Journal articles on the topic 'Proliferation index'
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Rajeshwari B, Rajeshwari B., Salapathi Shanmugam, Sadiya Niamath, Mitra Ghosh, and Siddhartha Ghosh. "Hormone Receptor Status and KI67 Proliferation Index in Meningiomas." Annals of Pathology and Laboratory Medicine 7, no. 2 (March 7, 2020): A76–82. http://dx.doi.org/10.21276/apalm.2641.
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Alexandrakis, Michael G., Freda H. Passam, Despina S. Kyriakou, Konstantina Dambaki, Maria Niniraki, and Efstathios Stathopoulos. "Ki-67 Proliferation Index." American Journal of Clinical Oncology 27, no. 1 (February 2004): 8–13. http://dx.doi.org/10.1097/01.coc.0000045810.91816.41.
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Tomaszewska, Romana, Krzysztof Okoń, Krystyna Nowak, and Jerzy Stachura. "Proliferation Index and Karyometric Features of Pancreatic Intraductal Proliferative Lesions." Analytical Cellular Pathology 19, no. 3-4 (1999): 175–85. http://dx.doi.org/10.1155/1999/783401.
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The increasing frequency and poor prognosis in pancreatic cancer prompt us to search for morphological lesions being a substrate for its development. Studies of autopsy and surgically resected material as well as recent molecular studies have proved that one of the possible pathways of pancreatic neoplasia is the intraepithelial proliferation – dysplasia – cancer sequence. In the present paper we studied the proliferative activity (Ki‐67 index) in pancreatic intraepithelial proliferative lesions and its correlation with geometric features of cell nuclei as signs of increasing dysplasia. The studies were carried out in a group of 35 patients operated on for pancreatic cancer, chronic pancreatitis and other conditions not associated with the pancreas. We used immunohistochemical methods and basic morphometric parameters. The results of our studies indicate that the cell proliferative activity depends both on the type of epithelial proliferation and underlying pancreatic disease. The values of Ki‐67 index are significantly different in low‐grade proliferation (flat and papillary hyperplasia) and high‐grade proliferation (atypical papillary hyperplasia and carcinomain situ). A set of karyometric features correlates with Ki‐67 index but there is no single feature which would have a diagnostic value.
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Petrov, S. V., R. N. Kulagin, D. E. Tsyplakov, O. V. Nefedov, V. V. Saveliev, A. R. Utkuzov, and N. T. Raikhlin. "Markers of tumor cell proliferation in cancerous tumors of the larynx." Kazan medical journal 81, no. 4 (February 2, 2022): 265–68. http://dx.doi.org/10.17816/kazmj99817.
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The cell proliferative process in the larynx cancer is studied. Contrary to the classical mitotic index the Ki-67 and PCNA indices are reliable and reproducible on the clinical material by the proliferative cell activity indices of the larynx tumors. There is a reverse connection between the proliferation index in cells of the squamous larynx cancer and the tumor differentiation. The direct correlation of the cell proliferation index of the squamous laxynx cancer with the disease stage is revealed. The preoperative radiation therapy significantly decreases the cell proliferation rates of the squamous larynx cancer.
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Green, S. E., P. Chapman, J. Burn, A. D. Burt, M. Bennett, D. R. Appleton, J. S. Varma, and J. C. Mathers. "Colonic epithelial cell proliferation in hereditary non-polyposis colorectal cancer." Gut 43, no. 1 (July 1, 1998): 85–92. http://dx.doi.org/10.1136/gut.43.1.85.
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Background—Despite the recent discovery of four genes responsible for up to 90% of all cases of hereditary non-polyposis colorectal cancer (HNPCC), there will still be families in whom predictive testing is not possible. A phenotypic biomarker would therefore be useful. An upwards shift of the proliferative compartment in colonic crypts is reported to be one of the earliest changes in premalignant mucosa.Aims—To assess the role of crypt cell proliferation as a phenotypic biomarker in HNPCC.Patients—Thirty five patients at 50% risk of carrying the HNPCC gene (21 of whom subsequently underwent predictive testing and hence gene carrier status was known) and 18 controls.Methods—Crypt cell proliferation was measured at five sites in the colon using two different techniques. Labelling index was determined using the monoclonal antibody MIB1 and whole crypt mitotic index was measured using the microdissection and crypt squash technique. The distribution of proliferating cells within the crypts was also assessed.Results—There were no significant differences in the total labelling index or mean number of mitoses per crypt, nor in the distribution of proliferating cells within the crypt, between the study and control groups at any site. When the 21 patients in whom gene carrier status was known were analysed separately there were no significant differences in the measured indices of proliferation between the HNPCC gene carriers and non-gene carriers.Conclusion—Crypt cell proliferation is not a discriminative marker of gene carriage in HNPCC.
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Phillips, Brenda S., Philip H. Kass, Diane K. Naydan, Michelle D. Winthrop, Stephen M. Griffey, and Bruce R. Madewell. "Apoptotic and Proliferation Indexes in Canine Lymphoma." Journal of Veterinary Diagnostic Investigation 12, no. 2 (March 2000): 111–17. http://dx.doi.org/10.1177/104063870001200202.
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Proliferative and apoptotic fractions of tumors were evaluated in 41 dogs with lymphoma for prediction of response to chemotherapy. All dogs had advanced clinical stage tumors, were untreated prior to study, and received identical induction-remission chemotherapy. Tumor cell proliferation was determined in all pretreatment biopsy specimens and in 18 specimens collected at the time of clinical relapse from remission. Quantitative measures included mitotic index and immunoreactivities for proliferating cell nuclear antigen (PCNA) and Ki-67. Apoptotic index was evaluated from 40 dogs pretreatment and from 16 dogs at the time of first relapse. Pretreatment tumor values for Ki-67, PCNA, and apoptosis were compared with posttreatment values. The median first relapse-free interval (RFI) and overall survival (OS) time were 174 days and 445 days, respectively. Of the proliferation markers, only the results of the Ki-67 analysis were predictive for duration of the first RFI but not OS. Pretreatment apoptotic index was also predictive of the duration of first RFI but not OS. No significant predictive value for comparison of the pretreatment and postrelapse values was demonstrated. Ki-67 labeling index and apoptotic indexes were combined to form both a proliferation/apoptotic ratio (PAR) and a sum, or turnover index. Only the PAR was predictive for duration of first RFI on multivariate analysis. Other variables that were evaluated for their influence on treatment outcome included patient age, weight, gender, clinical stage, clinical substage, and tumor immunophenotype. Of these variables, only immunophenotype was found to be of value for predicting duration of first RFI and OS.
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Chirieac, Lucian R. "Tumor cell proliferation, proliferative index and mitotic count in lung cancer." Translational Lung Cancer Research 5, no. 5 (October 2016): 554–56. http://dx.doi.org/10.21037/tlcr.2016.10.10.
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Kabraji, Sheheryar Kairas, Giorgio Gaglia, Danae Argyropoulou, Yang Dai, Shu Wang, Johann Bergholz, Shannon Coy, et al. "Temporal and spatial topography of cell proliferation in cancer." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 3122. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.3122.
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3122 Background: Tumors are complex ecosystems where exogenous and endogenous cues are integrated to either stimulate or inhibit cancer cell proliferation. However, the nature of these complex cell cycle states, their spatial organization, response to perturbation, and implications for clinical outcomes, are poorly characterized in tumor tissues. Methods: We used multiplexed tissue imaging to develop a robust classifier of proliferation, the multivariate proliferation index (MPI), using 513 unique tumors across five cancer types. Next, we used dimensionality reduction analysis to assess how the patterns of cell cycle protein expression in tumors were altered in response to perturbation. Results: The MPI outperforms single markers, like Ki67, when classifying proliferative index across diverse tumor types and reveals the proliferative architecture of tumors in situ. We find that proliferative and non-proliferative cancer cells are organized across microscopic (cell-to-cell) and macroscopic (tissue-level) scales. Both domains are reshaped by therapy, and local clusters of proliferative and non-proliferative tumor cells preferentially neighbor distinct tumor-infiltrating immune cells. We further phenotyped non-proliferating cancer cells using markers of quiescent cancer cells, cancer stem cells, and dormant cancer cells. We found that these types of non-proliferating cancer cells can occupy distinct regions within the same primary tumor. In high-dimensional marker space, populations of proliferative cancer cells express canonical patterns of cell cycle protein markers, a property we refer to as “cell cycle coherence”. Untreated tumors exist in a continuum of coherence states, ranging from optimal coherence, akin to freely cycling cells in culture, to reduced coherence characterized by either cell cycle polarization or non-canonical marker expression. Coherence can be stereotypically altered by induction and abrogation of mitogen signaling in a HER2-driven model of breast cancer. Cell cycle coherence is modulated by neoadjuvant therapy in patients with localized breast cancer, and coherence is associated with disease-free survival after adjuvant therapy in patients with colorectal cancer, mesothelioma and glioblastoma. Conclusions: The MPI robustly defines proliferating and non-proliferating cells in tissues, with immediate implications for clinical practice and research. The coherence metrics capture the diversity of post-treatment cell cycle states directly in clinical samples, a fundamental step in advancing precision medicine. More broadly, replacing binary metrics with multivariate traits provides a quantitative framework to study temporal processes from fixed static images and to investigate the rich spatial biology of human cancers.
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Molochkova, Yu V., A. N. Khlebnikova, V. A. Molochkov, L. E. Gurevich, and A. V. Molochkov. "Comparative study of Ki67 protein expression in oral lichen planus and leukoplakia." Vestnik dermatologii i venerologii 94, no. 4 (December 7, 2018): 15–20. http://dx.doi.org/10.25208/0042-4609-2018-94-4-15-20.
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Oral lichen planus (OLP) is included in the category of potentially malignant diseases. Benign processes are differentiated from malignant ones by the nature of cell proliferative activity. The aim of the present study was the comparative study of proliferative activity in OLP and leuk oplakia cells, as well as the cells of oral squamous cell carcinoma.Materials and methods. Biopsy specimens from 16 patients with OPL, 13 with leukoplakia, and 7 with oral squamous cell carcinoma were investigated. Immunohistochemical studies were performed using Ki67 monoclonal antibodies.Results. The average Ki67 index in OPL cells was 9.3 ± 2.3 %. Proliferating cells were located exclusively in the basal epidermis layer. In leukoplakia cells, the average Ki67 index was 20.5 ± 6.1 %; the proliferating cells were located in the basal layer and lower parts of the spinous (suprabasal) layer of the epidermis. In squamous cell carcinoma, the average Ki67 index was 57.4 ± 2.04 %. Proliferating cells were located diffusely over all cell complexes from the lower to the highest layers of the epidermis. Differences in the proliferation level were significant for the leukoplakia/OPL pair (p = 0.003) and squamous cell carcinoma/OPL pair (p < 0.001), while for squamous cell carcinoma/leukoplakia pair the difference was not significant (p = 0.211).Conclusion. The differences in the proliferation level and in the nature of the proliferating cell distributionin through the epidermis can be applied in the differential diagnosis of OPL and leuk oplakia.
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Weerasooriya, Viraine, Michael J. Rennie, Shri Anant, David H. Alpers, Bruce W. Patterson, and Samuel Klein. "Dietary fiber decreases colonic epithelial cell proliferation and protein synthetic rates in human subjects." American Journal of Physiology-Endocrinology and Metabolism 290, no. 6 (June 2006): E1104—E1108. http://dx.doi.org/10.1152/ajpendo.00557.2005.
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Although it has been proposed that high fiber consumption can prevent proliferative diseases of the colon, the clinical data to support this hypothesis have been inconsistent. To provide a more robust measure of the effects of fiber on colonic mucosal growth than previous studies, we evaluated both cell proliferation and colonic mucosal protein synthesis in nine healthy volunteers after they consumed a typical Western diet (<20 g fiber/day) or a Western diet supplemented with wheat bran (24 g/day) in a randomized crossover design. Biopsies taken from the sigmoid colon were used to assess mucosal proliferation by determining proliferating cell nuclear antigen (PCNA) in crypt cells and to assess mucosal protein synthetic rate using stable isotopically labeled leucine infusion. Fiber supplementation produced a 12% decrease in labeling index (%crypt cells stained with PCNA) ( P < 0.001) and an 11% decrease in mucosal protein fractional synthetic rate (FSR; P < 0.05). Moreover, mucosal protein FSR correlated directly with labeling index (r2= 0.22, P < 0.05). These data demonstrate that increased wheat bran consumption decreases colonic mucosal proliferation and support the potential importance of dietary fiber in preventing proliferative diseases of the colon.
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Chakraborti, Shrijeet, Ramadas Naik, CK Ballal, and SonamKumar Pruthi. "Pilomyxoid astrocytoma with high proliferation index." Journal of Pediatric Neurosciences 8, no. 3 (2013): 243. http://dx.doi.org/10.4103/1817-1745.123694.
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Atkin, Stephen L., Victoria L. Green, Leslie J. Hipkin, Alex M. Landolt, Patrick M. Foy, Richard V. Jeffreys, and Michael C. White. "A comparison of proliferation indices in human anterior pituitary adenomas using formalin-fixed tissue and in vitro cell culture." Journal of Neurosurgery 87, no. 1 (July 1997): 85–88. http://dx.doi.org/10.3171/jns.1997.87.1.0085.
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✓ The authors compared detection methods for cell proliferation in human anterior pituitary adenomas using histological sections and dispersed cell culture. After tumor cells had been grown for 4 days in dispersed culture, bromodeoxyuridine (BUdR), proliferating cell nuclear antigen (PCNA), and Ki-67 were compared by double immunostaining and contrasted with single staining of PCNA and Ki-67 indices in the corresponding histological sections from 12 human pituitary adenomas. In vitro, the BUdR labeling index was positive in six of 12 tumors (range < 0.1–5.1%), 10 of 12 tumors were PCNA-positive (range < 0.1–100%), and Ki-67 was positive in 10 of 12 adenomas (range < 0.1–8%). In vitro, BUdR and Ki-67 gave similar proliferative indices for 10 of 12 adenomas. In vivo, the PCNA labeling index was positive in 12 of 12 adenomas (range 0.9–95%) and Ki-67 was positive in 11 of 12 adenomas (range < 0.1–2%). Tumors with a labeling index less than 0.1% were considered to be negative for proliferation. High PCNA values were found in vitro and in vivo, whereas Ki-67 labeling indices were similar in vitro and in vivo for nine of 12 adenomas. It is concluded that Ki-67 proliferative indices in vivo reflect those found in vitro, at least after 4 days in dispersed culture, but that PCNA overestimates pituitary adenoma proliferation in histological sections as well as in dispersed culture.
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Jankovic-Velickovic, Ljubinka, Biljana Djordjevic, Gorana Rancic, and Goran Marjanovic. "Expression of nuclear Ki-67 antigen in prostatic high grade intraepithelial neoplasia and prostatic carcinoma." Vojnosanitetski pregled 64, no. 5 (2007): 325–30. http://dx.doi.org/10.2298/vsp0705325j.
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Background/Aim. Prostatic intraepithelial high grade neoplasia (PINHG) is accepted as preneoplastic lesion in prostatic carcinoma. One of the fundamental events in early oncogenesis is the disruption of proliferative activity. One of the numerous regulatory proteins is Ki-67 expressed in all proliferating cells. Index Ki-67 is considered to have prognostic significance. The aim of the study was to compare the level of proliferation in hyperplastic epithelium, prostatic carcinoma (Gleason score > 6) and PINHG. Methods. Micromorphological examination was done in 85 patients. Pathohistological analysis was performed on standard histologic specimens with the estimation of Gleason score and the presence of PINHG in its surroundings. Nuclear proliferative activity was analyzed immunohistochemically in 19 cases, using a monoclonal anti-Ki-67 antibody. Results. PINHG was found in prostatic carcinoma surrounding in 30% of the patients. In hyperplastic epithelia Ki-67 proliferative activity was 1,08, in PINHG 2,25 (p < 0,05), while in prostatic cancer, Ki-67 index was 17,64. Proliferative activity in prostatic carcinoma was significantly higher than in PINHG (p < 0,001) and hyperplasia (p < 0,001). Conclusion. This study confirmed that high grade PIN lesion predominately appears in the surrounding of poor or moderately differentiated prostate carcinoma, and that it represents progressive disorder of proliferation in preneoplastic and neoplastic prostatic epithelium. .
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Nikolaeva, Tatyana V., V. S. Polyakova, N. P. Setko, and L. G. Voronina. "RATIO OF PROCESSES OF CELL PROLIFERATION AND APOPTOSIS IN THE SKIN UNDER EXPOSURE TO HEAVY METAL SALTS AND CHELATORS OF ESSENTIAL METALS." Hygiene and sanitation 96, no. 7 (March 27, 2019): 690–94. http://dx.doi.org/10.18821/0016-9900-2017-96-7-690-694.
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In the model experiment on C57BL /6 mice there were established features of the impact of heavy metals and chelators of essential metals on proliferation and apoptosis of epithelial skin cells (keratinocytes). For the execution of a study 40 test animals were divided into seven experimental and 1 control groups, each consisted of five animals. The proliferative and apoptotic activity of keratinocytes was determined by the immunohistochemical method and evaluated by calculating the proliferation index and the index of apoptosis in the cells of the surface epithelium and the epithelial cells of hair follicles in the late anagen stage. Comparative analysis of the proliferation index of the control group and experimental groups showed administration of zinc sulfate, sodium dichromate and zinc chelator (N, N, N`, N`-tetrakis (2-pyridylmethyl) ethylenediamine) to animals to give rise in a statistically significant increase in the proliferative activity of keratinocytes. The decline of proliferation index was detected in animals treated with lead acetate and copper chelator (ammonium tetrathiomolybdate). Introduction of an iron chelator (deferoxamine) had no effect on the proliferative activity of keratinocytes in experimental animals. Induction of apoptosis of epithelial cell was noted under the administration of nickel sulfate, sodium dichromate, lead acetate and zinc chelator (N, N, N`, N`-tetrakis (2-pyridylmethyl) ethylenediamine) to animals. In mice received deferoxamine zinc sulfate and apoptotic activity of keratinocytes has not changed. The use of cluster analysis allowed to classify substances administered to experimental animals, taking into account their simultaneous effect on the studied cellular processes. Lead acetate, iron chelator (deferoxamine) and copper chelator (ammonium tetrathiomolybdate) were shown to reduce the proliferative activity of keratinocytes and have little effect on apoptosis of the epithelial cells of the skin. Zinc sulfate, nickel sulfate, sodium dichromate and zinc chelator (N, N, N`, N`-tetrakis (2-pyridylmethyl) ethylenediamine) activate cell proliferation and induce apoptosis of keratinocytes.
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Peña, Laura L., Ana I. Nieto, Dolores Pérez-Alenza, Pedro Cuesta, and Maria Castaño. "Immunohistochemical Detection of Ki-67 and PCNA in Canine Mammary Tumors: Relationship to Clinical and Pathologic Variables." Journal of Veterinary Diagnostic Investigation 10, no. 3 (July 1998): 237–46. http://dx.doi.org/10.1177/104063879801000303.
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The objectives of this study were to measure the proliferation indices in canine mammary tumors using immunohistochemical detection of Ki-67 and proliferating cell nuclear antigen (PCNA), to determine the relationship of these antigens to clinical and pathologic variables, and to investigate the usefulness of these antigens as prognostic indicators. Ninety-six female dogs with 115 primary nonmetastasized spontaneous mammary tumors and dysplasias were included in the study. Immunostaining was performed using MIB-1 and PC10 monoclonal antibodies against Ki-67 and PCNA, respectively. Ki-67 and PCNA proliferation indices were determined. Dogs were followed for 18 months, with clinical examinations every 3–4 months. There was a significant correlation between Ki-67 and PCNA indices in the dogs with dysplasias and benign tumors but not in the dogs with malignant tumors. The clinical stage at first presentation was related to the proliferative index measured with Ki-67 but not to that measured with PCNA. Proliferation indices were significantly lower in the nonmalignant tumors and dysplasias than in the malignant tumors. In malignant tumors, the PCNA index had a positive correlation with the histologic malignant grade and the nuclear grade. High index values of Ki-67 were positively correlated with metastasis, death from neoplasia, low disease-free survival rates, and low overall survival rates. PCNA displayed no significant association with these variables. Multivariate analyses concerning metastasis, disease-free survival, and overall survival revealed that the Ki-67 index had prognostic value.
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Sakuragi, N., I. Furuta, M. L. Luo, H. Watari, and S. ujimoto. "Apoptosis and proliferation index in human trophoblast." Placenta 19, no. 7 (September 1998): A27. http://dx.doi.org/10.1016/s0143-4004(98)91146-8.
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Henriques, S., E. Silva, S. Cruz, M. F. Silva, G. Ferreira-Dias, L. Lopes-da-Costa, and L. Mateus. "Oestrous cycle-dependent expression of Fas and Bcl2 family gene products in normal canine endometrium." Reproduction, Fertility and Development 28, no. 9 (2016): 1307. http://dx.doi.org/10.1071/rd14245.
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During the oestrous cycle canine endometrium undergoes cyclical cellular proliferation, apoptosis and differentiation. To study the regulation of endometrial apoptosis and proliferation events the expression of apoptosis-related genes was analysed by real-time polymerase chain reaction and cellular expression of their proteins was identified through immunohistochemistry. Cellular apoptosis and proliferation events were detected by TdT-mediated dUTP-biotin nick end labeling (TUNEL) and proliferation marker Ki67 immunostaining, respectively. The highest proliferative index was observed in the follicular phase (all endometrial cellular components) and at early dioestrus (basal glands). This was associated with a low apoptotic index and a strong expression of anti- (Bcl2) and pro-apoptotic proteins (Fas, FasL, Bax). Subsequently (Days 11–45 of dioestrus), basal glandular epithelium experienced the highest apoptotic index, coincidental with a decrease of Bcl2 expression and a low ratio of Bcl2/Bax transcription. An increase in the apoptotic index of crypts, stromal and endothelial cells was observed at late dioestrus and the beginning of anoestrus. These results indicate that pro- and anti-apoptotic proteins regulate the balance between cell proliferation and death in the canine endometrium during the oestrous cycle. High Bcl2 expression in both the follicular and early dioestrous phases stimulate glandular proliferation and prevent apoptosis but, in the non-pregnant uterus, a decrease in Bcl2 expression together with an increase in pro-apoptotic proteins induces apoptosis of basal glandular epithelium cells.
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Hose, Dirk, Thierry Rème, Thomas Hielscher, Jérôme Moreaux, Tobias Meißner, Anja Seckinger, Axel Benner, et al. "A Gene Expression Based Proliferation Index as Independent Prognostic Factor in Multiple Myeloma." Blood 112, no. 11 (November 16, 2008): 1667. http://dx.doi.org/10.1182/blood.v112.11.1667.1667.
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Abstract BACKGROUND. The proliferation-rate of primary myeloma cells is a strong adverse prognostic factor in various trials, but not routinely assessed, partially due to effort in obtaining it. AIM. As gene-expression profiling is increasingly considered a standard diagnostics in myeloma, we investigated the possibility to develop a prognostically relevant gene-expression based proliferation index (GPI). PATIENTS AND METHODS. Gene expression was determined by Affymetrix DNA-microarrays in 784 samples including two independent sets of 233 and 345 CD138-purified myeloma cells from previously untreated patients. The GPI was derived by selecting genes associated with proliferation (in terms of gene ontology) differentially expressed in proliferating malignant (human myeloma cell lines) and benign (plasmablastic) cells compared to non-proliferating, non-malignant cells (normal plasma cells and memory B-cells). The GPI comprises the sum of the expression values of 50 genes (ASPM, AURKA, AURKB, BIRC5, BRCA1, BUB1, BUB1B, CCNA2, CCNB1, CCNB2, CDC2, CDC20, CDC25C, CDC6, CDCA8, CDKN3, CEP55, CHEK1, CKS1B, CKS2, DLG7, ESPL1, GINS1, GTSE1, KIAA1794, KIF11, KIF15, KIF20A, KIF2C, KNTC2, MAD2L1, MCM10, MCM6, MKI67, NCAPD3, NCAPG, NCAPG2, NEK2, NPM1, PAK3, PCNA, PGAM1, PLK4, PTTG1, RACGAP1, SMC2, SPAG5. STIL, TPX2, ZWINT). Proliferation of primary myeloma cells was assessed by propidium iodinestaining (n=67). Chromosomal aberrations were assessed by comprehensive iFISH using a set of probes for the chromosomal regions 1q21, 6q21, 8p21, 9q34, 11q23, 11q13, 13q14.3, 14q32, 15q22, 17p13, 19q13, 22q11, as well as the translocations t(4;14)(p16.3;q32.3) and t(11;14)(q13;q32.3). RESULTS. In the two groups, 39 and 32 percent of primary myeloma cells show a GPI above the median plus three standard deviations of normal bone marrow plasma cells, respectively. The GPI is significantly higher in advanced- compared to early-stage myeloma (P=.001) and in patients harboring a gain of 1q21 (n=95, P<0.001). It correlates significantly with proliferation as determined by propidium iodine in primary myeloma cells (rs=.52, P<.001, n=67). The GPI as continuous variable is significantly predictive for event-free survival (EFS, n=120, P<.001, n=345, P<.001, respectively) and overall survival (OAS, n=345, P<.001) in patients treated with high-dose chemotherapy, independent of serum-β2-microglobulin (B2M) or ISS-stage. A GPI above the median (GPIhigh) delineated significantly inferior EFS (n=168, 41.6 vs. 26 months, P=.04, HR 1.57, CI [1.02,2.42]; n=345, 68.6 vs. 45.2 months, HR 1.55, CI [1.16,2.09], P=.003) and OAS (n=345, P<.001) in two independent cohorts of patients undergoing high-dose chemotherapy. By using B2M above 3.5 mg/l and GPI as staging variables, four groups with difference in median EFS (n=345, B2M <3.5mg/l, GPIhigh/low 76.1 months; B2M < 3.5mg/l, GPIhigh 62.4 months, B2M ≥3.5mg/l, GPIlow 41.8 months, B2M ≥3.5mg/l, GPI 36.1 months, P<.001) and OAS can be delineated. CONCLUSION. The GPI represents a validated tool for the assessment of proliferation in multiple myeloma patients, allows a risk stratification in terms of proliferation either alone or in combination with B2M or ISS, respectively, and has the potential to be used within a risk adapted targeting of anti-proliferative treatment.
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Meyer, John S., Consuelo Alvarez, Clara Milikowski, Neal Olson, Irma Russo, Jose Russo, Andrew Glass, Barbara A. Zehnbauer, Karen Lister, and Reza Parwaresch. "Breast carcinoma malignancy grading by Bloom–Richardson system vs proliferation index: reproducibility of grade and advantages of proliferation index." Modern Pathology 18, no. 8 (May 13, 2005): 1067–78. http://dx.doi.org/10.1038/modpathol.3800388.
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Yuko, Murase, Fesseha Meseret, Abbaspour Nazanin, and Young Hong Mee. "Watermelon Powder Supplementation Reduces Colonic Cell Proliferation by Upregulating p21Waf1/Cip1 Expression." Current Developments in Nutrition 4, Supplement_2 (May 29, 2020): 340. http://dx.doi.org/10.1093/cdn/nzaa044_039.
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Abstract Objectives Watermelon is high in L-citrulline, a precursor for L-arginine, which in turn may reduce the risk of colorectal cancer (CRC). Research has shown that L-arginine inhibits the hyperproliferation of colorectal tumor cells as a marker for CRC. The objective of this study was, therefore, to examine the effects of watermelon powder supplementation on colonic cell proliferation and their gene expression. The hypothesis was that watermelon powder supplementation would reduce CRC risk by regulating colonic expression of genes related to epithelial cell proliferation. Methods Thirty-two 21-day-old, male, Sprague Dawley rats were randomly assigned to one of the following isocaloric diets: 0.5% watermelon powder, 0.36% L-arginine, and control for 9 weeks. All animals were injected with azoxymethane (15 mg/kg body weight). Colonic cell proliferation was measured using ki-67 immunohistochemistry, and colonic gene expression was determined using a quantitative real-time polymerase chain reaction (PCR). Results Both watermelon powder and L-arginine groups exhibited lower proliferating index (P = 0.041) and lower proliferative zone (P = 0.041). In addition, watermelon powder and L-arginine supplementation upregulated p21Waf1/Cip1 gene expression (P = 0.048). There were no significant differences in the expression of Cyclin D1, Cyclin-dependent kinase 2 (CDK2), Cyclin-dependent kinase 4 (CDK4), and Peroxisome proliferator-activated receptor γ (PPARγ). Conclusions These results suggest that watermelon or L-arginine supplementation may decrease the risk of CRC as they both reduced proliferation by upregulating a cyclin-dependent kinase inhibitor. Additional markers for gene expression involving cell proliferation are needed to confirm the present findings. Funding Sources National Watermelon Promotion Board (NWPB 15–16) National Cancer Institutes of Health (U54CA132384 for SDSU and U54132379 for UCSD).
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Morales, E., L. M. Pastor, R. Horn, A. Zuasti, C. Ferrer, A. Calvo, L. Santamaría, and M. Canteras. "Effect of ageing on the proliferation and apoptosis of testicular germ cells in the Syrian hamster Mesocricetus auratus." Reproduction, Fertility and Development 15, no. 2 (2003): 89. http://dx.doi.org/10.1071/rd02071.
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The cellular mechanisms implicated in the atrophy of seminiferous epithelium in ageing are currently under debate, although recent reports suggest that apoptosis may be the primary mechanism implicated in aged germ cell loss. Other investigators have suggested that changes in spermatogonial proliferation are also involved. In the present work, the changes in proliferation and apoptosis in the seminiferous epithelium of aged (24 months) Syrian hamsters were examined in concert and compared with those in young (6 months) animals. Proliferation of germ cells was studied by bromodeoxyuridine labelling and apoptosis was assessed by transmission electron microscopy and in situ TUNEL labelling. Aged animals showed a significant decrease in the numbers of total and proliferating spermatogonia plus preleptotene spermatocytes per unit volume and per testis and in the proliferative index (24.8 ± 1.6%) compared with young animals (30.8 ± 1.2%) (P < 0.05). The number of apoptotic spermatogonia plus spermatocytes per unit volume and the apoptotic index were significantly higher in aged animals (1.51 ± 0.23% v. 0.77 ± 0.04%; P < 0.05). Apoptosis was confirmed by morphological characteristics: condensation of the chromatin and nuclear fragmentation. In aged hamsters, tubular degeneration could be classified into several categories, characterized by maturation arrest and an increase of apoptotic cells in tubular cross-sections in comparison with normal tubular cross-sections. Spermatogonial proliferation was also diminished as seen in tubular cross-sections showing hypospermatogenesis, sloughing off of germ cells and maturation arrest. The results obtained in the present study suggest that the decrease in the proliferation of spermatogonia and the increase in apoptosis constitute two consecutive mechanisms correlated with the ageing of the seminiferous epithelium.
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Sokołowska, J., K. Urbańska, S. Giziński, A. Wysocka, A. Cywińska, and R. Lechowski. "Survivin expression in canine lymphomas in relation with proliferative markers." Polish Journal of Veterinary Sciences 18, no. 1 (March 1, 2015): 113–22. http://dx.doi.org/10.1515/pjvs-2015-0015.
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Abstract Survivin is a member of apoptosis inhibiting proteins family. Apart from its antiapoptotic activity it plays a critical role in regulating the cell cycle and mitosis. It is overexpressed in most human malignancies. While the prognostic significance of survivin expression is widely investigated in human non-Hodgkin's lymphomas, little is known about its expression in canine lymphomas. The aim of the study was to evaluate the expression of survivin in canine lymphomas in relation to proliferation markers (mitotic index and percentage of Ki67-positive cells). Survivin was found in all examined lymphomas belonging to 6 different morphological subtypes with nuclear immunoreactivity. In most of lymphomas (18/25) survivin expression ranged 10%-25% of positive cells. Only single cases had lower (0-10% positive cells, 1/25) or higher (25-50% and >50% positive cells, 5/25 and 1/25, respectively) index of survivin. Neither mitotic index nor proliferative index correlated with survivin expression when the values quantified randomly in whole specimens were compared. However, when survivin expression were quantified in selected tumor areas of low and high proliferation activity the high correlations between survivin expression and proliferation index were found. The results indicated that survivin is commonly expressed in canine lymphomas. Nuclear labelling together with the relation of its expression and proliferative activity in highly proliferative areas of neoplastic tissue suggest a potential role of survivin in cell cycle activation in canine lymphoma cells. However, further studies of the relation between expression of survivin and other proteins involved in cell cycle regulation are needed. Moreover, the results suggest that survivin may pose the therapeutic target in canine lymphomas.
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Iżycka-Świeszewska, Ewa, Beata Stefania Lipska-Ziętkiewicz, Elżbieta Adamkiewicz-Drożyńska, Wiesława Grajkowska, Blanka Hermann, Ewa Bień, and Janusz Limon. "Original article Proliferation index revisited in neuroblastic tumors." Folia Neuropathologica 3 (2014): 243–52. http://dx.doi.org/10.5114/fn.2014.45565.
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Hwan Lee, Seung, Young Ho Jang, Kyung Tae, Yong Wook Park, Mi Jung Kang, Kyung Rae Kim, and Chul Won Park. "Telomerase activity and cell proliferation index in cholesteatoma." Acta Oto-Laryngologica 125, no. 7 (January 2005): 707–12. http://dx.doi.org/10.1080/00016480410024479.
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Châtillon, C. E., M. C. Guiot, D. Roberge, and R. Leblanc. "Cerebellar Liponeurocytoma with High Proliferation Index: Treatment Options." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 36, no. 5 (September 2009): 658–61. http://dx.doi.org/10.1017/s0317167100008210.
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Meyer, John S., Consuelo Alvarez, Clara Milikowski, Neal Olson, Irma Russo, Jose Russo, Andrew Glass, Barbara A. Zehnbauer, Karen Lister, and Reza Parwaresch. "Erratum: Breast carcinoma malignancy grading by Bloom–Richardson system vs proliferation index: reproducibility of grade and advantages of proliferation index." Modern Pathology 18, no. 12 (November 18, 2005): 1649. http://dx.doi.org/10.1038/modpathol.3800479.
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Nagata, J., and A. Yamane. "Progress of Cell Proliferation in Striated Muscle Tissues during Development of the Mouse Tongue." Journal of Dental Research 83, no. 12 (December 2004): 926–29. http://dx.doi.org/10.1177/154405910408301207.
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The developmental stages of and places for the proliferation of tongue muscle cells have not yet been determined. To determine the stages of and places for proliferation between embryonic day (E) 9 and birth, we analyzed the expression of cyclin D1 mRNA and the immunolocalization for proliferating cell nuclear antigen (PCNA). The ratio of PCNA-positive nuclei to total nuclei (PCNA-labeling index) was obtained in the anterior, middle, and posterior regions. Cyclin D1 mRNA was highly expressed between E11 and E13, but decreased thereafter until birth. The distribution of PCNA-positive cell nuclei was consistent with that of myogenic cells in the occipital somites at E9. The PCNA-labeling index was highest at E11, then decreased until birth without a significant difference among the 3 regions. These findings suggest that some tongue muscle progenitor cells begin proliferation in the occipital somites at E9, and that the proliferation in the whole tongue region occurred most actively between E11 and E13, then decreased until birth without regional differences.
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Kantarci, A., P. Augustin, E. Firatli, M. C. Sheff, H. Hasturk, D. T. Graves, and P. C. Trackman. "Apoptosis in Gingival Overgrowth Tissues." Journal of Dental Research 86, no. 9 (September 2007): 888–92. http://dx.doi.org/10.1177/154405910708600916.
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Variations in the balance between cell proliferation and apoptosis could contribute to the etiology of gingival overgrowth. The aim of this study was to test the hypothesis that, in fibrotic gingival lesions, fibroblast proliferation is stimulated and apoptosis is decreased. Apoptotic index, caspase 3 expression, the proliferative index, FOXO1 expression, and histological inflammation were measured in situ. Analysis of data showed that apoptosis decreased in all forms of gingival overgrowth examined (p < 0.05), and inflammation caused a small but significant increase compared with non-inflamed tissues (p < 0.05). The greatest decrease of apoptosis occurred in the most fibrotic tissues. Cell proliferation was elevated in all forms of gingival overgrowth tested, independent of inflammation (p < 0.05). To identify potential mechanisms of transcriptional regulation of apoptosis, we assessed FOXO1 and caspase 3 expression levels and found them to correlate well with diminished apoptosis. Analysis of data suggests that increased fibroblast proliferation and a simultaneous decrease in apoptosis contribute to gingival overgrowth.
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Sato, Shinji, Kiyoshi Ito, Hironobu Sasano, Keiko Watanabe, Nobuyoshi Ozawa, and Akira Yajima. "Immunohistochemical study of PCNA (proliferating cell nuclear antigen) in normal and abnormal endometrium." International Journal of Gynecologic Cancer 3, no. 2 (1993): 122–27. http://dx.doi.org/10.1046/j.1525-1438.1993.03020122.x.
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To investigate the cell kinetics of human endometrial disorders immunolocation of PCNA (proliferating cell nuclear antigen) was performed in 69 specimens of normal, hyperplastic, or malignant endometrial tissue that had been fixed in formalin and embedded in paraffin. Immunoreactivity of PCNA was observed in all specimens examined. In the proliferative phase, PCNA positive cells were present in both the glands and stroma. In the secretory phase PCNA positive cells were seen principally in the stromal cells. A PCNA labeling index was obtained by counting one thousand cells per case. PCNA positivity in the proliferative phase was significantly higher than in the secretory phase (P< 0.01), but lower than in moderately differentiated (P< 0.01) or poorly differentiated (P< 0.05) adenocarcinoma. No significant differences in the PCNA labeling index were observed between hyperplasia and adenocarcinoma. These findings indicate that possible biologic differences between these proliferative endometrial lesions are probably not due to differences in cell proliferative activity, but rather to factors other than proliferation such as their ability to invade.
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Nadasdy, T., Z. Laszik, K. E. Blick, L. D. Johnson, and F. G. Silva. "Proliferative activity of intrinsic cell populations in the normal human kidney." Journal of the American Society of Nephrology 4, no. 12 (June 1994): 2032–39. http://dx.doi.org/10.1681/asn.v4122032.
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The proliferative activity of various normal human renal cell populations is unknown. Recently, antibodies to cell proliferation-associated nuclear proteins, such as proliferating cell nuclear antigen (PCNA) and KI-67, which are applicable to archival paraffin sections, became available. With antibodies to PCNA and Ki-67 after microwave pretreatment of the paraffin sections, the proliferation indexes (ratio of positive nuclei with PCNA and Ki-67 antibodies/all nuclei counted x 100, i.e. percentage of positive cells) of 12 different intrinsic renal cell populations in 20 normal human kidneys have been determined. The following proliferation indexes (percentages of positive cells) were found with the PCNA and the Ki-67 antibodies, respectively: proximal tubular epithelium, 0.22, 0.24; thin limb of Henle, 0.29, 0.30; thick ascending limb of Henle, 0.32, 0.29; distal tubular epithelium (distal convoluted tubules and cortical collecting ducts, 0.33, 0.44; medullary collecting ducts, 0.32, 0.3; glomerular mesangial cells, 0.07, 0.12; glomerular visceral epithelial cells, 0.04, 0.08; glomerular parietal epithelial cells, 0.07, 0.1; glomerular capillary endothelium, 0.42, 0.47; peritubular capillary endothelial cells, 0.38, 0.43; endothelium of large intrarenal vessels (arteries and veins), 0.09, 0.12. Thus, normally capillary endothelium (glomerular and peritubular) appears to have the highest proliferation index in the human kidney by these techniques. These results indicate major variation in the proliferative activity of normal human renal cell populations, along with a significant correlation between PCNA and Ki-67 staining. Furthermore, this study provides normal values for the proliferative activity of different human renal cell populations.(ABSTRACT TRUNCATED AT 250 WORDS)
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Mestrum, Stefan G. C., Roanalis B. Y. Vanblarcum, Roosmarie J. M. Drent, Norbert C. J. De Wit, Bert T. Boonen, Wouter L. W. van Hemert, Anton H. N. Hopman, Frans C. S. Ramaekers, and Mathie P. G. Leers. "Flow Cytometric Detection of the Ki-67 Proliferation Index and the Bcl-2 Anti-Apoptotic Index in Myelodysplastic Syndromes and Acute Myeloid Leukemia, and Their Clinical Implications." Blood 138, Supplement 1 (November 5, 2021): 3444. http://dx.doi.org/10.1182/blood-2021-144906.
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Abstract Introduction: Standardization of the detection and quantification of leukocyte differentiation markers by the EuroFlow Consortium has led to a major step forward in the integration of flow cytometry in classification of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). To further advance the integration and objectification of flow cytometry for characterization of these malignancies, more dynamic parameters assessing cell behavioral characteristics could prove useful, such as proliferative and (anti-)apoptotic markers. Proliferation and (anti-)apoptosis are processes that are tightly related to the pathogenesis, progression and chemo-/immunotherapy response of cancers. As a result, proliferation and (anti-)apoptotic markers have proven their value as objective parameters in the field of histopathology for diagnostic and prognostic applications in solid tumors and lymphoma. Although use of proliferative and (anti-)apoptotic markers as objective parameters in the diagnostic process of MDS and AML was studied in the past decades, this did not result in the incorporation of these biomarkers in their clinical diagnosis. The recent developments in flow cytometric analyses now allow the quantification of proliferative and (anti-)apoptotic fractions at the level of individual maturing bone marrow cells. Therefore, we aim to determine the Ki-67 proliferation indices and Bcl-2 anti-apoptotic indices in maturing bone marrow cells in order to assess whether these parameters could have future clinical implications for the diagnostic work-up of MDS and AML. Methods: Fifty bone marrow aspirates from femoral heads of non-malignant cases, 20 aspirates of MDS patients and 20 aspirates of AML were included in this study. Ten-color flow cytometry in combination with a software-based maturation tool was used for analysis of the Ki-67 proliferative and Bcl-2 anti-apoptotic indices of blast cells and during the erythro-, myelo-, and monopoiesis. Results: Ki-67 proliferative indices of blast cells and immature erythroid, myeloid and monocytic cells were significantly lower in MDS patients compared to the non-malignant cases, while the Bcl-2 anti-apoptotic indices were significantly elevated in these cells. Furthermore, the Bcl-2 anti-apoptotic indices were also increased in mature erythroid, myeloid and monocytic cells of MDS patients. The decreased Ki-67 proliferative indices and increased Bcl-2 anti-apoptotic indices in blast cells and erythroid, myeloid and monocytic cells were even more prominently observed in AML patients. Conclusions: The lowered Ki-67 proliferative indices and elevated Bcl-2 anti-apoptotic indices in blast cells and immature progenitor cells led to a better understanding of the pathophysiology of MDS and AML, and explained the low chemotherapy response of these patients. Side-effects of such therapies can also be explained by the Ki-67 proliferation indices and Bcl-2 anti-apoptotic indices. Moreover, the increase of the Bcl-2 anti-apoptotic fraction is an important factor in the progression of MDS to AML. Future studies on the clinical applications of these parameters for MDS and AML are necessary and can include many applications, such as prediction of chemo-/immunotherapy response, diagnostic and prognostic applications. Disclosures Ramaekers: Nordic-MUbio: Current Employment.
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Page, D. L. "2–15 Breast Carcinoma Malignancy Grading by Bloom—Richardson System vs Proliferation Index: Reproducibility of Grade and Advantages of Proliferation Index." Breast Diseases: A Year Book Quarterly 17, no. 2 (July 2006): 149–50. http://dx.doi.org/10.1016/s1043-321x(06)80424-8.
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Amaral, Fabrício Rezende, Gláucia Cardoso Paixão Mateus, Lucas Alves Bonisson, Bruno Augusto Benevenuto de Andrade, Ricardo Alves Mesquita, Martinho Campolina Rebello Horta, and Helenice de Andrade Marigo. "Cell proliferation and apoptosis in ameloblastomas and keratocystic odontogenic tumors." Brazilian Dental Journal 23, no. 2 (April 2012): 91–96. http://dx.doi.org/10.1590/s0103-64402012000200001.
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A high proliferative activity of the odontogenic epithelium in ameloblastoma (AM) and keratocystic odontogenic tumor (KOT) has been demonstrated. However, no previous study has simultaneously evaluated cell proliferation and apoptotic indexes in AM and KOT, comparing both lesions. The aim of this study was to assess and compare cell proliferation and apoptotic rates between these two tumors. Specimens of 11 solid AM and 11 sporadic KOT were evaluated. The proliferation index (PI) was assessed by immunohistochemical detection of Ki-67 and the apoptotic index (AI) by methyl green-pyronine and in situ DNA nick end-labelling methods. KOT presented a higher PI than AM (p<0.05). No statistically significant difference was found in the AI between AM and KOT. PI and AI were higher in the peripheral cells of AM and respectively in the suprabasal and superficial layers of KOT. In conclusion, KOT showed a higher cell proliferation than AM and the AI was similar between these tumors. These findings reinforce the classification of KOT as an odontogenic tumor and should contribute to its aggressive clinical behavior.
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Del Poeta, Giovanni, Maria Ilaria Del Principe, Pasquale Niscola, Luca Maurillo, Adriano Venditti, Francesco Buccisano, Maria Irno Consalvo, et al. "Spontaneous Apoptosis and Proliferation Predict Disease Progression within ZAP-70 Negative B-Cell Chronic Lymphocytic Leukemia (B-CLL)." Blood 106, no. 11 (November 16, 2005): 1197. http://dx.doi.org/10.1182/blood.v106.11.1197.1197.
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Abstract Inhibition of spontaneous apoptosis and upregulation of the anti-apoptotic protein bcl-2 define clinical prognosis in B-CLL. However, increasing evidence exists that disease progression (DP) relies upon a proliferating pool of cells in lymph nodes and bone marrow which might feed the accumulating pool in the blood. Moreover, unmutated immunoglobulin VH genes predict for a rapid DP and an inferior overall survival. Unmutated B-CLL cells express ZAP-70 protein kinase associated with an early DP risk. The availability both of rapamycin or proteasome inhibitors effective against proliferating cells and bcl-2 targeting drugs incited us to evaluate the impact of proliferation and apoptosis pathways on B-CLL prognosis. The primary aims of our study were: 1) to determine progression-free survival (PFS) upon apoptosis/proliferation and ZAP-70 expression; 2) whether apoptosis/proliferation could predict varied outcome within ZAP-70 subgroups; and finally 3) whether ZAP-70 and apoptosis/proliferation were independent prognostic factors. Therefore, we investigated 249 pts, median age 64 years, almost all belonging to the intermediate Rai stage. ZAP-70 was quantified by a multicolor flow cytometric method. Bcl-2 (Bcl-2B/T) was determined dividing mean fluorescence intensity (MFI) of CD19+B-CLL cells by MFI of T-cells. CD71 was used as a measure of proliferation in percentage. Combining Bcl-2B/T with CD71 (Bcl2CD71) we enucleated three subgroups: 1) Bcl2CD71- [low proliferation (CD71<8%) and high apoptosis (Bcl-2B/T<1.6)]; 2) Bcl2CD71+ [high proliferation (CD71>8%) and low apoptosis (Bcl-2B/T>1.6)]; and 3) Bcl2CD71+/− [low proliferation/low apoptosis or high proliferation/high apoptosis]. ZAP-70+ B-CLL pts were 87/249 (35%). We found significant associations either between lower ZAP-70 and lower Bcl-2B/T (p=0.0008) or lower ZAP-70 and Bcl2CD71- (p=0.0007), showing that low ZAP-70 levels were characterized by high apoptosis and low proliferation. With regard to clinical outcome, a significant shorter PFS was observed in ZAP-70+ pts (6% vs 58% at 12 years; p<0.00001) and in Bcl2CD71+ pts (10% vs 56% at 12 years; p<0.00001). The Bcl2CD71+/− subgroup showed an intermediate outcome (30% at 12 years). To further explore the prognostic impact of Bcl2CD71 index, we investigated its expression within ZAP-70+ (87) and ZAP-70 negative (162) pts. As a matter of fact, Bcl2CD71 index was not able to identify different prognosic subsets within ZAP-70+ pts, because all these cases presented a similar short PFS. On the contrary, Bcl2CD71 clearly identified two subsets at different PFS within the ZAP-70 negative subgroup (73% for Bcl2CD71- pts vs 29% for Bcl2CD71+ pts at 12 years, p=0.00007). In multivariate analysis of PFS, ZAP-70 resulted to be the strongest indipendent prognostic factor (p=0.00002). However, the apoptotic/proliferative index Bcl2CD71 was very useful to identify our pts at different PFS within the ZAP-70 negative subgroup. In conclusion, ZAP-70 negative B-CLL represents a large and clinically heterogeneous population with a variable DP and the determination of the amount of apoptosis combined with the proliferation, could allow us both to distinguish early progressive pts and to take timely therapeutic decisions.
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Ahmed, Ishtiaq. "Proliferating Cell Nuclear Antigen Expression in Canine and Feline Spontaneous and Injection-site Fibrosarcomas." Pakistan Veterinary Journal 40, no. 04 (December 1, 2020): 531–33. http://dx.doi.org/10.29261/pakvetj/2020.019.
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Fibrosarcoma, a tumor composed of spindloid fibroblasts, is grouped in soft tissue sarcomas which constitute one of the most important tumors in companion animals. Cell proliferation index is a good indicator of the biological behavior of the tumors which is estimated either by mitotic index or cell proliferation markers. In the current study, we investigated the immunohistochemical expression of proliferating cell nuclear antigen (PCNA) in spontaneous and injection-site fibrosarcomas in dogs and cats. A positive correlation was noticed between the PCNA expression, mitotic index, tumor grade and degree of differentiation of the tumor cells in tumors from both of these species. PCNA expression was significantly different between different tumor grades in dogs and cats. It can be concluded from this study that PCNA is a useful marker for predicting the outcome of the canine and feline fibrosarcomas
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Minarik, Jiri, Vlastimil Scudla, Marta Ordeltova, Tomas Pika, Jaroslav Bacovsky, Michael Steinbach, Vipin Kumar, and Brian G. Van Ness. "Combined Measurement of Plasma Cell Proliferation and Apoptosis in Multiple Myeloma." Blood 114, no. 22 (November 20, 2009): 4884. http://dx.doi.org/10.1182/blood.v114.22.4884.4884.
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Abstract Abstract 4884 Background Plasma cell proliferation and apoptosis represent key factors in multiple myeloma (MM) expansion and tumor survival. Both the proliferative and the apoptotic index have been shown to be strong and independent prognosticators in MM. Moreover, they do not correlate with most standard prognostic factors, representing thus different inherent features of the myeloma clone. The aim of the study was to assess the combined measurement of proliferation and apoptosis, giving the best predictive value for long and short MM survivals. Methods We assessed a cohort of 181 patients with newly diagnosed multiple myeloma, treated using conventional chemotherapy (regimens MP, VBMCP, VAD, CyVAD). In all the patients we measured proliferative and apoptotic index at the time of diagnosis, before the start of treatment. The proliferative activity of myeloma plasmocytes in bone marrow aspirate was measured by flow- cytometry using propidium-iodide index (PC-PI), representing the percentage of plasma cells in S-phase of the cell cycle; apoptosis was assessed using flow cytometry using an annexin-V (PC-AI) index. Subsequent statistical analysis of the the Kaplan-Meier curves of overall survival was evaluated using the MATLAB routine. We assessed different PC-PI and PC-AI tresholds with the best separation of groups with good and poor prognosis, using the log rank procedure. Additional measures of performance were obtained looking at the success with which two groups selected using the PC-AI and PC-PI thresholds reflected short term and long term survivors. Results The median follow-up of the group was 25 months (range 1 – 117 months). At the time of analysis, 137 patients had died (76%). Plasma cell proliferative index varied in the range 1.2 – 4.2, with median 2.5; apoptotic index was in the range 1.4 – 24.5 with median 4.3. Patients were divided into 4 groups based on PC-PI and PC-AI thresholds and then keeping only those two groups that demonstrated the worst and best overall survival based on the survival analysis of PC-PI and PC-AI individually. The best discriminating values for patients with poor prognosis (n=20) were PC-PI > 3.0% and PC-AI < 4.75%, and for patients with good prognosis (n = 71) PC-PI ' 3.0% and PC-AI ≥ 4.75%, with median overall survival 8 months versus 40 months respectively, p = 0.0002. The precision of the correct prediction of individual patient prognosis based on this grouping was in the patients with short survival 0.70 and in long survivors 0.58. Due to an imbalanced number of patients especially with high proliferation we were unable to create a single significant combined index across the entire patient group. Moreover, the patients outside the defined ranges substantially influenced the sensitivity and especially the specificity of the test, suggesting that defining of the extreme groups using PC-PI and PC-AI creates a better prognosticator than the assessment of the whole cohort based on a single combined index. Conclusion Plasma cell proliferation and apoptosis reflect different processes of MM kinetics with the growth characteristics on one hand, and survival on the other. Their assessment as single factors provides valuable information about the biology of the clone and contributes to the estimation of overall survival. Their combined measurement, however, significantly separates two extreme groups of patients with different prognosis and may thus become a valuable auxiliary parameter in MM patients stratification. Disclosures No relevant conflicts of interest to declare.
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Arndt, W. J., A. Grazul-Bilska, J. S. Caton, E. Borowczyk, P. P. Borowicz, M. A. Ward, D. A. Redmer, L. P. Reynolds, and K. A. Vonnahme. "231 CELLULAR PROLIFERATION IN FETAL OVARIAN FOLLICLES FROM LATE PREGNANT SHEEP FED MAINTENANCE OR RESTRICTED DIETS WITH NORMAL OR ENHANCED SELENIUM CONCENTRATIONS." Reproduction, Fertility and Development 18, no. 2 (2006): 224. http://dx.doi.org/10.1071/rdv18n2ab231.
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Hypertrophy and hyperplasia are the major processes for tissue growth and development. The fetal ovaries represent a type of tissue that expresses high cellular proliferation rates. Selenium (Se) is a mineral that has diverse biological functions and affects cellular proliferation in numerous tissues including cancer, digestive tract, and placenta. It has been demonstrated that levels and sources (organic vs. inorganic) of Se may affect tissue growth. This experiment was designed to determine whether maternal consumption of differing levels of energy and Se impacts cell proliferation in fetal ovarian follicles. Sheep (n = 36) were fed a maintenance (M; 2.12 Mcal/kg) or energy restricted (ER; 60% of maintenance; nutrition restriction occurred from Day 50 to Day 135 of pregnancy) diet with high Se (HSe; 81.5 �g/kg body weight) or normal Se (NSe; 7.4 �g/kg body weight) concentration from 21 days before breeding to Day 135 of pregnancy. At slaughter on Day 135 of pregnancy, fetal tissues were collected and fixed in Carnoy's solution. Ovaries (n = 3-6/treatment group) were weighed, sectioned (one section along the longitudal axis/ovary) and stained for the presence of proliferating cell nuclear antigen (PCNA), a marker for proliferating cells. To determine the proportion of proliferating primordial follicles or the labeling index (percentage of proliferating cells; Jablonka-Shariff et al. 1994 Biol. Reprod. 51, 531) for primary, secondary, and antral follicles, digital images of the tissues were taken and analyzed using a computerized image analysis program (Image-Pro Plus; Media Cybernetics, Inc., Silver Spring, MD, USA). The primordial follicle was considered as proliferating when at least one granulosa cell was PCNA-positive. The number of proliferating and non-proliferating cells was determined for granulosa of primary follicles (n = 225 total) and for granulosa and theca cells of secondary (n = 198) and antral (n = 96) follicles, and used to calculate the labeling index. The data were analyzed using the general linear models procedure of SAS (SAS Institute, Inc., Cary, NC, USA). The number of proliferating primordial follicles was decreased (P < 0.05) by restricted energy diet and Se treatment (11.9 � 1.7 for NSe-M diet vs. 7.2 � 1.3 for HSe-M diet and 8.3 � 0.8 for NSe-ER diet vs. 4.7 � 0.8 for HSe-ER diet). However, energy restriction or Se did not affect labeling index in primary, secondary, and antral follicles. The labeling index was similar for theca and granulosa cells from secondary, or antral follicles. The labeling index was greatest (P < 0.05) for antral, less for secondary and least for primary follicles (24.2 � 1.1% vs. 20.2 � 0.7% vs. 13.3 � 0.4%). These results demonstrate that both level of energy and Se in the maternal diet affects cellular proliferation in primordial but not in primary, secondary, or antral follicles in fetal ovaries. In addition, cellular proliferation increases as fetal follicular development progresses. These data indicate that level of energy and Se in the maternal diet may impact fetal ovarian development during the early stage of folliculogenesis. This work ws supported by USDA grant 2005-35206-15281 and Hatch Project ND01712.
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McKeever, P. E., L. Junck, M. S. Strawderman, M. Blaivas, A. Tkaczyk, M. A. Cates, M. Yan, and L. Li. "Proliferation index is related to patient age in glioblastoma." Neurology 56, no. 9 (May 8, 2001): 1216–18. http://dx.doi.org/10.1212/wnl.56.9.1216.
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Narra, Krishna, Rachel Factor, and Mohamed E. Salama. "Proliferation Index in Breast Cancer: Is Digital Imaging Accurate?" American Journal of Clinical Pathology 138, suppl 2 (November 1, 2012): A242. http://dx.doi.org/10.1093/ajcp/138.suppl2.188.
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Wang, Sa A., Lan Wang, Ephraim P. Hochberg, Alona Muzikansky, Nancy Lee Harris, and Robert P. Hasserjian. "Low Histologic Grade Follicular Lymphoma With High Proliferation Index." American Journal of Surgical Pathology 29, no. 11 (November 2005): 1490–96. http://dx.doi.org/10.1097/01.pas.0000172191.87176.3b.
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Veronese, S. M., M. Gambacorta, O. Gottardi, F. Scanzi, M. Ferrari, and P. Lampertico. "Proliferation index as a prognostic marker in breast cancer." Cancer 71, no. 12 (June 15, 1993): 3926–31. http://dx.doi.org/10.1002/1097-0142(19930615)71:12<3926::aid-cncr2820711221>3.0.co;2-2.
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Mahtani, Reshma, Yuan Yuan, Kari B. Wisinski, Jay Morris, Max Salganik, Yi Zhang, Catherine A. Schnabel, and Vk Gadi. "Abstract PD9-09: Breast cancer index and assessment of tumor proliferation by molecular grade index (MGI) within distinct HOXB13/IL17BR (H/I) subsets." Cancer Research 82, no. 4_Supplement (February 15, 2022): PD9–09—PD9–09. http://dx.doi.org/10.1158/1538-7445.sabcs21-pd9-09.
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Abstract Background: Previous studies have demonstrated that proliferation- and ER-associated gene expression shows a time-dependent interaction with risk of recurrence. Breast Cancer Index (BCI) is a gene expression-based test that integrates biomarker panels of both proliferation (Molecular Grade Index, MGI), and endocrine response (HOXB13/IL17BR, H/I). BCI has been validated as a significant and independent prognostic factor both for risk of overall (0-10y) and late (>5y) distant recurrence and is predictive of extended endocrine benefit in patients with early-stage, hormone receptor-positive (HR+) breast cancer. In this study, correlative analyses were performed to evaluate molecular measures of proliferation and ER signaling by MGI and H/I that underly recurrence risk across clinical categories in patients receiving BCI testing as part of routine care. Methods: Analysis was performed using the BCI Clinical Database for Correlative Studies, an IRB-approved de-identified database which contains >50 data elements including clinicopathologic and molecular variables from 19,126 clinical cases submitted for BCI testing. Descriptive analyses assessed the distribution of MGI by H/I categories based on time of testing or BCI intervention point (time of diagnosis <1y for early recurrence vs 4-7y post diagnosis for late recurrence), lymph node status (N0 vs. N+), age (<50y vs. ≥50y), tumor size (T1-T3), and grade (1-3) to understand the molecular features that may be associated with recurrence in HR+ disease. Results: Analysis included 18,853 patients (88% ≥50y, 73% N0, 70% pT1, 51% grade 2). Comparative analysis of patients tested with BCI at <1y vs. those recurrence-free and tested at 4-7y post diagnosis showed a similar proportion of patients in the H/I categories (H/I-High: 44%1y, 43% 4-7y, P=0.510). An increased proportion of MGI-High was observed in 4-7y (61%) vs. 1y (53%) (P<0.001). The distribution of MGI categories within H/I-Low and High subsets was also similar based nodal status (N0 vs. N+), age (<50y vs. ≥50y), and tumor size. However, H/I status was inversely proportional to tumor grade (P<0.001): the proportion of H/I-Low decreased with increasing grade (Grade 1: 70%, 2: 59%, 3: 36%), whereas the proportion of H/I-High patients increased (Grade 1: 30%, 2: 41%, 3: 64%). In the H/I-Low subset, as grade increased, the proportion of MGI-Low patients decreased (1: 45%, 2: 23%, 3: 5%), while MGI-High remained relatively consistent across grade (1: 25%, 2: 36%, 3: 31%). In H/I-High patients, MGI-High increased as grade increased (1: 11%, 2: 26%, 3: 59%). Conclusion: BCI functional characterization using MGI for tumor proliferation and H/I for estrogen signaling in this large-scale analysis showed that over half (59%,1y vs. 67%, 4-7y) of endocrine responsive tumors (H/I-High) were also highly proliferative (MGI-High) irrespective of time of testing. Results showed that tumor grade correlated with MGI and H/I status, indicating that a subset of high-grade tumors were highly proliferative as well as endocrine responsive. These findings suggest that proliferation and endocrine signaling are combinatorial molecular drivers of recurrences in HR+ breast cancer. Table 1.Biomarker categorization by H/I and MGI status by time of testing, nodal status, age, tumor size, and grade.H/I-LowH/I-HighPatientsNMGI-Low (%)MGI-High (%)MGI-Low (%)MGI-High (%)Time of testing<1y1278282718264-7y1305725321429Nodal StatusN0950227311428N+344222311631Age<50y475824361129≥50y1409526301529Tumor SizeT1464930311524T2182619321435T319927311527Grade1224245251911239812336152631530531559 Citation Format: Reshma Mahtani, Yuan Yuan, Kari B Wisinski, Jay Morris, Max Salganik, Yi Zhang, Catherine A Schnabel, Vk Gadi. Breast cancer index and assessment of tumor proliferation by molecular grade index (MGI) within distinct HOXB13/IL17BR (H/I) subsets [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD9-09.
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Wu, Vernon, Muhammed A. Salyana, Mohammed Abdelwahed, Jacqueline Barrientos, Steven L. Allen, Jonathan E. Kolitz, Kristin Sticco, and Joanna M. Rhodes. "Clinical Outcomes of Low Histologic Grade Follicular Lymphoma with High Proliferation Index." Blood 138, Supplement 1 (November 5, 2021): 3552. http://dx.doi.org/10.1182/blood-2021-149525.
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Abstract Background: Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin lymphoma (NHL) accounting for ~35% of NHL and often have a clinically indolent course. PET/CT max SUV ≥10 and high proliferative index are associated with FL at high risk for transformation to aggressive lymphoma (Schöder, 2005; Rossi, 2020). A subset of patients (pts) with low histologic grade and high proliferation index (LG-HPI) have a more aggressive clinical course with inferior overall survival (OS) compared to low grade, low proliferation index (LG-LPI) FL patients (Wang, 2005). The aim of our study was to identify outcomes for patients with LG-HPI FL at our institution. Methods: We conducted a single center, retrospective study of FL diagnosed from 1/1/2015-1/1/2021. Demographic information, diagnoses, laboratory results, medications, pathology, and radiology reports were collected from pts' electronic medical records. Pathology specimens were de-identified and retrospectively reviewed by two pathologists. Review included comprehensive evaluation of histologic grade, proliferation index by Ki-67 percentage (Ki-67%), immunohistochemical staining, and c-MYC immunohistochemical staining. Biopsies were classified as LG-LPI if Grade 1-2 and Ki-67 was <30%, LG-HPI if Grade 1-2 and Ki-67 was ≥30%, and high grade (HG) if Grade 3A or 3B. The primary endpoint was progression free survival (PFS) defined as time from treatment until time of progression and last known follow up as determined by Kaplan-Meier method. OS was calculated from time of diagnosis to last follow up or death by Kaplan-Meier method. Comparisons were made using Log-rank model and Cox Proportional Hazards Model. Time to first treatment (TTFT) was calculated as time from diagnosis to first treatment. Receiver operating curve (ROC) was used to determine correlation between PET SUV values (defined as ≥10, or <10) and Ki-67%. Results: 152 pts were diagnosed with FL and included for analysis. Patient characteristics are summarized in Table 1. Median age at diagnosis for all pts was 65.9 years. Sixty-three pts had LG-LPI, 61 LG-HPI, and 28 HG pts. Ten pts transformed to DLBCL (2 LG-LPI, 5 LG-HPI, 3 HG). Treatment regimens included initial observation (n = 44), anti-CD20 therapy alone (n = 24), chemo-immunotherapy (n = 53), and other (n = 31). Median TTFT was 1.27 mo (range 0-115.2 mo). There was moderate correlation between SUV of biopsied lesion ≥10 and Ki-67 percentage (ROC Area 0.6175). Median PFS was longer for LG-LPI compared to LG-HPI (78.6 vs 57.8 mo, p = 0.04, HR 2.37) but not between LG-HPI and HG (57.8 vs 61.3 mo respectively, p = 0.32) (Figure 1A). Median OS was not reached in any cohort with median follow up of 29.5 mo. There was no difference in OS between LG-LPI vs LG-HPI (p = 0.53) (Figure 1B). Histologic grade, proliferation index, Ann Arbor Staging, FLIPI score, PET/CT SUV intensity (max or of biopsied lesion), presence of c-Myc staining, or initial treatment regimen were not associated with median PFS or OS in either subgroup on univariate analysis. Conclusions: In our cohort, PFS was shorter for LG-HPI compared to LG-LPI but with a similar trajectory to that of HG FL, consistent with prior reports. No differences were seen in OS between LG-HPI and LG-LPI, and no covariates of interest including histologic grade, proliferation index, Ann Arbor Staging, FLIPI score, PET/CT SUV intensity, presence of c-Myc staining, or initial treatment regimen were associated with differences in PFS or OS. Our study is limited by a short follow up time compared to prior published cohorts (29.5 vs 98.4 mo). PET/CT SUV values of ≥10 have moderate predictive value for higher proliferative disease and can aid in identifying patients with higher proliferative disease. Longer follow up is needed to determine if LG-HPI impacts OS. References: 1. SchöderH, et al. Intensity of 18fluorodeoxyglucose uptake in positron emission tomography distinguishes between indolent and aggressive non-Hodgkin's lymphoma. J Clin Oncol 2005;23:4643-51. 2. Rossi C, et al. Baseline SUVmaxis related to tumor cell proliferation and patient outcome in follicular lymphoma. Haematologica 2020;Online ahead of print. 3. Wang SA, et al. Low histologic grade follicular lymphoma with high proliferation index: morphologic and clinical features. Am J Surg Pathol2005;29:1490-6. Figure 1 Figure 1. Disclosures Allen: Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees; C4 Therapeutics: Other: Equity Ownership; Bristol Myers Squibb: Other: Equity Ownership; Alexon: Research Funding. Rhodes: Conquer Cancer Foundation Young Investigator Award: Other: Grant/Research Support; AbbVie, Genentech, Pharmacyclics, TG Therapeutics: Other: Consultant.
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Santos, F. G. A., L. Moro, G. D. Cassali, T. A. Paixão, P. P. Campos, S. S. Silva, and A. C. Vasconcelos. "Cell proliferation markers in the transplanted canine transmissible venereal tumor." Arquivo Brasileiro de Medicina Veterinária e Zootecnia 63, no. 6 (December 2011): 1345–52. http://dx.doi.org/10.1590/s0102-09352011000600010.
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Adult male mongrel dogs were subcutaneously transplanted with the canine transmissible venereal tumor (TVT) on the hypogastric region. Twelve specimens of tumors were collected, half during the proliferative phase and the other half during the regressive phase. Fragments of the tumor were fixed in 10% buffered formalin and routinely processed for light microscopy. Sections of 4µm were stained by Schorr or AgNOR or either immunostained for MIB1 (Ki67). Schorr stain, AgNOR and MIB1 showed an increased proliferative activity through mitotic index, nuclear argyrophilic protein stain and cycling tumoral cells in the growing tumors, respectively. All of the three cell proliferation markers were able to distinguish the TVT in both evolution phases. MIB1 monoclonal antibody was the best in the morphologic evaluation of growth and regression of TVT. This resulted in higher values than AgNORs counting and mitotic index. MIB1 immunostaining was the most effective parameter of the proliferative activity of TVT. However, a significant correlation has been detected only between mitosis counting and AgNORs.
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Buus, Richard, Ivana Sestak, Ralf Kronenwett, Sean Ferree, Catherine A. Schnabel, Frederick L. Baehner, Elizabeth A. Mallon, Jack Cuzick, and Mitch Dowsett. "Molecular Drivers of Oncotype DX, Prosigna, EndoPredict, and the Breast Cancer Index: A TransATAC Study." Journal of Clinical Oncology 39, no. 2 (January 10, 2021): 126–35. http://dx.doi.org/10.1200/jco.20.00853.
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PURPOSE The Onco type DX Recurrence Score (RS), Prosigna Prediction Analysis of Microarray 50 (PAM50) Risk of Recurrence (ROR), EndoPredict (EP), and Breast Cancer Index (BCI) are used clinically for estimating risk of distant recurrence for patients receiving endocrine therapy. Discordances in estimates occur between them. We aimed to identify the molecular features that drive the tests and lead to these differences. PATIENTS AND METHODS Analyses for RS, ROR, EP, and BCI were conducted by the manufacturers in the TransATAC sample collection that consisted of the tamoxifen or anastrozole arms of the ATAC trial. Estrogen receptor–positive/human epidermal growth factor receptor 2 (HER2)–negative cases without chemotherapy treatment were included in which all four tests were available (n = 785). Clinicopathologic features included in some tests were excluded from the comparisons. Estrogen, proliferation, invasion, and HER2 module scores from RS were used to characterize the respective molecular features. Spearman correlation and analysis of variance tests were applied. RESULTS There were moderate to strong correlations among the four molecular scores (ρ = 0.63-0.74) except for RS versus ROR (ρ = 0.32) and RS versus BCI (ρ = 0.35). RS had strong negative correlation with its estrogen module (ρ = −0.79) and moderate positive correlation with its proliferation module (ρ = 0.36). RS’s proliferation module explained 72.5% of ROR’s variance, while the estrogen module explained only 0.6%. Most of EP’s and BCI’s variation was accounted for by the proliferation module (50.0% and 54.3%, respectively) and much less by the estrogen module (20.2% and 2.7%, respectively). CONCLUSION In contrast to common understanding, RSs are determined more strongly by estrogen-related features and only weakly by proliferation markers. However, the EP, BCI, and particularly ROR scores are determined largely by proliferative features. These relationships help to explain the differences in the prognostic performance of the tests.
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Sato, Koichiro, Masaaki Yamaguchi, and Takanori Ishida. "Triple Negative and Younger Cases in Breast Cancer Showed Higher Ki–67 Proliferation Index, Nuclear Grade and Histological Grade." Nihon Gekakei Rengo Gakkaishi (Journal of Japanese College of Surgeons) 38, no. 4 (2013): 721–25. http://dx.doi.org/10.4030/jjcs.38.721.
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Sikka, K., S. C. Sharma, A. Thakar, and S. Dattagupta. "Evaluation of epithelial proliferation in paediatric and adult cholesteatomas using the Ki-67 proliferation marker." Journal of Laryngology & Otology 126, no. 5 (December 14, 2011): 460–63. http://dx.doi.org/10.1017/s002221511100315x.
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AbstractIntroduction:The aggressiveness of cholesteatoma in children compared with adults is well known. However, the factors influencing the poorer prognosis of paediatric cholesteatoma are not well understood. This study compared the proliferative potential of paediatric cholesteatoma with that of adult cholesteatoma, using Ki-67 as a proliferation marker.Methods:A prospective study of 67 patients with aural cholesteatoma was performed. Thirty-eight adult and 29 paediatric cases were evaluated using clinical parameters including bone erosion, complications and extent of disease. A surgical specimen underwent histological evaluation and measurement of the proliferation index using Ki-67 labelling. Normal epithelium from a control group was also examined.Results:Cholesteatoma epithelium has a greater rate of proliferation than normal skin. There were however no statistical differences between the paediatric and adult cholesteatoma groups in terms of clinical behaviour or proliferation potential. Paediatric cholesteatoma was similar to adult cholesteatoma in terms of complications, bone erosion and disease spread.Conclusion:Cholesteatoma is a disorder of epithelial proliferation. Although postulated to be more aggressive in children than adults, this study found no clinicopathological differences between paediatric and adult cases.
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Altunbas, K., A. Yagci, A. Bulbul, A. Sevimli, and V. Özdemir. "Effect of Ovarian Steroids on Colonic Epithelial Cell Proliferation and Apoptosis in Rats." Acta Veterinaria Brno 76, no. 4 (2007): 605–12. http://dx.doi.org/10.2754/avb200776040605.
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The aim of this study was to investigate the effects of steroid hormones on proliferation and apoptosis in the colon crypt epithelium. The research was conducted on adult ovariectomized (Ovx) rats (Sprague Dawley). Ovx rats were injected for 15 days with 0.2 ml of sesame oil (control; C), or 17β-oestradiol (10 μg/d; E), or progesterone (2 mg/d; P), or E + P. Proliferative activity in the colon was assessed by using proliferating cell nuclear antigen (PCNA) antibody. The proliferation index (PI), the number of PCNA positive cells divided by the total number of cells counted in the crypt column multiplied by 100, was calculated. PI was lower in the hormonetreated groups, especially in group P compared to that in group C. The apoptotic index (AI), the mean number of apoptotic cells, was detected by active caspase 3 immunoreactivity per crypt in the colon. AI was lower in the colon crypt epithelium of group E than that of the other groups. However, AI in the colon crypt epithelium in groups P and E + P was higher than that of both group E and group C. In addition, the colon crypt size (the number of epithelial cells lining one side of 10 well-oriented, longitudinally cut crypts) was considerably lower in group E than that of the other groups. In conclusion, we showed that the decrease of AI in group E was balanced by progesterone; the decrease of PI in group P was also depressed by oestrogen.
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Al-Bahlani, Shadia M., Ruqaya M. Al-Rashdi, Shiyam Kumar, Shadia S. Al-Sinawi, Maiya A. Al-Bahri, and Asem A. Shalaby. "Calpain-1 Expression in Triple-Negative Breast Cancer: A Potential Prognostic Factor Independent of the Proliferative/Apoptotic Index." BioMed Research International 2017 (2017): 1–10. http://dx.doi.org/10.1155/2017/9290425.
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Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer in which calpain system plays an important role in its cellular processes including apoptosis and proliferation. Although such roles have been assessed in tumor pathogenesis, the correlation of its expression to the proliferating/apoptotic index has not been studied yet. Immunohistochemical staining of calpain-1 was performed on paraffin-embedded tissues to correlate its expression with clinicopathological variables and outcome. The proliferation activity was determined by calculating the percentage of cells expressing the Ki-67 antigen. The apoptotic index was assessed morphologically and biochemically using Haematoxylin & Eosin method and Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, respectively. Calpain-1 was significantly expressed in TNBC tissues varying from low to high with a significant correlation to lymph node status but not with the other clinicopathological variables, suggesting its role as a prognostic factor. In addition, a positive correlation was found between both apoptotic counts assays (P<0.001, r=0.547) as well as with proliferation (P=0.045). Calpain-1 expression had no significant correlation with either proliferation (P=0.29) or apoptotic indices (P=0.071 and P=0.100). Determining calpain-1 expression may provide relevant prognostic value for TNBC cancer patients.
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Ozolek, John A., E. Leon Barnes, and Jennifer L. Hunt. "Basal/Myoepithelial Cells in Chronic Sinusitis, Respiratory Epithelial Adenomatoid Hamartoma, Inverted Papilloma, and Intestinal-Type and Nonintestinal-Type Sinonasal Adenocarcinoma: An Immunohistochemical Study." Archives of Pathology & Laboratory Medicine 131, no. 4 (April 1, 2007): 530–37. http://dx.doi.org/10.5858/2007-131-530-mcicsr.
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AbstractContext.—The pathogenesis of respiratory epithelial adenomatoid hamartoma (REAH) and inverted papilloma (IP) is poorly understood, especially compared with sinonasal adenocarcinoma (SNAC). One feature of malignant glandular lesions is loss of the basal/myoepithelial layer. The immunophenotype of the basal/myoepithelial layer has not been fully examined in benign glandular lesions of the sinonasal tract.Objective.—To examine benign and malignant glandular lesions in the sinonasal tract for the immunophenotype of basal/myoepithelial cells, proliferation index, and cytokeratin and intestinal differentiation profiles.Design.—Sinonasal adenocarcinoma (intestinal-type adenocarcinoma [ITAC] and nonintestinal type adenocarcinoma [non-ITAC]), REAH, IP, and chronic sinusitis (CS) were stained for cytokeratin (CK) 7, CK20, 34βE12, CDX-2, p63, Ki-67, smooth muscle actin (SMA), S100 protein, and calponin.Results.—Basal/myoepithelial cells in CS and REAH were positive for p63 and 34βE12 but negative for SMA, S100 protein, and calponin. Proliferative activity was localized to the compartment containing p63-positive cells. Inverted papilloma demonstrated broad areas staining for p63 and 34βE12, with intermediate proliferative activity in these areas. Sinonasal adenocarcinoma had the highest Ki-67 labeling index, and p63-positive SNACs had higher proliferation indices than p63-negative SNACs. REAH, IP, CS, and most SNACs expressed CK7. Only SNAC expressed CK20. Sixty percent of morphologic ITACs expressed CDX-2.Conclusions.—Basal/myoepithelial cells in CS and REAH should be considered basal and not myoepithelial cells. In benign lesions, proliferative activity is limited to the compartments with p63 staining. In SNAC and IP, p63 expression correlates with proliferation index. REAH, IP, and CS share similar immunoprofiles (CK7+, CK20−, and CDX-2−), contrasting with SNAC (CK7+, CK20+/−, CDX-2−/+).