Background and Aim
Currently, some countries still acknowledge double‐contrast barium enema (DCBE) as a backup confirmatory examination when colonoscopy is not feasible or incomplete in colorectal ...cancer (CRC) screening programs. This study aims to compare the performance of colonoscopy and DCBE in terms of the risk of incident CRC after negative results in the fecal immunochemical test (FIT)‐based Taiwan Colorectal Cancer Screening Program.
Methods
Subjects who had positive FITs and received confirmatory exams, either colonoscopy or DCBE, without the findings of neoplastic lesions from 2004 to 2013 in the screening program comprised the study cohort. Both the colonoscopy and DCBE subcohorts were followed until the end of 2018 and linked to the Taiwan Cancer Registry to identify incident CRC cases. Multivariate analysis was conducted to compare the risk of incident CRC in both subcohorts after controlling for potential confounders.
Results
A total of 102 761 colonoscopies and 5885 DCBEs were performed after positive FITs without neoplastic findings during the study period. By the end of 2018, 2113 CRCs (2.7 per 1000 person‐years) and 368 CRCs (7.6 per 1000 person‐years) occurred in the colonoscopy and DCBE subcohorts, respectively. After adjusting for major confounders, DCBE had a significantly higher risk of incident CRC than colonoscopy, with an adjusted HR of 2.81 (95% CI = 2.51–3.14).
Conclusions
In the FIT screening program, using DCBE as a backup examination was associated with a nearly threefold risk of incident CRC compared with colonoscopy, demonstrating that it is no longer justified as a backup examination for incomplete colonoscopy.
Background
To assess the impact of treatment delay on survival of oral/oropharyngeal cancer (OSCC).
Methods
We followed 5743 OSCCs between 2004 and 2009 from a population‐based screening program and ...ascertained death until the end of 2012.
Results
The hazard ratios (HRs) of mortality from OSCC were 1.46 (1.30‐1.65) and 1.18 (1.04‐1.33) in univariable and multivariable analyses, respectively, for treatment delay longer than 6 weeks compared with that shorter than 3 weeks. The corresponding figures were 1.12 (1.01‐1.24) and 1.00 (0.91‐1.11) for treatment delay between 3 and 6 weeks. Advancing age (1.01), higher stage (stage II: 1.84, stage III: 2.97, stage IV: 6.33), cancer in tongue (1.37), or hard palate (1.63) had higher HR of mortality (P < .05). However, treatment at medical center had a lower mortality (0.83, 0.75‐0.91) than local/regional hospital.
Conclusions
Treatment delay longer than 6 weeks for OSCCs detected via a population‐based screening program had unfavorable survival.
The WNT1 inducible signaling pathway protein 1 (WISP1), a member of the connective tissue growth factor family, plays a crucial role in several important cellular functions in a highly ...tissue-specific manner. Results of a RT-qPCR indicated that WISP1 expressed only in cells of the human prostate fibroblasts, HPrF and WPMY-1, but not the prostate carcinoma cells in vitro. Two major isoforms (WISP1v1 and WISP1v2) were identified in the HPrF cells determined by RT-PCR and immunoblot assays. The knock-down of a WISP1 blocked cell proliferation and contraction, while treating respectively with the conditioned medium from the ectopic WISP1v1- and WISPv2-overexpressed 293T cells enhanced the migration of HPrF cells. The TNFα induced WISP1 secretion and cell contraction while the knock-down of WISP1 attenuated these effects, although TNFα did not affect the proliferation of the HPrF cells. The ectopic overexpression of WISP1v1 but not WISP1v2 downregulated the N-myc downstream regulated 1 (NDRG1) while upregulating N-cadherin, slug, snail, and vimentin gene expressions which induced not only the cell proliferation and invasion in vitro but also tumor growth of prostate carcinoma cells in vivo. The results confirmed that WISP1 is a stroma-specific secreting protein, enhancing the cell migration and contraction of prostate fibroblasts, as well as the proliferation, invasion, and tumor growth of prostate carcinoma cells.
The androgen-dependent or -independent pathways are regarded as primary therapeutic targets for the neoplasm of the prostate. Mucosa-associated lymphoid tissue 1 (MALT1) acting as a paracaspase in ...the regulation of nuclear factor κB (NF-κB) signal transduction plays a central role in inflammation and oncogenesis in cancers. This study confirmed the potential linkages between androgen and NF-κB activation by inducing MALT1 in the androgen receptor-full length (ARFL)-positive LNCaP and 22Rv1 prostate cancer cells. Although androgen did not stimulate MALT1 expression in AR-null or ectopic ARFL-overexpressed PC-3 cells, the ectopic overexpression of the AR splicing variant 7 (ARv7) upregulated MALT1 to activate NF-κB activities in 22Rv1 and PC-3 cells. Since the nuclear translocation of p50 and p65 was facilitated by ARv7 to motivate NF-κB activity, the expressions of MALT1, prostate-specific antigen (PSA), and N-myc downstream regulated 1 (NDRG1) were therefore induced in ectopic ARv7-overexpressed prostate cancer cells. Ectopic ARv7 overexpression not only enhanced 22Rv1 or PC-3 cell growth and invasion in vitro but also the tumor growth of PC-3 cells in vivo. These results indicate that an androgen receptor induces MALT1 expression androgen-dependently and -independently in ARFL- or ARv7-overexpressed prostate cancer cells, suggesting a novel ARv7/MALT1/NF-κB-signaling pathway may exist in the cells of prostate cancer.
Oral cancer is the fourth most common cancer among men in Taiwan. The age-standardized incidence rate of oral cancer among men in Taiwan has increased since 1980 and became six times greater in 2014. ...To enable effective public health planning for oral cancer, research on the projection of oral cancer burden is essential. We conducted an age-period-cohort analysis on the incidence of oral cancer among men in Taiwan from 1997 to 2017 and extrapolated the trend to 2025. We found that the period trends for young adults aged between 25 and 44 have already peaked before 2017; the younger, the earlier, and then the trends declined. The cohort trends have peaked roughly at the 1972 birth cohort and then declined for all ages. Despite the increasing trend in the age-standardized incidence rate for oral cancer among men in Taiwan from 1997 to 2017, we forecast a peak attained, an imminent decline after 2017, and a decrease of 8.4% in age-standardized incidence rate from 2017 to 2025. The findings of this study contribute to developing efficient and comprehensive strategies for oral cancer prevention and control.
Caffeic acid phenethyl ester (CAPE), a honeybee propolis-derived bioactive ingredient, has not been extensively elucidated regarding its effect on prostate cancer and associated mechanisms. The ...mucosa-associated lymphoid tissue 1 gene (
) modulates NF-κB signal transduction in lymphoma and non-lymphoma cells. We investigated the functions and regulatory mechanisms of CAPE in relation to
in prostate carcinoma cells. In p53- and androgen receptor (AR)-positive prostate carcinoma cells, CAPE downregulated AR and
expression but enhanced that of p53, thus decreasing androgen-induced activation of MALT1 and prostate-specific antigen expressions. p53 downregulated the expression of MALT in prostate carcinoma cells through the putative consensus and nonconsensus p53 response elements. CAPE downregulated
expression and thus inhibited NF-κB activity in p53- and AR-negative prostate carcinoma PC-3 cells, eventually reducing cell proliferation, invasion, and tumor growth in vitro and in vivo. CAPE induced the ERK/JNK/p38/AMPKα1/2 signaling pathways; however, pretreatment with the corresponding inhibitors of MAPK or AMPK1/2 did not inhibit the CAPE effect on MALT1 blocking in PC-3 cells. Our findings verify that CAPE is an effective antitumor agent for human androgen-dependent and -independent prostate carcinoma cells in vitro and in vivo through the inhibition of MALT1 expression via the AR/p53/NF-κB signaling pathways.
Growth differentiation factor-15 (GDF15), a member of the TGF-β superfamily, affects tumor biology of certain cancers, but remains poorly understood in bladder cancer cells. This study determined the ...expression, regulation, function, and potential downstream target genes of GDF15 in bladder carcinoma cells. The transitional papilloma carcionoma cells (RT4) expressed higher levels of GDF15 as compared with the bladder carcinoma cells (HT1376 and T24). Treatments of recombinant human GDF15 (rhGDF15) reduced the proliferations of HT1376 and T24 cells. Expression of GDF15 was upregulated via DNA demethylation and p53. The cell proliferation, invasion, and tumorigenesis were reduced in ectopic overexpression of GDF15, while enhanced in GDF15 knockdown. The expressions of mammary serine protease inhibitor (MASPIN) and N-myc downstream-regulated family genes (NDRG1, NDRG2, and NDRG3) were upregulated by GDF15 overexpressions and rhGDF15 treatments in bladder carcinoma cells. GDF15 knockdown induced epithelial-mesenchymal transition (EMT) and F-actin polarization in HT1376 cells. Our results suggest that enhanced expressions of MASPIN and N-myc downstream-regulated family genes and the modulation of EMT may account for the inhibitory functions of GDF15 in the cell proliferation, invasion, and tumorigenesis of bladder carcinoma cells. The GDF15 should be considered as a tumor suppressor in human bladder carcinoma cells.
Colorectal cancer (CRC) remains a significant public health concern. This study aims to provide a comprehensive understanding of the effectiveness of fecal immunochemical test (FIT) screening on CRC ...incidence and mortality, leveraging the scale of over 1.5 million randomly selected Taiwanese and more than 11.7 million person-years of follow-up.
This prospective cohort study merges data from 3 robust Taiwanese health databases: the CRC screening program, cancer registration, and death registration databases. Incidence and mortality rates of CRC were calculated based on age, sex, urbanization, and past screening status. Cox proportional hazard models were used to assess the association between screening statuses and CRC incidence or mortality, adjusting for age, sex, and urbanization levels. Statistical analysis of the data was conducted in 2021–2022.
FIT screening was associated with a 33% reduction in CRC incidence and a 47% reduction in mortality. The study identified a dose-response relationship between the fecal hemoglobin concentration (f-HbC) levels and CRC risk. Participants with consistent FIT-negative results had significantly reduced CRC incidence and mortality risks, while those with one or more positive FIT results faced increased risks. Notably, compliance with follow-up examinations after a positive FIT significantly lowered mortality risk.
This large-scale study validates the efficacy of FIT screening in reducing CRC incidence and mortality. It offers a nuanced understanding of how various screening statuses impact CRC risks, thus providing valuable insights for public health strategies aimed at CRC prevention.
Gastric cancer is an inflammation-related cancer triggered by Helicobacter pylori infection. Understanding of the natural disease course has prompted the hypothesis that gastric cancer can be ...prevented by administering a short-course antibiotic treatment to eradicate the H. pylori infection and interrupt this carcinogenic cascade. Results from randomized controlled trials and cohort studies have repeatedly confirmed this concept, which has moved attention from individual management of H. pylori infection to population-wide implementation of screening programs. Such a paradigm shift follows a three-tier architecture. First, healthcare policy-makers determine the most feasible and applicable eligibility, invitation, testing, referral, treatment, and evaluation methods for an organized screening program to maximize the population benefits and cost-effectiveness. Second, provision of knowledge and effective feedback to frontline general practitioners, including choice of diagnostic tests, selection of eradication regimens, and the indication of endoscopic examination, ensures the quality of care and increases the likelihood of desired treatment responses. Third, initiatives to raise population awareness are designed regarding the impact of H. pylori infection and risky lifestyle habits on the stomach health. These programs, with increased accessibility and geographic coverage in progress, will accelerate the decline in morbidity, mortality, and associated costs of this preventable malignancy.
Functions of metallothionein 2A (MT2A) in bladder cancer have not been extensively explored even though metallothioneins are regarded as modulators in several biological regulations including ...oxidation and cancerous development. We evaluated MT2A in bladder carcinoma cells in terms of the mechanisms of regulation and the underlying functions. MT2A overexpression not only downregulated endogenous ROS but also blocked ROS induced by H2O2. We used the annexin V-FITC apoptosis assay to determine the modulation of H2O2-induced cell apoptosis by MT2A expression. Results of immunoblot and reporter assays indicated that caffeic acid phenethyl ester (CAPE) treatment induced MT2A and heme oxygenase-1 (HO-1) expressions; moreover, the involvement of CAPE in either upregulation of the HO-1 expression or downregulation of endogenous ROS is MT2A dependent in bladder carcinoma cells. Knockdown of MT2A increased invasion and cell growth in vitro and in vivo, whereas ectopic overexpression of MT2A had the reverse effect in bladder carcinoma cells. Unlike bladder cancer tissues, the real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) analysis showed a significant level of MT2A mRNA in the normal bladder tissues. Collectively, our results indicated that MT2A is acting as an antioxidant and also a tumor suppressor in human bladder carcinoma cells.
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