Gut microbiota have been implicated in the development of colorectal cancer. We evaluated the utility of fecal bacterial marker candidates identified by our metagenome sequencing analysis for ...colorectal cancer diagnosis.
Subjects (total 439; 203 colorectal cancer and 236 healthy subjects) from two independent Asian cohorts were included. Probe-based duplex quantitative PCR (qPCR) assays were established for the quantification of bacterial marker candidates.
Candidates identified by metagenome sequencing, including
(
),
(
),
(
),
(
), and one undefined species (labeled as
), were examined in fecal samples of 203 colorectal cancer patients and 236 healthy controls by duplex-qPCR. Strong positive correlations were demonstrated between the quantification of each candidate by our qPCR assays and metagenomics approach (
= 0.801-0.934, all
< 0.0001).
was significantly more abundant in colorectal cancer than controls (
< 0.0001), with AUROC of 0.868 (
< 0.0001). At the best cut-off value maximizing sum of sensitivity and specificity,
discriminated colorectal cancer from controls with a sensitivity of 77.7%, and specificity of 79.5% in cohort I. A simple linear combination of four bacteria (
+
+
-
) showed an improved diagnostic ability compared with
alone (AUROC = 0.886,
< 0.0001) in cohort I. These findings were further confirmed in an independent cohort II. In particular, improved diagnostic performances of
alone (sensitivity 92.8%, specificity 79.8%) and four bacteria (sensitivity 92.8%, specificity 81.5%) were achieved in combination with fecal immunochemical testing for the detection of colorectal cancer.
Stool-based colorectal cancer-associated bacteria can serve as novel noninvasive diagnostic biomarkers for colorectal cancer.
.
Colorectal cancer (CRC) is the third most prevalent cancer and the third highest cancer-related mortality in the United States. Bigelovin, a sesquiterpene lactone isolated from Inula helianthus ...aquatica, has been proven to induce apoptosis and exhibit anti-inflammatory and anti-angiogenic activities. However, the effects of bigelovin on CRC and underlying mechanisms have not been explored. The present study demonstrated that bigelovin exhibited potent anti-tumor activities against CRC in vitro and in vivo. Bigelovin suppressed cell proliferation and colony formation and induced apoptosis in human colorectal cancer HT-29 and HCT 116 cells in vitro. Results also revealed that bigelovin activated caspases, caused the G2/M cell cycle arrest and induced DNA damage through up-regulation of death receptor (DR) 5 and increase of ROS. In HCT 116 xenograft model, bigelovin treatment resulted in suppression of tumor growth. Bigelovin at 20 mg/kg showed more significant tumor suppression and less side effects than conventional FOLFOX (containing folinic acid, 5-fluorouracil and oxaliplatin) treatment. In addition, in vivo data confirmed that anti-tumor activity of bigelovin in CRC was through induction of apoptosis by up-regulating DR5 and increasing ROS. In conclusion, these results strongly suggested that bigelovin has potential to be developed as therapeutic agent for CRC patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Colorectal cancer is the third most frequently diagnosed cancer worldwide. Clinically, chemotherapeutic agents such as FOLFOX are the mainstay of colorectal cancer treatment. However, the side ...effects including toxicity of FOLFOX stimulated the enthusiasm for developing adjuvants, which exhibit better safety profile. Turmeric extract (TE), which has been previously shown to suppress the growth of human and murine colon xenografts, was further demonstrated here for its inhibitory effects on colon cancer patient-derived xenografts (PDX). PDX models were successfully established from tissues of colon cancer patients and the PDX preserved the heterogeneous architecture through passages. NOD/SCID mice bearing PDX were treated either with TE or FOLFOX and differential responses toward these treatments were observed. The growth of PDX, metastasis and tumor recurrence in PDX-bearing mice were suppressed after TE treatments with 60% anti-tumor response rate and 83.3% anti-metastasis rate. Mechanistic studies showed that TE reduced tumor cell proliferation, induced cell apoptosis, inhibited metastasis
modulating multiple targets, such as molecules involved in Wnt and Src pathways, EMT and EGFR-related pathways. Nevertheless, FOLFOX treatments inhibited the PDX growth with sharp decreases of mice body weight and only mild anti-metastasis activities were observed. Furthermore, in order to have a better understanding of the underlying mechanisms, network pharmacology was utilized to predict potential targets and mechanism. In conclusion, the present study demonstrated for the first time that oral TE treatment was effective to suppress the growth of colon PDX and the recurrence of colon tumors in mice. The findings obtained from this clinically relevant PDX model would certainly provide valuable information for the potential clinical use of TE in colorectal cancer patients. The application of PDX model was well illustrated here as a good platform to verify the efficacy of multi-targeted herbal extracts.
IntroductionFear of cancer recurrence (FCR) is a prevalent and frequently debilitating response to a cancer diagnosis, affecting a substantial proportion of cancer survivors. Approximately 30% of ...local Hong Kong Chinese cancer survivors in a recent survey reportedly experienced persistent high FCR over the first-year post-surgery. This was associated with lower levels of psychological well-being and quality of life. A manualised intervention (ConquerFear) developed primarily based on the Self-Regulatory Executive Function Model and the Rational Frame Theory, has been found to reduce FCR effectively among Caucasian cancer survivors. The intervention now has been adapted to a Chinese context; ConquerFear-HK. The primary aim of this study is to evaluate its efficacy vs a standard-survivorship-care control (BasicCancerCare) in FCR improvement in a randomised control trial (RCT).Methods and analysisIn this RCT, using the sealed envelope method, 174 eligible Chinese cancer survivors will be randomised to either the ConquerFear-HK or BasicCancerCare intervention. Both interventions include six sessions over 10 weeks, which will be delivered via face to face or online by trained therapists. The ConquerFear-HK intervention incorporates value classification, metacognitive therapy, attentional training, detached mindfulness and psychoeducation; BasicCancerCare includes relaxation training, dietary and physical activity consultations. Participants will be assessed at prior randomisation (baseline; T0), immediately postintervention (T1), 3 months (T2) and 6 months postintervention (T3) on the measures of FCR (Fear of Cancer Recurrence Inventory) as a primary outcome; metacognition (30-item Metacognitions Quesionnaire) and cognitive attentional syndrome (Cognitive-attentional Syndrome Questionnaire) as process outcomes; psychological distress (Hospital Anxiety and Depression Scale), cancer-related distress (Chinese Impact of Events Scale), quality of life (European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire) and treatment satisfaction are secondary outcomes.Ethics and disseminationEthics approval has been obtained from HKU/HA HKW Institutional Review Board (ref: UW19-183). The patients/participants provide their written informed consent to participate in this study. The study results will be disseminated through international peer-review publications and conference presentations.Trial registration numberNCT04568226.
Purpose: This study was performed to evaluate the outcome of implementation of transanal total mesorectal excision (TaTME) for low rectal cancer in a regional hospital and in comparison to ...laparoscopic (Lap) TME.Methods: Consecutive patients with low rectal cancer of which the lowest border of the tumour was located beween 1 and 5 cm from the puborectalis who underwent TME at North District Hospital between January 2013 and December 2019 were included. Clinical, operative, and pathologic outcomes were compared between Lap TME and TaTME. The primary end point was complication profile.Results: Thirty-five patients underwent Lap TME and 45 patients underwent TaTME for low rectal cancer. The conversion rate of the TaTME group was significantly lower than that of the Lap TME group (4.4% vs. 20%, P=0.029), but the operating time was longer (259 minutes vs. 219 minutes, P=0.009). The tumour location was significantly lower in the TaTME group, but the distal resection margins were adequate and not different between both groups. The TaTME group had higher incidence rates of prolonged ileus and urinary tract infection, but the other complications were similar between the two groups. The resection margin positivity rates of the TaTME and Lap TME groups were 2.2% and 5.7%, respectively (P=0.670). At a median follow up of 39 months, no abnormal early recurrence was detected.Conclusion: It is technically feasible and oncologically safe to perform TaTME in a medium-volume colorectal unit. Patients with difficult pelvic anatomy can benefit by reducing the risk of conversion and margin positivity rate.
Colorectal cancer(CRC)is one of the most prevalent cancers in developed countries.On the other hand,CRC is also one of the most curable cancers if it is detected in early stages through regular ...colonoscopy or sigmoidoscopy.Since CRC develops slowly from precancerous lesions,early detection can reduce both the incidence and mortality of the disease.Fecal occult blood test is a widely used non-invasive screening tool for CRC.Although fecal occult blood test is simple and cost-effective in screening CRC,there is room for improvement in terms of the accuracy of the test.Genetic dysregulations have been found to play an important role in CRC development.With better understanding of the molecular basis of CRC,there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC.In this review,the molecular basis of CRC development,the characteristics and applications of different non-invasive molecular biomarkers,as well as the technologies available for the detection were discussed.This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state,colorectal adenoma.
•Non-cirrhotic non malignant acute mescenteric thrombosis could lead to massive bowel ischaemia and is challenging to manage.•Conventional PV or SMV exploration is associated with significant blood ...lost, physiological disturbances and may need repeated procedures.•Catheter directed thrombolysis and thrombectomy provide minimal invasive option to restore patency of PV or SMV.•Literature review found high success rate and favourable outcome.•Catheter directed therapy should be the first line therapy.
To present two cases of acute non-cirrhotic and non-malignant mesenteric vein thrombosis (MVT) treated with early transcatheter thrombectomy and thrombolysis with tissue plasminogen activator (tPA) and to review the literature on transcatheter thrombectomy and thrombolytic therapy of such condition.
Two cases of acute MVT treated with transhepatic transcatheter thrombectomy and thrombolysis in addition to systemic anticoagulation upon diagnosis are presented. In addition, a Pubmed literature search was undertaken using keywords acute mesenteric vein thrombosis, thrombolysis and thrombectomy. The inclusion criteria were studies examining the impacts of transcatheter thrombolysis and thrombectomy in the management of acute MVT.
Early transcatheter thrombectomy and thrombolysis achieves technical success in both patients and result in nearly complete recanalization of the venous system, with no recurrent thrombosis to date in follow up. Both patients do not require extensive bowel resection despite extensive thrombus on presentation. However, both patients develop intra-abdominal bleeding requiring blood transfusion and embolization of the transcatheter tract.
Catheter-directed first approach provides a minimal invasive approach for management of non-malignant and non-cirrhotic acute mesenteric thrombosis. It offers the benefits of rapid venous recanalization and avoid massing bowel resection despite extensive thrombosis. Subsequent progression into chronic MVT was also reduced. However, the procedure could lead to bleeding from puncture site and hence embolization of the catheter tract is advised during catheter removal.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Environmental exposures are contributing factors to prostate cancer etiology, but these remain unclear. We aimed to document the associations between environmental risk factors and prostate cancer in ...Chinese, with special reference to bisphenol A (BPA).
We recruited 431 newly diagnosed prostate cancer cases and 402 age-matched controls from Prince of Wales Hospital in Hong Kong. We obtained each participant's clinical data and epidemiological information on chronic BPA exposure and other environmental risk factors (e.g., dietary habits, occupation and shift work) using a standard questionnaire. A new assessment tool of environmental BPA exposure was developed and replicated. Multiple logistic regression analysis was performed to examine odds ratio (OR) and 95% confidence interval (95% CI) for the association of prostate cancer with a novel cumulative BPA exposure index (CBPAI) and other environmental risk factors.
Weekly consumption of deep fried food (OR=1.85, 95% CI: 1.15–2.95) and pickled vegetable (OR=1.87, 95% CI: 1.07–3.28) was significantly associated with excessive prostate cancer risk. Prostate cancer was positively associated with nightshift work (OR=1.76, 95% CI: 1.07–2.89) and it was negatively associated with green tea drinking (OR=0.56, 95% CI: 0.34–0.91). There was a positive exposure-response relationship between CBPAI and prostate cancer, with the greatest and significant risk in the high versus reference category (OR=1.57, 95% CI: 1.01–2.44).
Frequent consumption of deep fried food and pickled vegetable, non-habitual green tea drinking and nightshift work are the contributing risk factors to prostate cancer in Hong Kong Chinese. More importantly, this study provides the first epidemiological evidence on carcinogenicity of BPA on the human prostate.
•We provide the first epidemiological evidence that environmental exposure to BPA may increase prostate cancer risk.•Weekly drinking of cold boiled water kept in plastic containers is probably the most significant dietary source of BPA.•Prostate cancer risk is positively linked to nightshift work, frequent intake of deep fried food and pickled vegetable.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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