...reports from Japan indicated similar (not inferior) outcomes to pre-COVID times, despite limited medical resources. 6 Liver Cancer: Munoz-Martinez and colleagues reported a 2.2% decrease in ...mortality rates for HCV (and HBV)-related HCC, while mortality rates for NAFLD (alcohol-related liver disease)-related hepatocellular carcinoma increased by 3%. ...there were no differences in metastasis rates (p = 0.39), TNM (p = 0.80), or treatment choices (p = 0.94) between pre-pandemic and during-pandemic periods. ...there was no significant difference in the 1-year survival rate between pre-pandemic (2019) and during-pandemic (2020–21) periods for surgery, chemotherapy, or best supportive care (BSC). CONFLICT OF INTEREST STATEMENT The author declare no conflicts of interest for this article.
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Three reviews summarize immune checkpoint inhibitor (ICI) treatments for colorectal cancer, various aspects of rectal cancer, and pathological consideration of tumor deposits. Because immunotherapy ...has been established as an additional treatment approach, multimodal therapy has become mainstream for treating gastrointestinal cancers. ...as these patients have a longer disease duration, the number of patients with cancer and dysplasia owing to inflammation is increasing. ...the authors caution that there is a need for care when malignancies are treated with biological agents, especially in older patients (DOI: 10.1002/ags3.12626). ...Ueno et al. have described tumor deposit (TD) categorization in the TNM classification.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The epithelial–mesenchymal transition (EMT) plays a critical role in embryonic development. EMT is also involved in cancer progression and metastasis and it is probable that a common molecular ...mechanism is shared by these processes. Cancer cells undergoing EMT can acquire invasive properties and enter the surrounding stroma, resulting in the creation of a favorable microenvironment for cancer progression and metastasis. Furthermore, the acquisition of EMT features has been associated with chemoresistance which could give rise to recurrence and metastasis after standard chemotherapeutic treatment. Thus, EMT could be closely involved in carcinogenesis, invasion, metastasis, recurrence, and chemoresistance. Research into EMT and its role in cancer pathogenesis has progressed rapidly and it is now hypothesized that novel concepts such as cancer stem cells and microRNA could be involved in EMT. However, the involvement of EMT varies greatly among cancer types, and much remains to be learned. In this review, we present recent findings regarding the involvement of EMT in cancer progression and metastasis and provide a perspective from clinical and translational viewpoints. (Cancer Sci 2009)
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Since the start of genome medicine in 2019, patients with colorectal cancer and other types of cancer who have been treated with molecular targeted drugs have shown prolonged survival. Recently, we ...were astounded by the efficacy of the clinical trial of Dostralimab, a PD-1 blockade agent which showed complete response in 12 (100%) out of 12 rectal cancer cases harboring deficient MMR genes. Colorectal cancer has critical genomic alterations in the WNT signaling pathway, including APC/β catenin, EGFR/PI3K signaling pathway including KRAS, notch signaling pathway, and TGFβ signaling pathway, and drug discovery targeting these pathways is being conducted worldwide. In general, it is challenging to develop inhibitors for nuclear transcription factors. This review article focuses on the colorectal cancer therapies that target these genetic mutations, including immunotherapy, and presents some relevant information on therapeutics.
The profiles of microRNAs change significantly in gastric cancer. MiR-146a is reported to be a tumor suppressor in pancreatic cancer, breast cancer, and prostate cancer. We investigated the clinical ...significance of miR-146a in gastric cancer, in particular focusing on hypothetical miR-146a target genes, such as epidermal growth factor receptor (EGFR) and interleukin-1 receptor-associated kinase (IRAK1).
We examined miR-146a levels in 90 gastric cancer samples by q-real-time (qRT)-PCR and analyzed the association between miR-146a levels and clinicopathologic factors and prognosis. The regulation of EGFR and IRAK1 by miR-146a was examined with miR-146a-transfected gastric cancer cells. Moreover, we analyzed the association between miR-146a levels and the G/C single nucleotide polymorphism (SNP) within pre-miR-146a seed sequences in 76 gastric cancer samples, using direct sequencing of genomic DNA.
In 90 clinical samples of gastric cancer, miR-146a levels in cancer tissues were significantly lower than those in the corresponding noncancerous tissue (P < 0.001). Lower levels of miR-146a were associated with lymph node metastasis and venous invasion (P < 0.05). Moreover, a lower level of miR-146a was an independent prognostic factor for overall survival (P = 0.003). Ectopic expression of miR-146a inhibited migration and invasion and downregulated EGFR and IRAK1 expression in gastric cancer cells. In addition, G/C SNP within the pre-miR-146a seed sequence significantly reduced miR-146a levels in the GG genotype compared with the CC genotype.
MiR-146a contains an SNP, which is associated with mature miR-146a expression. MiR-146a targeting of EGFR and IRAK1 is an independent prognostic factor in gastric cancer cases.
Colorectal cancer is driven by the accumulation of driver mutations, but the contributions of specific mutations to different steps in malignant progression are not fully understood. In this study, ...we generated mouse models harboring different combinations of key colorectal cancer driver mutations (
) in intestinal epithelial cells to comprehensively investigate their roles in the development of primary tumors and metastases.
mutation caused intestinal adenomas and combination with
mutation or
deletion induced submucosal invasion. The addition of
mutation yielded epithelial-mesenchymal transition (EMT)-like morphology and lymph vessel intravasation of the invasive tumors. In contrast, combinations of
with
and
mutation were insufficient for submucosal invasion, but still induced EMT-like histology. Studies using tumor-derived organoids showed that
was critical for liver metastasis following splenic transplantation, when this mutation was combined with either
plus
or
deletion, with the highest incidence of metastasis displayed by tumors with a
genotype. RNA sequencing analysis of tumor organoids defined distinct gene expression profiles characteristic for the respective combinations of driver mutations, with upregulated genes in
tumors found to be similarly upregulated in specimens of human metastatic colorectal cancer. Our results show how activation of Wnt and Kras with suppression of TGFβ signaling in intestinal epithelial cells is sufficient for colorectal cancer metastasis, with possible implications for the development of metastasis prevention strategies.
These findings illuminate how key driver mutations in colon cancer cooperate to drive the development of metastatic disease, with potential implications for the development of suitable prevention strategies.
.
Modeling colorectal cancer evolution Niida, Atsushi; Mimori, Koshi; Shibata, Tatsuhiro ...
Journal of human genetics,
09/2021, Volume:
66, Issue:
9
Journal Article
Peer reviewed
Open access
Understanding cancer evolution provides a clue to tackle therapeutic difficulties in colorectal cancer. In this review, together with related works, we will introduce a series of our studies, in ...which we constructed an evolutionary model of colorectal cancer by combining genomic analysis and mathematical modeling. In our model, multiple subclones were generated by driver mutation acquisition and subsequent clonal expansion in early-stage tumors. Among the subclones, the one obtaining driver copy number alterations is endowed with malignant potentials to constitute a late-stage tumor in which extensive intratumor heterogeneity is generated by the accumulation of neutral mutations. We will also discuss how to translate our understanding of cancer evolution to a solution to the problem related to therapeutic resistance: mathematical modeling suggests that relapse caused by acquired resistance could be suppressed by utilizing clonal competition between sensitive and resistant clones. Considering the current rate of technological development, modeling cancer evolution by combining genomic analysis and mathematical modeling will be an increasingly important approach for understanding and overcoming cancer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Inflammation plays an essential role in the development and progression of most cancers. Chemokine C‐C motif chemokine 2 (CCL2) and its receptor C‐C chemokine receptor type 2 (CCR2) constitute a key ...signaling axis in inflammation that has recently attracted much interest on the basis of evidence showing its association with cancer progression. Propagermanium (3‐oxygermylpropionic acid polymer) is an organogermanium compound that is given for the treatment of hepatitis B in Japan and which inhibits the CCL2‐CCR2 signaling pathway. Herein, we review the importance of the CCL2‐CCR2 axis as a target in cancer treatment as shown by studies in mice and humans with pharmacological agents including propagermanium.
The chemokine CCL2 and its receptor CCR2 constitute a key signaling axis in inflammation that has recently attracted much interest on the basis of evidence showing its association with cancer progression. Propagermanium (3‐oxygermylpropionic acid polymer) is an organogermanium compound that is given for the treatment of hepatitis B in Japan and which inhibits the CCL2‐CCR2 signaling pathway. Herein, we review the importance of the CCL2‐CCR2 axis as a target in cancer treatment as shown by studies in mice and humans with pharmacological agents including propagermanium.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Cancer is composed of multiple cell populations with different genomes. This phenomenon called intratumor heterogeneity (ITH) is supposed to be a fundamental cause of therapeutic failure. Therefore, ...its principle‐level understanding is a clinically important issue. To achieve this goal, an interdisciplinary approach combining genome analysis and mathematical modeling is essential. For example, we have recently performed multiregion sequencing to unveil extensive ITH in colorectal cancer. Moreover, by employing mathematical modeling of cancer evolution, we demonstrated that it is possible that this ITH is generated by neutral evolution. In this review, we introduce recent advances in a research field related to ITH and also discuss strategies for exploiting novel findings on ITH in a clinical setting.
In this review, we introduce recent findings on intratumor heterogeneity (ITH) revealed by genome analysis and mathematical modeling and also discuss treatment strategies based upon ITH in a clinical setting.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The biological significance of micro (mi)RNAs has traditionally been evaluated according to their RNA expression levels based on the assumption that miRNAs recognize and regulate their targets in an ...unvarying fashion. Here we show that a fraction of mature miRNAs including miR-17-5p, -21-5p, and -200c-3p and let-7a-5p harbor methyl marks that potentially alter their stability and target recognition. Importantly, methylation of these miRNAs was significantly increased in cancer tissues as compared to paired normal tissues. Furthermore, miR-17-5p methylation level in serum samples distinguished early pancreatic cancer patients from healthy controls with extremely high sensitivity and specificity. These findings provide a basis for diagnostic strategies for early-stage cancer and add a dimension to our understanding of miRNA biology.
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