OBJECTIVE: Patients diagnosed with advanced metastatic colorectal cancer (CRC) confront a bleak prognosis characterized by low survival rates. Anoikis, the programmed apoptosis resistance exhibited by metastatic cancer cells, is a crucial factor in this scenario.
METHODS: We employed bulk flow cytometry and RT-qPCR assays, conducted in vivo experiments with mice and zebrafish, and analyzed patient tissues to examine the effects of the B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1)-midkine (MDK) axis on the cellular response to anoikis. Bmi1 is pivotal in tumorigenesis. This study elucidated the involvement of Bmi1 in conferring anoikis resistance in CRC and explored its downstream targets associated with metastasis.
RESULTS: Elevated levels of Bmi1 expression correlated with distant metastasis in CRC. Suppression of Bmi1 significantly diminished the metastatic potential of CRC cells. Inhibition of Bmi1 led to an increase in the proportion of apoptotic SW620 cells detached from the matrix. This effect was further enhanced by the addition of irinotecan, a topoisomerase I inhibitor. Furthermore, Bmi1 was found to synergize with MDK in modulating CRC viability, with consistent expression patterns observed in in vivo models and clinical tissue specimens. In summary, Bmi1 acted as a regulator of CRC metastatic capability by conferring anoikis resistance. Additionally, it collaborated with MDK to facilitate invasion and distant metastasis.
CONCLUSIONS: Targeting Bmi1 may offer a promising adjunctive therapeutic strategy when administering traditional chemotherapy regimens to patients with advanced CRC.

The long-term impact of the coronavirus disease 2019 (COVID-19) pandemic on the disruption of gastrointestinal cancer diagnoses remains unclear. This study investigated the actual impact on esophagogastric cancer (EGC) and colorectal cancer (CRC) diagnoses up to the third year of the pandemic in Akita Prefecture, Japan, using population-based registry data. We collected data on the annual number of EGC and CRC diagnoses using a database from the collaborative Akita Prefecture hospital-based registration. The net number of cancers diagnosed in the first three years of the pandemic (2020-2022) were compared with those diagnosed in the three years before the pandemic (2017-2019). Changes in the proportion of cancer stage and initial treatment for diagnosed EGC and CRC after the pandemic were then compared. The total number of EGCs was 9.3% lower in the first three years of the pandemic than in the three years before, probably due to its long-term declining trend. The total number of CRCs in the first three years of the pandemic exceeded that in the three years before, suggesting successful recovery of the diagnostic procedure. The proportion of cancer stages and initial treatment for EGCs and CRCs remained largely unchanged after the onset of the pandemic. Based on the population-based registry data from the first three years of the pandemic, the disruption of gastrointestinal cancer diagnoses caused by the pandemic is settling down without any substantial disease progression, even in Akita Prefecture, the area with the highest incidence of cancer in all of Japan.

A series of mono- and heteronuclear platinum(II) and zinc(II) complexes with 4,4\',4″-tri-tert-butyl-2,2\':6\',2″-terpyridine ligand were synthesized and characterized. The DNA and protein binding properties of [ZnCl2(terpytBu)] (C1), [{cis-PtCl(NH3)2(μ-pyrazine)ZnCl(terpytBu)}](ClO4)2 (C2), [{trans-PtCl(NH3)2(μ-pyrazine)ZnCl(terpytBu)}](ClO4)2 (C3), [{cis-PtCl(NH3)2(μ-4,4\'-bipyridyl)ZnCl(terpytBu)}](CIO4)2 (C4) and [{trans-PtCl(NH3)2(μ-4,4\'-bipyridyl)ZnCl(terpytBu)}](CIO4)2 (C5) (where terpytBu = 4,4\',4″-tri-tert-butyl-2,2\':6\',2″-terpyridine), were investigated by electronic absorption, fluorescence spectroscopic, and molecular docking methods. Complexes featuring transplatin exhibited lower Kb and Ksv constant values compared to cisplatin analogs. The lowest Ksv value belonged to complex C1, while C4 exhibited the highest. Molecular docking studies reveal that the binding of complex C1 to DNA is due to van der Waals forces, while that of C2-C5 is due to conventional hydrogen bonds and van der Waals forces. The tested complexes exhibited variable cytotoxicity toward mouse colorectal carcinoma (CT26), human colorectal carcinoma (HCT116 and SW480), and non-cancerous mouse mesenchymal stem cells (mMSC). Particularly, the mononuclear C1 complex showed pronounced selectivity toward cancer cells over non-cancerous mMSC. The C1 complex notably induced apoptosis in CT26 cells, effectively arrested the cell cycle in the G0/G1 phase, and selectively down-regulated Cyclin D.

BACKGROUND: Tumor deposits (TDs) are emerging as an adverse prognostic factor in colorectal cancers (CRCs). However, TDs are somewhat neglected in the current staging system. It has been proposed either to add the TD count to the number of metastatic lymph nodes or to consider TDs as distant metastases; however, the scientific basis for these proposals seems questionable. This study aimed to investigate a new staging system.
METHODS: A total of 243 consecutive patients with stage III CRC who were undergoing curative resection and adjuvant chemotherapy were included. Each substage of stage III TNM was split according to the absence or presence of TDs. Receiver operating characteristic (ROC) curves and bootstrap methods were used to compare the current vs the new competing staging system in terms of oncologic outcome prediction.
RESULTS: A high rate of TDs was recorded (124 cases [51%]). TDs were correlated with other adverse prognostic indicators, particularly vascular and perineural invasions, and showed a negative correlation with the number of removed lymph nodes, suggesting a possible multimodal origin. In addition, TDs were confirmed to have a negative impact on oncologic outcome, regardless of their counts. Compared with the current staging system, the new classification displayed higher values at survival ROC analysis, a significantly better stratification of patients, and effective identification of patients at high risk of recurrence.
CONCLUSIONS: TDs negatively affect the prognosis in CRCs. A revision of the staging system could be useful to optimize treatments. The proposed new classification is easy to implement and more accurate than the current one. This study was registered online on the ClinicalTrials.gov website under the following identifier: NCT05923450.

Epidemiological studies have spotlighted the intricate relationship between individual oral bacteria and tumor occurrence. Porphyromonas gingivalis and Fusobacteria nucleatum, which are known periodontal pathogens, have emerged as extensively studied participants with potential pathogenic abilities in carcinogenesis. However, the complex dynamics arising from interactions between these two pathogens were less addressed. This narrative review aims to summarize the current knowledge on the prevalence and mechanism implications of P. gingivalis and F. nucleatum in the carcinogenesis of oral squamous cell carcinoma (OSCC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC). In particular, it explores the clinical and experimental evidence on the interplay between P. gingivalis and F. nucleatum in affecting oral and gastrointestinal carcinogenesis. P. gingivalis and F. nucleatum, which are recognized as keystone or bridging bacteria, were identified in multiple clinical studies simultaneously. The prevalence of both bacteria species correlated with cancer development progression, emphasizing the potential impact of the collaboration. Regrettably, there was insufficient experimental evidence to demonstrate the synergistic function. We further propose a hypothesis to elucidate the underlying mechanisms, offering a promising avenue for future research in this dynamic and evolving field.

A deficient DNA mismatch repair (MMR) system is identified in a non-negligible part of sporadic colorectal cancers (CRCs), and its prognostic value remains controversial. High tumor mutational burden, along with a poor response to conventional chemotherapy and excellent results from immunotherapy, are the main features of this subset. The aim of this study was to evaluate the predictive value of DNA MMR system status for its best treatment. Four hundred and three CRC patients, operated on from 2014 to 2021 and not treated with immunotherapy, entered this study. Immunohistochemistry and polymerase chain reaction, as appropriate, were used to unequivocally group specimens into microsatellite stable (MSS) and instable (MSI) tumors. The win-ratio approach was utilized to compare composite outcomes. MSI tumors accounted for 12.9% of all series. The right tumor location represented the most important factor related to MSI. The status of the DNA MMR system did not appear to correlate with outcome in early-stage CRCs not requiring adjuvant treatment; in advanced stages undergoing conventional chemotherapy, MSI tumors showed significantly poorer overall and disease-free survival rates and the highest win ratio instead. The determination of DNA MMR status is crucial to recommending correct management. There is clear evidence that instable CRCs needing adjuvant therapy should undergo appropriate treatments.

BACKGROUND: Recent nationwide studies of disparities in cancer incidence by income are scarce in Korea. This study investigated such disparities in cancer incidence and the stage at cancer diagnosis across income groups in Korea.
METHODS: This study utilized data from a national cancer database, specifically focusing on cases recorded in the year 2018. Income levels were categorized into quintiles according to the insurance premium paid in addition to the Medicaid benefit. The slope index of inequality (SII) and relative index of inequality (RII) were used to measure absolute and relative differences in cancer incidence by income. A multivariable logistic regression was performed to estimate the risk of a distant stage at cancer diagnosis.
RESULTS: The total number of cases of incident cancer was 223,371 (men: 116,320, women: 107,051) with shares of the total of 29.5% (5Q), 20.4% (4Q), 16.0% (3Q), 13.5% (2Q), 15.6% (1Q), and 5% (Medicaid). The most common cancer type was thyroid cancer, followed by gastric and colorectal cancers. The age-standardized incidence rate for all cancers was lowest in the highest income group, but the SII was not statistically significant (SII: -35.7), and the RII was -0.07. Colorectal and cervical cancers had lower incidence rates for higher income groups, while thyroid and prostate cancers had higher incidence rates for higher income groups. The odds ratio for a distant stage at diagnosis for all cancers increased for lower income groups relative to 5Q.
CONCLUSIONS: Disparities in cancer incidence in a Korean population differed by cancer type, and lower income was a significant predictor of a distant stage at diagnosis for cancers overall. These results emphasize the need for further study of the underlying causes of disparities in cancer incidence and the stage at diagnosis, as well as the need for interventions to mitigate these disparities.

Cannabidiol (CBD) is a chemical obtained from Cannabis sativa; it has therapeutic effects on anxiety and cognition and anti-inflammatory properties. Although pharmacological applications of CBD in many types of tumors have recently been reported, the mechanism of action of CBD is not yet fully understood. In this study, we perform an mRNA-seq analysis to identify the target genes of CBD after determining the cytotoxic concentrations of CBD using an MTT assay. CBD treatment regulated the expression of genes related to DNA repair and cell division, with metallothionein (MT) family genes being identified as having highly increased expression levels induced by CBD. It was also found that the expression levels of MT family genes were decreased in colorectal cancer tissues compared to those in normal tissues, indicating that the downregulation of MT family genes might be highly associated with colorectal tumor progression. A qPCR experiment revealed that the expression levels of MT family genes were increased by CBD. Moreover, MT family genes were regulated by CBD or crude extract but not by other cannabinoids, suggesting that the expression of MT family genes was specifically induced by CBD. A synergistic effect between CBD and MT gene transfection or zinc ion treatment was found. In conclusion, MT family genes as novel target genes could synergistically increase the anticancer activity of CBD by regulating the zinc ions in human colorectal cancer cells.

Colorectal cancer (CRC) is one of the deadliest malignancies in the US, ranking fourth after lung, prostate, and breast cancers, respectively, in general populations. It continues to be a menace, and the incidence has been projected to more than double by 2035, especially in underdeveloped countries. This review seeks to provide some insights into the disease progression, currently available treatment options and their challenges, and future perspectives. Searches were conducted in the PubMed search engine in the university\'s online library. The keywords were \"Colorectal Cancer\" AND \"disease process\" OR \"disease mechanisms\" OR \"Current Treatment\" OR \"Prospects\". Selection criteria were original articles published primarily during the period of 2013 through 2023. Abstracts, books and documents, and reviews/systematic reviews were filtered out. Of over 490 thousand articles returned, only about 800 met preliminary selection criteria, 200 were reviewed in detail, but 191 met final selection criteria. Fifty-one other articles were used due to cross-referencing. Although recently considered a disease of lifestyle, CRC incidence appears to be rising in countries with low, low-medium, and medium social demographic indices. CRC can affect all parts of the colon and rectum but is more fatal with poor disease outcomes when it is right-sided. The disease progression usually takes between 7-10 years and can be asymptomatic, making early detection and diagnosis difficult. The CRC tumor microenvironment is made up of different types of cells interacting with each other to promote the growth and proliferation of the tumor cells. Significant advancement has been made in the treatment of colorectal cancer. Notable approaches include surgery, chemotherapy, radiation therapy, and cryotherapy. Chemotherapy, including 5-fluorouracil, irinotecan, oxaliplatin, and leucovorin, plays a significant role in the management of CRC that has been diagnosed at advanced stages. Two classes of monoclonal antibody therapies have been approved by the FDA for the treatment of colorectal cancer: the vascular endothelial growth factor (VEGF) inhibitor, e.g., bevacizumab (Avastin®), and the epidermal growth factor receptor (EGFR) inhibitor, e.g., cetuximab (Erbitux®) and panitumumab (Verbitix®). However, many significant problems are still being experienced with these treatments, mainly off-target effects, toxic side effects, and the associated therapeutic failures of small molecular drugs and the rapid loss of efficacy of mAb therapies. Other novel delivery strategies continue to be investigated, including ligand-based targeting of CRC cells.

Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The applications of oncology, transplant medicine, and surgery are the core of transplant oncology to improve patients\' survival and quality of life. The main concept of transplant oncology is to radically cure cancer by removing the diseased organ and replacing it with a healthy one, aiming to improve the survival outcomes and quality of life of cancer patients. Subsequently, it seeks to expand the treatment options and research for hepatobiliary malignancies, which have seen significantly improved survival outcomes after the implementation of liver transplantation (LT). In the case of colorectal cancer (CRC) in the transplant setting, where the liver is the most common site of metastasis of patients who are considered to have unresectable disease, initial studies have shown improved survival for LT treatment compared to palliative therapy interventions. The indications of LT for hepatobiliary malignancies have been slowly expanded over the years beyond Milan criteria in a stepwise manner. However, the outcome improvements and overall patient survival are limited to the specifics of the setting and systematic intervention options. This review aims to illustrate the representative concepts and history of transplant oncology as an emerging discipline for the management of hepatobiliary malignancies, in addition to other emerging concepts, such as the uses of immunotherapy in a peri-transplant setting as well as the use of circulating tumor DNA (ctDNA) for surveillance post-transplantation.