scholarly journals Markers of cell proliferation in a GH-producing adenoma of a patient treated with pegvisomant

2005 ◽  
Vol 153 (2) ◽  
pp. 203-205 ◽  
Author(s):  
W M Drake ◽  
D M Berney ◽  
K Kovacs ◽  
J P Monson

We report our findings on markers of cell proliferation (Ki-67 labelling index and topoisomerase-α expression) in a somatotroph pituitary tumour before and after exposure to pegvisomant, a GH receptor antagonist developed for the treatment of acromegaly. Specimens from two separate pituitary operations, separated by a period of 17 years that included 4 years of pegvisomant treatment, were stained for markers of cellular proliferation. Ki-67 labelling index and topoisomerase-α expression were both markedly greater (1–3% compared with 0–0.5% and 15–80% compared with 2–10% respectively) in the pegvisomant-exposed tumour compared with the earlier specimen. Clearly, caution must be exercised when interpreting findings from a single case, particularly one sufficiently refractory to conventional therapies to require treatment with pegvisomant. However, our data reinforce the requirement for careful radiological surveillance of the pituitary in the context of a drug that does not target the tumour responsible and where serum GH cannot serve as a marker of disease activity or tumour size.

2015 ◽  
Vol 59 (2) ◽  
pp. 255-261
Author(s):  
Gulbin Sennazli ◽  
Funda Yildirim ◽  
Seckin Serdar Arun ◽  
Aydin Gurel ◽  
Kivilcim Sonmez

Abstract The objective of this study was to investigate the correlation between different histological types and grades of canine malignant mammary tumours, tumour cell proliferation and their angiogenic activity using immunohistochemical markers. Mammary tissue samples from 47 bitches with mammary cancer were evaluated. The expression of cellular proliferation marker Ki-67 and endothelial marker Von Willebrand’s factor (vWF) were immunohistochemically demonstrated. The tumours with the highest Ki-67 and vWF expressions were found to share similar histomorphological features. Simple solid carcinoma had the highest levels of Ki-67, vWF, and higher histological grade while complex carcinomas, osteosarcomas, and carcinosarcomas had the lowest ones. The differences between the expressions of Ki-67 and vWF in different tumour types were considered to be of great importance in determination of biological behaviour and prognosis of these tumours. This study is one of the few studies that evaluate these differences among the subtypes of malignant canine mammary tumours


2007 ◽  
Vol 330-332 ◽  
pp. 1305-1308 ◽  
Author(s):  
Hirotaka Maeda ◽  
Emile Hideki Ishida ◽  
Toshihiro Kasuga

A novel poly(lactic acid) (PLA)/calcium carbonates hybrid membrane containing siloxane was prepared using aminopropyltriethoxysilane (APTES) for biodegradable bone guided regeneration. The PLLA in the membrane was an amorphous phase. By heating the membrane at 100 °C for 1 h, the PLLA in the membrane crystallized. Numerous pores of 0.5-1 ,m in diameter were newly formed at the surface. After soaking the membranes before and after heat-treatment in simulated body fluid, the amount of silicon species in SBF released from the membrane after heat-treatment was higher than that before heat-treatment. A test of osteoblast-like cellular proliferation on the membrane showed the membrane after heat-treatment has much higher cell-proliferation ability than that before heat-treatment.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Ramón Gil Carreón-Burciaga ◽  
Rogelio González-González ◽  
Nelly Molina-Frechero ◽  
Ronell Bologna-Molina

Cell proliferation assays are performed using antibodies against nuclear proteins associated with DNA replication. These nuclear proteins have gained special interest to predict the biological and clinical behaviors of various tumors. The aim of this study was to analyze the presence of Ki-67 protein and the minichromosome maintenance-2 (MCM2) and maintenance-3 (MCM3) proteins in ameloblastoma.Materials and Methods. Cell proliferation marker expression levels were assessed via immunohistochemistry in 111 ameloblastoma cases (72 unicystic ameloblastoma samples, 38 solid/multicystic ameloblastoma samples, and 1 ameloblastic carcinoma). The label index was performed as described previously.Results.MCM2 and MCM3 showed higher proliferation indexes in all variants of ameloblastoma compared to the classic marker Ki-67. No correlation between the proliferation index and the clinical and protein expression data was observed.Conclusion.The results suggest that clinical features do not directly affect tumor cell proliferation. Moreover, the high levels of cellular proliferation of MCM2 and MCM3 compared with Ki-67 may indicate that MCM2 and MCM3 are more sensitive markers for predicting the growth rate and eventually might be helpful as a tool for predicting aggressive and recurrent behaviors in these tumors.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16045-16045
Author(s):  
J. Deloia ◽  
S. D. Richard ◽  
R. P. Edwards ◽  
E. Elishaev ◽  
S. Mason ◽  
...  

16045 Background: New imaging modalities for ovarian cancer disease burden are needed. Positron emission tomography (PET) with [F-18] fluorodeoxyglucose (FDG) has shown promise for early prediction of outcome and response to therapy when compared to CT alone. Recent studies have suggested that 3’-fluoro-3’ [F-18] deoxythymidine (FLT) has a higher specificity than FDG. The objective of this study was to correlate FLT tracer uptake with different in vitro quantitation of cellular proliferation. Methods: Patients with suspected or know ovarian cancer and an elevated Ca 125 were recruited for this trial. These patients were injected with 5 mCi of [F-18]FLT intravenously as a slow bolus. After an uptake period of 60 minutes, patients were scanned for approximately 36 minutes by CT and then PET, and images were co- registered. Standardized uptake values (SUV) of both hot and cold areas were obtained and these lesions were biopsied at the time of surgery. Tissue was divided and used for Ki-67 proliferation index staining to determine mitotic index, RNA isolation for rt-PCR for thymidine kinase-1 (TK1) levels, and grown ex vivo for cell proliferation analysis. Univariate analysis was preformed using the student's t-test. Results: PET positive lesions were found to have a significantly increased mitotic index when compared to control lesions (0.134 vs. 0.004, p<0.001). There were no significant differences in relative TK1 levels or ex vivo cell proliferation ability between PET positive and control lesions in the initial four patients. Conclusions: Increased mitotic index by Ki-67 staining correlates with increased FLT activity by PET scan, but not TK1 levels or DNA content. We will continue to explore this modality as compared to FDG-PET in patients with ovarian cancer. No significant financial relationships to disclose.


2004 ◽  
Vol 9 (1) ◽  
Author(s):  
W.F.P. GREATTI ◽  
A.S. AMARAL ◽  
S.B. SILVA ◽  
L.F.J. GASPAR ◽  
L.F. BARBISAN ◽  
...  

A citologia aspirativa com agulha fina (CAAF) foi usada como método de colheita de quinze amostras de tumor venéreo transmissível (TVT)em cães, oriundos do atendimento do Hospital Veterinário-FMVZ-UNESP de Botucatu, antes e após o início da quimioterapia. As amostras citológicas foram submetidas ao cálculo do índice mitótico e à avaliação de índices de proliferação por métodos citoquímico (concentração eletrolítica crítica – CEC) e imunocitoquímico (Ki-67, clone MIB-1). Todas as técnicas mostraram-se adequadas para avaliar a taxa proliferativa em amostras citológicas. O CEC permitiu observar que a aplicação do quimioterápico levou a uma redução significativa da proliferação celular. Em vista disso, conclui-se que essa metodologia pode ser aplicada para diagnosticar e monitorar o TVT. Proliferation indexes determination by CEC and Ki-67 in fine needle aspiration cytology of transmissible venereal tumor Abstract Fine needle aspiration biopsy (FNAB) was used to collect fifteen transmissible venereal tumor (TVT) samples from dogs at the Veterinary Hospital - FMVZ - UNESP Botucatu, São Paulo, Brazil, before and after beginning of chemotherapy. The cytological samples were submitted to determination of mitotic and proliferation indexes by means of cytochemical (critical electrolyte concentration – CEC) and immunocytochemical (Ki-67, MIB-1 clone) methods. All the techniques were adequate for the evaluation of proliferation rates displayed by the cytological samples. The CEC allowed the observation that chemotherapy induces to significant reduction in cellular proliferation. Thus, was concluded that this methodology is suitable to perform TVT diagnosis and monitoration.


Gut ◽  
1997 ◽  
Vol 41 (6) ◽  
pp. 740-747 ◽  
Author(s):  
A E Berstad ◽  
J G Hatlebakk ◽  
H Maartmann-Moe ◽  
A Berstad ◽  
P Brandtzaeg

Background—Helicobacter pylorigastritis may spread proximally in the stomach during profound acid inhibition.Aims—To examine histological gastric body changes and epithelial cell proliferation before and after treatment with lansoprazole.Patients and methods—Patients diagnosed as having reflux oesophagitis grade 1 or 2 were enrolled and treated for 12 weeks with lansoprazole (30 mg every morning). After 12 weeks, 103 of the 118 patients appeared endoscopically healed and were asymptomatic; they then received maintenance treatment with 15 or 30 mg lansoprazole daily. Biopsy specimens obtained from similar sites before and after treatment, were available from 90 patients after a median of 64 weeks (range 15–73 weeks). Epithelial cell proliferation was determined by the number of Ki-67 antigen positive cells per gland.Results—Of these 90 patients, 44 (49%) were found to be infected with H pylori. Their median inflammation score had increased from grade 1 before to grade 2 after treatment (p<0.0001). Initially, the number of Ki-67 antigen positive cells per gland was significantly higher in the H pyloriinfected than in the uninfected group and increased further after treatment (p<0.0001). In uninfected patients, no significant change in inflammation or proliferation occurred during treatment.Conclusions—A marked increase in body gastritis was observed in H pylori infected individuals during long term treatment with the proton pump inhibitor lansoprazole. Epithelial cell proliferation and atrophy also increased in infected but not in uninfected patients.


2008 ◽  
Vol 6 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Svjetlana Radović ◽  
Zora Vukobrat-Bijedić ◽  
Ivan Selak ◽  
Mirsad Babić

The aim of the study was to define the distribution of p53, bcl-2 and Ki-67 proteins in the inflammatory-regenerative and dysplastic lesionsof the colon mucosa. The relationship between the presentation of p53, bcl-2 and Ki-67 proteins and the intensity of the inflammatory-regenerative and dysplastic lesions in the colon flat mucosa was investigated as well. Biopsy specimens from 270 patients were examined: 74 were classified as inflammatory-regenerative and 196 as dysplastic lesions (108 mild, 58 moderate, and 30 severe dysplasia). The expression of all three proteins was assessed on the basis of location, quantity, and intensity of immunostaining, by counting antigen positive cells, in comparison with normal mucosa and adenocarcinoma. p53 protein appears only in sporadic cases (6.6%) of severe dysplasia. Bcl-2 expression appears significantly (p<0.005) more often in cases of mild dysplasia (61.1%) compared to inflammatory-regenerative mucosa (14.8%). In cases of mild dysplasia, bcl-2 positive cells were spreading from the lower third to the middle third of the crypts. Bcl-2 expression was maintained through the stadiums of moderate and severe dysplasia (75.8%), where antigen positive cells were found all along the crypts. A significant increase (p<0.005) in the expression of nuclear protein Ki-67 was noticed in the stadiums of moderate (labelling index =26.3) compared to mild dysplasia (labelling index=16.7), and severe (labelling index=36.7) compared to moderate dysplasia, where the zone of cellular proliferation was widen along the whole crypt length. In the process of the development of epithelial dysplasia in the flat mucosa of colon a degree of the gene p53 alteration is low and appears only in sporadic cases of severe dysplasia. Mutation of the bcl-2 gene is involved in the genesis of the lesion but not in its progression to carcinoma. Increased expressionof Ki-67 protein speaks in favour of an increased cellular proliferation which, together with the above mentioned mechanisms, is involved in the process of occurrence and progression of epithelial dysplasia in the flat mucosa of colon.


2020 ◽  
Vol 51 (1) ◽  
pp. 165-175 ◽  
Author(s):  
Lindsey A. Peters-Sanders ◽  
Elizabeth S. Kelley ◽  
Christa Haring Biel ◽  
Keri Madsen ◽  
Xigrid Soto ◽  
...  

Purpose This study evaluated the effects of an automated, small-group intervention designed to teach preschoolers challenging vocabulary words. Previous studies have provided evidence of efficacy. In this study, we evaluated the effects of the program after doubling the number of words taught from 2 to 4 words per book. Method Seventeen preschool children listened to 1 prerecorded book per week for 9 weeks. Each storybook had embedded, interactive lessons for 4 target vocabulary words. Each lesson provided repeated exposures to words and their definitions, child-friendly contexts, and multiple opportunities for children to respond verbally to instructional prompts. Participants were asked to define the weekly targeted vocabulary before and after intervention. A repeated acquisition single-case design was used to examine the effects of the books and embedded lessons on learning of target vocabulary words. Results Treatment effects were observed for all children across many of the books. Learning of at least 2 points (i.e., 1 word) was replicated for 74.5% of 149 books tested across the 17 participants. On average, children learned to define 47% of the target vocabulary words (17 out of 36). Conclusions Results support including 4 challenging words per book, as children learned substantially more words when 4 words were taught, in comparison to previous studies. Within an iterative development process, results of the current study take us 1 step closer to creating an optimal vocabulary intervention that supports the language development of at-risk children.


2001 ◽  
Vol 71 (3) ◽  
pp. 116-125
Author(s):  
Norina Basa ◽  
Daniela Lazar ◽  
Remus Cornea ◽  
Sorina Taban ◽  
Melania Ardelean ◽  
...  

Alteration of β-catenin expression is involved in the development and evolution of hepatocellular carcinoma (HCC); β-catenin is able to influence tumor cell proliferation. We analyzed the immunohistochemical (IHC) expression of β-catenin on a group of 32 patients diagnosed with HCC using the anti-β-catenin monoclonal antibody (clone E247). We correlated the expression of β-catenin with the proliferation index of Ki-67 (PI Ki-67), the mitotic index (MI) and other clinical and pathological features. We observed an altered β-catenin expression in 58.38% of all HCC cases. This expression was insignificantly correlated with tumor size (]5 cm) (p = 0.683), histological grade G1-G2 (p = 0.307), vascular invasion (p = 0.299) and advanced pT stage (p = 0.453); we obtained a significantly higher MI in HCC with altered β-catenin expression (p = 0.018), as compared to HCC without overexpression (1.66 � 1.37) (p = 0.038) and a PI Ki-67 of 22.49 � 20.1 and 28.24 � 18.2, respectively in tumors with altered β-catenin expression with insignificant differences compared to HCC without overexpression (25.95 � 15.2) (p = 0.682 and p = 0.731, respectively). According to the results we obtained, aberrant β-catenin expression in HCC was correlated with a high mitotic index, therefore playing an important role in tumor progression by stimulating tumor cell proliferation; non-nuclear β-catenin overexpression can have a pathological significance in HCC, especially in cases of HCC associated with hepatitis B virus (HBV) infection.


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