791 Results of Immunohistochemical Staining of Cell Cycle Regulators Predict a Progression-free Survival of Pituitary Adenoma

BackgroundKi-67 labeling index (LI) is currently regarded as a useful prognostic marker of pituitary adenoma (PA) clinical behavior, although its relevance as a reliable clinical indicator is far from being universally accepted, since both validations and criticisms are found in the literature. Minichromosome maintenance 7 (MCM7), a cell-cycle regulator protein, has been recently proposed as a marker of tumor aggressiveness in tumors from many sites, including the CNS. Therefore, we evaluated MCM7, in comparison to Ki-67, as a potential marker of clinical outcome in PA.Design and methodsIn this single-institution retrospective study, 97 patients with PA (23 ACTH, 12 GH, 29 PRL, 10 FSH/LH, and 23 non-secreting adenomas) were recruited and the prognostic value of both MCM7 and Ki-67 was evaluated by immunohistochemical techniques. In addition, p53 nuclear expression and mitotic index were also evaluated.ResultsTwenty-six of the 97 PA patients recurred during the follow-up period. Cox's regression analysis showed that high nuclear expression of MCM7 LI, unlike Ki-67 LI, was directly associated with a higher (7.7-fold) risk of recurrence/progression. Kaplan–Meier analysis of recurrence/progression-free survival curves revealed that patients with high MCM7 LI (≥15%) had a shorter recurrence/progression-free survival than those with low MCM7 LI (<15%). Moreover, among patients with invasive tumors, high MCM7 LI identified those with the highest risk of recurrence/progression.ConclusionsData from this study suggest that MCM7 is a prognostic marker of clinical outcome in PA patients, more reliable and informative than Ki-67.

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Genomic determinants of sensitivity to bipolar androgen therapy (BAT) in castrate-resistant prostate cancer (CRPC).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.200 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 200-200

Author(s):

Michael Thomas Schweizer ◽

Emmanuel S. Antonarakis ◽

Mario A. Eisenberger ◽

Peter Nelson ◽

Jun Luo ◽

...

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Progression Free Survival ◽

Cell Cycle Regulators ◽

Next Generation ◽

Damage Repair ◽

Somatic Alterations ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant ◽

Next Generation Sequencing Ngs

200 Background: BAT is a promising treatment for CRPC and preclinical work has shown that its effects may be mediated by inducing DNA damage or cell cycle arrest. We sought to evaluate if mutations in DNA damage repair (DDR) genes or cell cycle regulators were associated with improved outcomes. Methods: Biospecimens from CRPC patients enrolled to studies testing BAT underwent germline or somatic next-generation sequencing (NGS). Samples tested included plasma (i.e. cell-free DNA) (N = 79), tumor tissue (N = 21) and saliva (N = 10). A variety of clinical grade NGS platforms were generally used. Given the concern for false negatives, we excluded cases if plasma NGS did not reveal a somatic alteration. Absence of a germline alteration was not assumed to indicate absence of somatic alterations. Comparative analyses to assess candidate biomarkers of BAT efficacy were performed. Results: Most patients received BAT following one or more next generation hormonal therapy, while 6 received BAT as first-line CRPC therapy. Of 65 cases where a germline or somatic pathogenic alteration in any gene was detected, 30 (46%) had evidence of homologous recombination deficiency (HRD), with mutations found in BRCA2 (N = 10), ATM (N = 8), CHEK2 (N = 5), PALB2 (N = 4), CDK12 (N = 3), CHD1 (N = 2), FANCA (N = 1), FANCD2 (N = 1) and BRCA1 (N = 1). TP53 alterations were also common (27/65; 42%). HRD mutations associated with increased PSA50 responses, with a trend toward improved PSA50 responses in TP53 mutated cases too (Table). In a combined analysis, men with HRD and/or TP53 mutations had improved PSA50 responses and near-significant improvement in progression free survival (PFS). Conclusions: These preliminary data suggest that BAT may be most efficacious in cancers harboring mutations in genes involved in DDR and/or cell cycle regulation. These results require prospective confirmation. [Table: see text]

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Long Non-Coding RNA XLOC_006753 Promotes the Development of Multidrug Resistance in Gastric Cancer Cells Through the PI3K/AKT/mTOR Signaling Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000495499 ◽

2018 ◽

Vol 51 (3) ◽

pp. 1221-1236 ◽

Cited By ~ 18

Author(s):

Lisi Zeng ◽

Quanxing Liao ◽

Zhaowei Zou ◽

Yuefeng Wen ◽

Jingshu Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cell Proliferation ◽

Overall Survival ◽

Signaling Pathway ◽

Cell Lines ◽

Progression Free Survival ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

Free Survival

Background/Aims: The development of multidrug resistance (MDR), which results in disease recurrence and metastasis, is a crucial obstacle to successful chemotherapy for patients with gastric cancer (GC). Long non-coding RNAs (lncRNAs) have been found to play various roles in cancer. This study aimed to investigate the effect of XLOC_006753 on the development of MDR in GC cells. Methods: The expression levels of XLOC_006753 in GC patients and MDR GC cell lines (SGC-7901/5-FU and SGC-7901/DDP cell line) were assessed by qRT-PCR. Statistical analyses were conducted to determine the relationship between XLOC_006753 expression and clinical features and to assess the prognostic value of XLOC_006753 for overall survival and progression-free survival. Then, a CCK-8 assay was used to detect cell proliferation ability and chemosensitivity. Flow cytometry was used to detect cell cycle and cell apoptosis. A wound-healing assay and transwell assay were used to detect cell migration. The expression of markers for MDR, G1/S transition, epithelial–mesenchymal transition (EMT) and PI3K/ AKT/mTOR signaling pathway were examined by western blot. Results: XLOC_006753 was highly expressed in GC patients and MDR GC cell lines (SGC-7901/5-FU and SGC-7901/DDP cell lines), and its high expression was positively associated with metastasis, TNM stage, tumor size, and poor survival in GC patients. Moreover, XLOC_006753 was an independent prognostic biomarker of overall survival and progression-free survival for gastric cancer patients. Knocking down XLOC_006753 in the two MDR GC cell lines significantly inhibited cell proliferation, cell viability, cell cycle G1/S transition, and migration. XLOC_006753 knockdown also promoted apoptosis. Furthermore, western blots showed that XLOC_006753 knockdown decreased some markers of MDR, G1/S transition, and EMT expression, while increasing caspase9 expression and inhibiting the PI3K/AKT/mTOR signaling pathway in SGC-7901/5-FU and SGC-7901/DDP cells. Conclusion: High expression of XLOC_006753 promoted the development of MDR, which was activated by the PI3K/AKT/mTOR pathway in GC cells.

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Function of cell‑cycle regulators in predicting silent pituitary adenoma progression following surgical resection

Oncology Letters ◽

10.3892/ol.2017.7117 ◽

2017 ◽

Cited By ~ 2

Author(s):

Sung Hyun Park ◽

Ji Hwan Jang ◽

Young Min Lee ◽

Joon Soo Kim ◽

Kyu Hong Kim ◽

...

Keyword(s):

Cell Cycle ◽

Pituitary Adenoma ◽

Surgical Resection ◽

Cell Cycle Regulators ◽

Silent Pituitary Adenoma

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PLEK2 Gene Upregulation Might Independently Predict Shorter Progression-Free Survival in Lung Adenocarcinoma

Technology in Cancer Research & Treatment ◽

10.1177/1533033820957030 ◽

2020 ◽

Vol 19 ◽

pp. 153303382095703

Author(s):

Wenqian Zhang ◽

Tong Li ◽

Bin Hu ◽

Hui Li

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Dna Repair ◽

Lung Adenocarcinoma ◽

Single Cell ◽

Prognostic Value ◽

Progression Free Survival ◽

Single Cell Level ◽

Cell Level ◽

Free Survival

Objective: This study aimed to explore PLEK2 expression profile, its prognostic value, and the potential genomic alterations associated with its dysregulation in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Materials and methods: Data from The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx), and Kaplan-Meier plotter were used in combination for bioinformatic analysis. Results: PLEK2 mRNA was significantly upregulated in both LUAD and LUSC compared with their respective normal controls. PLEK2 upregulation showed independent prognostic value in progression-free survival (PFS) (HR: 1.169, 95%CI: 1.033 -1.322, p = 0.014). PLEK2 mRNA expression was positively correlated with invasion, cell cycle, DNA damage, and DNA repair of LUAD cells at the single-cell level. Genomic analysis showed that gene-level amplification might not directly lead to increased PLEK2 expression. Methylation profile analysis found 4 CpG sites (cg12199376, cg14437634, cg17641252, and cg06724236) had at least a weakly negative correlation with PLEK2 expression, among which cg12199376, cg14437634 and cg17641252 locate around the first exon of the gene. Conclusions: Increased PLEK2 expression might be a specific prognostic biomarker of poor PFS in LUAD patients. Its expression had significant positive correlations with invasion, cell cycle, DNA damage, and DNA repair of LUAD cells at the single-cell level. Promoter hypomethylation might be a potential mechanism leading to its upregulation.

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Enhancing the sensitivity of ovarian cancer cells to olaparib via microRNA-20b-mediated cyclin D1 targeting

Experimental Biology and Medicine ◽

10.1177/1535370221994077 ◽

2021 ◽

Vol 246 (11) ◽

pp. 1297-1306

Author(s):

Qian Zhong ◽

Ying Xiong ◽

Chen Ling ◽

Yanping Qian ◽

Xia Zhao ◽

...

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cyclin D1 ◽

Cancer Cells ◽

Cancer Patients ◽

Binding Sites ◽

Progression Free Survival ◽

Luciferase Reporter ◽

Ovarian Cancer Cells ◽

Free Survival

We previously reported that cyclin D1 silencing interferes with RAD51 accumulation and increases the sensitivity of BRCA1 wild-type ovarian cancer cells to olaparib. However, the mechanisms associated with cyclin D1 overexpression in ovarian cancer are not fully understood. TargetScan predicted the potential binding sites for microRNA-20b (miR-20b) and the 3′-untranslated region of cyclin D1 mRNA; thus, we used luciferase reporter assay to verify those binding sites. The Kaplan-Meier method and log-rank test were used to examine the relationship between miR-20b and progression-free survival of ovarian cancer patients in The Cancer Genome Atlas ( n = 367) dataset. In vitro experiments were performed to evaluate the effects of miR-20b on cyclin D1 expression, cell cycle and response to olaparib. A peritoneal cavity metastasis model of ovarian cancer was established to determine the effect of miR-20b on the sensitivity of olaparib. Immunohistochemistry was performed to evaluate molecular mechanisms. In this work, we demonstrated that miR-20b down-regulates cyclin D1, increases the sensitivity of ovarian cancer cells to olaparib, reduces the expression of RAD51, and induces cell cycle arrest in G0/G1 phase. Ovarian cancer patients with higher expression of miR-20b had significantly longer progression-free survival. These results indicate that miR-20b may be a potential clinical indicator for the sensitivity of ovarian cancer to olaparib and the survival of ovarian cancer patients. Our findings suggest that miR-20b may have therapeutic value in combination with olaparib treatment for ovarian cancer.

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