Spatial concordance of tumor proliferation and accelerated repopulation from pathologic images to 18F-FLT PET images.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23100-e23100
Author(s):  
Xue Meng ◽  
Xiaoli Zhang ◽  
Xindong Sun ◽  
Jinming Yu
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Treatment Time ◽  
Treatment Plan ◽  
Tumor Cell Proliferation ◽  
Ki 67 ◽  
Fractionated Radiotherapy ◽  
Flt Pet ◽  
Accelerated Repopulation ◽  
Spatial Concordance

e23100 Background: PET imaging with 18F-fluorothymidine (18F-FLT) can potentially be used to identify tumor subvolumes for selecting dose escalation in radiation therapy. The aim of this study was to monitor tumor cell proliferation and repopulation during fractionated radiotherapy and investigated the spatial concordance of tumor cell proliferation and repopulation with 18F-FLT tracer uptake. Methods: Mice bearing A549 xenograft tumors were assigned to 5 different irradiated groups (3f/6d, 6f/12d, 9f/18d, 12f/24d and 18f/36d) with 2 Gy/fractions and non-irradiated group. Serial 18F-FLT micro PET scans were performed at different time points, the maximum of standard uptake value (SUVmax) were measured to detect the feasible time of tumor repopulation during irradiation. Ex vivo images of the spatial pattern of intratumor 18F-FLT uptake and Ki-67 labeling index (LI) were obtained from thin tumor tissue sections. A layer-by-layer comparison between SUVmax and Ki-67 LI results, including the thresholds at which maximum overlap occurred between FLT-segmented areas and areas of active cell proliferation, were conducted to evaluate the spatial imaging pathology correlation. Results: The SUVmax were observed decreases in the 3f/6d group (P = 0.000), compared to these for non-irradiated tumors. However, it was significantly increased in the 6f/12d later, and then gradually reduced with treatment time prolonged again after 6f/12d group. Proliferation changes on pathology imaging at 6f/12d were also confirmed. Significant correlations were found between the SUVmax and Ki-67 LI of all ROIs in each in vitro tumor of cell proliferation group (Ps < 0.001). Similar results were also found in each tumor of accelerated repopulation group (Ps < 0.001). Furthermore, both of the mean ORRs were more than 50% in all layer of the tumor cell proliferation and accelerated groups. Regions of high-intensity 18F-FLT uptake in the autoradiographs exhibited prominent staining for Ki-67. Conclusions: 18F-FLT PET may be a promising imaging surrogate of tumor proliferative response to fractionated radiotherapy and might help make adaptive radiation oncology treatment plan.

Expression of β-Catenin in Hepatocellular Carcinoma

2001 ◽  
Vol 71 (3) ◽  
pp. 116-125
Author(s):  
Norina Basa ◽  
Daniela Lazar ◽  
Remus Cornea ◽  
Sorina Taban ◽  
Melania Ardelean ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Mitotic Index ◽  
Histological Grade ◽  
Proliferation Index ◽  
Tumor Cell Proliferation ◽  
Ki 67 ◽  
B Virus ◽  
Development And Evolution

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.

scholarly journals BAP31 Promotes Tumor Cell Proliferation by Stabilizing SERPINE2 in Hepatocellular Carcinoma

2020 ◽  
Vol 8 ◽  
Author(s):  
Xiyang Zhang ◽  
Dongbo Jiang ◽  
Shuya Yang ◽  
Yuanjie Sun ◽  
Yang Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Colony Formation ◽  
Clinical Stage ◽  
Tumor Cell Proliferation ◽  
Ki 67 ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) patients are mostly diagnosed at an advanced stage, resulting in systemic therapy and poor prognosis. Therefore, the identification of a novel treatment target for HCC is important. B-cell receptor-associated protein 31 (BAP31) has been identified as a cancer/testis antigen; however, BAP31 function and mechanism of action in HCC remain unclear. In this study, BAP31 was demonstrated to be upregulated in HCC and correlated with the clinical stage. BAP31 overexpression promoted HCC cell proliferation and colony formation in vitro and tumor growth in vivo. RNA-sequence (RNA-seq) analysis demonstrated that serpin family E member 2 (SERPINE2) was downregulated in BAP31-knockdown HCC cells. Coimmunoprecipitation and immunofluorescence assays demonstrated that BAP31 directly binds to SERPINE2. The inhibition of SERPINE2 significantly decreased the BAP31-induced cell proliferation and colony formation of HCC cells and phosphorylation of Erk1/2 and p38. Moreover, multiplex immunohistochemistry staining of the HCC tissue microarray showed positive associations between the expression levels of BAP31, SERPINE2, its downstream gene LRP1, and a tumor proliferation marker, Ki-67. The administration of anti-BAP31 antibody significantly inhibited HCC cell xenograft tumor growth in vivo. Thus, these findings suggest that BAP31 promotes tumor cell proliferation by stabilizing SERPINE2 and can serve as a promising candidate therapeutic target for HCC.

A clinical and translational phase II trial of sequential axitinib and carboplatin/paclitaxel in advanced melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8580-8580
Author(s):  
Alain Patrick Algazi ◽  
Edward Cha ◽  
Miguel H Pampaloni ◽  
Spencer Behr ◽  
Brandon Cortez ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Metastatic Melanoma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Advanced Melanoma ◽  
Tumor Cell Proliferation ◽  
Wild Type ◽  
Flt Pet ◽  
Pet Scans

8580 Background: Several clinical trials adding VEGF signaling inhibitors to chemotherapy have not demonstrated any benefit over chemotherapy alone in advanced melanoma potentially due to decreased tumor cell proliferation induced by VEGF blockade. We tested the hypothesis that sequential administration of axitinib followed by carboplatin and paclitaxel may be more effective than chemotherapy alone in metastatic melanoma. Methods: We conducted a prospective phase II trial of this combination in previously treated metastatic melanoma patients. Patients had an ECOG PS 0-1, and normal organ function. Axitinib 5 mg PO bid was taken on days 1 through 14 of each 21-day treatment cycle, and carboplatin (AUC=5) with paclitaxel (175 mg/m2) was administered on day 1 starting with cycle 2. FLT-PET scans were performed on 6 patients to assess tumor cell proliferation on days 1, 14, 17, and 20 of cycle 1. Results: Treatment has been well tolerated. The most common grade 3 AEs have been neutropenia, hypertension, and gastrointestinal events. Grade 4 non-hematologic AEs have not been observed. 4 of 5 patients completing FLT-PET scans to date showed increases (23% to 92%) in SUV values during the axitinib holiday. The fifth patient had a single, minimally FLT avid lesion at baseline (SUV=1.9). In 30 evaluable patients, there have been 4 confirmed PRs, 2 unconfirmed PRs, and 3 patients with 28.6, 29.3, and 29.5% decreases in tumor size by RECIST. Overall, 19 patients have had SD and 5 have had PD as the best response. With a median follow-up of 8.3 months and 17 patients still active, the median PFS is 6.9 months, and 23 patients (77%) are still alive. 26 of 30 evaluable patients have been wild type for BRAF-V600E/K mutations. Conclusions: Axitinib followed by carboplatin and paclitaxel has been well tolerated and effective in a largely BRAF wild-type metastatic melanoma population. Given the urgent need for effective therapies in this population, this regimen warrants phase III testing.

Expression of epidermal growth factor receptor (EGFR) associates with proliferation, apoptosis, and histologically aggressive features in hepatocellular carcinoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14039-14039
Author(s):  
S. Morinaga ◽  
Y. Nakamura ◽  
N. Sugano ◽  
K. Tsuchida ◽  
M. Shiozawa ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Epidermal Growth Factor Receptor ◽  
Tumor Cell ◽  
Growth Factor Receptor ◽  
Tumor Cell Proliferation ◽  
Curative Surgery ◽  
Ki 67 ◽  
Egfr Expression ◽  
Epidermal Growth

14039 Background: Epidermal growth factor receptor (EGFR) is over-expressed in many types of cancers, plays an important role in the tumorigenesis, and is indicated to be a promising target for cancer therapy. Hepatocellular carcinoma (HCC) is a cancer with one of the worst prognosis, and new therapeutic approaches are required. The aim of this study was to clarify a possible role of EGFR expression on clinico-pathology of HCC. Methods: HCC tissues were obtained from 36 HCC patients (23 men and 13 women, range 45–80 years old) who underwent curative surgery. EGFR status of the tumors was assessed by immunohistochemical (IHC) analysis on formalin-fixed paraffin-embedded tissue. The percentage of positive tumor cells was scored as follows: 0+, no positive tumor cells; 1+, 1–10% positive cells; 2+, 10–50% positive cells; 3+, >50% positive cells. The staining intensity of membrane was evaluated as follows: 0+, negative; 1+, weak; 2+, moderate; 3+, strong. A composite score (EGFR score) was obtained by calculating the sum of these two scores. The tumor cell proliferation and apoptosis were assessed with Ki-67 labeling and ssDNA labeling, respectively. Results: EGFR expression was detected in 33 (91.7%) of 36 tumors. EGFR score ranged from 0 to 6. Higher EGFR score was related with poorer histologic grade (P = 0.005 by Kruskal-Wallis) and advanced pathologic stage (P = 0.038 by Kruskal-Wallis). EGFR score correlated positively with Ki-67 labeling indices (r = 0.358 and P = 0.032 by Spearman), and correlated negatively with apoptosis indices (r = −0.388 and P = 0.019 by Spearman). EGFR score did not affect disease free survival (DFS) or over all survival (OS), after curative surgery. Conclusions: Higher expression of EGFR, assessed with IHC, associates with more aggressive pathologic features, increased tumor cell proliferation, and reduced tumor cell apoptosis. However, further examination is needed to clarify its predictive significance. No significant financial relationships to disclose.

scholarly journals Evaluation of Tumor Cell Proliferation by Ki-67 Expression and Mitotic Count in Lymph Node Metastases from Breast Cancer

PLoS ONE ◽  
2016 ◽  
Vol 11 (3) ◽  
pp. e0150979 ◽  
Author(s):  
Sura Aziz ◽  
Elisabeth Wik ◽  
Gøril Knutsvik ◽  
Tor Audun Klingen ◽  
Ying Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Lymph Node ◽  
Tumor Cell ◽  
Lymph Node Metastases ◽  
Mitotic Count ◽  
Tumor Cell Proliferation ◽  
Ki 67 ◽  
Node Metastases

Association of increase in thymidine uptake relative to tumor cell proliferation in indolent NHLs and DNA repair

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11116-11116
Author(s):  
M. E. Juweid ◽  
A. K. Buck ◽  
L. L. Ponto ◽  
F. M. Mottaghy ◽  
S. Syrbu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Dna Repair ◽  
Tumor Cell ◽  
Treatment Options ◽  
Thymidine Uptake ◽  
Tumor Cell Proliferation ◽  
Ki 67 ◽  
Repair Synthesis ◽  
Standardized Uptake Values ◽  
Dna Repair Synthesis

11116 Background: Uptake of radiolabeled thymidine (tdR) or its analogs is frequently used to assess tumor cell proliferation as well as tumor DNA repair synthesis after inhibition of tumor cell proliferation with certain drugs. We determined whether the relationship between thymidine (td) uptake and tumor cell proliferation may be different between indolent and aggressive NHLs. Methods: Twenty-four patients with histologically confirmed aggressive (n=16; all DLC) or indolent NHLs (n=8; 7 FL gr I-II, 1 MZL) underwent pretherapy imaging with the td analog 18F-fluorothymidine (FLT) and biopsy to determine the proliferative cell fraction by the Ki-67 index. Tumoral FLT uptake was determined by the maximum standardized uptake values (SUVmax) and correlated with the Ki-67 index. The FLT-SUV to Ki-67 ratio was also compared between indolent and aggressive NHLs. Results: Disproportional increase in FLT-SUVmax relative to tumor cell proliferation was found in indolent NHLs: median %Ki-67 was 5% in indolent vs. 80% in aggressive NHL whereas median FLT-SUVmax was 3.6 vs. 9.4, respectively. The disproportional increase in FLT-SUV in indolent NHLs could not be explained by nonspecific FLT uptake in tumor extracellular space estimated to account for <0.2 SUV unit. Difference in the ratio of FLT-SUVmax to Ki-67 index between indolent and aggressive NHLs was highly significant (1.21 ± 0.77 vs. 0.18± 0.20; P=0.006). These data are in line with a previous study using tdR where the ratios of median tdR (in cpm) to median %-Ki-67 or %-S phase cells in indolent were ∼1.5x those in aggressive NHLs which was associated with relatively increased expression of DNA repair proteins (PCNA) in indolent NHLs (Holte et. al. Acta Oncologica, 1999) Conclusions: Disproportional increase in td uptake relative to %proliferating tumor cells in indolent NHLs likely reflects enhanced DNA repair in quiescent cells or, less likely, constitutively increased Tk1 expression. Studies are underway to determine expression of proteins that, unlike Ki-67, are associated with both DNA repair and replication (e.g., RFA, PCNA). If enhanced DNA repair is confirmed in indolent NHLs this could have major implications with respect to understanding their natural course and treatment options. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document