal. Supplement, 2001
Understanding of the cellular and cytokine interactions associated with inflammation and fibrosis... more Understanding of the cellular and cytokine interactions associated with inflammation and fibrosis in interstitial lung diseases (ILDs) has increased substantially during the past few years. Presently, many agents are known to have the ability to induce ILDs, although only a small percentage of exposed individuals will develop the disease. In addition, the majority of ILDs are of unknown origin and many are labelled "idiopathic". Therefore, host susceptibility, genetic factors and, possibly, environmental cofactors may be important for the clinical expression of ILDs. The present review reports evidence of the genetic predisposition to develop ILDs of unknown origin, more specifically sarcoidosis, idiopathic pulmonary fibrosis (IPF), lymphangioleio-myomatosis and ILDs, in systemic sclerosis. For instance, for sarcoidosis and IPF several histocompatibility antigens have been associated with the development and/or the clinical presentation of the disease. Furthermore, there a...
Folia biologica, 2000
Retroviruses are implicated in a series of human and animal tumours such as leukaemias, mammary t... more Retroviruses are implicated in a series of human and animal tumours such as leukaemias, mammary tumours or skin cancer. The mechanism that they use to induce tumour formation varies. Insertional mutagenesis is a common mechanism in rodent, feline and avian retroviruses, where the retrovirus integrates into the host genome and affects the transcription of the neighbouring genes. Cloning of these affected genes led to identification of a series of oncogenes that play a significant role in the induction of human neoplasms. Retrovirus insertion also serves as a model to identify collaborating oncogenes. Human retroviruses use different, more complex mechanisms contributing to oncogenesis. Studies of the propagation and induction mechanisms used by retroviruses have given insight to the understanding of oncogenesis.
Gene expression, 2000
The level of RNA polymerase (pol) III transcription is tightly linked to the rate of growth; it i... more The level of RNA polymerase (pol) III transcription is tightly linked to the rate of growth; it is low in resting cells and increases following mitogenic stimulation. When mammalian cells begin to proliferate, maximal pol III activity is reached shortly before the G1/S transition; it then remains high throughout S and G2 phases. Recent data suggest that the retinoblastoma protein RB and its relatives p107 and p130 may be largely responsible for this pattern of expression. During G0 and early G1 phase, RB and p130 bind and repress the pol III-specific factor TFIIIB; shortly before S phase they dissociate from TFIIIB, allowing transcription to increase. At the end of interphase, when cells enter mitosis, pol III transcription is again suppressed; this mitotic repression is achieved through direct phosphorylation of TFIIIB. Thus, pol III transcription levels fluctuate as mammalian cells cycle, being high in S and G2 phases and low during mitosis and early G1. In addition to this cyclic...
Archives of Virology, 2015
Merkel cell polyomavirus (MCPyV) is a newly discovered human small, non-enveloped, double-strande... more Merkel cell polyomavirus (MCPyV) is a newly discovered human small, non-enveloped, double-stranded DNA virus, which was classified into the Polyomaviridae family. MCPyV is acquired in early childhood through close contact involving respiratory tract secretions and causes a widespread, previously unrecognised, asymptomatic infection in both immunocompetent children and adults. To date, several researchers have established that MCPyV is the potential causative agent of Merkel cell carcinoma, a relatively rare but life-threatening skin cancer of neuroendocrine origin. In our review, we present current data on the presence of MCPyV DNA in children and address the possible role that the respiratory tract plays in the route of viral transmission. Future studies are required to fully elucidate the potential implications of MCPyV infection in children.
Archives of Disease in Childhood, 2012
Pathology & Oncology Research, 2008
Viral-induced carcinogenesis has been attributed to the ability of viral oncoproteins to target a... more Viral-induced carcinogenesis has been attributed to the ability of viral oncoproteins to target and interact with the host cellular proteins. It is generally accepted that Human papilloma virus (HPV) E6 and E7 function as the dominant oncoproteins of 'high-risk' HPVs by altering the function of critical cellular proteins. Initially it was shown that HPV E6 enhances the degradation of p53, while HPV E7 inactivates the function of the retinoblastoma tumor suppressor protein Rb. However, recent studies during the last decade have identified a number of additional host cellular targets of both HPV E6 and E7 that may also play an important role in malignant cellular transformation. In this review we present the interactions of HPV E6 and E7 with the host cellular target proteins. We also present the role of DNA integration in the malignant transformation of the epithelial cell.
International Journal of Oncology, 2002
Oncology Letters, 2014
Human papillomavirus (HPV) is composed of a particularly heterogeneous family of DNA viruses, whi... more Human papillomavirus (HPV) is composed of a particularly heterogeneous family of DNA viruses, which has gained much attention in recent years due to the discoveries of Professor Harald zur Hausen, who first identified a connection between HPV and cervical cancer. Professor Harald zur Hausen, the 'Father of HPV Virology', was the recipient of the 2008 Nobel Prize. HPV can be transmitted through physical contact via autoinoculation or fomites, sexual contact, as well as vertically from the HPV-positive mother to her newborn, causing subclinical or clinical infections. In infancy and childhood, HPV-associated clinical infections include skin warts, genital warts and juvenile recurrent respiratory papillomatosis, while cervical squamous intraepithelial lesions have also been reported among adolescent girls. To date, several research teams, worldwide, have extensively investigated HPV from the paediatric point of view. This primitive effort has been performed before the recent great expansion of paediatric HPV research due to the vaccination programmes against HPV, which were introduced into clinical practice in 2006. In this review article, we present a brief overview of paediatric HPV research after the first report in 1978 involving children in the research of HPV until the time point of this great expansion. In the future, it is expected that further unresolved issues will be addressed and clarified, as the paediatric story of HPV remains a challenging research target.
International Journal of Oncology, 2007
Although it is well established that ras genes contribute to tumourigenesis either through the ac... more Although it is well established that ras genes contribute to tumourigenesis either through the accumulation of mutations or by aberrant expression in a wide range of human cancers, little is known regarding their involvement in human nasal polyps (NPs). In the present study, the occurrence of mutations in codons 11 and 12 of the ras family genes was examined by PCR/RFLP and direct sequencing in 23 human NPs and their adjacent turbinates, as well as in turbinates from 13 control subjects. Moreover, the expression pattern of ras mRNA levels was assessed in NP specimens and compared to adjacent and control tissues. K-ras codon 11 and 12 mutations were detected in 17 and 35% of NPs, respectively, and were found in the adjacent inferior turbinate (AIT) (22 and 16%, respectively) and adjacent middle turbinates (AMT) (16 and 26%, respectively). K-and H-ras expression levels were elevated, whereas N-ras mRNA levels were lower in NPs and adjacent turbinates as compared to the control tissues. K-ras mRNA levels were up-regulated in advanced-stage polyps (P=0.037), while N-ras levels were found elevated in small polyps (P=0.046). Statistically significant negative correlations between K-and N-ras expression profiles arose in NPs and AITs (P=0.009 and 0.003, respectively). This, to our knowledge, is the first report on ras mutations and expression analysis in NPs. Our findings suggest a potential key role for activated members of ras family genes in terms of their contribution to the development of NPs as well as to the hypertrophy of adjacent turbinates.