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Biomedicines
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Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches 3.0
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Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches 3.0

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 7288

Special Issue Editor

Dr. Valeria Barresi

E-Mail Website
Guest Editor
Department of Diagnostics and Public Health, P.le L.A. Scuro, University of Verona, 37129 Verona, Italy
Interests: brain tumors; meningioma; glioma; colorectal cancer; prognostic markers; tumor budding; poorly differentiated clusters
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Therapeutic approaches vary according to tumor location (colonic or rectal) and pTNM stage, the latter representing a main prognostic factor.

In spite of the improvement in the early diagnosis and therapy of CRC, several issues are still open. First, the identification of factors associated with a high risk of progression in non-metastatic (pN0M0) CRC still represents a research challenge and means it would be relevant to select patients for adjuvant treatments. Second, in view of the spreading endoscopic resection of CRC, predictors of nodal metastases in pT1 tumors would help in identifying patients needing surgery. Finally, pre-treatment clinical, endoscopic, or histological features able to predict the response of rectal adenocarcinoma to neo-adjuvant chemo-radiotherapy (CRT) would be useful to design tailored therapeutic strategies.

The aim of this Special Issue is to provide new insights into prognostic and predictive factors for early or pN0M0 CRC, and for locally advanced rectal carcinoma treated with neo-adjuvant CRT. These could be useful to develop individualized treatments.

Dr. Valeria Barresi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • liquid biopsy
  • epithelial-mesenchymal transition
  • tumor budding
  • poorly differentiated clusters
  • pT1
  • endoscopic treatment
  • rectal cancer
  • neo-adjuvant chemo-radiotherapy
  • tumor regression
  • pN0M0

Related Special Issue

Published Papers (4 papers)

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Research

14 pages, 4690 KiB  
Article
Blockade of the SRC/STAT3/BCL-2 Signaling Axis Sustains the Cytotoxicity in Human Colorectal Cancer Cell Lines Induced by Dehydroxyhispolon Methyl Ether
by Ya-Chu Hsieh, Yuan-Chang Dai, Kur-Ta Cheng, Wei-Ting Yang, Modukuri V. Ramani, Gottumukkala V. Subbaraju, Yi-Ju Chen and Chia-Che Chang
Biomedicines 2023, 11(9), 2530; https://doi.org/10.3390/biomedicines11092530 - 13 Sep 2023
Cited by 3 | Viewed by 1132
Abstract
Colorectal cancer (CRC) is the third most prevalent human cancer globally. 5-Fluorouracil (5-FU)-based systemic chemotherapy is the primary strategy for advanced CRC treatment, yet is limited by poor response rate. Deregulated activation of signal transducer and activator of transcription 3 (STAT3) is fundamental [...] Read more.
Colorectal cancer (CRC) is the third most prevalent human cancer globally. 5-Fluorouracil (5-FU)-based systemic chemotherapy is the primary strategy for advanced CRC treatment, yet is limited by poor response rate. Deregulated activation of signal transducer and activator of transcription 3 (STAT3) is fundamental to driving CRC malignant transformation and a poor prognostic marker for CRC, underscoring STAT3 as a promising CRC drug target. Dehydroxyhispolon methyl ether (DHME) is an analog of Hispolon, an anticancer polyphenol abundant in the medicinal mushroom Phellinus linteus. Previously, we have established DHME’s cytotoxic effect on human CRC cell lines by eliciting apoptosis through the blockade of WNT/β-catenin signaling, a preeminent CRC oncogenic pathway. Herein, we unraveled that compared with 5-FU, DHME is a more potent killer of CRC cells while being much less toxic to normal colon epithelial cells. DHME suppressed both constitutive and interleukin 6 (IL-6)-induced STAT3 activation represented by tyrosine 705 phosphorylation of STAT3 (p-STAT3 (Y705)); notably, DHME-induced CRC apoptosis and clonogenicity limitation were abrogated by ectopic expression of STAT3-C, a dominant-active STAT3 mutant. Additionally, we proved that BCL-2 downregulation caused by DHME-mediated STAT3 blockage is responsible for DHME-induced CRC cell apoptosis. Lastly, DHME inhibited SRC activation, and v-src overexpression restored p-STAT3 (Y705) levels along with lowering the levels of apoptosis in DHME-treated CRC cells. We conclude DHME provokes CRC cell apoptosis by blocking the SRC/STAT3/BCL-2 axis besides thwarting WNT/β-catenin signaling. The notion that DHME targets two fundamental CRC signaling pathways underpins the potential of DHME as a CRC chemotherapy agent. Full article
(This article belongs to the Special Issue Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches 3.0)
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17 pages, 2142 KiB  
Article
Can the Correlation of Periodontopathies with Gastrointestinal Diseases Be Used as Indicators in Severe Colorectal Diseases?
by Lavinia Alina Rat, Andrada Florina Moldovan, Daniela Florina Trifan, Loredana Matiș, Gelu Florin Murvai, Lavinia Maris, Timea Claudia Ghitea and Marius Adrian Maghiar
Biomedicines 2023, 11(2), 402; https://doi.org/10.3390/biomedicines11020402 - 29 Jan 2023
Cited by 1 | Viewed by 1289
Abstract
Gastrointestinal problems are among the most common health problems which can acutely affect the healthy population and chronically involve health risks, seriously affecting the quality of life. Identifying the risk of gastrointestinal diseases in the early phase by indirect methods can increase the [...] Read more.
Gastrointestinal problems are among the most common health problems which can acutely affect the healthy population and chronically involve health risks, seriously affecting the quality of life. Identifying the risk of gastrointestinal diseases in the early phase by indirect methods can increase the healing rate and the quality of life.: The proposal of this study is to verify a correlation between gastrointestinal and periodontal problems and the risk of inflammatory gastrointestinal diseases (IBD). The study was conducted on 123 people who were observed to have gastrointestinal and psychological problems. The participants were divided into three groups, depending on each one’s diagnosis. The control group (CG) was composed of 37 people who did not fit either irritable bowel syndrome (IBS) according to the ROME IV criteria, nor were inflammatory markers positive for IBD. Group 2 (IBS) was composed of 44 participants diagnosed with IBS according to the ROME IV criteria. Group 3 was composed of 42 participants who were diagnosed with IBD. All study participants underwent anthropometric, micro-Ident, and quality of life tests. A directly proportional relationship of the presence of bacteria with IBD patients with the exception of Capnocytophaga spp. and Actinobacillus actinomycetemcomitans was observed. These two bacteria correlated significantly with IBS. Follow-up of the study participants will help determine whether periodontal disease can be used as an indicator of severe colorectal disease. In addition, this study should be continued especially in the case of IBD more thoroughly to follow and reduce the risk of malignancy. Full article
(This article belongs to the Special Issue Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches 3.0)
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18 pages, 2822 KiB  
Article
Interleukin-8 in Colorectal Cancer: A Systematic Review and Meta-Analysis of Its Potential Role as a Prognostic Biomarker
by Chiara Bazzichetto, Michele Milella, Ilaria Zampiva, Francesca Simionato, Carla Azzurra Amoreo, Simonetta Buglioni, Chiara Pacelli, Loredana Le Pera, Teresa Colombo, Emilio Bria, Massimo Zeuli, Donatella Del Bufalo, Isabella Sperduti and Fabiana Conciatori
Biomedicines 2022, 10(10), 2631; https://doi.org/10.3390/biomedicines10102631 - 19 Oct 2022
Cited by 13 | Viewed by 2317
Abstract
Among soluble actors that have emerged as druggable factors, the chemokine interleukin-8 (IL-8) has emerged as a possible determinant of response to immunotherapy and targeted treatment in several cancer types; however, its prognostic/predictive role in colorectal cancer (CRC) remains to be established. We: [...] Read more.
Among soluble actors that have emerged as druggable factors, the chemokine interleukin-8 (IL-8) has emerged as a possible determinant of response to immunotherapy and targeted treatment in several cancer types; however, its prognostic/predictive role in colorectal cancer (CRC) remains to be established. We: (i) conducted a systematic review of published literature on IL-8 expression in CRC; (ii) searched public transcriptomics databases; (iii) investigated IL-8 expression, by tumor and infiltrating cells, in a series of CRC samples; and (iv) carried out a meta-analysis of published literature correlating IL-8 expression and CRC prognosis. IL-8 possesses an important role as a mediator of the bidirectional crosstalk between tumor/stromal cells. Transcriptomic analysis indicated that specific IL-8 transcripts were significantly overexpressed in CRC compared to normal colon mucosa. Moreover, in our series we observed a statistically significant correlation between PTEN-loss and IL-8 expression by infiltrating mononuclear and tumor cells. In total, 12 papers met our meta-analysis inclusion criteria, demonstrating that high IL-8 levels significantly correlated with shorter overall survival and progression-free survival. Sensitivity analysis demonstrated a highly significant correlation with outcome for circulating, but not for tissue-detected, IL-8. IL-8 is overexpressed in CRC tissues and differentially produced by tumor or stromal components depending on CRC genetic background. Moreover, circulating IL-8 represents a strong prognostic factor in CRC, suggesting its use in the refining of prognostic CRC assessment and potentially the tailoring of therapeutic strategies in individual CRC patients. Full article
(This article belongs to the Special Issue Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches 3.0)
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12 pages, 1812 KiB  
Article
H3K27me3 Immunohistochemical Loss Predicts Lower Response to Neo-Adjuvant Chemo-Radiotherapy in Rectal Carcinoma
by Serena Ammendola, Nicolò Caldonazzi, Paola Chiara Rizzo, Giulia Turri, Corrado Pedrazzani and Valeria Barresi
Biomedicines 2022, 10(8), 2042; https://doi.org/10.3390/biomedicines10082042 - 21 Aug 2022
Cited by 1 | Viewed by 1865
Abstract
A watch-and-wait approach was suggested to avoid the possible complications related to surgery in patients with rectal carcinoma showing clinical complete response after neoadjuvant chemo-radiotherapy (CRT). Since clinical response may not correlate with pathological response, markers with higher accuracy are needed to identify [...] Read more.
A watch-and-wait approach was suggested to avoid the possible complications related to surgery in patients with rectal carcinoma showing clinical complete response after neoadjuvant chemo-radiotherapy (CRT). Since clinical response may not correlate with pathological response, markers with higher accuracy are needed to identify patients who are likely responders and could be spared surgery. This study aims to assess whether H3K27me3 immunohistochemical expression in pre-treatment rectal carcinoma predicts response to neoadjuvant CRT or shows prognostic relevance. We assessed H3K27me3 immunostaining in 46 endoscopic biopsies of rectal carcinomas treated with neoadjuvant CRT and surgery. H3K27me3 immunostaining was lost in 20, retained in 19, and inconclusive (absent in neoplastic and non-neoplastic cells) in 7 cases. Retained H3K27me3 immuno-expression was significantly associated with ypTNM stage 0 (p = 0.0111) and high tumor regression, measured using either five-tiered (p = 0.0042) or two-tiered Dworak tumor regression grade (p = 0.0009). Poor differentiation, determined counting the number of poorly differentiated clusters (PDC grade) or tumor budding (TB) foci (TB grade), in the pre-treatment biopsy, was significantly associated with a shorter time to progression after surgery (p = 0.008; p = 0.0093). However, only PDC grade (p = 0.0023), together with radial margin involvement (p = 0.0001), retained prognostic significance in the multivariate analysis. The assessment of H3K27me3 immunostaining in pre-treatment endoscopic biopsy of rectal carcinoma could be useful to predict response to neo-adjuvant CRT and to identify patients who could safely undergo watch-and-wait approach. PDC and TB grade in the pre-treatment biopsy could provide additional prognostic information in patients with rectal carcinoma treated with neoadjuvant CRT and surgery. Full article
(This article belongs to the Special Issue Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches 3.0)
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