Rab5C enhances resistance to ionizing radiation in rectal cancer

AbstractRectal cancer represents one third of the colorectal cancers that are diagnosed. Neoadjuvant chemoradiation is a well-established protocol for rectal cancer treatment reducing the risk of local recurrence. However, a pathologic complete response is only achieved in 10 –40% of cases and the mechanisms associated with resistance are poorly understood. To identify potential targets for preventing therapy resistance, a proteomic analysis of biopsy specimens collected from stage II and III rectal adenocarcinoma patients before neoadjuvant treatment was performed and compared with residual tumor tissues removed by surgery after neoadjuvant therapy. Three proteins, Ku70, Ku80, and Rab5C, exhibited a significant increase in expression after chemoradiation. To better understand the role of these proteins in therapy resistance, a rectal adenocarcinoma cell line was irradiated to generate a radiotherapy-resistant lineage. These cells overexpressed the same three proteins identified in the tissue samples. Furthermore, radiotherapy resistance in this in vitro model was found to involve modulation of epidermal growth factor receptor (EGFR) internalization by Rab5 C in response to irradiation, affecting expression of the DNA repair proteins, Ku70 and Ku80, and cell resistance. Taken together, these findings indicate that EGFR and Rab5C are potential targets for the sensitization of rectal cancer cells and they should be further investigated.Key messages• Rab5C orchestrate...
Source: Journal of Molecular Medicine - Category: Molecular Biology Source Type: research

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Conclusion Multiparametric MRI of rectum, using ADC as the diffusion and ktrans as the perfusion parameter is a repeatable technique. This technique may potentially be used in prediction and evaluation of neoadjuvant treatment response. New studies with larger patient groups are needed to validate the role of multiparametric MRI. PMID: 32071023 [PubMed - as supplied by publisher]
Source: Diagnostic and Interventional Radiology : The Turkish Society of Radiology - Category: Radiology Authors: Tags: Diagn Interv Radiol Source Type: research
CONCLUSIONS: In a universal healthcare system, young age was associated with increased lymph node positivity of colon and rectal cancers, suggesting that factors other than access to care may play a role in this association. See Video Abstract at http://links.lww.com/DCR/B90. EDAD Y POSITIVIDAD DE GANGLIOS LINFÁTICOS EN PACIENTES CON CÁNCER DEL COLON Y EL RECTO EN EL SISTEMA DE SALUD MILITAR DE EE UU ANTECEDENTES: La edad temprana puede estar asociada con un mayor riesgo de compromiso de los ganglios linfáticos en el momento del diagnóstico de cáncer colorrectal. La accesibilidad a ...
Source: Diseases of the Colon and Rectum - Category: Gastroenterology Tags: Original Contributions: Colorectal Cancer Source Type: research
ConclusionDentate line involvement and ILN>  8 mm predicted the development of ILNM in patients with rectal cancer invading the anal canal. Treatment of the ILN should be considered for patients with the above predictors given the significant therapeutic outcomes.
Source: International Journal of Colorectal Disease - Category: Gastroenterology Source Type: research
Abstract The purpose of this study was to examine if the increased risk of colorectal cancer due to cigarette smoking differed by anatomical subsite and sex. We analyzed data from 188,052 participants (45% men, aged 45-75 years), who were enrolled in the Multiethnic Cohort Study in 1993-1996. During a mean follow-up of 16.7 years, we identified 4,879 incident cases of invasive colorectal adenocarcinoma. In multivariate Cox regression models, compared with never smokers of the same sex, male ever smokers had a 39% [hazard ratio (HR) =1.39; 95% Confidence interval (CI): 1.16,1.67] higher risk of left, but not of rig...
Source: Am J Epidemiol - Category: Epidemiology Authors: Tags: Am J Epidemiol Source Type: research
Conclusion: Our work contributes to the elucidation of the predictive value of DNp73 expression in rectal cancer patients who were given preoperative radiotherapy. Mathematical properties of fuzzy weighted recurrence networks of immunohistochemistry images are not only able to show the predictive factor of DNp73 expression in the patients, but also reveal the identification of non-effective application of radiotherapy to those who had poor overall survival outcome.
Source: Frontiers in Physiology - Category: Physiology Source Type: research
AbstractBackgroundEndoscopic tattooing is considered to be a safe procedure to mark a lesion for subsequent surgical resection, and the reported complications are relatively minor. However, here the present case shows tumor traveling through needle tract with tumor inoculation following endoscopic tattooing.Methods and ResultsA 68-year-old female who had a clinical stage I rectal cancer underwent laparoscopic rectal low anterior resection. The pathologic examination of the surgical specimen showed a pathologic stage pT1 invasive adenocarcinoma with a 3-mm focus of tumor cells traveling through a transmural tract and a 0.5-...
Source: International Journal of Colorectal Disease - Category: Gastroenterology Source Type: research
Conclusion: This case report helps in understanding the course of progression from rectal cancer to periorbital metastasis.
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
CONCLUSION: At 17% of its planned accrual, E5204 did not meet its primary endpoint. The addition of bevacizumab to FOLFOX6 in the adjuvant setting did not significantly improve OS in patients with stage II/III rectal cancer. IMPLICATIONS FOR PRACTICE: At 17% of its planned accrual, E5204 was terminated early owing to poor accrual. At a median follow-up of 72 months, there was no significant difference in 5-year overall survival (88.3% vs. 83.7%) or in 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. Despite significant advances in the treatment of rectal cancer, especially in improving local contro...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
ConclusionThe random forest classifier based on radiomics features derived from pre-treatment ADC images have the potential to predict tumor resistance to NCRT in patients with LARC, and the use of predicting model may facilitate individualized management of rectal cancer.
Source: International Journal of Colorectal Disease - Category: Gastroenterology Source Type: research
ConclusionsOne-fifth of patients with locally advanced rectal cancer are manageable with a rectum-sparing approach after neoadjuvant therapy. With this strategy, about 80% patients will have their rectum preserved and 90% will be without stoma at long term.
Source: International Journal of Colorectal Disease - Category: Gastroenterology Source Type: research
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