Rectal cancer

Rödel, Claus; Hofheinz, Ralf; Liersch, Torsten

doi:10.1097/cco.0b013e328352ea02

Cited by 35 publications

(14 citation statements)

References 38 publications

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“…Only 17 (26 %) patients were pN+ in the final histopathological workup while 58 (89 %) had initially been staged mriN+. This huge 63 % gap cannot only be explained by a possible downstaging effect of nCRT, because reported pathological complete remissions vary between 13 and 21 % [14] and only 11 % in this study. The valid treatment guidelines for patients with rectal cancer in Germany during the time period of this study recommended nCRT for patients with clinical evidence for N+ but did not specify on any diagnostic guidelines on how to asses this by MRI [15].…”

Section: Discussionmentioning

confidence: 49%

Clinical relevance of morphologic MRI criteria for the assessment of lymph nodes in patients with rectal cancer

Doyon

Attenberger

Dinter

et al. 2015

Int J Colorectal Dis

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Section: Discussionmentioning

confidence: 49%

Clinical relevance of morphologic MRI criteria for the assessment of lymph nodes in patients with rectal cancer

Doyon

Attenberger

Dinter

et al. 2015

Int J Colorectal Dis

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“…Preoperative CRT followed by radical surgical resection represents the standard of care for patients with locally advanced rectal cancer (4,11,26). However, the response of individual tumors to preoperative multimodal treatment is highly heterogeneous and ranges from complete clinical response to absence of any histopathological tumor regression (complete resistance).…”

Section: Discussionmentioning

confidence: 99%

“…We suggest that targeting Wnt/β-catenin signaling or one of the downstream pathways represent a promising strategy to increase therapeutic responsiveness of rectal cancers to CRT, the standard treatment for patients with locally advanced stages of this disease (4,11,26). …”

Section: Discussionmentioning

confidence: 99%

“…These observations are of both clinical and scientific relevance: First , resistance to preoperative CRT, the standard treatment for locally advanced rectal cancer, is a major clinical problem in the management of this disease (4,10,11). Secondly , the role of aberrant Wnt/β-catenin signaling in treatment resistance in rectal cancer has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Chemoradiotherapy Resistance in Colorectal Cancer Cells is Mediated by Wnt/β-catenin Signaling

Emons

Spitzner

Reineke

et al. 2017

Molecular Cancer Research

114

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Activation of Wnt/β-catenin signaling plays a central role in the development and progression of colorectal cancer (CRC). The Wnt-transcription factor, TCF7L2, is overexpressed in primary rectal cancers that are resistant to chemoradiotherapy (CRT) and TCF7L2 mediates resistance to CRT. However, it is unclear whether the resistance is mediated by a TCF7L2 inherent mechanism or Wnt/β-catenin signaling in general. Here, inhibition of β-catenin by siRNAs or a small molecule inhibitor (XAV-939) resulted in sensitization of CRC cells to CRT. To investigate the potential role of Wnt/β-catenin signaling in controlling therapeutic responsiveness, non-tumorigenic RPE-1 cells were stimulated with Wnt-3a, a physiological ligand of Frizzled-receptors, which increased resistance to CRT. This effect could be recapitulated by overexpression of a degradation-resistant mutant of β-catenin (S33Y), also boosting resistance of RPE-1 cells to CRT, which was, conversely, abrogated by siRNA-mediated silencing of β-catenin. Consistent with these findings, higher expression levels of active β-catenin were observed as well as increased TCF/LEF reporter activity in SW1463 cells that evolved radiation resistance due to repeated radiation treatment. Global gene expression profiling identified several altered pathways, including PPAR signaling and other metabolic pathways, associated with cellular response to radiation. In summary, aberrant activation of Wnt/β-catenin signaling not only regulates the development and progression of colorectal cancer, but also mediates resistance of rectal cancers to chemoradiotherapy. Implications Targeting Wnt/β-catenin signaling or one of the downstream pathways represents a promising strategy to increase response to CRT.

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“…This tissue was chosen for this study because with a continuously increasing incidence, colorectal cancer has become one of the three most frequent cancers in the western world [16]. One third of the colorectal cancers are rectal cancers and despite of advances in diagnostics and multimodality treatment using pre-operative (neoadjuvant) chemoradiotherapy followed by extended oncological TME-surgery, the long-term prognosis of patients with locally advanced rectal cancer is limited by the occurrence of distant metastases in nearly 30% of patients [17]–[19].…”

Section: Introductionmentioning

confidence: 99%

STED Super-Resolution Microscopy of Clinical Paraffin-Embedded Human Rectal Cancer Tissue

et al. 2014

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Formalin fixed and paraffin-embedded human tissue resected during cancer surgery is indispensable for diagnostic and therapeutic purposes and represents a vast and largely unexploited resource for research. Optical microscopy of such specimen is curtailed by the diffraction-limited resolution of conventional optical microscopy. To overcome this limitation, we used STED super-resolution microscopy enabling optical resolution well below the diffraction barrier. We visualized nanoscale protein distributions in sections of well-annotated paraffin-embedded human rectal cancer tissue stored in a clinical repository. Using antisera against several mitochondrial proteins, STED microscopy revealed distinct sub-mitochondrial protein distributions, suggesting a high level of structural preservation. Analysis of human tissues stored for up to 17 years demonstrated that these samples were still amenable for super-resolution microscopy. STED microscopy of sections of HER2 positive rectal adenocarcinoma revealed details in the surface and intracellular HER2 distribution that were blurred in the corresponding conventional images, demonstrating the potential of super-resolution microscopy to explore the thus far largely untapped nanoscale regime in tissues stored in biorepositories.

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Rectal cancer

Cited by 35 publications

References 38 publications

Clinical relevance of morphologic MRI criteria for the assessment of lymph nodes in patients with rectal cancer

Clinical relevance of morphologic MRI criteria for the assessment of lymph nodes in patients with rectal cancer

Chemoradiotherapy Resistance in Colorectal Cancer Cells is Mediated by Wnt/β-catenin Signaling

STED Super-Resolution Microscopy of Clinical Paraffin-Embedded Human Rectal Cancer Tissue

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