Neoadjuvant Percutaneous 4-Hydroxytamoxifen Decreases Breast Tumoral Cell Proliferation: A Prospective Controlled Randomized Study Comparing Three Doses of 4-Hydroxytamoxifen Gel to Oral Tamoxifen

2005 ◽  
Vol 23 (13) ◽  
pp. 2980-2987 ◽  
Author(s):  
Philippe Rouanet ◽  
Gustavo Linares-Cruz ◽  
François Dravet ◽  
Sylvain Poujol ◽  
Sophie Gourgou ◽  
...  
Keyword(s):  
Ductal Carcinoma ◽  
Randomized Study ◽  
Drug Efficacy ◽  
Nuclear Antigen ◽  
Hot Flushes ◽  
Ki 67 ◽  
Proliferation Markers ◽  
Tissue Samples ◽  
Estrogen Receptor Positive ◽  
Malignant Breast

Purpose Two chemoprevention randomized studies using tamoxifen showed drug efficacy; however, adverse effects such as hot flushes, endometrial cancer, and above all, thromboembolism, remain a problem. 4 hydroxytamoxifen (4-OHT) is a very active metabolite of tamoxifen. This randomized study was designed to analyze if 4-OHT gel, administered percutaneously on the breast skin, can inhibit the proliferation of malignant breast cells to the same extent as orally administered tamoxifen. Patients and Methods Fifty-five postmenopausal women with an invasive estrogen receptor–positive breast cancer were randomly assigned to receive (for 2 to 3 weeks) either 4-OHT gel (0.5, 1, or 2 mg/d) or oral tamoxifen (20 mg/d) or no treatment. Response was evaluated using proliferation markers (Ki-67, proliferating cell nuclear antigen) and apoptosis markers in tissue samples obtained by Tru-cut biopsy before treatment, and at surgery after treatment. Results Administration of 4-OHT gel resulted in reductions in tumor tissue proliferation indexes (Ki-67 and PCNA), with approximate equivalence between the1.0 mg/d or 2.0 mg/d 4-OHT dose, and oral tamoxifen, but had no effect on apoptotic markers. Plasma levels of 4-OHT were consistently higher in the oral tamoxifen group than in the gel groups. No dose-related pattern was shown for estrogen or progesterone receptor levels, and topical 4-OHT gel appeared to be generally well tolerated. Hot flushes are as common in the two higher gel doses as with tamoxifen. Conclusion Percutaneous 4-OHT gel has a local impact on tumor proliferation. It could be tested in future propective trials of chemoprevention or ductal carcinoma in situ adjuvant hormonotherapy.

scholarly journals Changes in Cellular Regulatory Factors before and after Decompression of Odontogenic Keratocysts

2020 ◽  
Vol 10 (1) ◽  
pp. 30
Author(s):  
Slmaro Park ◽  
Han-Sung Jung ◽  
Young-Soo Jung ◽  
Woong Nam ◽  
Jung Yul Cha ◽  
...  
Keyword(s):  
Recurrence Rate ◽  
Biological Behavior ◽  
Nuclear Antigen ◽  
Epithelial Cyst ◽  
Ki 67 ◽  
Proliferation Markers ◽  
Odontogenic Keratocysts ◽  
Wide Range ◽  
Before And After ◽  
Cyst Lining

Decompression followed by enucleation, which is one of the treatments used for odontogenic keratocysts (OKCs), is frequently used in OKC lesions of large sizes. This method offers the advantage of minimizing the possibility of sensory impairment without creating a wide-range bone defect; moreover, the recurrence rate can be significantly lower than following simple enucleation. This study aimed to assess the changes in histology and expression of proliferation markers in OKCs before and after decompression treatment. A total of 38 OKC tissue samples from 19 patients who had undergone decompression therapy were examined morphologically and immunohistochemically to observe changes in proliferative activity before and after decompression. The markers used for immunohistochemistry (IHC) staining were Bcl-2, epidermal growth factor receptor (EGFR), Ki-67, P53, PCNA, and SMO. The immunohistochemistry positivity of the 6 markers was scored by using software ImageJ, version 1.49, by quantifying the intensity and internal density of IHC-stained epithelium. The values of Bcl-2, Ki-67, P53, proliferating cell nuclear antigen (PCNA), and SMO in OKCs before and after decompression showed no significant change. No correlation between clinical shrinkage and morphologic changes or expression of proliferation and growth markers could be found. There was no statistical evidence that decompression treatment reduces potentially aggressive behavior of OKC within the epithelial cyst lining itself. This might indicate that decompression does not change the biological behavior of the epithelial cyst lining or the recurrence rate.

Analysis of proliferation markers and p53 expression in gliomas of astrocytic origin: relationships and prognostic value

1997 ◽  
Vol 86 (1) ◽  
pp. 121-130 ◽  
Author(s):  
Julie M. Cunningham ◽  
David W. Kimmel ◽  
Bernd W. Scheithauer ◽  
Judith R. O'Fallon ◽  
Paul J. Novotny
Keyword(s):  
Univariate Analysis ◽  
Tumor Grade ◽  
Nuclear Antigen ◽  
Clinicopathological Parameters ◽  
Proliferative Potential ◽  
Ki 67 ◽  
Proliferation Markers ◽  
P53 Expression ◽  
Content Type ◽  
Mib 1

✓ Consecutive paraffin sections of 105 astrocytomas and 15 oligoastrocytomas were examined for expression of p53, MIB-1 (Ki-67), and proliferating cell nuclear antigen (PCNA). The tumors had been examined previously for genetic abnormalities and by flow cytometry. Regardless of the tumor's stage and grade and the patient's age and gender, p53 expression was found in 40% of tumors. Although p53 expression was associated with a loss on chromosome 17p and was more frequent in aneuploid tumors, it had no association with survival time. The MIB-1 and PCNA labeling indices increased with increasing tumor grade but showed no association with other clinicopathological parameters. In individual tumors, there was poor concordance between any of the variables (MIB-1, PCNA, and p53). Results for p53 and MIB-1 were similar for both astrocytomas and oligoastrocytomas. The MIB-1 and PCNA values appeared to have prognostic utility in univariate analysis but not after adjusting for patient age and tumor grade. The poor concordance between MIB-1 and PCNA in individual tumors indicates that any one means of assessing proliferative potential in gliomas may not be reliable.

Comparison of Histological and Proliferation Features of Canine Oral Squamous Cell Carcinoma Based on Intraoral Location: 36 Cases

2017 ◽  
Vol 34 (2) ◽  
pp. 92-99 ◽  
Author(s):  
Lisa A. Mestrinho ◽  
Hugo Pissarra ◽  
Sandra Carvalho ◽  
Maria C. Peleteiro ◽  
Jerzy Gawor ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumor Staging ◽  
Treatment Strategies ◽  
Nuclear Antigen ◽  
Proliferation Index ◽  
Ki 67 ◽  
Proliferation Markers

Grade and labeling indices for immunohistochemical tumor proliferation markers Ki-67 and proliferating cell nuclear antigen (PCNA) were evaluated in 36 cases of canine oral squamous cell carcinoma (OSCC) based upon intraoral location. Grade was significantly associated with location ( P = .035). Grade II tumors were most frequently diagnosed. Grade I tumors were identified in the gingiva and the buccal mucosa, and grade III tumors were seen in the gingiva and the tonsillar region. Animals with tumors arising from the tonsils and of the tongue tended to be older ( P = .007), and those in the former group were more likely to have metastatic disease at the time of diagnosis ( P = .001). Mean expression of PCNA and Ki-67 proliferation index (PI) for all tumors were 62.54% and 50.70%, respectively, and there was a statistical significant association between the 2 variables ( R = .70; P < .001). Proliferation index was not associated with any of the intraoral locations evaluated, but higher PCNA PI was significantly associated with grade ( P = .031). Ki-67 PI was significantly associated with lymph node metastasis at the time of diagnosis, especially for OSCC of gingival location ( P = .028). The results obtained in this study are preliminary but clinically relevant, since they provide information that can explain differences in biologic behavior among intraoral locations and contribute to more accurate tumor staging to support the choice for different treatment strategies available for OSCC.

scholarly journals Association among T2 signal intensity, necrosis, ADC and Ki-67 in estrogen receptor-positive and HER2-negative invasive ductal carcinoma

2018 ◽  
Vol 54 ◽  
pp. 176-182 ◽  
Author(s):  
Soo-Yeon Kim ◽  
Eun-Kyung Kim ◽  
Hee Jung Moon ◽  
Jung Hyun Yoon ◽  
Ja Seung Koo ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Invasive Ductal Carcinoma ◽  
Signal Intensity ◽  
Ductal Carcinoma ◽  
Ki 67 ◽  
Estrogen Receptor Positive

Phyllanthus urinaria’s Inhibition of Human Osteosarcoma Xenografts Growth in Mice is Associated with Modulation of Mitochondrial Fission/Fusion Machinery

2016 ◽  
Vol 44 (07) ◽  
pp. 1507-1523 ◽  
Author(s):  
Sheng-Teng Huang ◽  
Chao-Chun Huang ◽  
Jer-Ming Sheen ◽  
Tsu-Kung Lin ◽  
Pei-Lin Liao ◽  
...  
Keyword(s):  
Dynamic Change ◽  
B Cell Lymphoma ◽  
Significant Inhibition ◽  
Nuclear Antigen ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Mitochondrial Dynamic ◽  
Ki 67 ◽  
Proliferation Markers ◽  
Human Osteosarcoma

Osteosarcoma is an aggressive bone cancer arising from primitive transformed cells of mesenchymal origin to form malignant osteoid. Phyllanthus urinaria [Formula: see text]P. urinaria[Formula: see text] is a widely used folk medicine in cancer treatment, however the mechanism of P. urinaria inhibited human osteosarcoma is unclear. The present study was aimed at investigating the antitumoral effects of an aqueous P. urinaria on human osteosarcoma in vivo and the related underlying mechanisms, mainly focusing on mitochondrial dynamic dysfunction. Our results showed that oral administration of P. urinaria to mice led to significant inhibition of tumor development without substantial changes to body weight or major organs. Histological examinations with H&E, Giemsa, and Masson trichrome stains confirmed inhibition of tumor growth by the P. urinaria treatment. Immunohistochemical staining of proliferation markers antigen KI-67 (Ki67) and proliferating cell nuclear antigen (PCNA), as well as a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay demonstrated a decrease of tumor proliferation and an increase of apoptosis, which was associated with the modulation of B-cell lymphoma 2 (Bcl-2) family activating the caspase cascade in the P. urinaria-treated mice. The neovascularization marker cluster of differentiation 31 (CD31) was inhibited in P. urinaria-treated xenografts, implicating the potential anti-angiogenic effect of P. urinaria. P. urinaria treatment resulted in a significant decrease in the mitochondrial fusion proteins, including mitofusin 1/2 (Mfn1/2) and optic atrophy type 1 (Opa1), as well as an increase in the fission protein dynamin-related protein 1 (Drp1). The results of this study suggest mitochondrial dysfunction is associated with dynamic change that is involved in the apoptosis and anti-angiogenesis elicited by P. urinaria.

scholarly journals Expression of proliferation markers in laryngeal squamous cell carcinoma: an association with clinico-pathological factors and treatment outcomes

2020 ◽  
Vol 6 (5) ◽  
pp. 858
Author(s):  
Elizabeth Mathew Iype ◽  
Rajan Balakrishna ◽  
Lakshmi Subhadradevi ◽  
Jissa Vinoda Thulaseedharan ◽  
Bharath Veerabadhran ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cyclin D1 ◽  
Treatment Outcomes ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Ki 67 ◽  
Proliferation Markers ◽  
Tissue Samples ◽  
Cyclin Dl

<p class="abstract"><strong>Background:</strong> The study was done with the objective to study the expression of epidermal growth factor receptor (EGFR), cyclin D1 and Ki-67 in laryngeal squamous cell carcinoma and to assess the correlation of all three proliferation markers with various clinic-pathological parameters, the treatment outcomes as well as survival.</p><p class="abstract"><strong>Methods:</strong> We prospectively evaluated the surgical specimens of 72 laryngeal squamous cell carcinoma (LSCC) patients, treated with primary surgery and post-operative adjuvant therapy. Tumor tissue samples were analysed for the expression of EGFR, cyclin D1 and Ki-67 markers and analysis were done by immune-histochemistry and western blot test.  </p><p class="abstract"><strong>Results:</strong> EGFR showed significant expression in 67.6% and was insignificant in 31.9% patients in our analysis of 72 tumor samples. Cyclin D1 showed intense expression in 43%, and was insignificant in 57% patients. Ki-67 was intensely expressed in 43% patients. There was no correlation between expression of these markers with age, T-stage and N-stage. However, all the three markers showed significantly intense expression in tumours with extra capsular disease as well as perineural invasion (PNI) both of which are features of invasiveness of the tumor.</p><p class="abstract"><strong>Conclusions:</strong> Estimation of biomarkers such as EGFR, cyclin Dl, and Ki-67 could be beneficial in predicting tumor aggressiveness, prognosis and survival in LSCC patients. Thus, all the three proliferation markers can be categorized as markers of invasiveness. Combination of proliferation markers-EGFR, cyclin D1 and Ki-67 is useful pre-operatively in planning surgical strategies so as to decide a more radical approach for the resection of the primary as well as neck dissection.</p>

scholarly journals Enzyme-based Antigen Localization and Quantitation in Cell and Tissue Samples (Midwestern Assay)

1997 ◽  
Vol 45 (12) ◽  
pp. 1629-1641 ◽  
Author(s):  
Kevin A. Roth ◽  
Jennifer W. Brenner ◽  
Lee A. Selznick ◽  
Murat Gokden ◽  
Robin G. Lorenz
Keyword(s):  
Cell Labeling ◽  
Nuclear Antigen ◽  
Limited Information ◽  
Reaction Products ◽  
Antigen Concentration ◽  
Ki 67 ◽  
Tissue Samples ◽  
Tissue Sections ◽  
Specificity And Sensitivity ◽  
Antigen Localization

Quantitation of antigen concentration in cell and tissue samples typically requires antigen extraction, which precludes antigen localization in the same sample. Similarly, antigen immunolocalization in fixed cells or tissue sections provides limited information about antigen concentration. We have developed a rapid and sensitive assay for simultaneous antigen localization and quantitation in cell and tissue samples that does not involve antigen extraction, radioactive materials, or image analysis. Fixed cells and/or tissue sections are used with antigen-specific enzyme-linked probes to generate soluble reaction products that are spectrophotometrically quantifiable and deposited reaction products that are microscopically localizable. The amount of soluble reaction product is dependent on several variables, including antigen concentration, probe specificity and sensitivity, sample size, and enzyme reaction time. These variables can be experimentally controlled so that soluble reaction product is proportional to antigen concentration in the sample. This assay was used in multiple applications including detection of Ki-67 nuclear antigen immunoreactivity in human brain tumors, in which it showed a clear relationship with visually determined Ki-67 cell labeling indexes. This assay, termed the Midwestern assay, should be applicable to a wide variety of antigens in both clinical and research samples.

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