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Casali C, Siciliani S, Zannino L, Biggiogera M. Histochemistry for nucleic acid research: 60 years in the European Journal of Histochemistry. Eur J Histochem 2022; 66:3409. [PMID: 35441834 PMCID: PMC9044459 DOI: 10.4081/ejh.2022.3409] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 04/07/2022] [Indexed: 11/23/2022] Open
Abstract
Since the discovery of DNA structure in 1953, the deoxyribonucleic acid has always been playing a central role in biological research. As physical and ordered nucleotides sequence, it stands at the base of genes existence. Furthermore, beside this 2-dimensional sequence, DNA is characterized by a 3D structural and functional organization, which is of interest for the scientific community due to multiple levels of expression regulation, of interaction with other biomolecules, and much more. Analogously, the nucleic acid counterpart of DNA, RNA, represents a central issue in research, because of its fundamental role in gene expression and regulation, and for the DNA-RNA interplay. Because of their importance, DNA and RNA have always been mentioned and studied in several publications, and the European Journal of Histochemistry is no exception. Here, we review and discuss the papers published in the last 60 years of this Journal, focusing on its contribution in deepening the knowledge about this topic and analysing papers that reflect the interest this Journal always granted to the world of DNA and RNA.
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Affiliation(s)
- Claudio Casali
- Laboratory of Cell Biology and Neurobiology, Department of Biology and Biotechnology, University of Pavia.
| | - Stella Siciliani
- Laboratory of Cell Biology and Neurobiology, Department of Biology and Biotechnology, University of Pavia.
| | - Lorena Zannino
- Laboratory of Cell Biology and Neurobiology, Department of Biology and Biotechnology, University of Pavia.
| | - Marco Biggiogera
- Laboratory of Cell Biology and Neurobiology, Department of Biology and Biotechnology, University of Pavia.
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Madan M, Chandra S, Raj V, Madan R. Evaluation of cell proliferation in malignant and potentially malignant oral lesions. J Oral Maxillofac Pathol 2016; 19:297-305. [PMID: 26980956 PMCID: PMC4774281 DOI: 10.4103/0973-029x.174613] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Aims: To evaluate the cell proliferation rate by the expression of proliferating cell nuclear antigen (PCNA) and argyrophilic nucleolar organizing region (AgNOR) counts and to assess its usefulness as a marker for malignant potential in oral epithelial lesions. Materials and Methods: The study group included 30 cases of leukoplakia, 15 nondysplastic (NDL), 15 dysplastic (DL), 15 cases of oral squamous cell carcinoma (OSCC) and 5 cases of normal oral mucosa. Formalin fixed paraffin embedded tissues were subjected to immunohistochemical staining for PCNA and AgNOR technique. The PCNA labeling index (LI) and the AgNOR dots were evaluated for the entire sample. Statistical Analysis Used: ANOVA, Tukey honestly significant difference, Pearson's correlation. Results: In this study, the AgNOR count of OSCC was lower than the DL lesions moreover the AgNOR counts were found to be higher in normal mucosa as compared to the DL and the NDL epithelium. The study results also showed that the mean AgNOR count failed to distinguish between DL and NDL lesions. Overall we observed increased PCNA expression from normal epithelium to NDL to DL lesion. Conclusions: Based on the findings of the present study on oral epithelial precancerous and cancerous lesions we conclude that mean AgNOR count alone cannot be a valuable parameter to distinguish between the normal, NDL, DL epithelium and OSCC but, on the other hand, we found out that PCNA can be a useful biomarker for delineating normal epithelium from DL epithelium and OSCC.
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Affiliation(s)
- Mani Madan
- Department of Oral Pathology and Microbiology, Babu Banarasi Das College of Dental Sciences, Lucknow, Uttar Pradesh, India
| | - Shaleen Chandra
- Department of Oral Pathology and Microbiology, KGMC, Lucknow, Uttar Pradesh, India
| | - Vineet Raj
- Department of Oral Pathology and Microbiology, Chandra Dental College and Hospital, Barabanki, Uttar Pradesh, India
| | - Rohit Madan
- Department of Periodontology, Saraswati Dental College and Hospital, Lucknow, Uttar Pradesh, India
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Arduino PG, Bagan J, El-Naggar AK, Carrozzo M. Urban legends series: oral leukoplakia. Oral Dis 2013; 19:642-59. [PMID: 23379968 DOI: 10.1111/odi.12065] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2012] [Revised: 11/29/2012] [Accepted: 12/18/2012] [Indexed: 02/06/2023]
Abstract
To date, the term oral leukoplakia (OL) should be used to recognize 'predominantly white plaques of questionable risk, having excluded (other) known diseases or disorders that carry no increased risk of cancer'. In this review, we addressed four controversial topics regarding oral leukoplakias (OLs): (i) Do tobacco and alcohol cause OLs?, (ii) What percentage of OLs transform into oral squamous cell carcinoma (OSCC)?, (iii) Can we distinguish between premalignant and innocent OLs?, and (iv) Is proliferative verrucous leukoplakia (PVL) a specific entity or just a form of multifocal leukoplakia? Results of extensive literature search suggest that (i) no definitive evidence for direct causal relationship between smoked tobacco and alcohol as causative factors of OLs, (ii and iii) the vast majority of OLs follow a benign course and do not progress into a cancer, and no widely accepted and/or validated clinical and/or biological factors can predict malignant transformation, and (iv) the distinction between multifocal/multiple leukoplakias and PVL in their early presentation is impossible; the temporal clinical progression and the high rate of recurrences and development of cancer of PVL are the most reliable features for diagnosis.
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Affiliation(s)
- P G Arduino
- Department of Surgical Sciences, Oral Medicine Section, Lingotto Dental School, University of Turin, Italy.
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Chen CY, Chang CY, Liu HJ, Liao MH, Chang CI, Hsu JL, Shih WL. Apoptosis induction in BEFV-infected Vero and MDBK cells through Src-dependent JNK activation regulates caspase-3 and mitochondria pathways. Vet Res 2009; 41:15. [PMID: 19846041 PMCID: PMC2785050 DOI: 10.1051/vetres/2009063] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Our previous report demonstrated that bovine ephemeral fever virus (BEFV)-infected cultured cells could induce caspase-dependent apoptosis. This study aims to further elucidate how BEFV activates the caspase cascade in bovine cells. BEFV replicated and induced apoptosis in Vero and Madin-Darby bovine kidney (MDBK) cells, and a kinetic study showed a higher efficiency of replication and a greater apoptosis induction ability of BEFV in Vero cells. Src and c-Jun N-terminal kinase (JNK) inhibitor, but not extracellular signal-regulated kinase (ERK) or p38 inhibitor, alleviated BEFV-mediated cytopathic effect and apoptosis. In BEFV-infected Vero and MDBK cells, BEFV directly induced Src tyrosine-418 phosphorylation and JNK phosphorylation and kinase activity, which was inhibited specifically by SU6656 and SP600125, respectively. The caspase cascade and its downstream effectors, Poly (ADP-ribose) polymerase (PARP) and DFF45, were also activated simultaneously upon BEFV infection. In addition, cytochrome c, but not Smac/DIABLO, was released gradually from mitochondria after BEFV infection. SU6656 suppressed Src, JNK, and caspase-3 and -9 activation, as well as PARP and DFF45 cleavage; SP600125 reduced JNK and caspase-3 and -9 activation, as well as PARP and DFF45 cleavage. Taken together, these results strongly support the hypothesis that a Src-dependent JNK signaling pathway plays a key role in BEFV-induced apoptosis. The molecular mechanism identified in our study may provide useful information for the treatment of BEFV.
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Affiliation(s)
- Chun-Yen Chen
- Graduate Institute and Department of Life Science, Tzu-Chi University, Hualien, Taiwan, Republic of China
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Brustmann H. Poly(ADP-ribose) polymerase (PARP) and DNA-fragmentation factor (DFF45): Expression and correlation in normal, hyperplastic and neoplastic endometrial tissues. Pathol Res Pract 2007; 203:65-72. [PMID: 17258405 DOI: 10.1016/j.prp.2006.12.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2006] [Revised: 11/25/2006] [Accepted: 12/08/2006] [Indexed: 02/07/2023]
Abstract
This study evaluated the immunohistochemical expression of poly(ADP-ribose) polymerase (PARP) and DNA fragmentation factor 45 (DFF45) in normal endometria (NE, n=13), non-atypical (NAH, n=22) and atypical hyperplasia (AH, n=14), endometrioid carcinoma (EC, n=34), serous carcinoma (SC, n=10), and clear cell carcinoma (CCC, n=2). With regard to quantity and intensity of positively stained cells, immunostaining was scored as negative, low, and strong. Nuclear PARP immunoreactivity was found in all cases. If present, DFF45 immunoreactivity was detected predominantly in the nucleus and to some extent in the cytoplasm. PARP immunoreactivity increased significantly from NE via NAH to AH (P=0.0004), and decreased from AH to endometrial carcinomas (P=0.0054). DFF45 immunoreactivity increased significantly from NE to NAH and to AH (P=0.0009). No significant differences were calculated between AH and endometrial carcinomas (P=0.7495). FIGO stages and tumor grades could not be characterized by PARP and DFF45 immunoexpression (P=1.000 and 0.7383, as well as P=0.3034 and 0.7533, respectively). Pearson correlation revealed significant associations of PARP and DFF45 immunoscores for all diagnostic categories of NE, NAH, AH, EC, and SC/CCC. Immunoexpression of PARP and DFF45 is apparently altered in endometrial carcinomas as compared with non-neoplastic endometrial tissues, indicating impaired mechanisms of apoptosis in the former.
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Affiliation(s)
- Hermann Brustmann
- Department of Pathology, Thermenklinikum, Sr. Maria Restitutagasse 12, A-2340 Moedling, Vienna, Austria.
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Brustmann H. DNA fragmentation factor (DFF45): Expression and prognostic value in serous ovarian cancer. Pathol Res Pract 2006; 202:713-20. [PMID: 16962250 DOI: 10.1016/j.prp.2006.06.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2006] [Accepted: 06/23/2006] [Indexed: 11/27/2022]
Abstract
This study investigated the expression of DNA fragmentation factor (DFF45), MIB-1, and p53 in formalin-fixed, paraffin-embedded archival tissues of 50 ovarian serous carcinomas. In addition, 10 benign serous cystadenomas and 10 serous neoplasms of low malignant potential (LMP) were included in this DFF45 immunostudy. With regard to quantity and intensity of positively stained cells, immunostaining for DFF45 was scored as low or strong. MIB-1 labeling indexes (LIs) were quantitated as the percentage of positively stained nuclei in 1000 nuclei. For p53, at least 10% of tumor cells had to display nuclear staining to consider a case positive. DFF45 staining was noted predominantly in the nucleus. Low DFF45 expression was identified in all serous cystadenomas and in LMPs, as well as in 18 (36%) ovarian serous carcinomas. The latter displayed strong expression in 32 cases (64%). DFF45 immunoreactivity increased with FIGO stage and with grade (P=0.0213 and 0.0084, respectively), as well as with p53 positivity (P=0.04), but not with MIB-1 LIs (P=0.076). A trend towards poor outcome was observed in patients whose tumors displayed high levels of DFF45 immunoexpression (P=0.0187). Apoptotic bodies were consistently DFF45-negative. This study indicates that DFF45 expression is frequently upregulated in ovarian serous carcinomas and may serve as a marker of aggressive behavior with prognostic value.
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Affiliation(s)
- Hermann Brustmann
- Department of Pathology, Thermenklinikum, Sr. Maria Restitutagasse, 12A-2340 Moedling/Vienna, Austria.
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Campisi G, Di Fede O, Giovannelli L, Capra G, Greco I, Calvino F, Maria Florena A, Lo Muzio L. Use of fuzzy neural networks in modeling relationships of HPV infection with apoptotic and proliferation markers in potentially malignant oral lesions. Oral Oncol 2005; 41:994-1004. [PMID: 16129653 DOI: 10.1016/j.oraloncology.2005.05.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2005] [Accepted: 05/27/2005] [Indexed: 10/25/2022]
Abstract
To evaluate in oral leukoplakia the relationship between HPV infection and markers of apoptosis (bcl-2, survivin) and proliferation (PCNA), also conditionally to age, gender, smoking and drinking habits of patients, by means of Fuzzy neural networks (FNN) system 21 cases of oral leukopakia, clinically and histologically diagnosed, were examined for HPV DNA presence, bcl-2, survivin and PCNA expression. HPV DNA was investigated in exfoliated oral mucosa cells by nested PCR (nPCR: MY09-MY11/GP5-GP6), and the HPV genotype determined by direct DNA sequencing. All markers were investigated by means of standardised immunohistochemistry procedure. Data were analysed by chi-square test, crude OR and the 95% CI; in blindness, FNN was applied. HPV DNA was found in 8/21 OL (38.1%); survivin, PCNA, and tobacco smoking were associated in univariate analysis (p = 0.04) with HPV DNA status. HPV-18 was the most frequently detected genotype (6/8), followed by HPV-16 (2/8). FNN revealed that survivin and PCNA, both being expressed in all of OL HPV+ve, were associated with HPV infection. In conclusion, the FNN allowed to hypothesise a model of specific variables associated to HPV infection in OL. The relevance of survivin and PCNA suggest that they may be involved in HPV-mediated deregulation of epithelial maturation and, conversely, that HPV may have a role in the expression level of these two markers. FNN system seems to be an effective tool in the analysis of correlates of OL and HPV infection.
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Affiliation(s)
- Giuseppina Campisi
- Department of Oral Sciences, University of Palermo, 90127 Palermo, Italy
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Abstract
AIM: To investigate the pathological characteristics and carcinogenesis mechanism of benign lymphoadenosis of oral mucosa (BLOM).
METHODS: The expressions of Ki-67, CD34 and apoptosis were evaluated by immunohistochemical SP staining in 64 paraffin-embedded tissue samples. Of them, 9 were from BLOM with dysplasia, 15 from BLOM without dysplasia, 15 from oral squamous cell carcinoma (OSCC), 15 from oral precancerosis, and 10 from normal tissues. Cell proliferation, apoptosis and angiogenesis of tissue samples were also analyzed.
RESULTS: The expression of Ki-67 in BLOM with dysplasia, oral precancerosis and OSCC was significantly higher than in BLOM without dysplasia and normal mucosa. The microvascular density (MVD) in BLOM with and without dysplasia, oral precancerosis, and OSCC was significantly higher than in normal mucosa. Apoptosis in BLOM and oral precancerosis was significantly higher than in OSCC and normal mucosa.
CONCLUSION: Benign lymphoadenosis of oral mucosa has potentialities of cancerization.
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Affiliation(s)
- Shu-Xia Li
- Department of Oral Pathology, School of Stomatology, Peking University, Beijing 100081, China.
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Lo Muzio L, D'Angelo M, Procaccini M, Bambini F, Calvino F, Florena AM, Franco V, Giovannelli L, Ammatuna P, Campisi G. Expression of cell cycle markers and human papillomavirus infection in oral squamous cell carcinoma: use of fuzzy neural networks. Int J Cancer 2005; 115:717-723. [PMID: 15729691 DOI: 10.1002/ijc.20940] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Our aim was to evaluate in oral squamous cell carcinoma (OSCC) the relationship between some cell cycle markers and HPV infection, conditionally to age, gender and certain habits of patients, and to assess the ability of fuzzy neural networks (FNNs) in building up an adequate predictive model based on logic inference rules. Eighteen cases of OSCC were examined by immunohistochemistry for MIB-1, PCNA and survivin expression; presence of HPV DNA was investigated in exfoliated oral mucosa cells by nested PCR (nPCR, MY09-MY11/GP5-GP6), and HPV genotype was determined by direct DNA sequencing. Data were analyzed by traditional statistics (TS) and FNNs. HPV DNA was found in 9/18 OSCCs (50.0 %) without any significant higher risk of HPV infection with respect to the sociodemographic variables considered (p > 0.2), apart from tobacco smoking, reported in 44.4% of OSCC HPV-positive vs. 100% HPV-negative subjects (p = 0.029). Regarding cell cycle markers, TS and FNN revealed that survivin was expressed significantly more in HPV-negative than in HPV-positive OSCC [root mean-square error (RMSE) = 5.89 x 10(-6), % predicted 100.0]; furthermore, smoking played a protective role for survivin expression in HPV-positive cases (OR = 0.019, 95%CI 0.001-0.723, RMSE = 0.20, % of prevision 94.4). FNN, although on a small sample size, allowed us to confirm data by TS and to hypothesize a different cell cycle pattern for HPV-positive vs. HPV-negative OSCC. In the latter cases, the relevance of apoptotic vs. proliferative markers suggested that they may be related to the different supposed outcome of HPV-negative OSCC and that HPV may have a protective role in the expression level of survivin, especially in tobacco smokers.
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Nikitakis NG, Sauk JJ, Papanicolaou SI. The role of apoptosis in oral disease: mechanisms; aberrations in neoplastic, autoimmune, infectious, hematologic, and developmental diseases; and therapeutic opportunities. ACTA ACUST UNITED AC 2004; 97:476-90. [PMID: 15088032 DOI: 10.1016/j.tripleo.2003.12.032] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Apoptosis is a genetically programmed form of cell death, which primarily functions to eliminate senescent or altered cells that are useless or harmful for the multicellular organism. Contrary to necrosis, apoptosis represents a physiologic cellular mechanism, normal function and control of which are critical for the development and homeostasis of multicellular organisms. In contrast, aberrations of the apoptotic mechanisms that cause excessive or deficient programmed cell death have been linked to a wide array of pathologic conditions. This review briefly summarizes the major apoptotic pathways and molecules and presents the most important oral diseases that are related to dysregulation of apoptosis. Knowledge of the association between aberrations in apoptotic mechanisms and human pathology hopefully will be implemented for the design of improved diagnostic and prognostic assays and the development of novel, more efficient, therapeutic strategies.
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Affiliation(s)
- Nikolaos G Nikitakis
- Department of Diagnostic Sciences and Pathology, University of Maryland, Baltimore 21201, USA.
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