Distribution of involucrin in normal and pathological human uterine cervix

Serra, Vicente; Ramírez, Ana; Lara, C.; Marzo, Carmen; Castells, A; Bonilla‐Musoles, Fernando

doi:10.1016/0020-7292(90)90693-f

Cited by 5 publications

(4 citation statements)

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“…In this paper, we demonstrate that ΔNp63α is the most abundantly expressed isoform in cervical tissues but it is expressed only at reduced or undetectable levels in moderately or poorly di erentiated cervical squamous cancer tissues and some cervical cancer cell lines. Involucrin is an epithelial cell di erentiation marker [9][10][11] and the expression levels of involucrin and ΔNp63α were found to be positively correlated in cervical cancer tissues, suggesting that ΔNp63α might be also involved in regulation of epithelial carcinoma cell di erentiation.…”

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confidence: 99%

Reduced expression of ΔΝp63α in cervical squamous cell carcinoma

Ying¹,

Xu²,

Ling³

et al. 2011

CIM

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Reduced expression of ΔΝp63α in cervical squamous cell carcinoma Abstract Purpose: As a member of the p53 family, p63 is considered to be an important di erentiation regulation transcriptional factor, but the roles of p63 in many epithelial tumourigenesis and metastasis processes are still not clear. is study was designed to investigate the expression of p63 and its isoform in normal tissues and squamous cell cancer tissues of uterine cervix, and its signi cance in cancer cell di erentiation.Methods: e expression of p63 was assessed in cervical tissue and cell lines by immunohistochemistry, RT-PCR and Western Blotting. e relationships between p63 protein, various clinico-pathological features, and the di erentiation marker involucrin were analyzed.Results: ΔΝp63α is the predominant isoform expressed in cervical epithelial tissues, and it is decreased in moderately or poorly di erentiated cervical squamous carcinoma, as well as in the HeLa, SiHa and C33A cervical cancer cell lines. e expression level of ΔΝp63α was positively correlated with that of involucrin in cervical squamous cancer tissue, and the expression of ΔΝp63α is decreased with the degree of tumour invasion.Conclusion: e decrease of ΔΝp63α in cervical squamous cell cancer appears to be associated with the tumour progression, and ΔΝp63α may be a sensitive marker for cervical squamous cancer di erentiation.

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confidence: 99%

Reduced expression of ΔΝp63α in cervical squamous cell carcinoma

Ying¹,

Xu²,

Ling³

et al. 2011

CIM

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“…Conversely, involucrin, as measured by immunoperoxidase staining by two groups of investigators, is present in nearly all normal epithelium and HPV lesions but disappears as the lesions progress to CIN and invasive carcinoma 115–117. Statistically significant decreases in involucrin were noted as the cervical lesions progressed to invasion in a preliminary study of 23 cone biopsy specimens that ranged from CIN‐1 to carcinoma 97.…”

Section: Differentiation Markersmentioning

confidence: 99%

Surrogate endpoint biomarkers and their modulation in cervical chemoprevention trials

Follen

Schottenfeld

2001

Cancer

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BACKGROUND. Surrogate endpoint biomarkers (SEBs) are used as intermediate indicators of a reduction in cancer incidence in chemoprevention studies. SEBs should be expressed differentially in normal and high risk tissue; appear at a well defined stage of carcinogenesis; be studied with reasonable sensitivity, specificity, and accuracy; and be modulated in chemoprevention trials. The concept of SEBs may be useful in the trials of many new therapies. METHODS.The current review includes a comprehensive review of the literature.Many SEBs have been the subject of intense study and include quantitative histopathology and cytology, proliferation markers, regulation markers, differentiation markers, general genomic instability markers, and tissue maintenance markers. Because of the critical biologic and epidemiologic role of the human papillomavirus (HPV) in cervical carcinogenesis, the relation between these markers and HPV should be considered. In addition, biomarkers of HPV infection and its regression should be sought. RESULTS. Several chemoprevention trials have beenpublished that have included the use of SEBs. The biomarkers that appear most promising in these clinical trials can be measured quantitatively and reproducibly: quantitative histology and cytology, proliferating cell nuclear antigen (PCNA), MIB-1, MPM-2, HPV viral load, epidermal growth factor receptor, polyamines, and ploidy. The markers that have been demonstrated to be modulated in chemoprevention trials in the literature are quantitative histology and cytology, PCNA, MPM-2, HPV viral load, and polyamines. CONCLUSIONS.The surrogate endpoint biomarkers of most interest in future research should correlate well with HPV infection, be modulated by several therapeutic agents, and have limited variability and ease in measurement. Cancer 2001;

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“…183.184 Differential expression of keratins and involucrin has been demonstrated in cervical cancer cell lines.lB5 Filaggrin, a differentiation-dependent cytoplasmic protein, is altered in cells with HPV, and its expression decreases as lesions progress to invasive cancer.I4' cer. [180][181][182] contribute to the ligand-binding site, whereas the cytoplasmic domains interact either directly or through linker molecules with the actin cytoskeleton. Three major integrins have been described in epithelial cells: a2b1, a3b1, and a6b4.…”

Section: Fibrillar Proteinsmentioning

confidence: 99%

Chemoprevention trials and surrogate end point biomarkers in the cervix

Mitchell

Hittelman

Lotan

et al. 1995

Cancer

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Cervical cancer is the second most common malignancy in women worldwide and remains a significant health problem for women, especially minority and underserved women. Despite an understanding of the epidemiologic risks, the screening Papanicolaou smear, and morbid and costly treatment, overall survival remains 40%. New strategies, based on the clinical and molecular aspects of cervical carcinogenesis, are desperately needed. Chemoprevention refers to the use of chemical agents to prevent or delay the development of cancer in healthy populations. Chemoprevention studies have several unique features that distinguish them from classic chemotherapeutic trials; these features touch on several disciplines and weave knowledge of the biology of carcinogenesis into the trial design. In the design of chemoprevention trials, four factors are important: high risk cohorts must be identified; suitable medications must be selected; study designs should include Phases I, II, and III; and studies should include the use of surrogate end point biomarkers. Surrogate end point biomarkers are sought because the cancer develops over a long period of time, and studies of chemopreventives would require a huge number of subjects followed for many years. Surrogate end point biomarkers serve as alternative end points for examination of the efficacy of chemopreventives in tissue. High risk cohorts include women with cervical intraepithelial neoplasia (GIN) or squamous intraepithelial lesions (SIL). Nutritional studies have helped define micronutrients of interest (folate, carotenoids, vitamin C, vitamin E). Other medications of interest include retinoids (4‐hydroxyphenylretinamide [4‐HPR], retinyl acetate gel, topical alltrans‐retinoic acid), polyamine synthesis inhibitors (alphadifluoromethylornithine [DFMO]), and nonsteroidal anti‐inflammatory drugs (ibuprofen). Phase I chemoprevention studies of the cervix have tested retinyl acetate gel and alltrans‐retinoic acid. Phase II trials of all‐trans‐retinoic acid, beta‐carotene, and folic acid have been and are being carried out, whereas Phase III trials of all‐trans‐retinoic acid have been completed and have shown significant regression of CIN 2 but not CIN 3. Phase I studies of DFMO and Phase II studies of DFMO and 4‐HPR are underway. Surrogate end point biomarkers under study include (1) quantitative cytology and histopathology; (2) human papillomavirus type testing; (3) biologic measures of proliferation, regulation, differentiation, and genomic instability; and 4) fluorescence spectroscopic emission. Clinical trials with biologic end points will contribute to our understanding of the neoplastic process and hence aid us in developing new preventive and therapeutic strategies. Cancer 1995; 76:1956–77.

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Distribution of involucrin in normal and pathological human uterine cervix

Cited by 5 publications

References 0 publications

Reduced expression of ΔΝp63α in cervical squamous cell carcinoma

Reduced expression of ΔΝp63α in cervical squamous cell carcinoma

Surrogate endpoint biomarkers and their modulation in cervical chemoprevention trials

Chemoprevention trials and surrogate end point biomarkers in the cervix

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