scholarly journals HER-2 expression in locally advanced rectal cancer. Fluorescencein situ hybridization in rectal cancer cells shows HER-2 amplification

2014 ◽  
Vol 105 (7) ◽  
pp. July cover-July cover
Author(s):  
Xiangjiao Meng ◽  
Renben Wang ◽  
Zhaoqin Huang ◽  
Jianbo Zhang ◽  
Rui Feng ◽  
...  
2021 ◽  
Author(s):  
Abdullah SAKİN ◽  
Suleyman Sahin ◽  
Sevda Saglampınar Karyagar ◽  
Savas Karyagar ◽  
Muhammed Mustafa atci ◽  
...  

Abstract Purpose:To investigate the prognostic effects of baseline volumetric PET/CT parameters including the maximum standard uptake value(SUVmax), metabolic tumor volume(MTV), and tumor lesion glycolysis(TLG) on treatment response and prognosis in locally-advanced rectal cancer(LARC) treated with neoadjuvant chemoradiotherapy(NACRT).Methods:Between 2015 and 2018, 51 patients with LARC treated with NACRT followed by surgery were included in this retrospective study. Patients were divided into 2 groups by tumor regression grade(TRG) as follows;Group I=TRG 1(No detectable cancer cells)+TRG 2(single cells and/or small groups of cancer cells) and Group II=TRG3(residual tumor outgrown by fibrosis)+TRG 4(remarkable fibrosis outgrown by tumor cells)+TRG 5(No fibrosis with extensive residual cancer).Results:Of the 51 patients, 34(66.7%) were male. The median age was 55(range,37-78) years. According to TRG status, 14(27.4%) patients were in group I and 37(72.6%) patients were in group II. The area under the curve(95% CI) was 0.749(0.593-0.905) in the ROC curve plotted for MTV. The cut of value for MTV was 12, with 70% sensitivity and 65% specificity. MTV was≥12 in 32(62.8%) patients. MTV and TLG values were significantly different between Group I and II, whereas there was no significant difference between the groups in terms of SUVmax values (p=0.006, p=0.033, and p=0.673, respectively). The disease-free survival was not reached in patients with MTV<12 vs. 20 months in those with MTV≥12 (p=0.323). In multivariate analysis, MTV(OR, 95% Cl, 5.00[1.17-21.383]) was found to be the factor that affected pathological complete response.Conclusion:In LARC treated with NACRT, MTV prior to treatment can help predict the response to treatment.


2021 ◽  
Vol 11 ◽  
Author(s):  
Fengpeng Wu ◽  
Bingyue Wu ◽  
Xiaoxiao Zhang ◽  
Congrong Yang ◽  
Chaoxi Zhou ◽  
...  

Neoadjuvant chemoradiotherapy has been widely used in the treatment of locally advanced rectal cancer due to the excellent advantages of irradiation in cancer therapy. Unfortunately, not every patient can benefit from this treatment, therefore, it is of great significance to explore biomarkers that can predict irradiation sensitivity. In this study, we screened microRNAs (miRNAs) which were positively correlated with irradiation resistance and found that miRNA-552 and miRNA-183 families were positively correlated with the irradiation resistance of rectal cancer, and found that high expression of miRNA-96-5p enhanced the irradiation resistance of rectal cancer cells through direct regulation of the GPC3 gene and abnormal activation of the canonical Wnt signal transduction pathway. Based on the radioreactivity results of patient-derived xenograft models, this is the first screening report for radio-resistant biomarkers in rectal cancer. Our results suggest that miRNA-96-5p expression is an important factor affecting the radiation response of colorectal cancer cells.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 493-493 ◽  
Author(s):  
Lena-Christin Conradi ◽  
Hanna Styczen ◽  
Thilo Sprenger ◽  
Heinz Becker ◽  
Michael B. Ghadimi ◽  
...  

493 Background: With the implementation of multimodal treatment strategies including neoadjuvant radiochemotherapy (RCT), the prognosis of locally advanced rectal cancer has been improved over the last two decades. Most actual clinical trials aim to further develop therapy by intensification of agents administered. We examined Her2/neu in rectal cancer patients to evaluate its expression as a potential drug target as well as its capacity as predictive and prognostic biomarker. Methods: Two-hundred-seventy-seven patients (205 male, 72 female; median age 63.5 years) with locally advanced rectal cancer (cUICC-II/III) were included in this study. Preoperative RCT (50.4 Gy and concomitant either 5-FU or 5-FU and oxaliplatin) was administered in 236 patients followed by surgical resection with total mesorectal excision (TME). Another 41 patients received postoperative RCT. All patients were treated within phase-II/-III-trials of the German Rectal Cancer Study Group or analogous to these standardized protocols. Her2-/neu expression from pre-treatment biopsies and corresponding resection specimens were assessed by immunohistochemical staining and SISH-analysis. Results: A positive Her-2/neu expression was found in 12.3% of all pre-treatment tumor biopsy samples and in 28.7% of the resection specimens. The correlation of the pre-treatment Her-2/neu status did not show a significant correlation with the grade of tumor regression. However, patients with a higher Her-2/neu protein expression as measured in the resection specimen showed a significant survival benefit (p=0.0277) compared with patients having low intratumoral Her-2/neu expression during the follow-up (median 43 months). The 10-year survival rate was 73.2% (Her-2/neu positive) versus 60.1% (Her-2/neu negative). Conclusions: The proportion of patients with a positive Her-2/neu status is relevant in rectal cancer. Her-2/neu might potentially serve as a promising drug target in rectal cancer and should be further assessed within prospective clinical trials. Furthermore the Her-2/neu status seems to be a valuable prognostic marker within the multimodal treatment of advanced rectal cancer.


2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
H Fowler ◽  
P Sutton ◽  
D Bowden ◽  
J Parsons ◽  
D Vimalachandran

Abstract Introduction Our proteomic data has validated that high levels of the protein myoferlin confers poorer response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Myoferlin plays a role in membrane repair and VEGF signal transduction, and is associated with worse prognosis in numerous other epithelial cancers. We aim to assess the impact of myoferlin on the radiosensitivity of rectal cancer. Method Clonogenic assays were performed using immortalised colorectal cancer cells (HCT116,HT29,LIM,MDST8) to assess survival at escalating radiation doses following knockdown with myoferlin siRNA or a small molecular inhibitor(WJ460). 3D models (spheroids) were used to examine the effect of WJ460 on tumour growth. Result Quantification of myoferlin using immunoblotting demonstrated that MDST8 and LIM were higher expressors than HCT116 and HT29. Higher levels correlated with increasing radio-resistance as calculated by colony formation efficiency (CFE). Using clonogenic assays, cells treated with myoferlin siRNA or WJ460 demonstrated increased radiosensitivity compared to controls across all radiation doses, most significantly at 4Gy. Treatment of spheroids with WJ460 significantly reduced growth compared to controls at all radiation doses (p&lt;0.05), with WJ460 limiting growth considerably more than treatment with the current gold standard 5-FU. HCT116 spheroid volume day 15; WJ460 4.96um3,5-FU 6.74um3,DMSO 24.9um3. Conclusion Inhibition of myoferlin is associated with increased radiosensitivity of colorectal cancer cells, and treatment with a small molecular inhibitor significantly reduces growth in spheroid models. Further work is required further validate its potential use as a biomarker in locally advanced rectal cancer. Take-home message We have found that myoferlin is a protein associated with poor response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Manipulation of this protein sensitises the cancer cells to radiotherapy.


2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Fei Fei ◽  
Mingqing Zhang ◽  
Bo Li ◽  
Lizhong Zhao ◽  
Hui Wang ◽  
...  

We previously reported that polyploid giant cancer cells (PGCCs) exhibit cancer stem cell properties and can generate daughter cells with the epithelial-mesenchymal transition phenotype. This study investigated the role of PGCC formation in the prognostic value of neoadjuvant chemoradiation therapy (nCRT) in locally advanced rectal cancer (LARC). The morphological characteristics were observed in patients with LARC after nCRT. Colorectal cancer cell lines were treated with irradiation or chemotherapeutic drugs, and the metastasis-related proteins were detected. 304 nCRT cases and 301 paired non-nCRT cases were collected for analysis. More PGCCs and morphologic characteristics related to invasion and metastasis appeared in tumor tissue after nCRT. Irradiation or chemicals could induce the formation of PGCCs with daughter cells exhibiting strong migratory, invasive, and proliferation abilities. In patients after nCRT, pathologic complete remission, partial remission, stable disease, and progressive disease were observed in 29 (9.54%), 125 (41.12%), 138 (45.39%), and 12 (3.95%) patients, respectively. Mucinous adenocarcinomas (MCs) occurred more frequently in nCRT than in non-nCRT patients (χ2 = 29.352, P=0.001), and the prognosis in MC patients was worse than that in non-MC patients (χ2 = 24.617, P=0.001). The difference in survival time had statistical significance for 60 days (χ2 = 5.357, P=0.021) and 70 days (χ2 = 18.830, P=0.001) rest interval time. On multivariable analysis, 60 days rest interval, Duke’s stage, and recurrence and/or distant metastasis remained significant predictors of survival. In conclusion, irradiation or chemicals induce the formation of PGCCs and PGCCs produce daughter cells with strong migration and invasion abilities after a long incubation period. Appropriate rest interval (incubation period) is very important for patients with LARC who will receive nCRT.


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