Ki-67 Correlates With In Vivo Bromodeoxyuridine Labeling Index in Operable Breast Cancer

2006 ◽  
Vol 24 (23) ◽  
pp. 3809-3809 ◽  
Author(s):  
William H. Goodson ◽  
Dan H. Moore ◽  
Frederick M. Waldman
1998 ◽  
Vol 49 (2) ◽  
pp. 155-164 ◽  
Author(s):  
William H. Goodson ◽  
Dan H. Moore ◽  
Britt-Marie Ljung ◽  
Karen Chew ◽  
Carmina Florendo ◽  
...  

Author(s):  
Jun-Xian Du ◽  
Yi-Hong Luo ◽  
Si-Jia Zhang ◽  
Biao Wang ◽  
Cong Chen ◽  
...  

Abstract Background Intensive evidence has highlighted the effect of aberrant alternative splicing (AS) events on cancer progression when triggered by dysregulation of the SR protein family. Nonetheless, the underlying mechanism in breast cancer (BRCA) remains elusive. Here we sought to explore the molecular function of SRSF1 and identify the key AS events regulated by SRSF1 in BRCA. Methods We conducted a comprehensive analysis of the expression and clinical correlation of SRSF1 in BRCA based on the TCGA dataset, Metabric database and clinical tissue samples. Functional analysis of SRSF1 in BRCA was conducted in vitro and in vivo. SRSF1-mediated AS events and their binding motifs were identified by RNA-seq, RNA immunoprecipitation-PCR (RIP-PCR) and in vivo crosslinking followed by immunoprecipitation (CLIP), which was further validated by the minigene reporter assay. PTPMT1 exon 3 (E3) AS was identified to partially mediate the oncogenic role of SRSF1 by the P-AKT/C-MYC axis. Finally, the expression and clinical significance of these AS events were validated in clinical samples and using the TCGA database. Results SRSF1 expression was consistently upregulated in BRCA samples, positively associated with tumor grade and the Ki-67 index, and correlated with poor prognosis in a hormone receptor-positive (HR+) cohort, which facilitated proliferation, cell migration and inhibited apoptosis in vitro and in vivo. We identified SRSF1-mediated AS events and discovered the SRSF1 binding motif in the regulation of splice switching of PTPMT1. Furthermore, PTPMT1 splice switching was regulated by SRSF1 by binding directly to its motif in E3 which partially mediated the oncogenic role of SRSF1 by the AKT/C-MYC axis. Additionally, PTPMT1 splice switching was validated in tissue samples of BRCA patients and using the TCGA database. The high-risk group, identified by AS of PTPMT1 and expression of SRSF1, possessed poorer prognosis in the stage I/II TCGA BRCA cohort. Conclusions SRSF1 exerts oncogenic roles in BRCA partially by regulating the AS of PTPMT1, which could be a therapeutic target candidate in BRCA and a prognostic factor in HR+ BRCA patient.


2021 ◽  
Vol 14 (3) ◽  
pp. 254
Author(s):  
Afnan H. El-Gowily ◽  
Samah A. Loutfy ◽  
Ehab M. M. Ali ◽  
Tarek M. Mohamed ◽  
Mohammed A. Mansour

Cancer is a complex devastating disease with enormous treatment challenges, including chemo- and radiotherapeutic resistance. Combination therapy demonstrated a promising strategy to target hard-to-treat cancers and sensitize cancer cells to conventional anti-cancer drugs such as doxorubicin. This study aimed to establish molecular profiling and therapeutic efficacy assessment of chloroquine and/or tioconazole (TIC) combination with doxorubicin (DOX) as anew combination model in MCF-7 breast cancer. The drugs are tested against apoptotic/autophagic pathways and related redox status. Molecular docking revealed that chloroquine (CQ) and TIC could be potential PI3K and ATG4B pathway inhibitors. Combination therapy significantly inhibited cancer cell viability, PI3K/AkT/mTOR pathway, and tumor-supporting autophagic flux, however, induced apoptotic pathways and altered nuclear genotoxic feature. Our data revealed that the combination cocktail therapy markedly inhibited tumor proliferation marker (KI-67) and cell growth, along with the accumulation of autophagosomes and elevation of LC3-II and p62 levels indicated autophagic flux blockage and increased apoptosis. Additionally, CQ and/or TIC combination therapy with DOX exerts its activity on the redox balance of cancer cells mediated ROS-dependent apoptosis induction achieved by GPX3 suppression. Besides, Autophagy inhibition causes moderately upregulation in ATGs 5,7 redundant proteins strengthened combinations induced apoptosis, whereas inhibition of PI3K/AKT/mTOR pathway with Beclin-1 upregulation leading to cytodestructive autophagy with overcome drug resistance effectively in curing cancer. Notably, the tumor growth inhibition and various antioxidant effects were observed in vivo. These results suggest CQ and/or TIC combination with DOX could act as effective cocktail therapy targeting autophagy and PI3K/AKT/mTOR pathways in MCF-7 breast cancer cells and hence, sensitizes cancer cells to doxorubicin treatment and combat its toxicity.


1998 ◽  
Author(s):  
J Horiguchi ◽  
Y Iino ◽  
H Takei ◽  
M Maemura ◽  
I Takeyoshi ◽  
...  

2011 ◽  
Vol 22 (3) ◽  
pp. 582-587 ◽  
Author(s):  
A. DeCensi ◽  
A. Guerrieri-Gonzaga ◽  
S. Gandini ◽  
D. Serrano ◽  
M. Cazzaniga ◽  
...  

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22190-e22190
Author(s):  
Kokoro Kobayashi ◽  
Yoshinori Ito ◽  
Akiko Ogiya ◽  
Naoya Gomi ◽  
Rie Horii ◽  
...  

e22190 Background: The metastatic breast tumor tends to be more aggressive with high proliferation, but this has not been proven in clinical sampling of metastatic tumors. Methods: Forty-eight patients who had histological specimens of both primary and metastatic sites of luminal breast cancer (ER and/or PgR positive and HER2 negative) were examined. We classified them as luminal A (LA) with Ki-67 labeling index of less than 14% and as luminal B (LB) with Ki-67 labeling index of more than 14%. We analyzed their overall survival (OS) and progression free survival (PFS) of 1st line treatment of each subtype of primary and metastatic tumors. Results: Subtypes of primary tumors and metastatic tumors were as follows; the primary tumor: LA; 34 patients (70.8%), LB; 14 (29.2%), metastatic tumors: LA; 21 (43.8%), LB; 27 (56.2%). Patients with LA of the primary tumor demonstrated statistically longer OS (LA; 72.5 months, LB 39.6 months, p=0.009). OS depended on the subtype of the primary tumor. In contrast, patients with LB of a metastatic tumor showed a statistically worse PFS (LA; 20.5 months, LB; 11.5 months, p=0.040). PFS of the 1st line treatment for MBC depended on the subtype of the metastatic tumor. Conclusions: The frequency of LB was increased on metastatic tumors and tended to acquire a higher proliferation index. This suggests that characterization of metastatic tumors could be better as an indicator of subsequent treatment for MBC. [Table: see text]


2012 ◽  
Vol 48 ◽  
pp. S174-S175
Author(s):  
M. Kochi ◽  
Y. Matsumi ◽  
M. Ito ◽  
S. Ohtani ◽  
K. Higaki

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